It was only two months ago when Bristol Myers Squibb’s Opdivo became the first immunotherapy approved in advanced esophageal cancer after prior chemotherapy regardless of PD-L1 status. Now the New Jersey pharma has two more gastrointestinal cancer trial wins under its belt, including one earlier in treatment.
On Tuesday, BMS said a phase 3 trial testing Opdivo in postsurgery patients with removed esophageal or gastroesophageal junction cancer had hit its primary mark. In the CheckMate-577 study, Opdivo beat placebo at keeping tumors from returning in those who had had tumors surgically removed after chemoradiation therapy failed to completely eradicate them.
For Opdivo, it's industry first as an adjuvant therapy improving disease-free survival in esophageal cancer. Investigators will continue the study for further analysis of its secondary endpoint, which is extending patients' lives.
Getting to patients prior to or right after surgery to prevent cancer recurrence represents the next frontier for immuno-oncology therapies, as it could potentially help patients more—and reach more of them, too.
"Where we’re also really heading now is into earlier stages of disease. Most of the data we’ve been discussing recently has been in the advanced setting, [but] potentially where we could have even more impact" is the adjuvant setting, said Nick Botwood, head of U.S. medical affairs and interim head of oncology development at BMS, in a recent interview. We "hope we can really move more patients into a cure by treating patients with our I-O therapies in an earlier-stage setting."
GI cancer marks the second adjuvant win for Opdivo. Back in 2017, the PD-1 drug snagged an FDA nod in melanoma to help reduce the risk of cancer recurrence after surgical removal of a tumor. Three-year analysis unveiled last year from the phase 3 CheckMate-238 study—which originally earned Opdivo’s adjuvant melanoma go-ahead—showed the drug’s recurrence-free survival rate at 58%.
In a separate trial that BMS also trumpeted Tuesday, adding Opdivo to chemotherapy significantly stalled the time to disease worsening and prolonged the lives of patients with previously untreated gastric and esophageal cancers whose levels of biomarker PD-L1 came in at or above a combined positive score of 5, Bristol said. Researchers found the life-extension benefit across the trialed population.
That was the same setting Merck & Co.’s market-leading checkpoint inhibitor Keytruda flopped in a year ago, making Opdivo the first I-O agent to show definitive strength in the first-line treatment of any gastrointestinal malignancies.
“The results from CheckMate-649, the largest study of gastric and esophageal cancers conducted to date, indicate the potential for Opdivo plus chemotherapy to change practice in the first-line setting and become a new standard of care for certain patients with gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma,” BMS' gastrointestinal cancers development lead, Ian Waxman, said in a statement.
Opdivo hit those primary goals on an interim analysis, and BMS will evaluate the existing data in full and discuss them with health authorities for potential regulatory filings, the company said. The same study is also evaluating a combination of Opdivo and BMS’ own CTLA-4 inhibitor Yervoy.
GI cancer, a notoriously tough disease area, has seen quite a few I-O disappointments. In 2017, Keytruda failed to extend the lives of second-line patients with PD-L1-positive gastric cancer. Then came the first-line crash from the Keynote-062 study, which served as a confirmatory trial to Keytruda’s third-line gastric cancer OK, which was restricted to those bearing the PD-L1 biomarker.
And last year, Pfizer and Merck KGaA’s Bavencio chalked up a failure as a maintenance therapy, where it couldn’t beat continuing chemo or best supportive care at extending the lives of patients with advanced stomach cancer after one round of successful chemo.