Melissa L. Johnson, MD, on the Approval of Tremelimumab Plus Durvalumab/Chemo in NSCLC

Approval Alert | <b>Tremelimumab Plus Durvalumab and Chemotherapy in Advanced Non–Small Cell Lung Cancer</b>

Melissa L. Johnson, MD, spoke about the design of the phase 3 POSEIDON trial how its data led to the recent approval of tremelimumab plus durvalumab and chemotherapy in patients with advanced non–small cell lung cancer.

CancerNetwork® spoke with Melissa L. Johnson, MD, director of Lung Cancer Research at Sarah Cannon Research Institute at Tennessee Oncology in Nashville, Tennessee, about the approval of tremelimumab (Imjudo) plus durvalumab (Imfinzi) and platinum-based chemotherapy in patients with metastatic non–small cell lung cancer with an EGFR mutation or ALK alteration.1 Johnson was also a lead investigator on the phase 3 POSEIDON trial (NCT03164616), the results of which helped to support the approval.2

A statistically significant and clinically meaningful overall survival (OS) was observed in the triplet arm vs platinum-based chemotherapy alone (HR, 0.77; 95% CI, 0.65-0.92; 2-sided P value = .00304). The median OS was 14.0 months (95% CI, 11.7-16.1) in the tremelimumab plus durvalumab and chemotherapy arm and 11.7 months (95% CI, 10.5-13.1) in the chemotherapy arm.

Transcript:

The POSEIDON trial was a randomized phase 3 clinical study in which patients with newly diagnosed non–small cell lung cancer were randomized to 1 of 3 treatment arms: chemotherapy alone—patients could get up to 6 cycles—vs chemotherapy and durvalumab followed by durvalumab maintenance until progression or undesired [adverse] effects [AEs] vs chemotherapy plus durvalumab and tremelimumab once every 4 weeks for 4 cycles. Patients also got a fifth dose of tremelimumab in week 16, and durvalumab maintenance [was given] until progression or undesired [AEs].

POSEIDON evaluated 2 questions that haven’t been evaluated before. First, what’s the effect of 4 doses of chemotherapy added to dual checkpoint immunotherapy, durvalumab, and tremelimumab. What’s the impact of a limited amount of CTLA4—5 doses of tremelimumab. Finally, POSEIDON allowed the comparison within the trial of a PD-L1 chemotherapy regimen vs PD-L1 and chemotherapy plus tremelimumab [regimen].

This is only the second FDA approval for anti-CTLA4 [agent] tremelimumab. The HIMALAYA trial [NCT03298451] just last month led to the first approval of tremelimumab for patients with [hepatocellular carcinoma]. Now, the POSEIDON-[based] approval of durvalumab plus tremelimumab and chemotherapy allows another option for patients with newly diagnosed non–small cell lung cancer who are looking for chemotherapy and an immune therapy regimen. This is going to be for patients who don’t have a driver oncogene like EGFR, ALK, or ROS1. Patients are eligible to receive the POSEIDON regimen of durvalumab plus tremelimumab and chemotherapy irrespective of PD-L1 expression; a patient’s PD-L1 can be anywhere from 0% to 100%.

References

  1. FDA approves tremelimumab in combination with durvalumab and platinum-based chemotherapy for metastatic non-small cell lung cancer. News release. FDA. November 10, 2022. Accessed November 17, 2022. https://bit.ly/3Us5sf8
  2. Johnson ML, Cho BC, Luft A, et al. Durvalumab with or without tremelimumab in combination with chemotherapy as first-line therapy for metastatic non–small-cell lung cancer: the phase III POSEIDON study. J Clin Oncol. Published online November 3, 2022. doi:10.1200/JCO.22.00975