AstraZeneca Announces Positive Phase 3 Results for Imfinzi-Tremelimumab-Chemotherapy Triplet Therapy in First-Line Stage IV NSCLC

Today, AstraZeneca announced that its triple-combination therapy, comprising the anti-PD-L1 monoclonal antibody Imfinzi, the anti-CTLA-4 antibody tremelimumab, and chemotherapy, met both the primary and key secondary endpoints in the Phase 3 POSEIDON trial for the first-line treatment of patients with stage IV non-small cell lung cancer (NSCLC). Compared with chemotherapy alone, the triple-combination regimen demonstrated a statistically significant and clinically meaningful improvement in overall survival. The press release noted that this marks the first time tremelimumab has shown an overall survival benefit in a Phase 3 clinical trial.

Lung cancer is the leading cause of cancer-related deaths, accounting for approximately one-fifth of all cancer fatalities. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, representing 80%–85% of all cases. Stage IV is the most advanced stage of lung cancer and is often referred to as metastatic disease. Among patients with NSCLC, they are categorized into those with squamous cell carcinoma (approximately 25%–30%) and those with non-squamous cell carcinoma (the most prevalent subtype, accounting for approximately 70%–75% of NSCLC cases). The majority of NSCLC patients are diagnosed at an advanced stage.

Imfinzi (durvalumab) is a humanized monoclonal antibody that binds to PD-L1. It blocks the inhibitory effect of PD-L1 on immune responses by preventing its interaction with the PD-1 and CD80 receptors. Imfinzi has been approved in the United States, the European Union, Japan, and many other countries worldwide for the treatment of extensive-stage small cell lung cancer (ES-SCLC).

Tremelimumab is a humanized monoclonal antibody targeting CTLA-4. Tremelimumab can block the activity of CTLA-4, helping to activate T cells and initiate an immune response against cancer, thereby promoting cancer cell death. Clinical trials of Imfinzi in combination with tremelimumab for the treatment of NSCLC, small cell lung cancer, bladder cancer, and liver cancer are ongoing.

POSEIDON is a randomized, open-label, multicenter Phase 3 clinical trial designed to compare the efficacy of Imfinzi in combination with platinum-based chemotherapy, or Imfinzi plus tremelimumab in combination with chemotherapy, versus chemotherapy alone as first-line treatment for patients with stage IV non-small cell lung cancer (NSCLC). The trial enrolled 1,013 patients with stage IV NSCLC who expressed PD-L1 and did not harbor epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations.

Final results of the trial demonstrated that, compared with chemotherapy alone, the triple combination therapy of Imfinzi plus tremelimumab plus chemotherapy significantly improved patients’ progression-free survival (PFS) and overall survival (OS). The combination regimen of Imfinzi plus chemotherapy significantly improved PFS compared with chemotherapy alone; however, the OS trend observed in this analysis did not reach statistical significance. All combination regimens exhibited acceptable safety profiles, with no new safety signals identified. The addition of tremelimumab did not result in an increased number of treatment discontinuations.

Note: The original text has been abridged.

References:

[1] Imfinzi and tremelimumab with chemotherapy demonstrated overall survival benefit in POSEIDON trial for 1st-line Stage IV non-small cell lung cancer. Retrieved May 7, 2021, from https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/imfinzi-and-tremelimumab-showed-survival-in-poseidon.html

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