AstraZeneca and its MedImmune subsidiary acknowledged today that their marketed anticancer treatment Imfinzi™ (durvalumab) failed the second of two primary endpoints in a Phase III trial designed to assess the programmed death-ligand 1 (PD-L1) blocking antibody alone and in combination with the companies’ anti-CTLA4 antibody tremelimumab in a form of non-small cell lung cancer (NSCLC).

The Imfinzi-tremelimumab combination missed the second primary endpoint of the MYSTIC trial (NCT02453282) by failing to generate statistically-significant improvement in overall survival compared with standard-of-care (SoC) platinum-based chemotherapy in previously-untreated patients with Stage IV (metastatic) NSCLC, AstraZeneca and MedImmune said.

The Imfinzi-tremelimumab combo missed the first primary endpoint of progression-free survival (PFS), AstraZeneca acknowledged last year, by failing to improve PFS compared with platinum-based standard-of-care (SoC) in patients whose tumors express PD-L1 on at least 25% of their cancer cells.

Today, however, AstraZeneca and MedImmune added that data from MYSTIC further supported analysis in exploratory subgroups since the combination therapy had a hazard ratio of 0.85, compared with the 0.76 HR of Imfinzi monotherapy.

“We are encouraged to see that Imfinzi monotherapy activity is in-line with that of the anti-PD-1 class in previously-untreated patients with Stage IV non-small cell lung cancer; however, we are disappointed that these results missed statistical significance,” Sean Bohen, AstraZeneca EVP, global medicines development and CMO, said in a statement.

Immuno-Oncology Cornerstone

“We remain confident in Imfinzi as the cornerstone of our IO [immuno-oncology] program and continue to evaluate its potential in ongoing non-small cell lung cancer trials, including Imfinzi and Imfinzi plus tremelimumab in combination with chemotherapy,” Bohen added.

Imfinzi is approved for unresectable, Stage III NSCLC in more than 40 countries—including the U.S., the European Union, and Japan—based on the Phase III PACIFIC trial (NCT02125461). Imfinzi won its first accelerated FDA approval in May 2017 as therapy for previously treated patients with locally advanced or metastatic urothelial carcinoma (mUC).

MYSTIC is a randomized, open-label, multi-center global Phase III trial intended to assess Imfinzi monotherapy or Imfinzi in combination with tremelimumab versus SoC chemotherapy in the first-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type, locally-advanced or metastatic (Stage IV) non-small cell lung cancer. The trial was conducted in 167 centers across 17 countries, including the U.S., Canada, Europe, Russia, Australia, and parts of Asia, including Japan, Korea, Thailand, Taiwan, and Vietnam.

MYSTIC is one of several Phase III trials designed to assess Imfinzi in patients with Stage IV NSCLC. Other trials include: