EGFR-MET bispecific antibody! Johnson amivantamab treatment EGFR No. 20 exon insertion of mutant lung cancer (NSCLC) shows lasting remission!

2020 May 19 News / BioValley BIOON / - Johnson & Johnson (JNJ) subsidiary Janssen Pharmaceutica Inctoday announced the results of Phase II CHRYSALIS study (NCT02609776), which study evaluated the bispecific antibodies amivantamab (JNJ-61186372, JNJ-6372) carrying the treatment of epidermal growth factor receptor (EGFR) mutations in exon 20 insertion of advanced non-small cell lung cancer (NSCLC) patientsThe results show, amivantamab treatment shows durable remissions:(1) patient assessment at all, the overall response rate (ORR) was 36%, the median duration of response (the DOR) 10 months of clinical benefit rate (≥ partial response [PR] + stable disease ≥12 weeks) was 67%; (2) in previously treated patients with platinum-containing chemotherapy may evaluation, the ORR was 41%, with a median of 7 months DOR, clinical benefit rate 72%amivantamab immune cell is a bispecific antibody directed epidermal mass conversion factor (MET) activity between EGFR- targeted drug and the activation and amplification of EGFR and MET mutationsamivantamab production and development follows a licensing agreement to use DuoBody technology platform with Janssen Biotech company Genmab signedworldwide, lung cancer is the most common type of cancer, non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancersThe main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, large cell carcinomaThe most common mutations in NSCLC are driving change in the EGFR gene, EGFR is a receptor tyrosine kinase, helps cells to grow and divideEGFR mutations are present in 10-15% of patients with NSCLC, 40% -50% of patients with NSCLC adenocarcinoma AsiaNoouter EGFR exon 20 insertion mutants is a unique subpopulation of lung cancer, accounting for at least 9% of all EGFR mutationsCurrently, the 5-year survival of patients with metastatic NSCLC only 6%A Noouter EGFR exon 20 insertion mutations in NSCLC have generally not sensitive to the approved listing of GFR receptor tyrosine kinase inhibitor (the TKI) therapy, with more common EGFR mutations (exon 19 compared with patients deletions / L858R substitutions), the prognosis is even worseAt present, for the EGFR No 20 exons in patients with lung cancer insertional mutagenesis, the estimated median overall survival (OS) was 16 months, the standard of care program on clinically conventional cytotoxic chemotherapy, there is no FDA-approved target to therapy based on overall response rate CHRYSALIS study (ORR) and duration of response (DOR) data, in March this year, the US FDA granted amivantamab breakthrough drugs qualifications (BTD), for the progress of the disease after receiving platinum-containing chemotherapy, No outer EGFR exon 20 metastatic NSCLC insertion mutations principal investigator of the study, Dr KeunchilPark professor of Sungkyunkwan Samsung Medical Center, Department of Hematology and Oncology, Medical University School of Medicine, said: "Lung cancer is the leading cause of cancer deaths worldwide, EGFR mutations and other genetic factors may occur for NSCLC and progress have a significant impact we look forward to sharing these data, a preliminary understanding amivantamab as a treatment option for the potential treatment of patients with NSCLC carrying the No EGFR exon 20 insertion mutations, these patients have a high unmet medical needs and generally do not respond to the current standard of care program "
CHRYSALIS a human body for the first time, open-label, multicenter phase I study is evaluating amivantamab as a monotherapy, as well as the new third-generation EGFR-TKI drugs lazertinib combination therapy safety, pharmacokinetics and efficacy in adult patients with advanced NSCLC this study, NSCLC patient No 20 of the outer insertion mutation in exon 50 cases of carrying EGFR, accepted recommendation II dose (RP2D: 1050mg, patient weight ≥80kg is 1400mg) amivantamab treatment These 50 patients, 39 evaluable remission and received ≥2 episodes of disease assessment, 29 patients previously treated with platinum-containing chemotherapy 39 patients were found in 13 different outer No 20 EGFR mutation in exon inserted data show: in all patient assessment, the observed overall response rate (ORR) was 36% (95% CI: 21-53); ORR in patients previously treated with platinum-containing chemotherapy, observed It was 41% (95% CI: 24-61) Further, in all 14 patients in remission, the median duration of response (DoR,) 10 months; remission in patients previously treated with platinum-containing chemotherapy, median DOR 7 months In all patients, the median progression-free survival (PFS) was 8.3 months (95% CI: 3.0-14.8); in patients previously treated with platinum-containing chemotherapy, the median PFS was 8.6 months (95% CI : 3.7-14.8) In all patients, the clinical benefit rate (≥ partial response [PR], or stable disease ≥11 weeks) was 67% (95% CI: 50-81); in patients previously treated with platinum-containing chemotherapy, clinical benefit rate 72% (95% CI: 53-87) In the previous treatment and patients previously treated with platinum-containing chemotherapy was observed in remission The most common tumor response assessment for the first time the disease after treatment started study, the most common adverse events of all grades (AE) is rash, infusion related reactions (IRR) and paronychia IRR occurs primarily during the first infusion, it does not prevent a subsequent infusion treatment No grade ≥3 rash report, grade 3 diarrhea (6% of patients with any level of diarrhea) occurred in one patient 6% of patients with treatment-related grade ≥3 AE, including hyperamylasemia, hypokalemia, elevated lipase and shoulder / chest pain 6% of patients reported serious adverse events related to treatment, such as cellulitis, interstitial lung disease, shoulder / chest pain detailed results of the study will be held May 29 presentation and discussion (Abstract 9512) at the 2020 American Society of Clinical Oncology (ASCO) virtual science project a Original Source: JanssenAnnouncesPhase1ResultsforBispecificAntibodyAmivantamabintheTreatmentofPatientswithAdvancedNon-SmallCellLungCancerHarboringExon20InsertionMutations