On November 10, 2022, the U.S. Food and Drug Administration (FDA) approved tremelimumab (Imjudo®) in combination with durvalumab (Imfinzi®) and platinum-based chemotherapy for adult patients with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) variant or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
Efficacy was evaluated in POSEIDON (NCT03164616), a randomized (1:1:1), multicenter, active-controlled, open-label study in patients with metastatic NSCLC who had not received prior systemic treatment. Patients were randomized to one of three treatment arms: (1) tremelimumab, durvalumab, and platinum-based chemotherapy for four cycles, followed by durvalumab and maintenance chemotherapy every four weeks, then a fifth tremelimumab dose at week 16; (2) durvalumab plus platinum-based chemotherapy for four cycles followed by durvalumab and maintenance chemotherapy; or (3) platinum-based chemotherapy for six cycles followed by maintenance chemotherapy.
Patients continued on their treatment arm until they experienced disease progression or unacceptable toxicity. The approval is based on a comparison of treatment arm one and three from 675 patients.
The major efficacy outcome measures were progression-free survival (PFS) assessed using blinded independent central review according to RECIST v1.1. and overall survival (OS). Patients treated with tremelimumab plus durvalumab and platinum-based chemotherapy had a statistically significant and clinically meaningful improvement in OS compared to platinum-based chemotherapy (hazard ratio [HR] = 0.77 [95% CI = 0.65, 0.92], 2-sided p = 0.00304); median OS was 14 months (95% CI = 11.7, 16.1) and 11.7 months (95% CI = 10.5, 13.1) in the treatment arm 1 and 3, respectively. Median PFS was 6.2 months (95% CI = 5.0, 6.5) and 4.8 months (95% CI = 4.6, 5.8) in the treatment arms, respectively (HR = 0.72 [95% CI = 0.60, 0.86], 2-sided p = 0.00031).
Overall response rate was 39% (95% CI = 34,44) in and 24% (95% CI = 20, 29) in the treatment arm one and three, respectively. Median duration of response was 9.5 months (95% CI = 7.2, not reached) and 5.1 months (95% CI = 4.4, 6.0) in the two treatment arms.
The most common adverse reactions reported by at least 20% of patients treated with tremelimumab in combination with durvalumab and platinum-based chemotherapy were nausea, fatigue, decreased appetite, musculoskeletal pain, rash, and diarrhea. Grade 3 or 4 laboratory abnormalities reported by at least 10% of patients treated with tremelimumab in combination with durvalumab and platinum-based chemotherapy were neutropenia, anemia, leukopenia, lymphocytopenia, lipase increased, hyponatremia, and thrombocytopenia.
The recommended dose for patients weighing 30 kg or more is 75 mg of IV tremelimumab every three weeks with 1,500 mg of IV durvalumab and platinum-based chemotherapy for four cycles, then 1,500 mg of durvalumab with maintenance chemotherapy every four weeks. A fifth 75 mg tremelimumab dose should be given at week 16.
Patients weighing 30 kg or less should follow the same schedule using the recommended tremelimumab dose of 1 mg/kg and durvalumab dose of 20 mg/kg.
View the full prescribing information for tremelimumab.
View the full prescribing information for durvalumab.
The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.