On November 10, 2022, tremelimu-mab in combination with durvalumab and platinum-based chemotherapy was approved for patients with metastatic non–small cell lung cancer (NSCLC) with no sensitizing EGFR mutation or ALK genomic tumor aberrations.1
Supporting Efficacy Data
Approval was supported by findings in the tremelimumab/durvalumab plus chemotherapy group vs the chemotherapy group in the phase III, open-label POSEIDON trial (ClinicalTrials.gov identifier NCT03164616). In these groups, patients with no prior systemic treatment were randomly assigned to receive tremelimumab, durvalumab, and chemotherapy for up to four 21-day cycles followed by durvalumab every 4 weeks, with a fifth tremelimumab dose at week 16 (n = 338) or chemotherapy for six cycles (n = 337).
Median progression-free survival on blinded independent central review was 6.2 months (95% confidence interval [CI] = 5.0–6.5 months) with tremelimumab/durvalumab plus chemotherapy vs 4.8 months (95% CI = 4.6–5.8 months) with chemotherapy (hazard ratio [HR] = 0.72, 95% CI = 0.60–0.86, P = .00031). Median overall survival was 14 months (95% CI = 11.7–16.1 months) vs 11.7 months (95% CI = 10.5–13.1 months), with a hazard ratio of 0.77 (95% CI = 0.65–0.92, P = .00304).
How It Is Used
The recommended tremelimumab dose for patients weighing at least 30 kg is 75 mg intravenously (IV) every 3 weeks with durvalumab at 1,500 mg IV and platinum-based chemotherapy for four cycles, then durvalumab at 1,500 mg every 4 weeks; a fifth tremelimumab dose should be given at week 16. For patients weighing less than 30 kg, the recommended tremelimumab dose is 1 mg/kg, and the durvalumab dose is 20 mg/kg using the same schedule.
In POSEIDON, the most common adverse events of any grade (≥ 20%) with tremelimumab/durvalumab plus chemotherapy were nausea (42% vs 37% with chemotherapy), fatigue (36% vs 32%), musculoskeletal pain (29% vs 22%), decreased appetite (28% vs 25%), rash (27% vs 10%), and diarrhea (22% vs 15%). The most common grade 3 or 4 adverse events included pneumonia (8% vs 4.2%) and rash (2.4% vs 0.6%). The most common grade 3 or 4 laboratory abnormalities were neutropenia (37% vs 32%), anemia (24% vs 25%), and leukopenia (21% vs 18%).
Tremelimumab has warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, and embryofetal toxicity.
Serious adverse events occurred in 44% of patients given tremelimumab/durvalumab plus chemotherapy, most commonly pneumonia (11%) and anemia (5%). Adverse events led to discontinuation of tremelimumab or durvalumab in 17% of patients. Fatal adverse events occurred in 4.2% of patients, with causes including sepsis, pneumonitis, and acute kidney injury in two patients each.
Tremelimumab has warnings/precautions for immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, dermatologic reactions, nephritis with renal dysfunction, and pancreatitis; infusion-related reactions; and embryofetal toxicity. Patients should be advised not to breastfeed while receiving tremelimumab.
1. Imjudo (tremelimumab-actl) injection, for intravenous use, prescribing information, AstraZeneca, November 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761270s000lbl.pdf. Accessed November 16, 2022.