• Data demonstrates compelling clinical activity, highlights adagrasib potential as monotherapy in solid tumors
• Clinical data also presented at the ASCO Plenary Series: April 2023 Session
• Data follows recent inclusion of KRAZATI^® (adagrasib) in NCCN Guidelines for CNS Cancers

SAN DIEGO, April 26, 2023 /PRNewswire/ -- Mirati Therapeutics, Inc.^® (NASDAQ: MRTX), a commercial stage biotechnology company, announced today the Journal of Clinical Oncology published in a Rapid Communication data indicating adagrasib, a potent and selective KRAS^G12C 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 KRAS^G12C mutation. Rapid Communications are reserved for publications deemed to represent timely and late breaking research that may have an immediate impact on patient care.

In addition, findings were presented last week at the April session of the American Society of Clinical Oncology (ASCO) 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 KRAS^G12C-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 KRAS^G12C-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 KRAS^G12C-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 KRAS^G12C-mutated solid tumor types in addition to NSCLC and CRC."

"We're pleased to share this data which demonstrates meaningful clinical activity in KRAS^G12C-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 KRAS^G12C 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 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 KRAS^G12C Mutation." The full abstract for the presentation can be found here: Program Guide – ASCO 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 KRAS^G12C 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 KRAS^G12C-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 KRAS^G12C-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).

About Mirati Therapeutics, Inc.^®

Mirati Therapeutics, Inc.^® is a commercial stage biotechnology company whose mission is to discover, design and deliver breakthrough therapies to transform the lives of patients with cancer and their loved ones. The company is relentlessly focused on bringing forward therapies that address areas of high unmet need, including lung cancer, and advancing a pipeline of novel therapeutics targeting the genetic and immunological drivers of cancer. Unified for patients, Mirati's vision is to unlock the science behind the promise of a life beyond cancer.

For more information about Mirati, visit us at Mirati.com or follow us on Twitter, LinkedIn and Facebook. 

Forward Looking Statements

This press release includes forward-looking statements regarding Mirati's business, financial guidance and the therapeutic and commercial potential of KRAZATI^® (adagrasib), sitravatinib (TAM receptor inhibitor), MRTX1719 (MTA-cooperative PRMT5 inhibitor), MRTX0902 (SOS1 inhibitor), and MRTX1133 (selective KRASG12D inhibitor), Mirati's technologies and Mirati's other products in development. Any statement describing Mirati's goals, expectations, intentions or beliefs, financial or other projections, is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines.

Mirati's forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Mirati's forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Mirati. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Mirati's programs are described in additional detail in Mirati's annual report on Form 10-K, and most recent Form 10-Q, which are on file with the Securities and Exchange Commission and available at the SEC's Internet site (www.sec.gov). These forward-looking statements are made as of the date of this press release, and Mirati assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law.

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References
1. Wang-Gillam A, Hubner RA, Siveke JT et al. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall analysis and characteristics of long-term survivors. Eur J Cancer 2019. 108:78-87
2. Huffman BD, Basu Mallick A, Horick NK, et al. Effect of MUC5AC Antibody (NPC-1C) administered with second-line gemcitabine and nab-paclitaxel on the survival of patients with advanced pancreatic ductal adenocarcinoma. JAMA Network Open 2023;6(1)e2249720
3. Lamarca A, Palmer DH, Singh Wasan H, et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3 open-label, randomised, controlled trial. Lancet Oncol 2021;22:690-701