Incyte's retifanlimab (Zynyz) in combination with platinum-based chemotherapy has demonstrated a clinically meaningful and statistically significant improvement in overall survival (OS) for patients with previously untreated metastatic non-small cell lung cancer (NSCLC). The Phase 3 POD1UM-304 trial results, presented at the European Society for Medical Oncology (ESMO) Asia Congress 2024, support a planned supplemental Biologics License Application (sBLA) submission to the U.S. Food and Drug Administration (FDA) in 2025. Lung cancer is the leading cause of cancer deaths globally, with NSCLC accounting for approximately 85% of all cases.
The POD1UM-304 trial, a global, multicenter, randomized, double-blind study, evaluated retifanlimab or placebo in combination with platinum-based chemotherapy in patients with first-line, metastatic squamous or non-squamous NSCLC. Patients received retifanlimab or placebo intravenously with pemetrexed and carboplatin/cisplatin for non-squamous NSCLC, and with paclitaxel and carboplatin for squamous NSCLC. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS), overall response rate (ORR), and duration of response (DOR).
Key Findings from the POD1UM-304 Trial
The trial results showed a clinically meaningful and statistically significant improvement in overall survival (OS) with the retifanlimab and chemotherapy combination. The median OS was 18.1 months in the retifanlimab group compared to 13.4 months in the placebo group (Hazard Ratio [HR]: 0.75; 95% Confidence Interval [CI]: 0.60, 0.93; P = 0.0042).
Secondary endpoints were also met:
- Patients receiving retifanlimab plus chemotherapy had a 2-month improvement in median progression-free survival (PFS) compared to the placebo plus chemotherapy group (7.7 vs 5.5 months; HR: 0.64; 95% CI: 0.52, 0.79; P < 0.0001).
- The overall response rate (ORR) was 52% in the retifanlimab group versus 39% in the placebo group (P = 0.0012).
- The duration of response (DOR) was 12.7 months in the retifanlimab group versus 6.1 months in the placebo group.
Safety and Tolerability
Retifanlimab was generally well-tolerated, and no new safety signals were identified. The most common treatment-emergent adverse events (TEAEs) in the retifanlimab and chemotherapy combination group were anemia (62.7%), decreased appetite (22.6%), and decreased neutrophil count (22.1%). Chemotherapy administration was not compromised by the addition of retifanlimab.
Expert Commentary
"I am encouraged by the observed safety and efficacy profile of retifanlimab when added to platinum-based chemotherapy in this patient population and believe the positive results from the POD1UM-304 trial support retifanlimab in combination with chemotherapy as an additional treatment option for previously untreated metastatic NSCLC," said Shun Lu, M.D., Ph.D., Shanghai Chest Hospital.
About Retifanlimab (Zynyz)
Retifanlimab, marketed as Zynyz, is an intravenous PD-1 inhibitor. It is currently approved in the U.S. for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC). In Europe, it is approved as a monotherapy for the first-line treatment of adult patients with metastatic or recurrent locally advanced MCC not amenable to curative surgery or radiation therapy.
Next Steps
Incyte plans to submit a supplemental Biologics License Application (sBLA) to the FDA in 2025, seeking approval for retifanlimab in combination with platinum-based chemotherapy for the first-line treatment of metastatic NSCLC.
