FDA to Speed Up Review of Krazati Combo for Metastatic CRC

The Food and Drug Administration (FDA) granted a priority review for a supplemental new drug application (sNDA) to Krazati (adagrasib) plus Erbitux (cetuximab) for patients with previously treated KRAS G12C-mutant locally advanced or metastatic (spread to other parts of the body) colorectal cancer (CRC), according to Bristol Myers Squibb, the manufacturer of Krazati.

A priority review is given to drugs that show promise in treating serious illnesses and, if approved, would serve an unmet need. When a drug is granted a priority review, the FDA agrees to speed up the review and potential approval of a therapy. Now, the agency set a goal date of June 21, 2024 to make its approval decision on the Krazati/Erbitux combination.

In short, the priority review process may bring drugs to patients quicker.

“Pretreated KRAS G12C-mutated CRC is associated with poor outcomes and the current standard of care offers limited clinical benefit for patients,” Anne Kerber, senior vice president, head of late clinical development, Hematology, Oncology, Cell Therapy (HOCT) at Bristol Myers Squibb, said in a company-issued press release.

About Krazati

Krazati is a drug taken orally and works by inhibiting KRAS G12C, a mutation that, according to findings from the New England Journal of Medicine, is present in approximately 3% to 4% of metastatic colorectal cancer cases and is associated with poorer survival compared to patients without KRAS G12C mutations.

The drug was initially approved for the treatment of KRAS G12C-mutant lung cancer in 2022, which one expert called a “watershed moment” for the disease.

Later, in the spring of 2023, the National Comprehensive Cancer Network recommended that Krazati be the standard of care for patients with KRAS G12C-mutant pancreatic cancer.

READ MORE:NCCN Recommends Krazati for Treatment of Pancreatic Cancer Subset

KRYSTAL-1 Trial Leads to Priority Review

The priority review for the sNDA is based on findings from the phase 1/2 KRYSTAL-1 clinical trial, which is evaluating Krazati and Krazati-based combinations in patients with advanced solid tumors with KRAS G12C solid tumors.

Findings, which were published in an April issue of the Journal of Clinical Oncology, showed that among patients with measurable disease, overall response rate (ORR; percentage of patients whose disease shrunk or disappeared from treatment) was 35.1%, all of which were partial responses, meaning that the cancer shrunk but did not completely go away.

The disease control rate was 86%, with a median duration of response of 5.3 months. Median progression-free survival, which is the time patients live before their disease gets worse, was 7.4 months, while median overall survival (time patients live before death of any cause) was 14 months.

Although no patients died from treatment-related toxicity, study findings showed that most patients (96.8%) experienced at least one side effect of any severity. The most common side effects were nausea (49.2%), diarrhea (47.6%), fatigue (41.3%) and vomiting (39.7%). Moderate (grade 3) side effects occurred in 25.4% of patients, while severe (grade 4) side effects occurred in 1.6% of patients.

According to the press release from Bristol Myers Squibb, these results show that Krazati was well tolerated and had promising activity in this patient population and that the safety profile of Krazati and Erbitux together was “manageable and consistent with previous reports and the known safety profile of each drug individually.”

“The acceptance of this filing for Krazati in combination with [Erbitux] is a positive step toward providing a potential new option for patients and their physicians. It reinforces our commitment to developing potentially transformative targeted cancer therapies for patients for whom few treatment options exist,” Kerber said.

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