USE OF A CATIONIC LIPOSOME OF PACLITAXEL IN THE PREPARATION OF A MEDICINE AND METHOD FOR TREATING AN ADVANCED SOLID TUMOR AND IMPROVING THE EFFICACY OF A SYSTEMIC THERAPEUTIC DRUG IN A TUMOR

Abstract

The present invention provides a use of a paclitaxel cationic liposome in preparation of a drug for treating advanced solid tumors, a use of the paclitaxel cationic liposome and a system therapeutic drug in preparation of a drug for treating advanced solid tumors, and a method for treating advanced solid tumors. A therapeutically effective amount of paclitaxel cationic liposome is administered to patients with advanced solid tumors, or a therapeutically effective amount of paclitaxel cationic liposome and system therapeutic drug is administered to patients with advanced solid tumors.

Description

1 / 40 USE OF A CATIONIC LIPOSOME OF PACLITAXEL IN THE PREPARATION OF A MEDICINE AND METHOD FOR TREATING AN ADVANCED SOLID TUMOR AND IMPROVING THE EFFICACY OF A SYSTEMIC THERAPEUTIC DRUG IN A TUMOR. CROSS-REFERENCE ON RELATED REQUEST.

[0001] This application claims the benefit of priority from Chinese Patent Application No. 202310046953.0, filed January 31, 2023, the entire content of which is incorporated herein by reference. TECHNICAL FIELD

[0002] This disclosure pertains to the antitumor field and relates specifically to an arterial infusion regimen of paclitaxel cationic liposomes in combination with systemic therapy, an arterial infusion regimen of paclitaxel cationic liposomes alone, and use in the preparation of a medicament to treat tumors, particularly advanced solid tumors such as gastric cancer, pancreatic cancer, and liver metastases of colorectal cancer. FUNDAMENTALS

[0003] Paclitaxel is a tricyclic diterpenoid that was first isolated from the bark of Taxus brevifolia by Wani et al., who also confirmed the chemical structure of paclitaxel. Paclitaxel is an antimicrotubule drug capable of inducing and promoting microtubule assembly and with the functions of polymerizing and stabilizing microtubules, which interfere with microtubule rearrangement and result in the cessation of mitosis, thus inhibiting the growth of tumor cells.

[0004] The cationic liposome is a novel form of drug delivery. Paclitaxel cationic drugs are not yet available worldwide. A similar drug, Endo TAG-1, is currently in clinical trials.

[0005] Gastric cancer refers to a malignant tumor of origin Petition 870260061141, dated 06 / 22 / 2026, page 11 / 90 2 / 40 epithelial originating in the stomach. According to the most recent data from China in 2020, gastric cancer ranks third in incidence and mortality among all types of malignant tumors. There are approximately 1.2 million new cases of gastric cancer worldwide each year, about 40% of which occur in China. Early gastric cancer in China accounts for a very low proportion, only about 20%. Most gastric cancers are already in the progressive stage when detected, with an overall 5-year survival rate of less than 50%.

[0006] The incidence and mortality of colorectal cancer in China rank third and fifth, respectively, among all malignant tumors, with 376,000 new cases and 191,000 deaths. Among these, the incidence and mortality in urban areas are much higher than in rural areas, and the incidence of colon cancer has increased significantly. Most patients were diagnosed at mid- to advanced stages, and the five-year survival rate for advanced rectal cancer is less than 10%.

[0007] Statistics from the National Central Cancer Institute of China in 2021 show that pancreatic cancer ranks 7th in men and 11th in women in the incidence of malignant tumors and is responsible for the 6th highest mortality associated with malignant tumors.

[0008] Ovarian cancer, as one of the common malignant tumors in women, is mainly found in intermediate and advanced stages due to the lack of typical symptoms and signs, and the survival period is very short. In 2020, there were 55,342 new cases of ovarian cancer and 37,519 new deaths in China. Ovarian cancer ranks third in terms of incidence and second in terms of mortality among malignant tumors of the female reproductive system.

[0009] Cholangiocarcinoma is a common malignant tumor of the bile ducts, representing about 15-20% of all hepatobiliary cancers. Petition 870260061141, dated 06 / 22 / 2026, page 12 / 90 3 / 40 primary cases. It occurs mainly in people over 50 years of age. Its five-year survival rate is also less than 25%.

[0010] Prostate cancer is one of the most common malignant tumors in the male reproductive system, and its incidence ranks third, behind only breast cancer and lung cancer; deaths represent 3.8% of systemic malignant tumors, and mortality ranks 8th. In 2015, prostate cancer ranked sixth in incidence and tenth in mortality among male malignant tumors in China.

[0011] Lung cancer is the fastest-growing malignant tumor in China over the past 30 years. In 2015, there were 630,000 lung cancer deaths in China, including 433,000 men and 197,000 women, representing 27.0% of all malignant tumor deaths. The 5-year survival rate for lung cancer is estimated to be only 8.9% in Europe, China, and developing countries.

[0012] Primary liver cancer is currently the fourth most common malignant tumor and the second leading cause of tumor-related death in China, seriously threatening the lives and health of the Chinese people. According to the National Cancer Institute's SEER database, the median five-year survival rate for HCC patients in the United States is 19.6%, but the median five-year survival rate for advanced metastatic disease can be as low as 2.5%.

[0013] Systemic therapy, or so-called generalized therapy, refers to treatment methods primarily administered orally, intramuscularly, or intravenously, including molecularly targeted drug therapy, immunotherapy, chemotherapy, traditional Chinese medicine therapy, etc. It includes, but is not limited to, for example, CSCO-recommended tumor treatment regimens, such as the XELOX regimen (also referred to as the regimen). Petition 870260061141, dated 06 / 22 / 2026, page 13 / 90 4 / 40 CAPEOX (capecitabine + oxaliplatin) is a first-line treatment regimen for advanced gastric cancer, colorectal cancer, and pancreatic cancer. Research results show that after first-line treatment with the XELOX regimen, the median PFS of patients with colorectal cancer is 8.0 months and the median OS is 19.8 months. The FOLFOX regimen (5-fluorouracil, leucovorin calcium, and oxaliplatin) can be used for systemic chemotherapy for cholangiocarcinoma; platinums and fluorouracils can be used for systemic chemotherapy for esophageal cancer; carboplatin and gemcitabine can be used for systemic chemotherapy for ovarian cancer; sorafenib can be used for systemic chemotherapy for hepatocellular carcinoma; and PD-1 inhibitors can be used for systemic therapy for lung cancer.

[0014] For gastrointestinal tumors, the most common site of metastasis in the progression stage is the liver. Systemic chemotherapy tends to be ineffective for liver metastases. Due to the special anatomy of the liver, for patients with inoperable primary hepatocellular carcinoma, interventional modalities such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) are frequently used for local treatment, which has been recommended by the CSCO Guidelines for its remarkable effectiveness, and this technology is relatively mature. The Chinese National Health Commission Guidelines for gastric cancer, colorectal cancer, and pancreatic cancer also recommend interventional therapy including HAIC for these tumors after liver metastasis.

[0015] Arterial infusion allows several effective chemotherapeutic agents to be combined, finds the tumor's blood supply artery through catheter technology, and directly injects anticancer drugs into the tumor tissue or tumor bed to exert the first-pass effect of drug therapy, so as to increase Petition 870260061141, dated 06 / 22 / 2026, p. 14 / 90 5 / 40 significantly reduces the local concentration of the drug in the tumor. Meanwhile, after arterial infusion, chemotherapeutic agents will also circulate throughout the body via the blood, so they also exert a systemic chemotherapy effect to some extent. Several clinical studies have proven that hepatic arterial infusion chemotherapy is effective. The CSCO Guidelines for Liver Cancer (2022) include HAIC as a back-line therapy for locally advanced hepatocellular carcinoma (HCC). The arterial infusion administration method is expected to achieve efficacy in patients with liver metastases, improve their quality of life, and prolong their survival period. List of Citations

[0016] Non-patent literature 1: Chinese tumor intervention expert consensus on the application principles of transcatheter arterial infusion chemotherapy. J Intervent Radiol 2017-11, Vol.26, No. 11

[0017] Literatura não patentária 2: Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Saltz L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil / folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 20 de abril de 2008; 26(12):2006-12.

[0018] Literatura não patentária 3: S. Strieth, M.E. Eichhorn, B. Sauer, et al. Neovasculartargeting chemotherapy: encapsulation of paclitaxel in cationic liposomes impairs functional tumor microvasculature. Int. J. Cancer, 110:117-124 (2004)

[0019] Literatura não patentária 4: Ma WW, Hidalgo M. The winning formulation: the development of paclitaxel in pancreatic cancer. Clin Cancer Res. 15 de outubro de 2013; 19(20):5572-9. doi: 10.1158 / 1078-0432.CCR13-1356. Epub 5 de agosto de 2013. PMID: 23918602.

[0020] Non-patent literature 5: Camacho LH, Kurzrock R, Cheung Petition 870260061141, dated 06 / 22 / 2026, page 15 / 90 6 / 40 A, Barber DF, Gupta S, Madoff DC, Wallace MJ, Kim EE, Curley SA, Hortobagyi GN, Mavligit G. Pilot study of regional, hepatic intra-arterial paclitaxel in patients with breast carcinoma metastatic to the liver. Cancer. June 1, 2007; 109(11):2190-6. SUMMARY

[0021] This disclosure provides the use of a cationic liposome of paclitaxel in the preparation of a drug to treat an advanced solid tumor.

[0022] This disclosure further provides the use of a cationic liposome of paclitaxel and a systemic therapeutic drug in the preparation of a medicament for treating an advanced solid tumor, preferably the systemic therapeutic drug being capecitabine and oxaliplatin, or cisplatin, or gemcitabine, or capecitabine.

[0023] This disclosure further provides the use of a cationic liposome of paclitaxel in the preparation of a medicament to improve the efficacy of a systemic therapeutic drug in an advanced solid tumor.

[0024] This disclosure provides a method for treating an advanced solid tumor, in which a therapeutically effective amount of a cationic liposome of paclitaxel is administered to a patient with an advanced solid tumor.

[0025] This disclosure provides a method for treating an advanced solid tumor, wherein a therapeutically effective amount of a paclitaxel cationic liposome and a systemic therapeutic drug are administered to a patient with an advanced solid tumor, preferably a therapeutically effective amount of the paclitaxel cationic liposome, capecitabine and oxaliplatin are administered to the patient with the advanced solid tumor, or preferably the paclitaxel cationic liposome is administered by arterial infusion. Petition 870260061141, dated 06 / 22 / 2026, page 16 / 90 7 / 40

[0026] This disclosure further provides a method for improving the efficacy of a systemic therapeutic drug in an advanced solid tumor, wherein a therapeutically effective amount of a cationic liposome of paclitaxel is additionally administered to a patient in addition to the systemic therapeutic drug, preferably the systemic therapeutic drug is capecitabine and oxaliplatin, or cisplatin, or gemcitabine, or capecitabine.

[0027] In some modalities, the advanced solid tumor described above includes, but is not limited to, gastrointestinal tumors (gastric cancer, esophageal cancer, pancreatic cancer, colorectal cancer, cholangiocarcinoma, and liver cancer), lung cancer, gynecological tumors (ovarian cancer, endometrial cancer, and cervical cancer), prostate cancer, bladder cancer, and liver metastases.

[0028] In some forms, advanced solid tumor includes gastric cancer, pancreatic cancer, and liver metastases from colorectal cancer.

[0029] In some modalities, advanced solid tumor comprises untreated liver metastases, including, but not limited to, liver metastases from gastric cancer, liver metastases from colorectal cancer, and liver metastases from pancreatic cancer.

[0030] The aforementioned systemic therapy includes, but is not limited to, for example, CSCO-recommended oncotherapy regimens, for example, the XELOX regimen (also referred to as the CAPEOX regimen, capecitabine + oxaliplatin) which is a first-line therapy regimen for advanced gastric cancer, colorectal cancer, and pancreatic cancer. The FOLFOX regimen (5-fluorouracil, leucovorin calcium, oxaliplatin) can be used for systemic chemotherapy for cholangiocarcinoma; platinum-based drugs and fluorouracil can be used for systemic chemotherapy for Petition 870260061141, dated 06 / 22 / 2026, page 17 / 90 8 / 40 esophageal cancer; carboplatin and gemcitabine can be used for systemic chemotherapy for ovarian cancer; sorafenib can be used for systemic chemotherapy for hepatocellular carcinoma; and PD1 inhibitor can be used for systemic therapy for lung cancer.

[0031] This disclosure further provides a method for improving the efficacy of a combination of capecitabine and oxaliplatin in an advanced solid tumor, for example, advanced gastric cancer, colorectal cancer or pancreatic cancer, wherein a therapeutically effective amount of a cationic liposome of paclitaxel is additionally administered to a patient in addition to capecitabine and oxaliplatin.

[0032] This disclosure further provides a method for improving the efficacy of a platinum- or fluorouracil-based drug in esophageal cancer, wherein a therapeutically effective amount of a cationic liposome of paclitaxel is additionally administered to a patient in addition to the platinum- or fluorouracil-based drug.

[0033] This disclosure further provides a method for improving the efficacy of carboplatin or gemcitabine in ovarian cancer, wherein a therapeutically effective amount of a cationic liposome of paclitaxel is additionally administered to a patient in addition to carboplatin or gemcitabine.

[0034] This disclosure further provides a method for improving the efficacy of sorafenib in hepatocellular carcinoma, wherein a therapeutically effective amount of a cationic liposome of paclitaxel is additionally administered to a patient in addition to sorafenib.

[0035] This disclosure further provides a method for improving the efficacy of a PD-1 inhibitor in lung cancer, wherein a therapeutically effective amount of a cationic liposome of paclitaxel is additionally administered to a patient in addition to the PD-1 inhibitor. Petition 870260061141, dated 06 / 22 / 2026, page 18 / 90 9 / 40

[0036] Preferably, the paclitaxel cationic liposome, according to the present disclosure, is present in the form of a powder for injection or a liquid injection. When the paclitaxel cationic liposome is a liquid injection, it contains, in a paclitaxel base, 0.05 to 1 mg / ml, preferably 0.2 to 0.3 mg / ml, more preferably 0.25 mg / ml of an active ingredient.

[0037] Preferably, the therapeutically effective amount of paclitaxel cationic liposome, on a paclitaxel basis, refers to 5 to 100 mg / m2, preferably 5 to 80 mg / m2, more preferably 11 to 55 mg / m2, or even more preferably 24 to 70 mg / m2, or any value within the range, for example, 11 mg / m2, 22 mg / m2, 24 mg / m2, 33 mg / m2, 36 mg / m2, 44 mg / m2, 48 mg / m2, 55 mg / m2, 60 mg / m2 or 70 mg / m2. Preferably, the paclitaxel cationic liposome is administered by arterial infusion. Preferably, the dosing cycle is once every 3 weeks.

[0038] In some embodiments, the cationic liposome of paclitaxel, according to the present disclosure, contains: paclitaxel, 1,2-dioleoyl-singlycerol-3-phosphocholine (DOPC), 1,2-dioleoyl-3-trimethylammoniumpropane chloride (DOTAP) and trehalose.

[0039] Preferably, the paclitaxel cationic liposome contains 5 to 10 mg of paclitaxel, 72 to 144 mg of DOPC, 68 to 136 mg of DOTAP and 1500 to 2500 mg of trehalose in each preparation (or preparation unit).

[0040] More preferably, each preparation (preparation unit) contains 10 mg of paclitaxel, 144 mg of DOPC, 136 mg of DOTAP and 2500 mg of trehalose, or each preparation (preparation unit) contains 5 mg of paclitaxel, 72 mg of DOPC, 68 mg of DOTAP and 2000 mg of trehalose, or each preparation (preparation unit) contains 5 mg of paclitaxel, 72 mg of DOPC, 68 mg of DOTAP and 1500 mg of trehalose. Petition 870260061141, dated 06 / 22 / 2026, page 19 / 90 10 / 40

[0041] Paclitaxel cationic liposome, according to the present disclosure, can be prepared by a conventional method in the art or can be a paclitaxel cationic liposome prepared by any of the methods disclosed in the prior art, for example, prepared according to the prescription and method described in US7794747B.

[0042] All dosages of paclitaxel cationic liposome, according to this disclosure, are on a paclitaxel basis. Advantageous effects of the invention

[0043] Animal experiments in this disclosure prove that paclitaxel cationic liposomes used in combination with other drugs or treatment methods, for example, in combination with cisplatin, or gemcitabine or capecitabine, can significantly improve antitumor efficacy and achieve a remarkably better effect than paclitaxel injection Taxol at the same dose.

[0044] Co-administration of paclitaxel cationic liposome via arterial infusion and the XELOX regimen to patients with gastric cancer, pancreatic cancer, or liver metastases from colorectal cancer may enhance the efficacy of the XELOX regimen in patients with gastric cancer, pancreatic cancer, or liver metastases from colorectal cancer, increase the disease remission rate, particularly the complete remission rate (CR rate) and the partial remission rate (PR rate), and control disease progression, and paclitaxel cationic liposome is safe and tolerable with few toxic side effects.

[0045] Administration of paclitaxel cationic liposome or paclitaxel cationic liposome in combination with systemic therapeutic drugs to patients with an advanced solid tumor may improve the efficacy of systemic therapeutic drugs in patients with the tumor, increase the disease remission rate and control disease progression, and paclitaxel cationic liposome is safe and tolerable with Petition 870260061141, dated 06 / 22 / 2026, page 20 / 90 11 / 40 few toxic side effects. BRIEF DESCRIPTION OF THE FIGURES

[0046] FIG. 1 shows the distribution of drug-related AE grades for the treatment regimen in Example 5. DETAILED DESCRIPTION

[0047] The examples described below are specific descriptions of this disclosure and should not be interpreted as limiting the scope of this disclosure. Example 1: Preparation of cationic liposomes of paclitaxel

[0048] The prescriptions for paclitaxel cationic liposomes were as follows: Table 1: Prescriptions of paclitaxel cationic liposomes Ingredients: 1-1 Paclitaxel 10 mg 5 mg 5 mg 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) 144.2 mg 72.1 mg 72.1 mg 1,2-Dioleoyl-3-trimethylammonium-propane chloride (DOTAP) 136.4 mg 68.2 mg 68.2 mg Trehalose 2500 mg 2000 mg 1500 mg

[0049] The preparation method was as follows: (1) Paclitaxel, DOPC and DOTAP were weighed according to the prescribed doses and dissolved in anhydrous ethanol to obtain an organic phase after dissolution; (2) trehalose was dissolved in water for injection to provide 10% to 12.5% ​​trehalose solution as an aqueous phase; (3) the oil phase and the aqueous phase were mixed in a certain ratio to form a liposome; (4) the liposome obtained in step 3 was subjected to granule sizing to provide a liposome with a relatively uniform grain size; (5) the liposome obtained in step 4 was dialyzed and the trehalose solution Petition 870260061141, dated 06 / 22 / 2026, page 21 / 90 12 / 40 obtained in step 2 was used as dialysate; and (6) the liposome solution obtained in step 5 was lyophilized or spray dried to provide solid powder.

[0050] When used, the solid powder was redissolved to provide a paclitaxel cationic liposome injection, such that the osmotic pressure of the resulting injection was equal to the plasma osmotic pressure. The paclitaxel cationic liposome injections used in subsequent examples were all obtained by redissolving the products of Example 1. Prescriptions 1-1, 1-2, and 1-3 had substantially the same physical and chemical properties and pharmacological and clinical effects.

[0051] The paclitaxel cationic liposome injections used in Examples 2 to 4 were obtained by redissolving product 1-2 from Example 1 and were simplified as A1. The paclitaxel cationic liposome injections used in Examples 5 and 6 were obtained by redissolving product 1-1 from Example 1 and were simplified as A2. Example 2: Inhibitory effect of the combination of cationic liposome paclitaxel for injection and cisplatin (DDP) in RM-1 prostate cancer allografts in mice.

[0052] Experimental animal: female C57 / BL6 mice provided by Beijing Vital River Laboratory Animal Technology Co., Ltd.

[0053] Experimental method: Female C57 / BL6 mice were subcutaneously inoculated with mouse prostate RM-1 cells. On day 6 after inoculation, mice were pooled when the mean tumor volume was approximately 140 mm3 (d0). Drugs were administered (intravenously, except that DDP was administered intraperitoneally) on d0, d2, d4, d6, d8, and d10 for a total of 6 times. The experiment was terminated on d15. In the high-dose A1 group, A1 was administered at a dose of 12 mg / kg for the first three times and 6 mg / kg for the last three times, with a cumulative dose of 54 mg / kg; in the group of Petition 870260061141, dated 06 / 22 / 2026, p. 22 / 90 13 / 40 low dose A1, A1 was administered at a dose of 6 mg / kg on all six occasions, with a cumulative dose of 36 mg / kg; in the DPP group, DPP was administered at a dose of 1 mg / kg on all six occasions, with a cumulative dose of 6 mg / kg; in the vehicle control group, a 5% glucose injection (in a volume equal to that of the high dose A1 group) was administered; in the A1 + DDP-1 group, A1 was administered at a dose of 6 mg / kg on all six occasions, with a cumulative dose of 36 mg / kg, and DPP was administered at a dose of 1 mg / kg on all six occasions, with a cumulative dose of 6 mg / kg; In the A1+ DDP-2 group, A1 was administered at a dose of 12 mg / kg the first three times and 6 mg / kg the last three times, with a cumulative dose of 54 mg / kg, and DPP was administered at a dose of 1 mg / kg all six times, with a cumulative dose of 6 mg / kg.During the experiment, the animals' body weight and tumor volume were monitored three times a week, and the values ​​for tumor volume (TV), relative tumor volume (RTV), and relative tumor proliferation rate (T / C) were calculated.

[0054] The related calculation formulas were as follows: Tumor volume (TV) = 1 / 2xaxb2, where a and b represent the major and minor diameters of the tumor, respectively. RTV = TVt / TVo. TVo was the tumor volume measured at pooling for administration (i.e., d0) and TVt was the tumor volume at each measurement. T / C(%) = (TRTV / CRTV)x100% (TRTV: RTV in the treatment group; CRTV: RTV in the vehicle control group).

[0055] Methods for formulating test drugs: A1: paclitaxel cationic liposome was dissolved by adding water for injection and then diluted with glucose and sodium chloride injection to the desired concentration; DDP: DDP powder was dissolved in 5% glucose injection and subjected to ultrasound to formulate the desired concentration.

[0056] Experimental results: Compared to the group of Petition 870260061141, dated 06 / 22 / 2026, page 23 / 90 14 / 40 vehicle control (Vehicle), RM-1 tumor growth of prostate cancer in mice could be significantly inhibited in each of the treatment groups (P <0.05). Compared with the single DDP group, the A1 high or low dose + DDP group exhibited a significantly potentiated inhibitory effect on tumors (P<0.01). Specific results are listed in Table 2. Table 2: Inhibitory effect of the combination with DDP in allografts RM-1 of prostate cancer in mice (x ± sd, n=9) Group Cumulative Dose (mg / kg) Dosage Tumor Volume (mm3) RTV T / C (%) d0 d15 Vehicle — Dosage on d0, d2, d4, d6, d8, d10 DDP (ip) Rest (iv) 145.2±23.4 4684.7±1333.4 32.3±8.1 — A1 36 141.8±21.1 2704.7±678.1** 19.5±6.0** 60.5 A1 54 136.7±20.1 2169.2±634.2** 15.9±4.0** 49.2 A1+DDP-1 36 / 6 144.2±22.2 2151.5±416.4**** # 12.1±8.1**# 37.5 A1+DDP-2 54 / 6 144.3±22.3 1471.8±578.4**** 9.0±4.5***# # 28.0 DDP 1 mg / kg 6 145.1±22.8 3494.6±710.9* 24.9±7.6 77.1 p <0.05, ** p <0.01 compared to the Vehicle control group; #p<0.05,##p<0.01 compared to A1 at the same dose; ★p<0.05, ★★p<0.01 compared to DDP at the same dose Example 3: Inhibitory effect of paclitaxel cationic liposomes for injection in CFPAC-1 xenografts of human pancreatic cancer in mice

[0057] Experimental animal: Nu / Nu female naked mice supplied by Beijing Vital River Laboratory Animal Technology Co., Ltd.

[0058] Experimental method: Nude / Nu female mice were subcutaneously inoculated with human pancreatic cancer CFPAC-1 cells. On day 5 after inoculation, the mice were divided into 7 Petition 870260061141, dated 06 / 22 / 2026, page 24 / 90 15 / 40 groups when the mean tumor volume was 228 mm3(d0), namely, the vehicle control group (5% glucose injection), the 6 mg / kg A1 group, the 3 mg / kg or 6 mg / kg A1 + 20 mg / kg gemcitabine (GEM) injection group, the 6 mg / kg paclitaxel (Taxol) injection group, the 6 mg / kg Taxol + 20 mg / kg GEM group, and the 20 mg / kg GEM group, respectively. There were 10 mice in each group. The drugs were administered (intravenously, except that gemcitabine (GEM) injection was administered intraperitoneally 5 times (at the first five time points)) on d0, d3, d6, d9, d13, and d16 for a total of 6 times. After the last administration, the mice were additionally observed for 11 days (i.e., day 27) and the experiment was terminated. During the experiment, the animals' body weight and tumor volume were monitored twice a week, and the tumor volume (TV) was calculated.At the end of the experiment, the tumor weight was weighed and the rate of inhibition of tumor weight was calculated.

[0059] The related calculation formulas were as follows: Tumor volume (TV) = 1 / 2xaxb2, where a and b represent the major and minor diameters of the tumor, respectively. Tumor weight inhibition rate (%) = (1 - tumor weight in the treatment group / tumor weight in the vehicle control group) x 100%.

[0060] Methods for formulating test drugs: A1 was formulated by the same method as in Example 2. Gemcitabine for injection was formulated with saline solution to the desired concentration. Paclitaxel (Taxol) injection was formulated by diluting with saline solution to the desired concentration.

[0061] Experimental results: Compared to the vehicle control group, administration of 6 mg / kg of A1 alone could significantly inhibit CFPAC-1 tumor growth in human pancreatic cancer (P <0.01), and a combination of A1 and gemcitabine exhibited a stronger inhibitory effect on the tumor than administration of A1 or gemcitabine alone. Petition 870260061141, dated 06 / 22 / 2026, page 25 / 90 16 / 40 alone (P<0.01). Administration of 6 mg / kg of A1 alone or in combination with gemcitabine exhibited a significantly potentiated inhibitory effect on the tumor (P<0.01) compared with paclitaxel (Taxol) injection under the same administration conditions. Specific results are listed in Table 3. Table 3: Inhibitory effect on CFPAC-1 xenografts from human pancreatic cancer (x ± sd, n=10) Group Dose (mg / kg) Dosage Tumor volume (mm3) Tumor weight (g) Tumor weight inhibition rate (%) d0 d27 Vehicle — Dosage on d0, d3, d6, d9, d13, d16 GEM (ip) Rest (iv) 226.3±50.1 1599.4±607.7 1.5968±0.6144 — A1 6 227.6±65.9 412.8±237.0**AA^ △ 0.4176±0.3314**AA^ 73.8 A1+GME 3 / 20 230.2±58.6 52.5±42.2**★★ 0.0221±0.0138**★★ 98.6 A1+GME 6 / 20 227.0±52.0 26.3±24.6**△△★★” 0.0104±0.0127**△△★★## 99.4 Taxol 6 227.0±52.0 854.3±266.4** 0.6905±0.1243** 56.8 Taxol+GE M 6 / 20 227.0±52.0 404.3±190.6**★ 0.3688±0.1937**★★ 76.9 GME 20 227.3±52.8 720.9±152.8** 0.8238±0.3253** 48.4 *p<0.05, **p<0.01 compared to the vehicle control group; △p<0.05 compared to Taxol at the same dose; ★p<0.05, ★★p<0.01 compared to GEM; ##p<0.01, A1 + GEM compared to A1 at the same dose Example 4: Inhibitory effect of paclitaxel cationic liposomes for injection in MDA-MB-231 xenografts of human triple-negative breast cancer in mice.

[0062] Experimental animal: female NOD / SCID mice provided by Beijing Vital River Laboratory Animal Technology Co., Ltd.

[0063] Experimental method: Female NOD / SCID mice were subcutaneously inoculated with MDA-MB-231 human triple-negative breast cancer cells. On day 7 after inoculation, the mice were divided into 7 groups when the mean tumor volume was 120 to 130 mm3(d0), i.e., the vehicle control group (5% injection of Petition 870260061141, dated 06 / 22 / 2026, page 26 / 90 The experiment consisted of three groups: the 17 / 40 glucose group, the 6 mg / kg A1 group, the 3 mg / kg or 6 mg / kg A1 + 400 mg / kg capecitabine (CAP) injection group, the 6 mg / kg paclitaxel (Taxol) injection group, the 6 mg / kg Taxol + 400 mg / kg CAP group, and the 400 mg / kg CAP group, respectively. Capecitabine (CAP) injection was administered intragastrically twice weekly, and the other drugs were administered intravenously twice weekly for a total of 7 times (d0, d3, d7, d10, d14, d17, and d21). The experiment was terminated on d28. During the experiment, the animals' body weight and tumor volume were monitored twice weekly, and tumor volume (TV) was calculated. At the end of the experiment, the tumor weight was weighed and the rate of inhibition of tumor weight was calculated.

[0064] The related calculation formulas were as follows: Tumor volume (TV) = 1 / 2xaxb2, where a and b represented the major and minor diameters of the tumor, respectively. Tumor weight inhibition rate (%) = (1 - tumor weight in the treatment group / tumor weight in the vehicle control group) χ 100%.

[0065] Methods for formulating test drugs: CAP was formulated by diluting with water for injection to the desired concentration and the rest of the drugs were formulated as they were in Example 3.

[0066] Experimental results: Compared to the vehicle control group, administration of 6 mg / kg of A1 alone could significantly inhibit the growth of MDA-MB-231 human triple-negative breast cancer tumors (P <0.05), and a combination of A1 and capecitabine exhibited a stronger inhibitory effect on the tumor than administration of A1 or capecitabine alone (P <0.05). Administration of 6 mg / kg of A1 alone or in combination with capecitabine exhibited a significantly enhanced inhibitory effect on the tumor (P <0.05) compared to paclitaxel (Taxol) injection under the same administration conditions. Specific results are listed in Table 4. Petition 870260061141, dated 06 / 22 / 2026, page 27 / 90 18 / 40 Table 4: Inhibitory effect on MDA-MB-231 xenografts of human triple-negative breast cancer (x ± sd, n=10) Group Dose (mg / kg) Dosage m Tumor volume (mm3) Tumor weight (g) Tumor weight inhibition rate (%) d0 d20 Vehicle — Dosage m on d0, d3, d7, d10, d14, d17, d21, CAP (po) Rest (iv) 129.1±11.6 2599.7±531.6 2.0547±0.1379 — A1 6 124.4±18.9 1326.2±520.3”A 1.0908±0.2914**A ▲△ 46.9 A1+CAP 3 / 400 124.1±17.9 1375.7±341.3** 1.1727±0.2492“* ★ 42.9 A1+CAP 6 / 400 123.8±17, 9 748.6±400.0**** △# 0.6565±0.1935*** ★△## 68.0 Taxol 6 123.9±18, 1 1659.9±607.9** 1.4165±0.2541** 31.1 Taxol+CA P 6 / 400 124.1±19.3 1128.4±210.0**★ 0.9434±0.1890*** ★ 54.1 CAP 400 124.5±19.4 1708.3±564.8** 1.3679±0.2649** 33.4 *p<0.05, **p<0.01 compared to the vehicle control group; △p<0.05, △△p<0.01 compared to Taxol; ★p<0.05, ★★p<0.01 compared to CAP; #p<0.05,##p<0.01, A1+ CAP compared to A1 at the same dose Example 5: Clinical studies on first-line therapy for gastric cancer, pancreatic cancer, and liver metastases from colorectal cancer by arterial infusion of cationic liposome paclitaxel injection.

[0067] This study was a single-arm, open-label, single-center (IIT) investigator-initiated clinical trial in which patients with treatment-unexposed liver metastases (including, but not limited to, liver metastases from gastric cancer, liver metastases from colorectal cancer, and liver metastases from pancreatic cancer), whose primary lesions were confirmed histopathologically or cytologically, were enrolled and administered different doses of paclitaxel cationic liposome injection by arterial infusion plus fixed doses in the regimen. Petition 870260061141, dated 06 / 22 / 2026, page 28 / 90 19 / 40 XELOX. This study aimed to explore the safety and tolerability of the combined regimen, determine the ideal dosage of paclitaxel cationic liposome injection in the combined regimen, while evaluating efficacy and observing pharmacokinetic characteristics. I. Essay Project [00 68] This study was divided into a dose escalation phase and a dose expansion phase. 1. Dose escalation phase (1) Trial design

[0069] The study included a screening period, a treatment period, and an end-of-study follow-up period.

[0070] After signing the Informed Consent Form and completing all initial assessments within the screening period, eligible subjects would be enrolled in the treatment period and treated by administration of paclitaxel cationic liposome injection in combination with the XELOX regimen. The dosage of paclitaxel cationic liposome injection would be gradually escalated from a low-dose group to a high-dose group. The dosage administered to subjects was the current or intended dosage at entry into this study. The dosing regimen was followed once every three weeks. The first cycle in the treatment period was the DLT (Dose-Limiting Toxicity) observation period.Subjects who completed the treatment and 3-week observation period may continue to participate in the next administration cycle until relapse / progression or death occurs, the subject or their legal representative requests withdrawal from the study, an alternative treatment method is applied, or the entire study is completed (whichever occurs first). Administration was expected to last 6 to 8 cycles. Efficacy was assessed once every 2 cycles (6 weeks) during treatment. All subjects underwent sample collection. Petition 870260061141, dated 06 / 22 / 2026, page 29 / 90 20 / 40 blood samples were collected for PK (pharmacokinetic) analysis at different time points before and after administration according to the protocol, and participants completed the relevant tests specified in the protocol during the study to observe safety and tolerability. The end-of-treatment follow-up visit began on day 30 after the last dose. (2) Dose escalation protocol

[0071] Paclitaxel cationic liposome: 11 mg / m2 was taken as the initial dose (on a paclitaxel basis) and a total of five dose groups (11 mg / m2, 22 mg / m2, 33 mg / m2, 44 mg / m2 and 55 mg / m2) were designed.

[0072] The corresponding treatment of subjects who presented with DLT would be determined by the investigators according to the standard for clinical diagnosis and treatment, and these subjects may continue to participate in the next administration cycle, maintaining the original dose or downregulating it by one dose level. The dose was not permitted to be increased for the same subject.

[0073] XELOX regimen: oxaliplatin administered at a dose of 130 mg / m2 by intravenous infusion on D1; and capecitabine administered orally at a dose of 1000 mg / m2 on D1 to D14. (3) Prolonged dosing after completion of the DLT observation period

[0074] The corresponding treatment of subjects who presented with DLT would be determined by the researchers according to the standard for clinical diagnosis and treatment, and these subjects may continue to participate in the next administration cycle, delaying administration for no more than 2 weeks, maintaining the original dose or downregulating it by one dose level. The dose was not permitted to be increased for the same subject.

[0075] If the MTD (maximum tolerated dose) of liposome injection Petition 870260061141, dated 06 / 22 / 2026, page 30 / 90 If the 21 / 40 cationic paclitaxel dose was identified, the MTD would be selected as RP2D (recommended dose for phase II). If the MTD of the cationic paclitaxel liposome injection was not identified, RP2D would be determined by the researchers after internal discussion based on the research results during the DLT observation period in the dose escalation phase. Furthermore, RP2D was selected for expansion in the dose expansion phase. 2. Dose expansion phase

[0076] Dose expansion may be conducted, if necessary, based on data such as safety, tolerability and efficacy obtained from the dose escalation study.

[0077] One to three tumor types were selected for dose expansion, including, but not limited to, liver metastases from gastric cancer, liver metastases from colorectal cancer, liver metastases from pancreatic cancer, etc. The specific cohorts to be expanded could be determined by the investigators through internal discussion after the expansion dose was determined, and 5 to 15 cases were expanded for each cohort. II. Test population (I) Inclusion criteria

[0078] Subjects who met all of the following criteria were eligible for enrollment in this study: 1. Subjects aged between 18 and 75 years (inclusive), regardless of sex. 2. Subjects with liver metastases not exposed to treatment, including, but not limited to, liver metastases from gastric cancer, liver metastases from colorectal cancer, and liver metastases from pancreatic cancer, and with primary lesions confirmed histopathologically or cytologically. Petition 870260061141, dated 06 / 22 / 2026, page 31 / 90 22 / 40 3. If the liver metastasis consisted of a single measurable target lesion, the diameter of the single target lesion should be >2 cm. If the liver metastasis consisted of two or more target lesions, at least two of the target lesions should have a diameter of >1 cm. 4. ECOG performance status score: 0 to 2. 5. Life expectancy greater than 3 months. III. Effectiveness Assessment Indicators

[0079] Efficacy was assessed by CT / MRI according to the RECIST1.1 / mRECIST standard. 1. Key effectiveness indicators:

[0080] Overall remission rate (ORR): Defined as the proportion of subjects in the study whose ideal overall responses were CR or PR, as assessed by the researchers according to RECIST v1.1 / mRECIST.

[0081] Disease control rate (DCR): Defined as the proportion of subjects with CR or PR responses and stable disease (SD) (i.e., CR+PR+SD) at the optimal time point during the period from the time of first administration of the study drug to the end of the study, as assessed according to the RECIST 1.1 / mRECIST standard. 2. Indicator of exploratory effectiveness:

[0082] Rate of change of target lesions in the arterial infusion area: All measurable lesions (it was necessary that, if there was only one target lesion in the arterial infusion area, the target lesion had a diameter >2 cm; and if there were two or more target lesions, at least two target lesions had a diameter >1 cm) in the arterial infusion area were measured according to RECIST v1.1 / mRECIST. The sum of the diameters of the target lesions in the blood supply area was calculated as the baseline assessment data, and the rate of change of the sum of the diameters of the target lesions in the blood supply area at each efficacy assessment was Petition 870260061141, dated 06 / 22 / 2026, page 32 / 90 23 / 40 calculated. When lesions in the blood supply area were shrunk and then reconstructed, the rate of change relative to the sum of the minimum diameters of the target lesions in the blood supply area was calculated. 3. Safety indicators

[0083] AE (Adverse Event) and SAE (Serious Adverse Event / Reaction) were used as safety assessment indicators. IV. Research Results

[0084] Arterial infusion of cationic liposome paclitaxel in combination with systemic therapy (e.g., XELOX regimen) has shown good effects in the treatment of liver metastases from advanced solid tumors (e.g., gastric cancer, pancreatic cancer, and colorectal cancer), could improve therapeutic efficacy and reduce the incidence of adverse reactions, and has a good prospect for clinical application.

[0085] In this example, a total of 5 patients (the first five cases in Table 5) were enrolled, including one case of liver metastases from gastric cancer and 4 cases of liver metastases from colorectal cancer, and none of them received any systemic therapy for metastatic disease. One case of liver metastases from colon cancer was undergoing pre-screening assessments (the last case in Table 5 with the subject number pending). Detailed information is listed in Table 5. Table 5 Dose Group Subject No. Gender and Age Diagnosis Tumor Staging (First Visit) Previous Surgery Previous Antitumor Therapy 11 mg / m2 01002 Male 63 years Liver metastases from gastric cancer Stage IIIA (T4aN2M0) Laparoscopic radical resection of gastric cancer (6-52022) 4 cycles of chemotherapy per SOX regimen on 4-72022, 25-7, 16-8 and 1-9 (Tegafur- Petition 870260061141, dated 06 / 22 / 2026, page 33 / 90 24 / 40 Gimeracil (Oteracil Potassium 60 mg bid d1-14 + oxaliplatin 150 mg d1) 22 mg / m2 01003 Male 58 years Liver metastases from sigmoid colon cancer Stage IIIA (pT2N1M0) Laparoscopic radical resection of sigmoid colon cancer (6-2019) One chemotherapy regimen XELOX after surgery in 6.2019 (capecitabine + oxaliplatin), not regularly reviewed 22 mg / m2 01004 Male 61 years Liver metastases from ascending colon cancer Stage IV (pT3N0M1a) Laparoscopic right hemicolectomy of colon cancer (5-2023) None 22 mg / m2 01005 Male 57 years Liver, lung and bone metastases from rectal cancer Stage IV (TxNxM1) None None 33 mg / m2 01006 Male 59 years Liver metastases from sigmoid colon cancer Stage IV (TxNxM1) None None 33 mg / m2 TBD Male 37 years Liver metastases from colon cancer Stage IV (TxNxM1) None None to co ω -Q co Tumor assessment (3rd time) PD (+50%) Target 1: 12.79 mm Target 2: 22.09 mm PR (-72%) Target 1: 28.5 mm Target 2: 0 PR (-89%) Target 1: 3.74 mm Target 2: 0 Non-target: absent Tumor assessment (2nd time) SD (-21%) Target 1: 8.19 mm Target 2: 15.01 mm SD (-15%) Target 1: 86.39 mm Target 2: 0 PR (-59.8%) Target 1: 5.36 mm Target 2: 4.46 mm Non-target: absent SD (-16%) Target 1: 8.01 mm Target 2: 35.94 mm Target 3: 11.76 mm Target 4: 12.47 mm Non-target: present Petition 870260061141, dated 06 / 22 / 2026, page 34 / 90 25 / 40 Tumor assessment (1st time) SD (-1%) Target 1: 10.94 mm Target 2: 18.1 mm SD (-15%) Target 1: 86.39 mm Target 2: 0 PR (-51%) Target 1: 5.94 mm Target 2: 5.94 mm Non-target: present SD (-10%) Target 1: 9.92 mm Target 2: 38.83 mm Target 3: 11.79 mm Target 4: 13 mm Non-target: present PR (-37%) Target 1: 15.8 mm Target 2: 11.2 mm Time of first infusion of cationic liposome DTV 20 / 4 / 2023 26 / 6 / 2023 29 / 6 / 2023 22 / 8 / 2023 31 / 10 / 2023 Non-target lesion None No Right lobe of the liver Center L3, L4 Right lobe of the liver Descending sigmoid junction Target lesion Hepatic segment VI (1): 11.0 mm Hepatic segment VIII (2): 18.3 mm Hepatic interlobar junction zone (1): 91.37 mm Lower portion of the right hepatic lobe (2): 10.34 mm Posterior lobe of the liver (1): 13.83 mm Right lobe of the liver (2): 13.17 mm Rectosigmoid junction (1): 12.46 mm Hepatic segment IV (2): 43.22 mm Hepatic segment IV (3): 11.16 mm Posterior segment RUL: (4): 13.97 mm Right lobe of the liver: 26.7 mm Right lobe of the liver: 16,3 mm Diagnosis Liver metastases from gastric cancer Liver metastases from sigmoid colon cancer Liver metastases from colon cancer Liver metastases from rectal cancer Liver metastases from colon cancer Subject No. O T- 8 T- T- O T- O T- Dose Group CN EE CN EE CM CM CN EE CM CM CN EE CM CM CN EE CO CO,

[0086] The results are shown in Table 6. A total of 4 cases were evaluated for efficacy, of which 2 cases of ideal efficacy were evaluated as SD and 2 cases were evaluated as PR (01003 and 01004 achieved CR evaluated by mRECIST), i.e., ORR was 50% and DCR was 100%. Petition 870260061141, dated 06 / 22 / 2026, page 35 / 90 26 / 40

[0087] Safety and tolerability: No DLT was observed in the 11 to 33 mg / m2 dose groups. Safety and tolerability were good, and no abnormal safety signals were found. All currently reported drug-related AEs were Grade 1 to 2 (FIG. 1, frequency of occurrence indicated by the vertical axis) and were recoverable after symptomatic treatment. Related AEs (inclusive, but possibly irrelevant) included decreased platelet count, elevated procalcitonin, fever, nausea, increased white blood cell count, and decreased lymphocyte count.

[0088] Note: Adverse events in clinical trials were divided into the following five grades: Grade 1: Mild, asymptomatic, or mild symptoms observed only in clinical or diagnostic practice; no treatment required. Grade 2: moderate, requiring minimal, local or non-invasive treatment; instrumental activities of daily living are limited and age-appropriate. Grade 3: severe or clinically significant, but not immediately life-threatening, causing hospitalization or prolonged hospitalization, disability, or limited self-care. Grade 4: life-threatening, treatment required. Grade 5: Death related to aortic stenosis. Example 6: Clinical study on the treatment of advanced solid tumor by arterial infusion of cationic liposome paclitaxel injection.

[0089] This study was a single-arm, open-label, multicenter Phase 1 trial in which patients histopathologically or cytologically confirmed to have an advanced solid tumor were enrolled and administered different doses of paclitaxel cationic liposome injection via arterial infusion. This study aimed to Petition 870260061141, dated 06 / 22 / 2026, page 36 / 90 27 / 40 explore the safety and tolerability of paclitaxel cationic liposomes administered alone via arterial infusion, while evaluating efficacy and observing pharmacokinetic characteristics. I. Essay Project

[0090] This study was divided into a dose escalation phase and a dose expansion phase. 1. Dose escalation phase (1) Trial design

[0091] The dose escalation phase included a screening period (within 28 days), a treatment period, and a PFS follow-up period. After signing the Informed Consent Form and completing all initial assessments within the screening period, eligible subjects would be enrolled in the treatment period. The dosage of paclitaxel cationic liposome for injection would be gradually escalated from a low-dose group to a high-dose group every 3W (21 days) as a cycle. DLT was observed in the first dosing cycle. Subjects underwent blood sampling for PK analysis at different time points before and after administration according to the protocol and completed the relevant examinations specified in the protocol during treatment in order to observe safety, tolerability, and efficacy.The same subject could only receive the treatment and dosing regimen during the trial. Dosing was expected to last 6 to 8 cycles. Efficacy was assessed once every 2 cycles (6 weeks) during treatment. (2) Dose escalation protocol

[0092] Paclitaxel cationic liposome: 24 mg / m2 was taken as the initial dose (on a paclitaxel basis) and a total of five dose groups (24 mg / m2, 36 mg / m2, 48 mg / m2, 60 mg / m2 and 70 mg / m2) were Petition 870260061141, dated 06 / 22 / 2026, page 37 / 90 28 / 40 projected.

[0093] The corresponding treatment of subjects who presented with DLT would be determined by the investigators according to the standard for clinical diagnosis and treatment, and these subjects may continue to participate in the next administration cycle, maintaining the original dose or downregulating it by one dose level. The dose was not permitted to be increased for the same subject. (3) Prolonged dosing after completion of the DLT observation period

[0094] The corresponding treatment of subjects who presented with DLT would be determined by the researchers according to the standard for clinical diagnosis and treatment, and these subjects may continue to participate in the next administration cycle, delaying administration for no more than 2 weeks, maintaining the original dose or downregulating it by one dose level. The dose was not permitted to be increased for the same subject.

[0095] If the MTD (maximum tolerated dose) of paclitaxel cationic liposome injection was identified, the MTD would be selected as the RP2D (recommended phase II dose). If the MTD of paclitaxel cationic liposome injection was not identified, the RP2D would be determined by the researchers after internal discussion based on the research results during the DLT observation period in the dose escalation phase. Furthermore, the RP2D was selected for expansion in the dose expansion phase. 2. Dose expansion phase [0 096] Dose expansion may be conducted, if necessary, based on data such as safety, tolerability, and efficacy obtained from the dose escalation study. One to three tumor types were selected for dose expansion, including, but not limited to, Petition 870260061141, dated 06 / 22 / 2026, page 38 / 90 29 / 40 liver metastases from gastric cancer, liver metastases from colorectal cancer, liver metastases from pancreatic cancer, etc. The specific cohorts to be expanded can be determined by the investigators through internal discussion after determining the expansion dose, and 5 to 15 cases were expanded for each cohort. II. Test population (I) Inclusion criteria

[0097] Subjects who met all of the following criteria were eligible for enrollment in this study: 1. Subjects aged between 18 and 75 years (inclusive), regardless of sex. 2. Subjects with an advanced solid tumor confirmed histopathologically or cytologically, which included, but was not limited to, the following tumor types: Gastrointestinal tumors (including, but not limited to: gastric cancer, liver cancer, cholangiocarcinoma, pancreatic cancer, colorectal cancer, etc.); Gynecological tumors (including, but not limited to: ovarian cancer, endometrial cancer, etc.); Lung cancer; and liver metastases. 3. Target lesion requirements: if there was only a single target lesion in the arterial infusion area, the diameter of the single target lesion should be >2 cm; if there were two or more target lesions in the blood supply area, at least two target lesions should have a diameter of >1 cm. 4. ECOG performance status score: 0 to 2. 5. Life expectancy greater than 3 months. III. Evaluation indicators

[0098] Efficacy was assessed by CT / MRI according to the standard. Petition 870260061141, dated 06 / 22 / 2026, page 39 / 90 30 / 40 RECIST1.1.

[0099] Cases planned to be enrolled in this study: Approximately 18 to 24 cases were included in the dose escalation study; The cases enrolled in the dose expansion study were decided by the researchers after internal discussion. Effectiveness assessments: Key effectiveness indicators:

[0100] Overall remission rate (ORR): Defined as the proportion of subjects in the study whose ideal overall responses were CR or PR, as assessed by the researchers in accordance with RECIST v1.1.

[0101] Disease control rate (DCR): Defined as the proportion of subjects with CR or PR responses and stable disease (SD) (i.e., CR+PR+SD) at the optimal time point during the period from the time of first administration of the study drug to the end of the study, as assessed according to the RECIST 1.1 standard.

[0102] Progression-free survival (PFS): Defined as the period from the time of the first administration of the study drug until the date of the first documented disease progression (PD) or the date of death, whichever occurred first.

[0103] Duration of remission (DoR): Defined as the period from when the tumor was first assessed as CR or PR until when the tumor was first assessed as PD or a subject died of any cause. Safety assessment indicators

[0104] AE (Adverse Event) and SAE (Serious Adverse Event / Reaction) were used as safety assessment indicators. IV. Research Results

[0105] Arterial infusion of paclitaxel cationic liposomes exhibited Petition 870260061141, dated 06 / 22 / 2026, page 40 / 90 31 / 40 good effects in the treatment of advanced solid tumors (e.g., gastric cancer, pancreatic cancer, and liver metastases from colorectal cancer), could improve therapeutic efficacy and reduce the incidence of adverse reactions, and had a good prospect for clinical application. Example 7: Clinical studies on safety, tolerability, and pharmacokinetic characteristics of paclitaxel cationic liposomes for injection for the treatment of patients with advanced solid tumors via transcatheter arterial infusion. I. Primary and secondary objectives and outcomes 1. Primary objective (1) To evaluate the safety and tolerability of paclitaxel cationic liposome for injection for the treatment of advanced solid tumors via transcatheter arterial infusion. (2) To determine the maximum tolerated dose (MTD) and / or recommended dose for expansion (RDE) of cationic liposome paclitaxel for injection for the treatment of advanced solid tumors via transcatheter arterial infusion. Key outcome indicators (1) Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) (according to NCI CTCAE 5.0). (2) Frequency of dose-limiting toxicity (DLT). 2. Secondary objective (1) To evaluate the pharmacokinetic (PK) characteristics of paclitaxel cationic liposomes for injection for the treatment of advanced solid tumors via transcatheter arterial infusion. (2) To evaluate the preliminary antitumor activity of paclitaxel cationic liposome for injection for the treatment of advanced solid tumors via transcatheter arterial infusion. Secondary outcome indicators Petition 870260061141, dated 06 / 22 / 2026, page 41 / 90 32 / 40 (1) Pharmacokinetic indicators: PK parameters including, but not limited to, AUCo-t, AUCo-, Cmax, Kel, Tmax, Vd, ti / 2, CL, etc. (2) Efficacy indicators: overall remission rate (ORR), disease control rate (DCR), duration of remission (DOR), progression-free survival (PFS) and overall survival (OS). II. General essay design

[0106] This study included two phases: Phase Ia (dose escalation and expansion phases) and Phase Ib (cohort expansion phase).

[0107] The dose escalation phase included a screening period (0 to approximately 28 days), a treatment period (a DLT observation period and a subsequent treatment period), and a follow-up period (safety follow-up visit and survival follow-up visit). The first cycle (21 days), in which participants received the study drug, was the DLT observation period. After the DLT observation period, participants would proceed to the subsequent treatment period, provided they did not experience DLT. The dose expansion phase and the cohort expansion phase included a screening period (0 to approximately 28 days), a treatment period, and a follow-up period (safety follow-up visit and survival follow-up visit). Paclitaxel cationic liposome was administered via arterial infusion on day 1 of each cycle, with three weeks as a treatment cycle.Eligible participants would undergo 4 to 6 cycles of experimental treatment. Treatment may be terminated early if any of the following occur: disease progression, intolerable toxicity, initiation of a new antitumor therapy, withdrawal of the Informed Consent Form, loss to follow-up, death, or other criteria for treatment discontinuation (whichever occurs first). If a participant experienced their first disease progression, but the researchers assessed that the participant... Petition 870260061141, dated 06 / 22 / 2026, page 42 / 90 33 / 40 could still benefit from continued treatment and the participant was willing to continue, the participant may proceed with the study treatment for 1 to 2 cycles until disease progression occurs again.

[0108] During the trial, participants would undergo efficacy assessments once every 6 weeks ± 7 days from the first dose. For patients who discontinued treatment for reasons other than disease progression, tumor assessments should be continued until the following occur: disease progression or initiation of new antitumor therapy, withdrawal of the Informed Consent Form by the participant, loss to follow-up, death, etc. (whichever occurs first). 1. Dose escalation phase

[0109] The initial dose of paclitaxel cationic liposome for injection was provisionally set at 22 mg / m2 and may be appropriately adjusted after discussion by the SMC (Scientific Monitoring Committee established for this study) based on data obtained from previous studies on treatment with this product via arterial infusion. The maximum dose was currently predefined at 66 mg / m2. If this dose is safe and tolerable, the investigators and sponsor may discuss and decide whether or not to attempt a higher dose. If participants in the low-dose group did not experience DLT during the DLT observation period and this dose level demonstrated good safety and tolerability, these participants could receive a higher dose of the study drug subsequently after SMC discussion.

[0110] The specific dose groups in the dose escalation phase were designed according to the modified Fibonacci approach and shown in the table below. Table 7: Dose group design in the dose escalation phase (dosing once every 3 weeks) Petition 870260061141, dated 06 / 22 / 2026, page 43 / 90 34 / 40 Dose group 1 2 3 4 5 Escalation rate - 50% 33% 25% 20% Dose (mg / m2) 22 33 44 55 66 Method of administration Chemotherapy via transcatheter arterial infusion

[0111] In addition to the initial dose, escalating doses may be discussed by researchers and the sponsor based on data obtained, such as drug safety and PK, to decide whether or not to proceed to the next dose group and whether or not to adjust dosages or dosing regimens for other dose groups.

[0112] In this study, the first dose group followed the accelerated dose titration design, and subsequent dose groups followed the 3+3 dose escalation design. Paclitaxel cationic liposome DLT was observed in the first cycle (within 21 days). If participants in the accelerated titration group experienced moderate toxicity (including drug-related AEs of the following levels requiring intervention: a single occurrence of other Grade 3 AEs that were not DLT or two occurrences of Grade 2 or higher AEs), not only this dose group but also subsequent dose groups followed the 3+3 design. 3+3 Dose Escalation Project:

[0113] Three cases were enrolled in each dose group. After DLT observation, the cases were evaluated to determine if they could participate in the next dose group based on the following rules: (1) Three participants were enrolled in the first dose group (or a specific dose group) and completed the DLT observation; (2) if none of the three participants in a dose group experienced DLT, the dose would be escalated to the level of the next dose group; (3) if two or more of the three participants in a dose group Petition 870260061141, dated 06 / 22 / 2026, p. 44 / 90 35 / 40 presented DLT, the dose would be de-escalated to the level of the previous dose group; (4) if one of the three participants in a dose group developed DLT, three more participants would be enrolled in this dose group; if 1 / 6 participants developed DLT, the dose would be escalated to the level of the next dose group; if 2 / 6 or more participants developed DLT, the dose would be escalated to the level of the previous dose group; (5) if the dose was de-escalated to the level of the previous dose group and there were only 3 participants in this dose group, three more participants would be enrolled. If there were 6 participants in this dose group, the dose escalation trial was terminated and this dose was MTD. Maximum tolerated dose (MTD):

[0114] MTD: Defined as the maximum dose at which 33% or less of participants experienced DLT. In general, if two or more of 3 participants enrolled at a dose level experienced DLT, the dose immediately preceding this dose was MTD; if one of 3 participants enrolled at a dose level experienced DLT and if 2 / 6 or more of the participants experienced DLT after the enrollment of three more participants at the same dose level, the dose immediately preceding this dose was MTD. [01 15] A new dose may be selected for testing between the previous dose and the intolerable dose, if necessary. 2. Dose expansion phase

[0116] Based on data such as PK, safety, tolerability and efficacy obtained from the dose escalation study, 1 to 3 recommended dose groups can be selected and enrollment can be expanded to 15 to 30 participants (including those in the corresponding dose groups in the dose escalation phase). 3. Cohort expansion phase

[0117] After the Recommended Dose for Expansion (RDE) has been Petition 870260061141, dated 06 / 22 / 2026, page 45 / 90 36 / 40 determined, 1 to 3 potentially active tumor types were selected for cohort expansion, including, but not limited to: liver cancer, liver metastases, pancreatic cancer, lung cancer, etc. The specific population with indications and sample size can be determined by the SMC after a full discussion. III. Dose-limiting toxicity (DLT)

[0118] Dose-limiting toxicity was defined as an adverse event that occurred during the first cycle (21 days) in the dose escalation phase (definitely, probably, or possibly) related to paclitaxel cationic liposome for injection and met the following severity levels (according to NCI CTCAE 5.0). Except for drug combinations and therapies prohibited in the protocol, clinical diagnosis and treatment routines should be followed in the study, and adequate and appropriate symptomatic support should be provided in a timely manner. Table 8: Dose-limiting toxicity Toxicity Determined as DLT in the case of any of the following events: Hematologic toxicity • Grade 4 neutropenia (absolute neutrophil count [ANC] <500 / mm3) persisting for more than 3 days • Febrile neutropenia >Grade 3 (ANC<l000 / mm3 com uma temperatura axilar única de > 38.3 °C or a sustained axillary temperature of >38.0 °C for more than 1 h) • Grade 4 thrombocytopenia (platelet count <25,000 / mm3) persisting for more than 5 days • Grade 3 thrombocytopenia (platelet count <50.• 000 / mm3) with clinically significant bleeding • Grade 4 anemia (life-threatening) Non-hematological toxicity • Grade 4 or higher toxicity • Special monitoring: Grade 3 or higher thromboembolic events and arterial thromboembolism, Grade 1-2 cerebrovascular ischemia • Other Grade 3 toxic responses of no special concern, except for: o Grade 3 fatigue, headache, nausea, diarrhea, vomiting, electrolyte imbalance (including hypokalemia, hypophosphatemia, hypocalcemia, etc.), which has recovered to Grade 1 or initial assessment within 48 h after symptomatic treatment; o Grade 3 fever (>40 °C, not more than 24 h), resolvable by symptomatic treatment o Disease-related or isolated non-clinical laboratory abnormalities determined by investigators as having no clinical significance. Petition 870260061141, dated 06 / 22 / 2026, page 46 / 90 37 / 40 Other • Other toxic reactions determined by the researchers to justify permanent discontinuation of the test drug • Late toxicities that occurred after the DLT observation period, but may increase the risk to participants

[0119] If the following circumstances occurred within the DLT observation period, the DLT observation period was considered incomplete and the cases must be replenished: - the dosage was less than 75% of the total planned dose for reasons unrelated to DLT; - termination of drug administration for reasons unrelated to DLT. IV. Test population Groups and participants Dose escalation phase: 15 to 30 cases; Dose expansion phase: 1 to 3 recommended dose groups were selected and enrollment was expanded to 15 to 30 participants (including those in the corresponding dose groups in the dose escalation phase); Cohort expansion phase: to be determined (by SMC after discussion based on data obtained in the dose escalation and expansion phases). Inclusion criteria: 1. Age >18 years; 2. Advanced solid tumors diagnosed histologically or cytologically as suitable for arterial infusion chemotherapy, including, but not limited to, the following tumor types: • Gastrointestinal tumors (including, but not limited to: gastric cancer, liver cancer, cholangiocarcinoma, pancreatic cancer, colorectal cancer, etc.); • Gynecological tumors (including, but not limited to: ovarian cancer, endometrial cancer, etc.); Petition 870260061141, dated 06 / 22 / 2026, page 47 / 90 38 / 40 • Non-small cell lung cancer; • Liver metastases; 3. at least one measurable lesion in the arterial infusion area, according to RECIST 1.1; 4. If the primary life-threatening injuries were within the arterial infusion area, limited injuries outside the arterial infusion area were acceptable in the initial assessment; 5. Eastern Cooperative Oncology Group (ECOG) performance status score from 0 to 2; 6. life expectancy of at least 3 months; 7. Adequate organ function, with laboratory test results meeting the following criteria (no transfusion or hematopoietic growth factor therapy within 14 days): a. absolute neutrophil count (ANC) > 1.5 x 10⁹ / L b. platelet count (PLT) >100 x 109 / L c. hemoglobin (Hb) >90 g / L d. Total bilirubin (TBIL) <1.5 x upper limit of normal (ULN); TBIL <2 x ULN for individuals with liver metastasis or liver cancer. e. alanine aminotransferase (ALT), aspartate aminotransferase (AST) <2.5 x ULN; ALT, AST <5 x ULN for individuals with liver metastasis or liver cancer f. creatinine clearance (Ccr) >50 mL / min (calculated according to the Cockcroft-Gault formula) g. activated partial thromboplastin time (APTT) <1.5 x ULN, international normalized ratio (INR) <1.5 x ULN 8. Eligible fertile individuals (men and women) had to agree to use reliable contraceptive methods (hormonal contraceptives, barrier methods, or abstinence) with their partners during the study and for at least 6 months after the last dose; male and female individuals Petition 870260061141, dated 06 / 22 / 2026, page 48 / 90 Women aged 39 / 40 of childbearing age had to take a negative blood pregnancy test within 7 days prior to registration; 9. To have a complete understanding of this clinical trial and voluntarily sign a written Informed Consent Form. Exclusion criteria: 1. Subjects who received chemotherapy, radiation therapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy, or other antitumor therapies within 4 weeks prior to the first administration of the study drug, or participated in another clinical trial within 4 weeks or 5 half-lives of the treatment drug (whichever is shorter); 2. subjects with known clinical symptoms of central nervous system metastases or meningeal metastases, or uncontrolled central nervous system metastases or meningeal metastases indicated by other evidence and considered by the investigators to be unsuitable for enrollment; 3. subjects with adverse reactions from previous antitumor therapies who had not yet recovered to CTCAE 5.0 Grade <1 (except for toxicities such as alopecia considered non-risky by the investigators); 4. subjects who participated in another clinical trial simultaneously, unless it was observational (non-interventional) or during the follow-up period of an interventional trial; 5. subjects who underwent major surgery or invasive procedure in the 28 days prior to the first dose; 6. Subjects who took any Chinese herbal medicine or Chinese patented medicine with anticancer activity approved by the China National Medical Products Administration (NMPA) within 14 days prior to the first dose (regardless of cancer type). V. Research results Petition 870260061141, dated 06 / 22 / 2026, page 49 / 90 40 / 40

[0120] Arterial infusion of cationic liposome paclitaxel has shown good effects in the treatment of advanced solid tumors (e.g., gastric cancer, pancreatic cancer, and liver metastases from colorectal cancer), could improve therapeutic efficacy and reduce the incidence of adverse reactions, and has a good prospect for clinical application.

[0121] Although the foregoing descriptions are merely specific embodiments of the present disclosure, the scope of protection of the present disclosure is not limited to them. Any variations or substitutions within the technical scope of the present disclosure that are readily conceivable to a person skilled in this technical field shall be included within the scope of protection of the present disclosure. Therefore, the scope of protection of the present disclosure shall be subject to the scope of protection of the claims. Petition 870260061141, dated 06 / 22 / 2026, pp. 50 / 90

Claims

1 / 1 Claims 1. Use of a cationic liposome of paclitaxel, characterized by being in the preparation of a medicament to treat an advanced solid tumor.

2. Use of a cationic liposome of paclitaxel and a systemic therapeutic drug, characterized by being in the preparation of a medicament to treat an advanced solid tumor, preferably the systemic therapeutic drug being capecitabine and oxaliplatin, or cisplatin, or gemcitabine, or capecitabine.

3. Use, according to claim 1 or 2, characterized in that the advanced solid tumor comprises gastrointestinal tumors, including gastric cancer, esophageal cancer, pancreatic cancer, colorectal cancer, cholangiocarcinoma and liver cancer; lung cancer; gynecological tumors, including ovarian cancer, endometrial cancer and cervical cancer; prostate cancer; bladder cancer; and liver metastases.

4. Use, according to claim 1 or 2, characterized in that the advanced solid tumor comprises gastric cancer, pancreatic cancer or liver metastases from colorectal cancer, preferably the advanced solid tumor comprises liver metastases not exposed to treatment, including liver metastases from gastric cancer, liver metastases from colorectal cancer or liver metastases from pancreatic cancer.

5. Use, according to claim 1 or 2, characterized in that the paclitaxel cationic liposome contains: paclitaxel, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-3-trimethylammonium-propane chloride (DOTAP) and trehalose; preferably, each paclitaxel cationic liposome preparation contains 5 to 10 mg of paclitaxel, 72 to 144 mg of 1,2-dioleoyl-sn-glycero-3-phosphocholine, 68 to 136 mg of 1,2-dioleoyl-3-trimethylammonium-propane chloride and 1500 to 2500 mg of trehalose. Petition 870250067051, dated 07 / 31 / 2025, p. 10 / 11

Images