Summary of latest advances in non-small cell lung cancer, MET-positive targeted treatment

2020ASCO series small cell lung cancer, immuno-targeted treatment latest progress summary non-small cell lung cancer, targeted treatment latest progress summary non-small cell lung cancer, MET-positive targeted treatment latest progress summary non-small cell lung cancer, immunotherapy latest progress summary full text summary 1PROFILE1001 study (coctininib): 32% ORR and PFS 7.3 months 2GEOMETRY mono-1 Study (Kamatini): aMET exon 14 jump, initial treatment OF ORR is 68%, after treatment ORR is 41%, bchallenge MET high level of expansion of lung cancer population, the initial treatment of ORR is 40%, after treatment ORR is 29%3VISION Study (Teperinib): THE ORR is 56% 4NCT02897479 (Volitinib): Brain metastasis as high as 31%, ORR still up to 48.8% lung cancer, MET-positive target treatment new breakthrough lung cancer (Ohitini drug resistance) secondary MET amplification, may try Oichitini met exon-14 jump frequency in non-small cell lung cancer frequency of 3%-4%, and other common drivers (E.g., Patients with NSCLC who were more than 70 years old had a worse prognosis and were less sensitive to chemotherapyAlthough MET-TKI inhibitors such as cratinib have been approved for treatment of such patients, their objective remission rate is only 32%To further improve efficacy, highly selective MET-TKI inhibitors have become the focus of research and development in recent yearsToday, we share the latest research advances in MET-targeted therapyMET-TKI inhibitors are divided into non-selective class 1a inhibitors (e.gcratinib) and selective class 1b inhibitors (e.gCapatinib Camatinib, Tepotinib tepotinib, Savolitinib VolitinibPS: Non-selective inhibitors, not really MET inhibitorsPROFILE1001 Study 2015 Paik et al first reported four cases of nSCLC patients who treated effective MET exon-14 jumpmutations with keroctini and cabotinib Subsequently, in the Phase I PROFILE1001 trial, the patient with met exosome 14-mutant NSCLC was treated with gramenoni, the objective remission rate (ORR) was 32%, the median progression-free survival (PFS) was 7.3 months, and the reaction duration was 9.1 months Based on this, the FDA approved in May 2018 for the use of creditinib for NSCLC, which carries the MET exon 14 jump mutation after the progression of chemotherapy in the platinum-containing regimen GEOMETRY mono-1 study MET exon 14 jump This is an open-label, multicenter, one-arm II study that recruited 97 patients with NSCLC who were identified by RNA clinical analysis to carry MET exon 14 jumps, and gave Capmatinib 400mg until the disease progresses or becomes intolerable toxicity, with the main endpoint being the overall response rate (ORR), and other end-point response duration (DOR) The Independent Data Monitoring Board's assessment showed that Capmatinib had an ORR of 68% for patients with primary treatment, 47% of patients with DOR over 12 months, 41% for patients who had been treated in the past, and 32% for patients with a dOR over 12 months Safety: The rate of adverse events associated with Capmatinib treatment was 35.6 percent, with the most common adverse reactions being peripheral edema (42 percent), nausea (33 percent), hyperneanine (20 percent), vomiting (19 percent), fatigue (14 percent), decreased appetite (13 percent) and diarrhea (11 percent) Based on this, on May 6, 2020, the FDA approved Novartis Tabrecta (Capmatinib) for the treatment of patients with locallate or metastatic MET exon 14 jump (MET EX 14) mutation sized cell lung cancer (NSCLC) MET high amplification in addition, this year ASCO reported met high-amplification NSCLC queue Queue 1 is nSCLC for treatment (1-2 previously treated lines) MET high amplification (requires MET gene copy number of 10), and queue 5 is nSCLC for the initial treatment of MET high amplification (requires MET gene copy number of 10) The main research endpoint is the independent evaluation evaluation ORR, and the key secondary study endpoint is the independent evaluation evaluation DoR Queue 1 included 69 patients and queue 5a included 15 patients For patients treated with Capmatinib's ORR of 29%, DoR s 8.31m, PFS s 4.07m For patients with primary treatment Capmatinib's ORR of 40%, DoR s 7.54m, PFS s 4.17m Common adverse reactions edema (51.1%), nausea (44.8%), vomiting (28.0%) (Abstract 9509) In summary, compared with met14 exon jump mutation, Capmatinib treatment MET high amplification NSCLC efficacy seems to be general, the future need seismost high amplification NSCLC screening of more accurate biological markers The VISION Study was presented at the 2020 ASCO Annual Meeting, and its paper was also published in N Engl J Med This is a one-arm, open-label, multi-center Phase II trial in which patients with advanced or metastatic NSCLC who are confirmed to carry MET exon 14 jump mutations received Tepotinib treatment (dose son once a day, 500 mg) The main endpoint is an objective remission rate of patients who have been independently audited and subjected to follow-up for at least 9 months As of 1 January 2020, a total of 152 patients had received teperinib treatment and 99 patients had been followed for at least nine months Clinical Pathological Characteristics Teperinib Adverse Reactions Results The combined biopsy group had a remission rate of 46% (95% CI, 36-57) and a median duration of 11.1 months (95% CI, 7.2-incalculable) The remission rate was 48% (95% CI, 36-61) in 66 patients in the liquid biopsy group, 50% (95% CI, 37-63) in 60 patients in the tissue biopsy group, and 27 patients who tested positive for both biopsy methods The researchers determined a remission rate of 56% (95% CI, 45 -66), and a similar rate regardless of previous treatments for advanced or metastatic lung cancer ORR PFS researchers found a 28 percent rate of adverse events associated with teperinib treatment at level 3 or higher, of which the incidence of peripheral edema was 7 percent Eleven percent of patients had adverse events that led to the permanent discontinuation of teperinib The researchers judged molecular remission by detecting free DNA in the blood circulation, and 67 percent of patients with matching liquid biopsy samples during baseline and treatment observed that molecular remission was achieved In March 2020, Japan's Ministry of Health, Labour (MHLW) approved the listing of MET inhibitor Tepotinib, making it the world's first treatment for patients carrying MET Gene No 14 exon (METex14) leap, non-removable, advanced or recurrent non-small cell lung cancer (NSCLC) NCT02897479 is a multi-center, multi-queue single-arm ii phase study, 2020 ASCO annual meeting Shanghai Jiaotong University affiliated chest hospital Professor Lu Wei reported on the original Chinese MET inhibitor Savolitinib, 600mg (50kg or more), 400mg (50kg or less) psC (lung sarcoma-like cancer, prognosis) or other NSCLC patient studies (NCT02897479, abstract No 9519), which is also the first prospective study of METExon14 plus PSC patients in the world to include up to 35.7% Of the 593 patients, 87 had MET14 exon jump mutations and 70 received daily oral treatment of Volitinib until the disease progressed or toxicity was not tolerated The proportion of PSC (pulmonary sarcoma-like cancer) is as high as 35.7%, especially in the initial treatment of nearly half of patients with PSC patients Excluding PSC patients, there were 45 patients with other types of MET 14 exosome jump mutation NSCLC, of which the proportion of treated patients who underwent chemotherapy, immunity, and targeted treatment was as high as 2/3 (30/45), and the proportion of brain metastasis was as high as 31.1% (14/45) Efficacy Evaluation Set Full Group Analysis Set In Terms of Efficacy: 1 The validity assessment data for 61 patients showed that THER was still 49.2%, DCR was 93.4%, and the duration of remission (DoR) was 9.6 months 2 If PSC is excluded, 41 patients who can effectively assess efficacy still use Volitinib's ORR at 48.8%, DCR as high as 95.1%, and PFS for 9.7 months As a result, both MET 14 exon jump inge-jumping PSC patients and other NSCLC patients have achieved considerable efficacy
In terms of security: Wallitini is safe The most common treatment-related adverse events are peripheral edema, nausea, vomiting and hypoproteinemia, which are less common in the treatment of Volitinib for patients with more concern 14.3% of patients stopped taking the drug because of adverse reactions Reference VISION Research, Tepotinibin non-small-cell lung cancer with MET exon 14 skipping dayers, DOI: 10.1056/ NEJMoa2004407 Capmatinib instructions, Source: eDrug Safety