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FDA Grants Accelerated Approval to Bristol Myers Squibb’s Krazati for Previously Treated, Locally Advanced, or Metastatic Colorectal Cancer


Accelerated approval for Krazati is based on results from the Phase 1/2 KRYSTAL-1 study, which demonstrated a 34% objective response rate in patients with previously treated, locally advanced, or metastatic colorectal cancer.

Colorectal cancer awareness medical concept. Concept of cancer treatment and prevention, 3D illustration. Image Credit: Adobe Stock Images/Dr_Microbe

Image Credit: Adobe Stock Images/Dr_Microbe

The FDA has granted accelerated approval to Bristol Myers Squibb’s (BMS) Krazati (adagrasib) in combination with cetuximab to treat adults with previously treated, locally advanced, or metastatic colorectal cancer (CRC) with the KRASG12C mutation. The approval was based on results from the Phase I/II KRYSTAL-1 trial, which showed an objective response rate (ORR) of 34% and a median duration of response (DOR) of 5.8 months among patients administered Krazati. The regulatory action marks the second FDA approval for Krazati and the first under BMS's expanded oncology portfolio.1

“CRC with a KRASG12C mutation occurs in approximately 3%-4% of CRC patients and has historically been challenging to treat,” said Rona Yaeger, MD, gastrointestinal oncologist, early drug development specialist, Memorial Sloan Kettering Cancer Center, in a press release. “The FDA approval of Krazati combined with cetuximab now provides a new treatment option to these patients when their tumors do not respond well to prior therapies.”

KRYSTAL-1 is an open-label study that evaluated Krazati 600 mg tablets administered orally twice daily in combination with cetuximab. Investigators enrolled 94 patients with heavily pretreated CRC harboring a KRASG12C mutation. The primary endpoint of the study was ORR, with secondary endpoints that included DOR. The 34% ORR consisted of partial responses, which investigators said is significantly higher than response rates with current late-line standard of care options, which have ORR rates between 1% and 6%.

Krazati’s safety profile remained consistent with previously known reports of each drug individually. Serious adverse events (AEs) occurred in 30% of study participants, with the most common AEs being rash, nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, headache, dry skin, abdominal pain, decreased appetite, edema, anemia, dizziness, cough, constipation, and peripheral neuropathy.

BMS stated that CRC patients with KRASG12C mutations have been historically challenging to treat. Additionally, KRASG12C mutations make up approximately 3%-4% of all CRC cases. The company also cautions that treatment with Krazati may cause a number of AEs, including severe gastrointestinal AEs, QTc interval prolongation, hepatotoxicity, and interstitial lung disease/ pneumonitis. Further, it is suggested to avoid use of Krazati while taking a number of other medications.1

Treatment for CRC depends on factors such as stage of the disease, patient preference, and the treating physician. The prognosis of CRC can be related to the degree of penetration of the tumor through the bowel wall, presence or absence of nodal involvement, or the presence or absence of distant metastases.

According to the National Cancer Institute, treatment for recurrent CRC is determined by sites of recurrent disease demonstrable by physical examination and/or radiographic studies. Current options include, but aren’t limited to surgical resection, surgical resection and anastomosis or bypass of obstructing or bleeding primary lesions in selected metastatic cases, targeted therapy, and palliative chemotherapy or radiation therapy.2

“Today’s approval of Krazati in CRC is the second in the US for this therapy and the first for BMS' recently expanded oncology portfolio. This is an important milestone for BMS and the patients we serve as we deliver on our commitment to provide innovative medicines for cancer,” said Wendy Short Bartie, SVP, US oncology and hematology, Bristol Myers Squibb, in the press release. “We are proud to make Krazati—the first KRASG12C inhibitor to be FDA approved beyond non-small cell lung cancer—available to CRC patients and look forward to further evaluating Krazati through our ongoing development program.”


1. Bristol Myers Squibb Announces U.S. FDA Accelerated Approval of KRAZATI® (adagrasib) in Combination with Cetuximab for Adult Patients with Previously Treated KRAS G12C-Mutated Locally Advanced or Metastatic Colorectal Cancer (CRC). BMS. June 21, 2024. Accessed June 24, 2024. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Announces-U.S.-FDA-Accelerated-Approval-of-KRAZATI-adagrasib-in-Combination-with-Cetuximab-for-Adult-Patients-with-Previously-Treated-KRAS-G12C-Mutated-Locally-Advanced-or-Metastatic-Colorectal-Cancer-CRC/default.aspx 

2. Colon Cancer Treatment (PDQ®)–Health Professional Version. National Cancer Institute. Accessed June 24, 2024. https://www.cancer.gov/types/colorectal/hp/colon-treatment-pdq#_145

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