Combinatorial therapies comprising of anti-MET and anti-EGFR programmed drugs for advanced NSCLC treatment
| Combination studied | Optimizations of clinical trails | Key findings | Results/Generalizations affirmed |
|---|---|---|---|
| Tepotinib and gefitinib | A single phase Ib/II multicenter randomized trial, screened patients were EGFR mutant sufferers with overexpressed MET. Phase II study examined 55 patients, of which 31 received 500 mg tepotinib and 250 mg gefitinib daily. Twenty four patients received pemetrexed (500 mg/m2) + cisplatin (75 mg/m2) or carboplatin | Enhanced survival for tepotinib + gefitinib co-administered patients, exhibiting 37.3 months OS and 8.3 months PFS contrary to 17.9 months and 4.4 months for chemotherapy administered sufferers | Anti-EGFR and Anti-MET combinatorial therapies exhibited a better potential than standard chemotherapy in patients harbouring acquired resistance to EGFR inhibition |
| Osimertinib and savolitinib | Examined patients prevailed in B and D expansion cohorts, group B comprised 3 sub-cohorts (B1, B2 and B3). B1 included (n = 69) patients pretreated with osimertinib. Sub-cohorts B2 and B3 included patients with T790M positivity (n = 18) and negativity (n = 51) but no prior osimertinib treatment. Cohort D included MET overexpressing and EGFR mutant sufferers, earlier treated with 1st or 2nd generation EGFR-TKIs, all patients in this group were T790M negative | Sub-cohorts B and D responded better with 67%, 64% and 11 months, 9.1 months ORR and mPFS, contrary to those who received an earlier treatment of 3rd generation EGFR-TKI | Osimertinib + savolitinib combination responded significantly in NSCLC sufferers harboring MET initiated resistant response towards EGFR-TKIs |
| Capmatinib and gefitinib | Patients exhibiting MET amp and mutant EGFR expression were examined in a a phase Ib/II settings, with failure of EGFR inhibiting therapy. Sample size comprised 100 patients who were administered 400 mg capmatinib + 250 mg gefitinib | Screening revealed 29% ORR with 5.5 months PFS for capmatinib + gefitinib. Subgroup screening revealed a better response for more than 6 MET gene copy number (GCN) with an ORR of 47% | Results established the capmatinib and gefitinib combination as highly feasible and promising treatment option for EGFR-mutated, MET dysregulated NSCLC and morespecifically for those having MET-amplified tumors |
| Combinations of small molecule inhibitor and mAb (capmatinib with gefitinib, telisotuzumab with erlotinib, savolitinib with gefitinib, onartuzumab with erlotinib, capmatinib with erlotinib and emibetuzumab with erlotinib) | Chosen patients were all MET mutant, a noted attempt (phase II study) by Camidge and colleagues [180] co-delivered emibetuzumab (750 mg, every 2 weeks) with erlotinib (150 mg, OD) intravenously and compared the outcome with emibetuzumab monotherapy (750 mg, intravenous) in the sufferers with acquired resistance to erlotinib and MET positive sufferers | All combinations revealed a better response with 3.3–5.6 months PFS In the study by Camidge and colleagues [180], emibetuzumab + erlotinib responded better with 3.3 months PFS and 3% PRR contrary to the 1.6 months PFS and 4.3% ORR for emibetuzumab alone | Emibetuzumab-erlotinib combination is more effective to treat MET mutated NSCLC than the singular treatment with emibetuzumab |
PRR: pattern recognition receptor
