AstraZeneca’s Tremelimumab Offers Survival Benefit With IMFINZI in Advanced Lung Cancer

A final analysis of AstraZeneca’s Phase III POSEIDON trial shows IMFINZI (durvalumab), the company’s human monoclonal antibody and cancer immunotherapy, offered improvements in overall survival (OS) when added to tremelimumab and chemotherapy versus chemotherapy alone in patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC).

IMFINZI is an approved, potentially curative immunotherapy used for unresectable, post-chemotherapy Stage III NSCLC. Regions worldwide, including the U.S., EU, Japan, and others, have approved IMFINZI for extensive-stage small cell lung cancer (ES-SCLC). Approval for the ES-SCLC indication in these regions was based on findings from the Phase III CASPIAN trial.

Merck & Co.’s combination regimen comprising Keytruda and chemotherapy is currently the standard of care for first-line NSCLC treatment. A PD-1/CTLA4 cocktail consisting of Opdivo and Yervoy from Bristol Myers Squibb received U.S. Food and Drug Administration (FDA) approval a year ago for the treatment of patients with tumors expressing PD-L1. IMFINZI may be seen as a potential rival, considering it binds to PD-L1 and subsequently blocks an interaction of PD-L1 with PD-1 and CD80 and counters the immune-evading strategy of the tumor.

The randomized, global Phase III POSEIDON study enrolled 1,013 patients with metastatic NSCLC, including patients with non-squamous or squamous disease, as well as a full range of PD-L1 expression levels. Patients randomized to the experimental arms received a flat 1,500 mg dose of IMFINZI in addition to four chemotherapy cycles once every four weeks. In the control arm, patients received up to six chemotherapy cycles. 

The first-line triple immunotherapy combination regimen comprising IMFINZI, tremelimumab, and chemotherapy was associated with significant and clinically meaningful benefit in OS versus chemotherapy alone in the POSEIDON clinical trial. 

Several previous flops with tremelimumab have placed doubts on whether further research into the CTLA4 inhibitor was worth the time. In February, findings from another trial showed a combination of tremelimumab with Imfinzi failed to offer a significant OS benefit compared with chemotherapy plus cetuximab in recurrent or metastatic head and neck squamous cell carcinoma with tumors expressing high PD-L1. However, the benefit observed with IMFINZI in the POSEIDON trial offers hope it could still prove helpful in certain settings.

The triple combination therapy in the POSEIDON trial was also associated with significant improvements in progression-free survival (PFS), a finding which was comparable to that reported back in October 2019. While this previous analysis of the study showed a significant improvement in PFS with IMFINZI plus chemotherapy, the investigators did not find a significant benefit in the OS trend. 

In terms of safety, each combination had an acceptable safety profile. Similar to findings from the previous analysis, there were no newly identified safety signals in the new assessment. Overall, the treatment combination with tremelimumab featured a mostly similar safety profile as the profile for IMFINZI plus chemotherapy. In addition, the combination with tremelimumab did not result in a higher rate of treatment discontinuation.

“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,” said AstraZeneca’s Executive Vice President, Oncology Business Unit, Dave Fredrickson, in a statement on the findings.