Dosage and administration of bispecific SCFV conjugates in combination with anti-cancer therapeutics
A bispecific and dosing technology, applied in antineoplastic drugs, antibody medical components, anti-animal/human immunoglobulin, etc., can solve problems such as changing bioavailability and affecting safety characteristics
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example 1
[0114] Example 1: Treatment with Lapatinib, Paclitaxel, Trastuzumab, and MM-111
[0115]Lapatinib and trastuzumab have been shown to have demonstrated synergy compared to single agents (Blackwell et al., 2010). The combination of trastuzumab and paclitaxel is an effective regimen in patients with HER2-positive breast cancer. Recently, Baselga et al. reported the results of a neoadjuvant study in which patients were randomized into three groups to receive (1) daily oral lapatinib 1500 mg alone ( N=154) or (2) trastuzumab loading dose 4 mg / kg and 2 mg / kg maintenance dose (N=149) or (3) lapatinib (1000 mg) and trastuzumab (N=152 ) for six weeks. Afterwards, patients received combined weekly 80mg / m 2 The same treatment with paclitaxel continued for an additional twelve weeks. The primary endpoint of this Phase III study (NeoALTTO) was pathological complete response rate (pCR).
[0116] The rate of pCR was significantly higher in the group given lapatinib and trastuzumab (78...
example 2
[0143] Example 2: Treatment with Docetaxel and Trastuzumab + MM-111
[0144] In preclinical terms, the combination of docetaxel and MM-111 is additive from an efficacy standpoint. By inhibiting ErbB3, the addition of MM-111 to this regimen could prevent resistance to HER-directed therapy as well as tumor regrowth and presumably enhance the efficacy of this potent regimen.
[0145] In current multigroup studies, MM-111 has been combined with a taxane (paclitaxel) and trastuzumab given weekly and has been well tolerated so far. There was no evidence of any overlapping toxicity of paclitaxel, trastuzumab, and MM-111. Both a three-week docetaxel regimen plus trastuzumab and weekly paclitaxel plus trastuzumab are approved for HER2-positive breast cancer (FDA; [trastuzumab] US package insert 2010). The ultimate intention is to develop a three-weekly regimen comprising docetaxel, trastuzumab, and MM-111. This protocol can be used to evaluate the effect of MM-111 when added t...
example 3
[0168] Example 3: Treatment with Capecitabine, Cisplatin, and Trastuzumab + MM-111
[0169] Patients with HER2 positive cancer (eg, HER22+ or HER23+) are treated with MM-111 combination therapy. In one example, patients with previously untreated HER2+ metastatic gastric or GEJ cancer can be enrolled in a study group of cisplatin, capecitabine, and trastuzumab + MM-111. This study has a standard 3+3 design. In one embodiment, the initial dose of MM-111 is 10 mg / kg. In some embodiments, the initial dose of MM-111 is 5 mg / ml, but in other embodiments, MM-111 can be administered at an initial dose, eg, from about 500 μg / mL to about 5.0 mg / mL. In some embodiments, the dose of capecitabine is from 1000mg / m 2 Reduced to 800mg / m 2 .
[0170] Anticancer therapy should be administered in the following order: 1) capecitabine, 2) cisplatin, 3) trastuzumab, and 4) MM-111.
[0171]
[0172] aAdministered via IV infusion for 2 hours on Day 1 of every three weeks for six cycles. A...
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