Imfinzi-Tremelimumab Combo Fails to Prolong Overall Survival in Metastatic NSCLC, Phase 3 Trial Shows

A combination of tremelimumab plus Imfinzi (durvalumab) is no better than standard chemotherapy at extending the survival of people with metastatic non-small cell lung cancer (NSCLC) with a high tumor mutational burden, findings from a Phase 3 trial show.

The open-label NEPTUNE trial (NCT02542293) was examining the immunotherapy combination in people who had not received prior therapy for metastatic disease, and who had no mutations in the EGFR or ALK genes.

While not achieving its primary goal of overall survival in patients with highly mutated tumors, the combination’s safety and tolerability was consistent with prior clinical trials.

Imfinzi and the investigational medicine tremelimumab — both in development by AstraZeneca — belong to a type of cancer antibody treatment called immune checkpoint inhibitors.

While Imfinzi targets the PD-L1 protein on cancer cells, tremelimumab selectively binds to the CTLA-4 protein on T-cells. By binding to their targets, both therapies are intended to block mechanisms used by cancer to evade immune attack, boosting the body’s anti-tumor response.

NEPTUNE was carried out at more than 200 centers across 29 countries. It included 955 metastatic NSCLC patients, randomly selected to receive standard first-line treatment with a platinum-based chemotherapy or a combination of Imfinzi plus tremelimumab.

The trial included people with any mutational burden — a measure of the number of mutations present in the tumor’s DNA. However, because the immune system is better at recognizing highly mutated tumors, the primary goal was to determine if the combination worked better in these patients. A high mutational burden was defined as having 20 mutations or more per megabase of DNA.

In addition to testing overall survival in this population, researchers also sought to measure overall survival in the entire study group and the time patients lived without disease worsening. Other outcomes included the overall response rate and duration of responses.

AstraZeneca will be presenting full study results at an upcoming medical meeting.

“We are fully committed to a deep analysis of the vast clinical and biomarker data from this trial to gain further insights to improve Immuno-Oncology approaches for patients with metastatic non-small cell lung cancer,” José Baselga, executive vice-president of oncology R&D at AstraZeneca, said in a press release.

Imfinzi is approved for inoperable Stage 3 NSCLC — generally indicating cancers that have spread into nearby tissue — in more than 40 countries, including the U.S., the E.U., and Japan, based on progression-free survival results from the Phase 3 PACIFIC trial (NCT02125461).

It is being evaluated as a stand-alone therapy or in combination with tremelimumab and/or chemotherapy in Phase 3 trials of small and non-small cell lung cancer, bladder cancer, liver cancer, head and neck cancer, cervical cancer, and biliary tract cancer, as well as other solid blood cancers.