On 10 November 2022, the US Food and Drug Administration (FDA) approved tremelimumab (Imjudo, AstraZeneca Pharmaceuticals) in combination with durvalumab (Imfinzi, AstraZeneca Pharmaceuticals) and platinum-based chemotherapy for adult patients with metastatic non-small cell lung cancer (NSCLC) with no sensitising epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumour aberrations.

Efficacy was evaluated in POSEIDON (NCT03164616), a randomised (1:1:1), multicentre, active-controlled, open-label study in patients with metastatic NSCLC who had not received prior systemic treatment. Patients were randomised to one of three treatment arms: 1. tremelimumab, durvalumab, and platinum-based chemotherapy for 4 cycles, followed by durvalumab and maintenance chemotherapy every 4 weeks; patients were treated with a fifth tremelimumab dose at week 16; 2. durvalumab plus platinum-based chemotherapy for 4 cycles followed by durvalumab and maintenance chemotherapy; or 3. platinum-based chemotherapy for 6 cycles followed by maintenance chemotherapy.

Treatment was continued until disease progression or unacceptable toxicity. This approval is based on a comparison of treatment arm 1 and 3 (675 patients).

The major efficacy outcome measures were progression-free survival (PFS) assessed by using blinded independent central review according to RECIST v1.1. and overall survival (OS). Tremelimumab plus durvalumab and platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS compared to platinum-based chemotherapy (hazard ratio [HR] of 0.77, 95% confidence interval [CI] 0.65, 0.92; 2-sided p-value = 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-value = 0.00031).

Overall response rate was 39% (95% CI 34,44) in and 24% (95% CI 20, 29) in the treatment arm 1 and 3, 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 (occurring in ≥ 20% of patients) were nausea, fatigue, decreased appetite, musculoskeletal pain, rash, and diarrhoea. Grade 3 or 4 laboratory abnormalities (≥ 10%) were neutropenia, anaemia, leukopenia, lymphocytopenia, lipase increased, hyponatraemia, and thrombocytopenia.

The recommended tremelimumab dose for patients weighing 30 kg or more is 75 mg i.v. every 3 weeks with durvalumab 1500 mg i.v. and platinum-based chemotherapy for 4 cycles, then durvalumab 1500 mg with maintenance chemotherapy every 4 weeks. A fifth tremelimumab dose (75 mg) should be given at week 16.

Using the above schedule, for patients weighing 30 kg or less, the recommended tremelimumab dose is 1 mg/kg and the durvalumab dose is 20 mg/kg.

Full prescribing information for Imjudo is available here and for Imfinzi here.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the 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.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Centre of Excellence Project Facilitate.