Zai Lab Partner Mirati Therapeutics Presents Late-Breaking Results Evaluating Concurrent Adagrasib and Pembrolizumab in First-Line Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC)
- Adagrasib in combination with pembrolizumab demonstrates favorable tolerability and promising preliminary efficacy in patients with first-line advanced/metastatic NSCLC harboring a KRASG12C mutation
- Findings will be presented on
December 7at the 2022 ESMO Immuno-Oncology Annual Congress, as an oral presentation from 2:05 p.m.-2:15 p.m. CET/ 8:05 a.m.-8:15 a.m. ET(Presentation #LBA4) during the “Proffered Paper session 1” session
Summary of Clinical Results
- The KRYSTAL-7 and KRYSTAL-1 trials represent the largest dataset evaluating a KRASG12C inhibitor in combination with a PD-1/L1 checkpoint inhibitor as a first-line treatment for patients with NSCLC harboring a KRASG12C mutation.
- 75 patients were enrolled and evaluable for safety with a median follow-up of 3.5 months (duration of treatment: 2 months). Treatment-related adverse events (TRAEs) were Grade 1–2 (39%), Grade 3 (40%) and Grade 4 (4%); there were no Grade 5 TRAEs observed. TRAEs led to discontinuation of both adagrasib and pembrolizumab in 2 patients and only pembrolizumab in 2 patients; there were no patients who discontinued only adagrasib due to a TRAE.
- Increases in alanine transaminase (ALT) / aspartate transaminase (AST) were consistent with either agent as a monotherapy with Grade 3 TRAEs being highest grade and total incidence of Grade 3 liver function test (LFT) increases of 9%. Median time from onset to an increase in ALT and AST was 26 and 37 days, respectively, and only 1 patient experienced new onset treatment-related ALT/AST increase after 3 months.
- Of patients who were clinically evaluable and received at least one on-study scan (n=53), adagrasib and pembrolizumab demonstrated promising preliminary clinical activity across all PD-L1 subgroups with an objective response rate (ORR) of 49%.
- In a subset of response-evaluable patients enrolled at least 6 months prior to the data cutoff date, 6 of 26 clinical responses occurred at second on-study scan or later, and the ORR was 56%.
- 7 evaluable patients enrolled in the KRYSTAL-1 Phase 1b cohort (with a median follow-up of 19.3 months) reported an ORR of 57% and a disease control rate (DCR) of 100%. The four patients who responded maintained response for over nine months while two continued to receive treatment and remain in response beyond 18 months.
- Safety in the KRYSTAL-1 Phase 1b cohort was consistent with what has been observed in KRSTYAL-7 and demonstrated a manageable safety profile with no Grade 4–5 TRAEs.
“Initial results across all cohorts suggest the concurrent combination of adagrasib and pembrolizumab may provide a chemotherapy-free option for treatment-naïve NSCLC with a manageable safety profile and encouraging clinical activity,” said Pasi A. Jänne, MD, PhD,
The data (Presentation #LBA4) will be presented in an oral presentation on
“We are delighted to see the data that further underscores the potential of adagrasib as a well-tolerated treatment option for patients in the first-line setting,” said
About Adagrasib (MRTX849)
Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24-48 hours. Studies of adagrasib have shown that the drug has a long half-life and extensive tissue distribution, and is well tolerated. In clinical trials, adagrasib also has shown, central nervous system penetrance and single-agent responses in non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer and other solid tumors with KRASG12C mutations. Adagrasib is being evaluated in several clinical trials in combination with other anti-cancer therapies in patients with advanced solid tumors. Registration-enabling studies are ongoing in NSCLC and colorectal cancer. For more information visit Mirati.com/science.
Virtual Investor Event
Mirati Therapeutics will host an Investor Event on
Mirati company executives will provide an overview of the adagrasib and pembrolizumab combination data presented 2022 ESMO Immuno-Oncology Annual Congress.
About NSCLC in China
KRASG12C is the most common KRAS mutation in NSCLC. The mutation is a biomarker of poor prognosis in Chinese patients with NSCLC. Lung cancer consists of NSCLC in approximately 85% of cases and small cell lung cancer (SCLC) in approximately 15% of cases. According to the World Health Organization, the incidence of lung cancer in China in 2020 was 815,563 cases, with 714,699 deaths.
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This press release contains forward-looking statements relating to future expectations, plans, and prospects, including, without limitation, statements relating to the potential benefits, safety, and efficacy of adagrasib; the treatment of lung cancer; and clinical trial data, data readouts, and presentations. These forward-looking statements include, without limitation, statements containing words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” and other similar expressions. Such statements constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not statements of historical fact nor are they guarantees or assurances of future performance. Forward-looking statements are based on our expectations and assumptions as of the date of this press release and are subject to inherent uncertainties, risks and changes in circumstances that may differ materially from those contemplated by the forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including but not limited to (1) our ability to successfully commercialize and generate revenue from our approved products; (2) our ability to obtain funding for our operations and business initiatives, (3) the results of our clinical and pre-clinical development of our product candidates, (4) the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approvals of our product candidates, (5) the effects of the novel coronavirus (COVID-19) pandemic on our business and general economic, regulatory, and political conditions, (6) risks related to doing business in
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