On April 26, 2023 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a commercial stage biotechnology company, reported that the Journal of Clinical Oncology published in a Rapid Communication data indicating adagrasib, a potent and selective KRASG12C inhibitor, is well tolerated and demonstrates meaningful clinical activity in patients with pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC), and other solid tumors harboring a KRASG12C mutation (Press release, Mirati, APR 26, 2023, View Source [SID1234630557]). Rapid Communications are reserved for publications deemed to represent timely and late breaking research that may have an immediate impact on patient care.

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In addition, findings were presented last week at the April session of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series Program. This publication follows the recent inclusion of KRAZATI(adagrasib) in the National Comprehensive Center Network (NCCN) Guidelines for Central Nervous System (CNS) Cancers for patients living with previously treated KRASG12C-mutant non-small cell lung cancer (NSCLC) and CNS metastases.

The Phase 2 data of the KRYSTAL-1 study demonstrates the potential of adagrasib as a monotherapy in patients with unresectable or metastatic KRASG12C-mutated solid tumors beyond NSCLC and colorectal cancer (CRC). The data presented was based on confirmed blinded, independent, central review (BICR) responses. This is the largest Phase 2 dataset evaluating KRAS G12C mutated solid tumors other than non-small cell lung cancer and colorectal cancer.

The enrolled and treated population (n=63) included 21 PDAC, 12 BTC, 9 appendiceal adenocarcinoma, 4 gastroesophageal/esophageal adenocarcinoma, 3 small bowel adenocarcinoma, 5 ovarian adenocarcinoma, 4 unknown primary, 3 endometrial adenocarcinoma, 1 breast adenocarcinoma and 1 glioblastoma. The median prior lines of systemic therapy was two. Results showed an objective response rate (ORR) of 35% for the overall cohort. In patients with PDAC, ORR was 33%; for patients with BTC, ORR was 42%. Notably, findings demonstrate the safety profile of adagrasib is aligned with previously reported data in patients with pretreated NSCLC and CRC.

These findings demonstrate a meaningful improvement relative to the historically reported standard of care for PDAC and BTC. For patients with previously treated metastatic PDAC, current standard of care (gemcitabine + nab-paclitaxel or liposomal irinotecan + 5FU/leucovorin) has resulted in limited ORR (3-16%).1-2 In a biomarker-unselected BTC patient population, the ABC-06 phase 3 trial investigating FOLFOX in the second-line setting reported an ORR of 5%.3

"We are thrilled to see the results of this Phase 2 study, which demonstrate a marked improvement on the current standard of care for patients with unresectable or metastatic KRASG12C-mutated solid tumors, including PDAC, BTC, other gastrointestinal (GI) and non-GI tumors, where few treatment options exist. It is particularly encouraging to see meaningful clinical activity in pancreatic and biliary tract cancers tumors," said Shubham Pant, M.D., M.B.B.S., The University of Texas MD Anderson Cancer Center. "The data indicates that adagrasib has the potential to be an effective treatment for KRASG12C-mutated solid tumor types in addition to NSCLC and CRC."

"We’re pleased to share this data which demonstrates meaningful clinical activity in KRASG12C-mutated tumor types in addition to NSCLC and CRC, indicating a potential path to regulatory approval for adagrasib in additional indications," said Alan Sandler, M.D., chief medical officer, Mirati Therapeutics, Inc. "We look forward to continuing to advance adagrasib as a potential best-in-class treatment option for patients harboring a KRASG12C mutation."

The primary endpoint for the Phase 2 cohort of the KRYSTAL-1 study was objective response rate. Secondary endpoints included duration of response, progression-free survival, overall survival and safety.

Findings were presented last week at the April session ASCO (Free ASCO Whitepaper) Plenary Series Program as a data presentation (Abstract 425082) titled, "KRYSTAL-1: Activity and Safety Of Adagrasib (MRTX849) In Patients With Advanced Solid Tumors Harboring A KRASG12C Mutation." The full abstract for the presentation can be found here: Program Guide – ASCO (Free ASCO Whitepaper) Meeting Program Guide.

The full Journal of Clinical Oncology article can be found here.

About KRAZATI (adagrasib)

In the U.S., KRAZATI was approved by the FDA for Accelerated Approval (Subpart H), which allows for the approval of drugs that treat serious conditions, and that fill an unmet medical need based on surrogate endpoints. KRAZATI was reviewed under the FDA Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process that ensures safe and effective treatments are made available to patients as early as possible. Mirati submitted a Marketing Authorization Application (MAA) in the EU in May 2022. In 2021, adagrasib achieved Breakthrough Therapy Designation in the U.S. as a potential treatment for patients with NSCLC harboring the KRASG12C mutation who have received at least one prior systemic therapy. For Prescribing Information, visit Mirati.com/KRAZATI_USPI

Adagrasib continues to be evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including NSCLC, colorectal cancer, and pancreatic cancer. For more information, visit Mirati.com/science.

KRAZATI (adagrasib) U.S. Indication

KRAZATI is indicated for the treatment of adult patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).