Bristol Myers Squibb announced topline data from the Phase III CheckMate -648 trial on Thursday, with positive results in esophageal cancer.
Bristol Myers Squibb announced topline data from the Phase III CheckMate -648 trial on Thursday, with positive results in esophageal cancer.
The study evaluated the company’s checkpoint inhibitor Opdivo (nivolumab) plus chemotherapy or Opdivo plus another of its checkpoint inhibitors, Yervoy (ipilimumab), in patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer death around the globe, with about 604,000 new cases and more than 544,000 deaths last year. The two most common forms of esophageal cancer are squamous cell carcinoma (ESCC) and adenocarcinoma, which make up about 90% and 10% of all esophageal cancers, respectively.
Opdivo plus chemotherapy demonstrated a statistically significant and clinically meaningful benefit for both the primary and secondary endpoints of overall survival (OS) in patients whose tumors were tested to express PD-L1, as well in the complete randomized patient population at the pre-specified interim analysis. That combination also showed statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS) in tumors that express PD-L1, as evaluated by a blinded independent central review (BICR).
In the other part of the trial, Opdivo plus Yervoy also hit the primary and secondary endpoints, demonstrating statistically significant and clinically meaningful improvement in OS in patients with tumors expressing PD-L1 as well as in the all-randomized population. However, this combination did not hit the other primary endpoint, PFS by BICR in patients testing to express PD-L1.
“The results for these Opdivo-based combinations represent a significant advancement for patients with esophageal cancer who are often diagnosed after their disease has spread and would benefit from new therapeutic options,” said Ian M. Waxman, development lead, gastrointestinal cancers, Bristol Myers Squibb. “This study further demonstrates our commitment to pursue combination strategies that improve outcomes for patients with high unmet need, such as those with gastrointestinal cancers.”
CheckMate -648 studied Opdivo plus Yervoy or Opdivo plus fluorouracil and cisplatin against fluorouracil plus cisplatin alone in this patient group. The primary endpoints were OS and PFS by BICR in patients whose tumors express PD-L1, for both Opdivo-based combinations compared to chemotherapy. Secondary endpoints included OS and PFS by BICR in the all-randomized population.
CheckMate -648 built on data from CheckMate -649, which together indicated that Opdivo was the first and only PD-1/L1 inhibitor to show superior first-line survival in upper GI cancers across histologies and tumor locations, including stomach, gastroesophageal junction, and esophagus.
In July 2014, Opdivo was the first PD-L1 immune checkpoint inhibitor to be approved anywhere in the world. It is now approved in more than 65 countries. Then, in 2015, the combination of Opdivo and Yervoy was the first immuno-oncology combination therapy to receive regulatory approval for metastatic melanoma and is approved for that indication in more than 50 countries. While Opdivo is an immune checkpoint against PD-L1, Yervoy is an inhibitor against a different checkpoint, CTLA-4.
Bristol Myers Squibb plans to finish analyzing the data and sharing the results at an upcoming medical meeting, in addition to various regulatory agencies.
