FDA rejects sintilimab with chemotherapy for non-small cell lung cancer
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The FDA issued a complete response letter indicating it cannot approve a biologics license application for sintilimab in combination with chemotherapy for first-line treatment of advanced nonsquamous non-small cell lung cancer.
The letter recommended additional study — specifically a multiregional clinical trial designed to compare the experimental regimen with standard of care for first-line metastatic NSCLC, with a noninferiority design that includes OS as an endpoint.
The decision came about 6 weeks after FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 14-1 that a regulatory decision on sintilimab (Innovent Biologics/Eli Lilly) for this indication should not be made until additional study demonstrates applicability to U.S. patients.
Innovent Biologics and Eli Lilly are evaluating next steps, according to an Eli Lilly-issued press release.
Sintilimab, a PD-1 inhibitor, is approved in China for multiple indications but is not approved in the United States.
Innovent Biologics submitted a biologics license application to the FDA seeking approval of the agent in combination with pemetrexed and platinum-based chemotherapy for first-line treatment of patients with stage IIIB, IIIC or IV nonsquamous NSCLC with no EGFR or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
The application cited data from the ORIENT-11 study, which included 397 patients in China with previously untreated locally advanced or metastatic nonsquamous NSCLC without EGFR or ALK mutations and an ECOG performance status of 0 or 1.
Researchers randomly assigned patients 2:1 to 200 mg sintilimab (n = 266; median age, 61 years; 76.7% men) or placebo (n = 131; median age, 61 years; 75.6% men) plus 500 mg/m2 pemetrexed and either 75 mg/m2 cisplatin or carboplatin area under the curve 5 every 3 weeks for four cycles. Patients then received maintenance therapy with either sintilimab or placebo with pemetrexed. Treatment continued until disease progression, and participants in the placebo group could cross over to sintilimab.
PFS served as the primary endpoint. Secondary endpoints included OS, overall response rate, time to response, duration of response and safety.
As Healio previously reported, results after median follow-up of 8.9 months (range, 0.6-14.8) showed longer median PFS in the sintilimab group (8.9 months vs. 5 months; HR = 0.48; 95% CI, 0.36-0.64). Researchers reported 6-month PFS rates of 68.3% (95% CI, 62-73.8) for the sintilimab group vs. 42% (95% CI, 32.8-50.9) for the placebo group.
During an ODAC meeting on Feb. 10, members who supported the need for additional study cited several factors for their votes. These included ORIENT-11’s single-country design, the fact the comparator regimen did not reflect standard therapy in the United States, and the decision by the study sponsors not to use OS as the primary endpoint.
The FDA is not required to follow ODAC’s recommendation but often does.
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