Mirati Presents Late-Breaking Results Evaluating the Combination of Adagrasib and Pembrolizumab in First-Line Non-Small Cell Lung Cancer (NSCLC)

Rhea-AI Summary

Mirati Therapeutics announces updated results from the KRYSTAL-7 Phase 2 study evaluating adagrasib combined with pembrolizumab in first-line NSCLC patients with KRASG12C mutation.

Positive

• In patients with PD-L1 TPS ≥50%, adagrasib and pembrolizumab demonstrated an overall response rate (ORR) of 63% and disease control rate (DCR) of 84%.
• The 63% confirmed response rate compares favorably to pembrolizumab monotherapy which has demonstrated an ORR of 39-45%.
• No patients discontinued both adagrasib and pembrolizumab due to ALT/AST increase or hepatic-related TRAEs.
• Mirati plans to initiate a Phase 3 clinical study to evaluate adagrasib in combination with pembrolizumab in the first line setting for KRASG12C-mutated NSCLC with PD-L1 TPS ≥50%. Initial patient enrollment is expected by year-end 2023.

Negative

• None.

SAN DIEGO, Oct. 17, 2023 /PRNewswire/ -- Mirati Therapeutics, Inc.^®  (NASDAQ: MRTX), a commercial stage biotechnology company, today announced updated results from the KRYSTAL-7 Phase 2 study evaluating adagrasib combined with pembrolizumab in patients for the treatment of first-line NSCLC harboring a KRAS^G12C mutation at the European Society of Medical Oncology Congress (ESMO) 2023. These data demonstrate a manageable safety profile and early signs of durability of adagrasib in combination with a checkpoint inhibitor in the first-line NSCLC setting.

Summary of Clinical Results

• In patients with PD-L1 TPS ≥50%, adagrasib and pembrolizumab demonstrated an overall response rate (ORR) of 63% and disease control rate (DCR) of 84% and promising early signs of durability. The 63% confirmed response rate compares favorably to pembrolizumab monotherapy which has demonstrated an ORR of 39-45%.^1,2
• A median progression free survival has not been reached at 10.1 months median follow up.
• The safety profile of the adagrasib and pembrolizumab combination was consistent with either agent as monotherapy, with a low rate of treatment related adverse events (TRAEs) leading to discontinuation of both drugs in only 4% of patients.
• Treatment related hepatic events occurred in <10% of patients and were predominantly low grade. No patients discontinued both adagrasib and pembrolizumab due to ALT/AST increase or hepatic-related TRAEs.

"Data presented to date indicate that adagrasib prescribed following or in combination with immunotherapy offers a tolerable safety regimen for first-line NSCLC patients with a KRAS^G12C mutation," said Marina C. Garassino, M.D., professor of medicine, UChicago Medicine. "Adagrasib is the only KRAS^G12C inhibitor to be feasibly combined concurrently or following immunotherapy with a well-managed hepatoxicity profile, and still exhibits positive efficacy signals."

"We are pleased to see these significant findings, which further support the initiation of a global Phase 3 study evaluating the combination of adagrasib plus immunotherapy in the first-line setting for KRAS^G12C-mutated NSCLC with PD-L1 TPS ≥50% for the benefit of patients," said Alan Sandler, M.D., chief medical officer, Mirati Therapeutics. "Potential combinability with an immunotherapy, in addition to encouraging clinical activity in other tumor types and demonstrated central nervous system (CNS) penetration, reinforces our confidence in the differentiation of adagrasib from other potential treatment options and the benefit it offers to patients."

Mirati plans to initiate a Phase 3 clinical study to evaluate adagrasib in combination with pembrolizumab in the first line setting for KRAS^G12C-mutated NSCLC with PD-L1 TPS ≥50%. Initial patient enrollment is expected by year-end 2023.

About Mirati Therapeutics, Inc.^®
Mirati Therapeutics, Inc. is a commercial stage research and development 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), 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 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.

Mirati Contacts
Investor Relations: ir@mirati.com
Media Relations: media@mirati.com

References

1. Mok TSK, et al. Lancet 2019;393:1819–1830
2. Reck M, et al. N Engl J Med 2016;375:1823–1833

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SOURCE Mirati Therapeutics, Inc.

What are the results of the KRYSTAL-7 Phase 2 study?

In patients with PD-L1 TPS ≥50%, adagrasib and pembrolizumab demonstrated an overall response rate (ORR) of 63% and disease control rate (DCR) of 84%.

How does the response rate of adagrasib and pembrolizumab compare to pembrolizumab monotherapy?

The 63% confirmed response rate compares favorably to pembrolizumab monotherapy which has demonstrated an ORR of 39-45%.

What is the safety profile of the adagrasib and pembrolizumab combination?

The safety profile of the adagrasib and pembrolizumab combination was consistent with either agent as monotherapy, with a low rate of treatment related adverse events (TRAEs) leading to discontinuation of both drugs in only 4% of patients.

What are the future plans for adagrasib?

Mirati plans to initiate a Phase 3 clinical study to evaluate adagrasib in combination with pembrolizumab in the first line setting for KRASG12C-mutated NSCLC with PD-L1 TPS ≥50%. Initial patient enrollment is expected by year-end 2023.