Anti-tumor pharmaceutical composition, application and kit for treating non-small cell lung cancer

Abstract

The invention discloses an anti-tumor pharmaceutical composition, application and a kit for treating non-small cell lung cancer, and relates to the technical field of medicines. The pharmaceutical composition comprises a PD-L1 inhibitor, a PCSK9 inhibitor, a platinum chemotherapeutic drug and a paclitaxel chemotherapeutic drug, and can be used for preparing drugs for treating non-small cell lung cancer. The kit comprises the pharmaceutical composition and an operation instruction. Wherein the application of the pharmaceutical composition in the treatment of non-small cell lung cancer is described in the specification. Through the synergistic effect of the three mechanisms of immune activation, cytotoxicity killing and metabolic regulation, the bottleneck of existing resectable non-small cell lung cancer perioperative treatment can be effectively broken through, the complete remission rate of lesion and pathology of a patient is remarkably increased, and long-term survival is achieved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to an antitumor drug composition and its use, and a kit for treating non-small cell lung cancer. Background Technology

[0002] Malignant tumors are a major disease posing a serious threat to global human health, with their incidence and mortality rates showing an increasing trend year by year. Taking common tumors such as lung cancer, gastric cancer, and breast cancer as examples, most patients are diagnosed at an advanced stage, missing the optimal time for radical surgical treatment. Among them, lung cancer has long ranked among the top cancers in terms of incidence and mortality worldwide. As the most common pathological type of lung cancer, non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases, and its treatment challenges are particularly prominent. For the perioperative treatment of NSCLC, although PD-1 / PD-L1 inhibitors combined with chemotherapy have become the standard treatment regimen, its pathological complete response rate is still generally less than 25%, and about 40% of patients relapse within two years after surgery, showing a significant bottleneck in efficacy. Existing treatment regimens have three key technical deficiencies: First, the treatment mechanism is limited to the simple superposition of immune checkpoint blockade and chemotherapy drugs, failing to utilize the regulatory role of cholesterol metabolism on the tumor immune microenvironment; second, there is a lack of precision treatment strategies for patients with comorbid lipid metabolism abnormalities, failing to translate comorbid management into a treatment advantage; and third, the transition between neoadjuvant and adjuvant therapy phases lacks dynamic optimization based on drugs with different mechanisms.

[0003] Therefore, there is an urgent need in the field for innovative drug combinations and treatment strategies that can work synergistically through multiple mechanisms and cover the entire treatment process to bring better clinical outcomes to NSCLC patients. Summary of the Invention

[0004] The present invention aims to solve at least one of the technical problems existing in the prior art or related art.

[0005] Therefore, in a first aspect, the present invention provides an antitumor pharmaceutical composition comprising a PD-L1 inhibitor, a PCSK9 inhibitor, a platinum-based chemotherapy drug, and a taxane-based chemotherapy drug.

[0006] Furthermore, the PD-L1 inhibitor is adebelimab, the PCSK9 inhibitor is ricarcillin, the platinum-based chemotherapy drug is carboplatin, and the paclitaxel-based chemotherapy drug is albumin-bound paclitaxel.

[0007] Furthermore, the pharmaceutical composition is an injectable dosage form.

[0008] A second aspect of the invention provides the use of the pharmaceutical composition in the preparation of a medicament for treating non-small cell lung cancer.

[0009] Furthermore, the use of the pharmaceutical composition in the preparation of a perioperative medicament for the treatment of resectable non-small cell lung cancer.

[0010] Furthermore, the pharmaceutical composition is suitable for patients with non-small cell lung cancer of any PD-L1 expression level, including patients with non-small cell lung cancer complicated by lipid metabolism abnormalities.

[0011] A third aspect of the present invention provides a kit for the treatment of non-small cell lung cancer, comprising: the aforementioned pharmaceutical composition, and instructions for use; wherein, The instructions for use state that the pharmaceutical composition is used for the treatment of non-small cell lung cancer.

[0012] Furthermore, the instructions for use also include: during the neoadjuvant therapy phase of resectable non-small cell lung cancer in the perioperative period, the components of the pharmaceutical composition are administered in combination.

[0013] Furthermore, the neoadjuvant therapy phase consists of three cycles; the dosing regimen for each cycle is as follows: Adebelimumab: Fixed dose 1200 mg, administered on day 1, every 3 weeks; Albumin-bound paclitaxel: 130 mg / m² 2 Administer on day 1 and day 8, every 3 weeks; Carboplatin: AUC=5, administered on day 1, every 3 weeks; Recarbazil: fixed dose 150 mg, administered on day 1, every 3 weeks.

[0014] Furthermore, the instructions for use also include: During the adjuvant therapy phase of resectable non-small cell lung cancer in the perioperative period, adebelimab is used for treatment, with a treatment duration not exceeding one year; the dosing regimen is as follows: Adbelimumab: Fixed dose 1200 mg, administered on day 1, every 3 weeks.

[0015] Compared with the prior art, the present invention has at least the following beneficial effects: This invention provides a pharmaceutical composition of "PD-L1 inhibitor + chemotherapy (platinum-based chemotherapy drugs and paclitaxel-based chemotherapy drugs) + PCSK9 inhibitor". Through the synergistic effect of the three mechanisms of immune activation, cytotoxic killing and metabolic regulation, it can effectively break through the bottleneck of the existing perioperative treatment of resectable non-small cell lung cancer, significantly improve the complete pathological remission rate of patients and achieve long-term survival. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments recorded in the embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings.

[0017] Figure 1 A flowchart illustrating the perioperative treatment protocol for resectable non-small cell lung cancer provided in this embodiment of the invention. Detailed Implementation

[0018] To better understand the above technical solutions, the technical solutions of the embodiments of this application will be described in detail below with reference to the accompanying drawings and specific embodiments. It should be understood that the embodiments of this application and the specific features in the embodiments are detailed descriptions of the technical solutions of the embodiments of this application, rather than limitations on the technical solutions of this application. In the absence of conflict, the embodiments of this application and the technical features in the embodiments can be combined with each other.

[0019] In a first aspect, an antitumor drug composition is provided, comprising a PD-L1 inhibitor, a PCSK9 inhibitor, a platinum-based chemotherapy drug, and a paclitaxel-based chemotherapy drug.

[0020] In some embodiments, the PD-L1 inhibitor is adebenone, the PCSK9 inhibitor is ricarcillin, the platinum-based chemotherapy drug is carboplatin, and the paclitaxel-based chemotherapy drug is albumin-bound paclitaxel.

[0021] In some embodiments, the above-described pharmaceutical composition is an injectable formulation, including intravenous injection and subcutaneous injection formulations, wherein adebelimumab, carboplatin, and albumin-bound paclitaxel are intravenous injection formulations, and recarcissumab is a subcutaneous injection formulation.

[0022] Adebelimumab, a PD-L1 inhibitor, is a humanized monoclonal antibody independently developed in my country. Its Fab fragment specifically binds to PD-L1, thereby blocking the interaction between PD-1 and PD-L1. The engineered Fc fragment enhances antibody-dependent cytotoxicity, thus synergistically eliminating PD-L1-expressing tumor cells. Preclinical studies have shown that adebelimumab has an affinity for PD-L1 at the nM level, effectively reversing T cell exhaustion and restoring anti-tumor immune responses.

[0023] Albumin-bound paclitaxel utilizes a nanotechnology platform with an average particle size of approximately 130 nm. This drug crosses vascular endothelium via GP60 receptor-mediated transcytosis and is specifically enriched in the tumor stroma via the SPARC protein, a cysteine-rich acidic secretory protein. Compared to conventional paclitaxel, this drug achieves a 33% higher concentration in tumor tissue and significantly reduces the risk of allergic reactions.

[0024] Carboplatin is a second-generation platinum compound. Its DNA binding kinetics show that carboplatin can form an intra-chain crosslink with the N7 site of guanine, thereby exerting a broad-spectrum anti-tumor effect by disrupting DNA structure and function. Furthermore, the dosage of carboplatin can be precisely calculated using the Calvert formula, ensuring the safety and controllability of treatment.

[0025] Recasimoab is a humanized monoclonal antibody targeting PCSK9. Its complementarity-determining region (CDG) specifically binds to the ligand-binding domain of PCSK9, thereby inhibiting the interaction between PCSK9 and the low-density lipoprotein receptor (LDLR). This antibody belongs to the IgG1 subtype, and its Fc region has been modified, such as by introducing a YTE mutation, to extend its half-life to 27 to 35 days. Clinical data show that this antibody reduces LDL-C levels by 50% to 60%, an effect also attributed to its long half-life.

[0026] The pharmaceutical compositions in the embodiments of the present invention can maximize their anti-tumor effects through the following sequential and synergistic mechanisms: The combination chemotherapy of albumin-bound paclitaxel and carboplatin initially induces immunogenic cell death in tumor cells, thereby releasing tumor-associated antigens, damage-associated molecular patterns (MAS), and ATP, and activating the antigen-presenting function of dendritic cells. Damage-associated MAS includes, for example, high-mobility group box 1 (HMBB1).

[0027] Adebelimumab specifically binds to PD-L1 via its Fab fragment, blocking the PD-1 / PD-L1 pathway and relieving immunosuppression. Simultaneously, its engineered Fc fragment enhances antibody-dependent cell-mediated cytotoxicity, further eliminating PD-L1-positive tumor cells and immunosuppressive cells. Preclinical animal model data have shown that this sequential strategy increases the number of CD8-positive cytotoxic T lymphocytes infiltrating the tumor microenvironment by 3.2-fold, accompanied by elevated levels of pro-inflammatory factors such as interferon-γ and tumor necrosis factor-α, significantly enhancing the anti-tumor immune response.

[0028] Recarcasizumab, a novel PCSK9 inhibitor, is being innovatively incorporated into perioperative treatment for the first time to modulate the tumor immune microenvironment. Metabolic mechanism studies show that it exerts its effects through the following pathways: 1. Interfering with tumor cell cholesterol metabolism: By reducing circulating LDL-C levels, the uptake of exogenous cholesterol by tumor cells is indirectly reduced, and lipid raft formation is downregulated, thereby disrupting the stability of PD-L1 on the cell membrane surface. The lipid raft is a key structure for PD-L1 membrane localization. 2. Antigen presentation regulation: Preclinical studies have confirmed that PCSK9 inhibition can indirectly promote the expression of MHC-I molecules in dendritic cells through the LDLR-related pathway; 3. Regulation of immune cell function: In vitro studies suggest that PCSK9 may regulate CD8. + Cholesterol uptake by T cells enhances TCR signal transduction efficiency.

[0029] The combination of four drugs creates a closed-loop synergistic effect in perioperative medication, encompassing "immune killing - immune activation - immune maintenance": Immune killing: Chemotherapy induces immunogenic cell death, releasing tumor antigens; Immune activation: Immune checkpoint inhibitors relieve the inhibition of T cells by the PD-1 / PD-L1 pathway; Immune maintenance: PCSK9 inhibitors enhance T cell function and the tumor microenvironment by regulating cholesterol metabolism.

[0030] Through the synergistic effects of the drugs, a complete anti-tumor immune closed loop is formed. The embodiments of this invention also fully utilize the unique advantages of each drug: Adebelimumab – a domestically developed innovation with high accessibility; Albumin-bound paclitaxel – targeted delivery with excellent safety; Carboplatin – precise dosage and controllable toxicity; Recarcasmab – a long-acting formulation with high compliance.

[0031] A second aspect of the present invention provides the use of the above-described pharmaceutical composition in the preparation of a medicament for treating non-small cell lung cancer.

[0032] In some embodiments, the above-described pharmaceutical composition can be used to prepare a perioperative medicine for treating resectable non-small cell lung cancer.

[0033] Currently, no combination of the above four drugs in the perioperative treatment of resectable non-small cell lung cancer has been found in public databases.

[0034] In some embodiments, the above-described pharmaceutical composition is suitable for patients with non-small cell lung cancer of any PD-L1 expression level, including those with non-small cell lung cancer and concurrent lipid metabolism abnormalities. It inhibits tumor growth, recurrence, and metastasis through a multiple synergistic mechanism of targeting and enhancing tumor immunogenicity, relieving immunosuppression, and remodeling the tumor metabolic microenvironment.

[0035] Specifically, the aforementioned drug composition is used to treat a broad range of non-small cell lung cancer (NSCLC) patients regardless of PD-L1 expression levels, providing a new and effective option for patients with different biomarker statuses. It is particularly useful for treating NSCLC patients with dyslipidemia. This drug composition offers a superior treatment strategy for resectable NSCLC patients with dyslipidemia. Clinical data show that for patients with dyslipidemia, the objective response rate of PCSK9 inhibitors combined with immunotherapy can be 35% higher than that of immunotherapy alone, while reducing the risk of cardiovascular events by 60%. The close integration of each treatment phase forms a complete perioperative treatment pathway, achieving anti-tumor efficacy while synergistically managing patient comorbidities, improving long-term prognosis, and bringing dual health benefits.

[0036] A third aspect of the present invention provides a kit for the treatment of non-small cell lung cancer, comprising: the above-described pharmaceutical composition, and instructions for use; wherein the instructions for use describe the use of the pharmaceutical composition for the treatment of non-small cell lung cancer.

[0037] In some embodiments, the kit described above can be used for perioperative treatment of resectable non-small cell lung cancer, wherein perioperative treatment includes a neoadjuvant therapy phase and an adjuvant therapy phase. The instructions for use also include: during the neoadjuvant therapy phase of perioperative treatment for resectable non-small cell lung cancer, the components of the above pharmaceutical composition are administered in combination.

[0038] In some embodiments, during the neoadjuvant therapy phase, the treatment duration is 3 cycles; the dosing regimen for each cycle is: adebelimumab: fixed dose 1200 mg, administered on day 1, every 3 weeks; albumin-bound paclitaxel: 130 mg / m². 2 Administer on day 1 and day 8, every 3 weeks; Carboplatin: AUC=5, administered on day 1, every 3 weeks; Recarbazil: fixed dose 150 mg, administered on day 1, every 3 weeks.

[0039] In some embodiments, the instructions for use also include: treatment with adebelimumab during the adjuvant therapy phase of resectable non-small cell lung cancer in the perioperative period, for a duration not exceeding 1 year; the dosing regimen is: adebelimumab: fixed dose 1200 mg, administered on day 1, once every 3 weeks.

[0040] By designing a sequence of four-drug combination therapy in the neoadjuvant phase and single-drug maintenance immunotherapy in the adjuvant phase, dynamic optimization of treatment intensity was achieved. Tumor killing was maximized in the neoadjuvant phase, while immune memory formation and metabolic regulation were emphasized in the adjuvant phase. This fully leveraged the efficacy of multi-drug combination therapy at different perioperative stages, forming a long-term protective management model and enabling patients to better tolerate multi-drug therapy.

[0041] The aforementioned drug composition and kit are the first to integrate the PCSK9 inhibitor ricarcillin into the perioperative treatment system for resectable non-small cell lung cancer, establishing a multidimensional synergistic mechanism of "immunity-chemotherapy-metabolic regulation" and precisely targeting metabolic reprogramming in the tumor immune microenvironment. In addition to improving tumor control and prolonging survival, it can also address the problem of immunotherapy resistance.

[0042] By precisely coordinating the above-mentioned specific drug combinations with the treatment stages, an innovative solution is provided to address the technical problem of existing perioperative treatment protocols having a single mechanism and limited efficacy.

[0043] Example 1 Scheme Design 1. Single-arm, open-label, prospective phase II clinical trial 1.1 Research Subjects In the clinical study of the perioperative treatment regimen of this invention, 35 evaluable subjects were planned to be enrolled. The sample size was calculated using NCSS PASS 21 software, based on an expected pathological complete remission rate of 38%, and determined to ensure that the lower limit of the two-sided 95% confidence interval (Clopper-Pearson method) for the pCR rate was not less than 22%.

[0044] 1.2 Main Inclusion Criteria include: (1) Age ≥ 18 years, gender not limited, ECOG score 0 or 1.

[0045] (2) EGFR or ALK mutation negative.

[0046] (3) Patients with stage II-III NSCLC (stage II, IIIA and T3N2M0 IIIB) confirmed by histology or cytology, with measurable lesions and surgical treatment; N2 patients with non-mass metastases expected to be completely resectable.

[0047] (4) Those who have not received anti-tumor treatment before enrollment, including radiotherapy, chemotherapy, surgery, targeted therapy, and those who have been assessed as being able to tolerate R0 resection.

[0048] (5) There are fresh or preserved tumor tissue samples.

[0049] (6) The major organs are functioning normally, and the blood routine and blood biochemistry meet the inclusion criteria.

[0050] (7) The subjects voluntarily enrolled, signed informed consent forms, had good compliance, and cooperated with follow-up.

[0051] 1.3 Researchers The clinical trial was led by Professor Wang Jinghui, an expert in the field, with Beijing Chest Hospital, affiliated with Capital Medical University, as the responsible unit. The trial process, including patient screening, inclusion, exclusion, treatment, surgery, and evaluation, was completed there.

[0052] Example 2 Evaluation Indicators 1. Primary endpoint Pathological complete remission (pCR): No residual surviving tumor cells in the tumor bed (including no residual tumor in lymph nodes) in the postoperative specimen pathological response assessment.

[0053] 2. Secondary endpoint (1) Significant pathological remission (MPR): The tumor residual rate is less than 10%.

[0054] (2) Objective response rate (ORR): refers to the proportion of patients whose tumors shrink to a certain extent and remain so for a certain period of time. Specifically, it refers to the proportion of the total number of cases with complete remission (CR) + partial remission (PR) after treatment to the total number of evaluable cases.

[0055] (3) Event-free survival (EFS): Event-free survival refers to the time from enrollment to the occurrence of any event, including death, disease progression, change of chemotherapy regimen, switching to chemotherapy, addition of other treatments, occurrence of fatal or intolerable side effects, etc.

[0056] (4) Disease-free survival (DFS): Disease-free survival refers to the time from randomization / treatment start to disease relapse or death from any cause.

[0057] Example 3 Treatment Plan 1. Patient population characteristics This protocol is applicable to patients with histologically or cytologically confirmed resectable stage II-III non-small cell lung cancer (NSCLC) (according to the UICC / AJCC 8th edition TNM staging), including stage II, IIIA, and T3N2M0 stage IIIB patients. PD-L1 expression level is not limited, but patients with known EGFR-sensitive mutations or ALK fusion-positive status must be excluded. It is particularly suitable for surgically resectable NSCLC patients with concomitant lipid metabolism abnormalities (such as hypercholesterolemia).

[0058] 2. Dosage adjustment and safety monitoring 2.1 Dosage adjustments should be made during treatment based on patient tolerance. Hematologic toxicity: When ANC < 1.5 × 10 9 / L or PLT < 100 × 10 9 When the dose reaches / L, discontinue administration until it is resumed; If liver function is abnormal: ALT / AST > 2 times ULN, discontinue administration. Renal function adjustment: Adjust carboplatin dosage according to creatinine clearance rate; Immune-related adverse reactions: Classified and managed according to NCI CTCAE 5.0 standards.

[0059] 2.2 Safety Monitoring This includes regular monitoring of blood routine tests, liver and kidney function tests, myocardial enzyme levels, and blood lipid levels, as well as close monitoring of immune-related adverse events.

[0060] 2.3 Surgical Treatment Assessment and Standards Efficacy evaluation should be conducted within 3-4 weeks after the completion of neoadjuvant therapy; Imaging assessment: Tumor changes were assessed using RECIST 1.1 criteria; Surgical feasibility assessment: The thoracic surgeon assesses the patient's performance status (ECOG score 0 or 1) and lung function; Surgical criteria: The goal is to achieve R0 resection, and radical resection is performed within a time window of 3-4 weeks after the end of neoadjuvant therapy.

[0061] 2.4 Neoadjuvant therapy phase In the neoadjuvant therapy phase, a four-drug combination therapy regimen is used: Adebelimumab: Fixed dose 1200 mg, intravenous infusion over 30-60 minutes, once every 3 weeks (dose on day 1). Albumin-bound paclitaxel: 130 mg / m³ 2 Administer intravenously over 30 minutes, once every 3 weeks (on day 1 and day 8). Carboplatin: AUC=5, intravenous infusion, once every 3 weeks (dose on day 1); Recarcasmab: 150 mg, subcutaneous injection, once every 3 weeks (dose on day 1); Neoadjuvant therapy with adebenone in combination with albumin-bound paclitaxel, carboplatin, and ricarcisumab for 3 cycles.

[0062] 2.5 Surgical Treatment Stage Radical tumor resection is performed within 3-4 weeks after the completion of neoadjuvant therapy.

[0063] 2.6 Adjunctive Therapy Stage Adjuvant therapy begins 3-4 weeks post-surgery: Adebelimumab: 1200 mg, intravenous infusion, once every 3 weeks (dose on day 1). The duration of adjuvant therapy should not exceed one year.

[0064] like Figure 1 As shown in the figure, the core technical solution of the embodiment of the present invention is clearly illustrated, including the screening period, the neoadjuvant therapy stage (four-drug combination), the surgical stage, the adjuvant therapy stage (immunotherapy monotherapy maintenance), and the complete process and dosing time nodes of the protocol.

[0065] The triple perioperative treatment regimen of "PD-L1 inhibitor (adebecilimab) + chemotherapy (carboplatin + albumin-bound paclitaxel) + PCSK9 inhibitor lipid-lowering drug (recarbazine)" provided in this invention has been validated through a prospective phase II clinical trial (13 evaluable subjects have been enrolled). The clinical trial demonstrated the following technical effects in antitumor activity: Table 1. Overview of treatment efficacy in enrolled patients

[0066] As shown in Table 1, among the 13 evaluable subjects who were actually enrolled, 8 patients achieved the objective response rate (ORR). Subsequently, 12 patients completed R0 resection, of whom 6 patients achieved complete pathological remission and 3 patients achieved significant pathological remission. In addition, 4 patients have received more than 6 cycles of adjuvant therapy, and all patients' conditions are currently stable.

[0067] (1) Significantly induces deep pathological remission Patients receiving the neoadjuvant combination therapy regimen in this embodiment of the invention achieved a pathological complete response rate of 46.2% (6 / 13), a significant pathological response rate of 23.1% (3 / 13), and an overall objective response rate as high as 61.5% (8 / 13). The pCR rate was significantly higher than the approximately 20%-25% pCR rate reported internationally for neoadjuvant therapy with PD-1 inhibitors combined with chemotherapy in resectable non-small cell lung cancer. This breakthrough demonstrates that, based on the dual mechanism of "immunotherapy + chemotherapy," the introduction of the PCSK9 inhibitor lecasimab for metabolic regulation produces a significant synergistic effect, thereby solving the efficacy bottleneck problem of existing immunotherapy + chemotherapy combination regimens.

[0068] (2) Achieving an extremely high radical resection rate Patients using the combined treatment regimen of this invention achieved an R0 resection rate of 92.3% (12 / 13). The only patient who could not undergo R0 resection also achieved a PR for one year after receiving neoadjuvant therapy. This indicates that this perioperative regimen can effectively shrink the primary tumor and remove micrometastases, significantly improve surgical conditions, enable the vast majority of patients to undergo radical resection, thereby improving the overall effectiveness of surgical treatment and providing a strong guarantee for prolonging patients' overall survival.

[0069] (3) Maintain and consolidate the therapeutic effect in the long term Among the patients who underwent surgery, several successfully received adjuvant therapy for nearly a year, and none of them showed signs of disease recurrence or progression. Clinical trial data from the adjuvant therapy phase confirmed the significant success of the "neoadjuvant potent clearance + adjuvant immune maintenance" timing strategy employed in this regimen. The immunotherapy monotherapy during the adjuvant therapy phase effectively prolonged and consolidated the deep pathological remission achieved by neoadjuvant therapy, which is of significant clinical importance in preventing recurrence of minimal residual disease after surgery and achieving long-term disease-free survival.

[0070] (4) Verify the effectiveness and safety of the “immunotherapy-metabolism regulation” synergistic mechanism. Clinical trials, from a prognostic and efficacy perspective, validated the intrinsic synergistic mechanism of this invention: chemotherapy induces immunogenic cell death, PD-L1 inhibitors relieve immunosuppression and activate T cells, and PCSK9 inhibitors enhance T cell function by regulating cholesterol metabolism and may disrupt the membrane stability of PD-L1 in tumor cells. These three sequentially act to form a closed-loop treatment mechanism of "immune killing - immune activation - immune maintenance." Regarding safety, treatment-related adverse events were consistent with the known toxicity profile of chemotherapy and immunotherapy, primarily manifesting as mild myelosuppression. With timely treatment, these adverse events were effectively controlled and resolved within 1 to 2 treatment cycles. No unexpected serious adverse events occurred throughout the treatment process, and patients generally tolerated the treatment well.

[0071] In summary, the embodiments of the present invention, through innovative combined schemes and unique perioperative timing design, and after rigorous clinical trials, have achieved deep pathological remission and high R0 resection rate in the treatment of resectable non-small cell lung cancer, demonstrating efficacy significantly superior to existing standard therapies.

[0072] It will be readily understood by those skilled in the art that the above-described advantageous methods can be freely combined and superimposed without conflict. The above are merely preferred embodiments of this application and are not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application. The above are merely preferred embodiments of this application. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the technical principles of this application, and these improvements and modifications should also be considered within the protection scope of this application.

Claims

1. An antitumor drug composition, characterized in that, The pharmaceutical composition comprises a PD-L1 inhibitor, a PCSK9 inhibitor, a platinum-based chemotherapy drug and a paclitaxel-based chemotherapy drug.

2. The pharmaceutical composition of claim 1, wherein, The PD-L1 inhibitor is atezolizumab, the PCSK9 inhibitor is evolocumab, the platinum-based chemotherapy drug is carboplatin, and the paclitaxel-based chemotherapy drug is nab-paclitaxel.

3. The pharmaceutical composition according to claim 1 or 2, characterized in that, The pharmaceutical composition is in the form of an injection.

4. Use of the pharmaceutical composition of any one of claims 1-3 in the preparation of a drug for treating non-small cell lung cancer.

5. Use according to claim 4, characterized in that, The pharmaceutical composition is used in the preparation of a drug for treating perioperative non-small cell lung cancer.

6. Use according to claim 4 or 5, characterized in that, The pharmaceutical composition is suitable for non-small cell lung cancer patients with unlimited PD-L1 expression levels, including non-small cell lung cancer patients with abnormal lipid metabolism.

7. A kit for the treatment of non-small cell lung cancer, characterized in that, Comprise: The pharmaceutical composition of any one of claims 1-3, and instructions for use; wherein, The instructions for use record the use of the pharmaceutical composition of any one of claims 1-3 for the treatment of non-small cell lung cancer.

8. The kit of claim 7, wherein The record of the instructions for use also includes: in the neoadjuvant therapy stage of resectable non-small cell lung cancer, the components in the pharmaceutical composition are administered in combination.

9. The kit of claim 8, wherein The neoadjuvant therapy stage, the treatment time is 3 cycles; the administration scheme of each cycle is: Ado-trastuzumab emtansine: fixed dose 1200 mg, Day 1, every 3 weeks; nab-paclitaxel: 125 mg / m2, Day 1, every 3 weeks; carboplatin: AUC = 5, Day 1, every 3 weeks; bevacizumab: fixed dose 15 mg / kg, Day 1, every 3 weeks. 2 Ado-trastuzumab emtansine: fixed dose 1200 mg, Day 1, every 3 weeks; nab-paclitaxel: 125 mg / m2, Day 1, every 3 weeks; carboplatin: AUC = 5, Day 1, every 3 weeks; bevacizumab: fixed dose 15 mg / kg, Day 1, every 3 weeks.

10. The kit of claim 7, wherein The record of the instructions for use also includes: in the adjuvant therapy stage of resectable non-small cell lung cancer, atezolizumab is used for treatment, and the treatment duration is not more than 1 year; the administration scheme is: Atezolizumab: fixed dose of 1200 mg, administered on day 1, once every 3 weeks.

Images