Data reported from the phase 3 POSEIDON trial are the first to demonstrate a statically significant overall survival benefit with tremelimumab.
Combination therapy with durvalumab (Imfinzi) and tremelimumab plus chemotherapy resulted in a statistically significant improvement in overall survival (OS) versus chemotherapy alone in patients with stage IV non–small cell lung cancer (NSCLC), according to the sponsor of the phase 3 study, AstraZeneca.
In addition to a reduction in the risk death, the randomized, open-label, multicenter POSEIDON trial (NCT03164616) indicated a significant progression-free survival (PFS) benefit with the PD-L1/CTLA-4 inhibitor combination versus standard of care. This is the first phase 3 trial to demonstrate an OS benefit with tremelimumab.
“We are pleased to see the POSEIDON phase 3 trial demonstrate, for the first time, a significant and clinically meaningful overall survival benefit for Imfinzi plus tremelimumab with chemotherapy in metastatic non-small cell lung cancer,” Dave Fredrickson, Executive Vice President of the Oncology Business Unit at AstraZeneca, said in a press release. “We were particularly pleased by the safety profile. We’ve seen encouraging uptake of novel combinations in this setting and believe this new approach will add a further option for patients with high unmet medical need. We look forward to discussing next steps with regulatory authorities.”
The trial included 3 treatment arms, with patients receiving standard chemotherapy either alone, in combination with durvalumab, or with durvalumab/tremelimumab. A prior analysis of all 3 arms demonstrated an acceptable safety profile for each, with the tremelimumab combination having a broadly similar profile to that of durvalumab and chemotherapy.
The primary end points of the trial are OS and PFS in the durvalumab plus chemotherapy combination arm. Secondary end points include OS and PFS with the durvalumab/tremelimumab combination.
Patients received durvalumab at a fixed dose of 1500 mg every 3 weeks with chemotherapy, then every 4 weeks until progression. Tremelimumab was administered at 75 mg every 3 weeks for 4 cycles with chemotherapy, and extra doses were given as maintenance following chemotherapy. Chemotherapy alone was given for up to 6 cycles. Maintenance pemetrexed was allowed in non-squamous patients if given during induction.
Eligible patients had histologically or cytologically documented stage IV NSCLC, a confirmed PD-L1 status prior to randomization, no activating EGFR or ALK mutations or ALK fusions, no prior therapies for metastatic disease, and a WHO or ECOG status of 0 or 1. Both squamous and non-squamous histology were allowed.
According to the company, data from the trial will be made available at an upcoming medical meeting. In addition to this indication, the combination is being explored in lung, bladder, and liver cancer settings.
Imfinzi and tremelimumab with chemotherapy demonstrated overall survival benefit in POSEIDON trial for 1st-line Stage IV non-small cell lung cancer. News release. AstraZeneca. May 7, 2021. Accessed May 7, 2021. https://bit.ly/3tqfiQs