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ASCO 2022 | KRYSTAL-1: activity and safety of adagrasib in patients with advanced/metastatic KRASG12Cm NSCLC

The multicohort Phase I/II KRYSTAL-1 (NCT03785249) trial is investigating adagrasib, a KRAS G12C inhibitor, as a monotherapy or in combination with other agents in patients with advanced solid tumors harboring a KRAS G12C mutation. KRAS G12C mutations occurs in approximately 14% of non-small cell lung cancer. Alexander I. Spira, MD, Virginia Cancer Specialists, Fairfax, VA, reports on the results of Cohort A of the KRYSTAL-1 trial evaluating adagrasib in patients with NSCLC previously treated with platinum-based chemotherapy and anti-PD-1/L1 therapy. The study aims include assessing objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. ORR was 42.9%, median DOR was 8.5 months, median PFS was 6.5 months and median OS was 12.6 months, thus demonstrating promising efficacy. Additionally, adagrasib was well tolerated in this patient population. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.

Transcript (edited for clarity)

So we presented today, the results of KRYSTAL-1 which was using adagrasib for KRSG12C mutated non-small cell lung cancer after patients received chemotherapy and immunotherapy. The top line results, 43% response rate. Duration of response of around 8.5 months. Obviously this is a data cutoff that was relatively early. We’ll get some updated data down the road.

It appears to be pretty well tolerated...

So we presented today, the results of KRYSTAL-1 which was using adagrasib for KRSG12C mutated non-small cell lung cancer after patients received chemotherapy and immunotherapy. The top line results, 43% response rate. Duration of response of around 8.5 months. Obviously this is a data cutoff that was relatively early. We’ll get some updated data down the road.

It appears to be pretty well tolerated. There were significant number of patient with dose reductions, however, a very low discontinuation rate. So despite dose reductions patients were able to benefit and stay on. Only 7% of patients discontinued, which was identical, which was seen with sotorasib before. We also saw evidence of CNS activity. Patients were allowed to enroll if they had evidence of treated stable brain metastases by investigative discretion, and we saw some reasonable, what we call, disease control rate in the CNS, as well as responses in the CNS as well. These were patients previously treated mostly with radiation, but six set of the patients did not get radiation and were just treated with drugs before. So we believe there’s some activity and there’ll be a follow up presentation by my colleague, Dr. Josh Vari on Monday of ASCO, looking at some of the CNS activity and untreated brain metastases.

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