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Two NSCLC trials fail to meet primary endpoints
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Two randomized phase 3 trials designed to evaluate treatments for patients with non–small cell lung cancer failed to meet their primary endpoints of PFS.
The CheckMate-026 trial evaluated nivolumab (Opdivo, Bristol-Myers Squibb) monotherapy in treatment-naive patients with advanced PD-L1–positive NSCLC.
The SELECT-1 trial evaluated the addition of selumetinib (AstraZeneca) to docetaxel chemotherapy as second-line treatment for patients with KRAS mutation–positive, locally advanced or metastatic NSCLC.
Manufacturers of both agents released topline results of the trials in early August.
CheckMate-026
The CheckMate-026 trial evaluated nivolumab in 541 previously untreated patients with advanced NSCLC whose tumors express PD-L1.
Patients received nivolumab 3 mg/kg via IV every 2 weeks or investigator’s choice of chemotherapy. Treatment continued for six cycles, or until disease progression or unacceptable toxicity.
The study failed to meet its primary endpoint of PFS among patients whose tumors expressed PD-L1 at levels of 5% or more.
“Opdivo has become a foundational treatment that is transforming cancer care across multiple tumor types,” Giovanni Caforio, MD, Bristol-Myers Squibb’s CEO, said in a company-issued press release. “While we are disappointed CheckMate-026 did not meet its primary endpoint in this broad patient population, we remain committed to improving patient outcomes through our comprehensive development program, including the ongoing phase 3 CheckMate-227.”
CheckMate-227 is designed to evaluate the first-line combination of nivolumab plus ipilimumab (Yervoy, Bristol-Myers Squibb) for PD-L1–positive patients with advanced NSCLC, as well as the addition of nivolumab to either first-line ipilimumab or chemotherapy in PD-L1–negative patients.
Nivolumab, a PD-1 immune checkpoint inhibitor, is approved in the United States for patients with metastatic NSCLC who progressed on or after platinum-based chemotherapy. It also is approved for treatment of certain patients with melanoma, renal cell carcinoma and classical Hodgkin lymphoma.
SELECT-1
The SELECT-1 trial included 510 patients with NSCLC.
All patients received 75 mg/m2 docetaxel via IV on day 1 of each 21-day cycle. Researchers randomly assigned study participants to also receive 75 mg oral selumetinib (AstraZeneca) — an oral, highly selective MEK 1/2 inhibitor — twice daily or placebo.
The study failed to meet its primary endpoint of PFS. The combination also had no significant effect on OS.
“A randomized phase 2 trial showed promising activity of selumetinib in combination with docetaxel in patients with KRAS mutation–positive lung cancer,” Sean Bohen, executive vice president of global medicines development and chief medical officer at AstraZeneca, said in a company-issued press release. “It is disappointing for patients that these results have not been confirmed in phase 3.”
The adverse event profiles for selumetinib and docetaxel were consistent with those seen in previous trials, according to the press release.
Complete data from SELECT-1 will be submitted for presentation at a future medical meeting.
“We remain committed to further developing treatments in the lung cancer setting, such as our immunotherapy combinations and targeted EGFR treatments,” Bohen said.
The FDA previously granted selumetinib orphan drug designation for treatment of patients with differentiated thyroid cancer. The agent also is being studied as a possible treatment for patients with neurofibromatosis type 1, a genetic disorder that causes tumors to grow along nerve tissue.