Trial for Opdualag in Metastatic Colorectal Cancer Ends Prematurely

The phase 3 RELATIVITY-123 trial was discontinued because it was unlikely for it to reach its goals.

A phase 3 trial that evaluated treatment with Opdualag (nivolumab/relatlimab) for patients with metastatic microsatellite stable (MSS) colorectal cancer who have been previously treated will be discontinued, according to a news release from Bristol Myers Squibb, the manufacturer of the drug.

The phase 3 RELATIVITY-123 trial was reported to be discontinued because it was unlikely for it to reach its primary endpoints (the main results measured at the end of a study to see if a treatment worked) by the completion of the trial, the news release stated.

The primary endpoint for the trial was overall survival (OS; the length of time from diagnosis or start of treatment when a patient lives with the cancer).

Secondary endpoints included objective response rate (ORR; the percentage of people in a study who had a partial or complete response to treatment), progression-free survival (PFS; the length of time during and after treatment when a patient lives with the cancer but does not worsen) and duration of response (DOR; the length of time when a tumor responds to treatment without the cancer spreading or worsening).

Other secondary endpoints the trial aimed for were safety and time until a patient’s physical function and quality of life diminished. The news release noted that safety was not related to the discontinuation of the trial and reported that the safety profile of Opdualag was consistent with previous studies.

The trial included approximately 700 patients with MSS metastatic colorectal cancer who had one to four previous lines of therapy for metastatic disease. Patients were randomly assigned to two treatment groups to receive either Opdualag in group A or Stivarga (regorafenib) or Lonsurf (TAS-102) in group B, as noted in the clinicaltrials.gov listing for RELATIVITY-123. The trial was originally expected to be completed in early 2025.

“Metastatic colorectal cancer is a challenging cancer to treat with high unmet needs. Though there have been advances in treating patients with microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) colorectal cancers, patients with microsatellite stable tumors continue to have limited treatment options in later lines of therapy,” Dr. Jeffrey Walch, vice president and global program lead at Bristol Myers Squibb, said in the news release.

“While we know immunotherapies have historically demonstrated limited efficacy in MSS colorectal cancers, we had hoped to demonstrate meaningful clinical benefit in this patient population and are disappointed in this outcome,” he said.

According to the American Cancer Society, colorectal cancer is the third most common type of cancer that is diagnosed in people in the United States, and the third leading cause of cancer-related deaths. In 2023, the estimated number of new cases of colon cancer is 106,970 new cases and 46,050 new cases of rectal cancer.

Data has shown that from 2011 to 2019, rates of colorectal cancer have dropped by approximately 1% each year, commonly in older adults. However, the rates have been increasing by 1% to 2% in people younger than 50 years old since the mid-1990s, the American Cancer Society stated.

“We continue to be committed to the development of I-O therapies, including Opdivo (nivolumab) and Yervoy (ipilimumab), in MSI-H/dMMR colorectal cancers,” Walch said, “and we thank the investigators, patients, and their loved ones who participated in this trial.”

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