Krazati Monotherapy Shows Significant Survival Benefit in KRAS G12C-Mutated NSCLC Per Phase III KRYSTAL-12 Trial Data
Krazati (adagrasib) was previously granted accelerated approval by the FDA to treat patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer who were previously administered at least one systemic therapy.
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Findings from the Phase III KRYSTAL-12 trial demonstrated that Krazati (adagrasib; Bristol Myers Squibb) monotherapy led to a survival benefit in patients with pretreated locally advanced or metastatic non-small cell lung cancer (NSCLC) with a KRASG12C mutation.1 Prior trials of Krazati, an oral, highly selective KRASG12C inhibitor, show that the drug has a long half-life, extensive tissue distribution, and is well tolerated.2
“Today’s news is an important reinforcement of the power of a targeted therapy for patients with locally advanced or metastatic KRASG12C-mutated lung cancer. FDA approval of Krazati in the US has allowed us to provide a new treatment option for these patients, and topline results of the KRYSTAL-12 confirmatory study will build greater trust in the medical and patient community,” Abderrahim Oukessou, MD, vice president, global program lead, Krazati, Bristol Myers Squibb, said in a press release. “We are encouraged by the results from KRYSTAL-12 and look forward to helping more patients with KRASG12C-mutated lung cancer.”1
In December 2022, Krazati was granted accelerated approval to treat patients with KRASG12C-mutated locally advanced or metastatic NSCLC who were previously administered at least one systemic therapy.2 In February 2024, the FDA granted Priority Review status to Krazati plus cetuximab for patients who received prior treatment for KRASG12C-mutated locally advanced or metastatic colorectal cancer based on findings from the open-label, multicenter, multiple expansion cohort of the Phase I/II KRYSTAL-1 trial.3
The open-label, multicenter, randomized KRYSTAL-12 trial is comparing Krazati monotherapy vs. standard-of-care chemotherapy alone, in patients with KRASG12C-mutated NSCLC. The trial’s primary endpoint is progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR), with secondary endpoints that include overall survival (OS), overall response rate (ORR), duration of response, and safety.
Krazati monotherapy achieved the primary endpoint of a statistically significant and clinically meaningful benefit in PFS and ORR per BICR, compared to standard-of-care chemotherapy in the second-line or later treatment of this patient population. Additionally, there were no new safety signals identified, with the data consistent with the drug’s known profile.1
In prior trials, the most common adverse events reported with Krazati are reduced appetite, diarrhea, dyspnea, edema, fatigue, hepatotoxicity, musculoskeletal pain, nausea, renal impairment, and vomiting. The most common grade three or four laboratory abnormalities reported with Krazati were reduced hemoglobin, reduced leukocytes, reduced lymphocytes, reduced neutrophils, hypokalemia, hyponatremia, elevated alanine aminotransferase, elevated alkaline phosphatase, elevated aspartate aminotransferase, and elevated lipase.4
Bristol Myers Squibb stated that it will complete a full evaluation of the trial data to share at an upcoming medical conference and will discuss the findings with health authorities.1
References
1. Bristol Myers Squibb Announces Pivotal KRYSTAL-12 Confirmatory Trial Evaluating KRAZATI (adagrasib) Meets Primary Endpoint of Progression-Free Survival for Patients with Pretreated KRAS G12C-Mutated Locally Advanced or Metastatic Non-Small Cell Lung… Bristol Myers Squibb. News release. March 28, 2024. Accessed March 29, 2024. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Announces-Pivotal-KRYSTAL-12-Confirmatory-Trial-Evaluating-KRAZATI-adagrasib-Meets-Primary-Endpoint-of-Progression-Free-Survival-for-Patients-with-Pretreated-KRAS-G12C-Mutated-Locally-Advanced-or-Metastatic-Non-Small-Cell-Lung-/default.aspx
2. Mirati Therapeutics Announces U.S. FDA Accelerated Approval of KRAZATI™ (adagrasib) as a Targeted Treatment Option for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with a KRASG12C Mutation. Mirati Therapeutics. News release. December 12, 2022. Accessed March 29, 2024. https://www.multivu.com/players/English/8999051-mirati-therapeutics-fda-accelerated-approval-of-krazati-adagrasib/
3. U.S. Food and Drug Administration (FDA) Accepts Supplemental New Drug Application for KRAZATI® (adagrasib) in Combination with Cetuximab as a Targeted Treatment Option for Patients with Previously Treated KRAS G12C-Mutated Locally Advanced or... Bristol Myers Squibb. News release. February 20, 2024. Accessed March 29, 2024. https://news.bms.com/news/details/2024/U.S.-Food-and-Drug-Administration-FDA-Accepts-Supplemental-New-Drug-Application-for-KRAZATI-adagrasib-in-Combination-with-Cetuximab-as-a-Targeted-Treatment-Option-for-Patients-with-Previously-Treated-KRAS-G12C-Mutated-Locally-Advanced-or/default.aspx
4. Krazati. Prescribing information. Mirati Therapeutics Inc; 2022. Accessed March 29, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/216340s000lbl.pdf
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