BioPharma, Pharma

Imfinzi looks flimsy in AstraZeneca’s Phase III head and neck cancer study

Results of the Phase III EAGLE study leave Merck’s Keytruda and Bristol’s Opdivo as the dominant players in the space of HNSCC after progression on platinum-based chemotherapy.

An immunotherapy drug under development by pharmaceutical giant AstraZeneca suffered its latest setback Friday as an analysis of a clinical trial showed it failed to improve survival in head and neck cancer patients.

The London-based company said the Phase III EAGLE study of the PD-L1 checkpoint inhibitor Imfinzi (durvalumab) – both alone and combined with the CTLA-4 inhibitor tremelimumab – failed to show improved overall survival in patients with recurrent or metastatic head and neck squamous cell carcinoma – or HNSCC – whose disease had progressed following platinum-based chemotherapy, when compared against standard of care chemotherapy.

Imfinzi has accelerated Food and Drug Administration approval for locally advanced or metastatic urothelial carcinoma in patients with disease progression following platinum-based chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with the same, an indication it received last year.

The news comes around three weeks after Imfinzi and tremelimumab failed in another major Phase III study, MYSTIC, in first-line non-small cell lung cancer. Not only did Imfinzi and tremelimumab fail to extend overall survival among patients in that study, but the hazard ratios indicated the combination performed even worse than Imfinzi by itself. While the company said the data for Imfinzi monotherapy warranted further subgroup analysis, the results of MYSTIC greatly diminish the potential for Imfinzi to compete against the only checkpoint inhibitor approved for the significant first-line NSCLC setting, Merck & Co.’s PD-1 inhibitor Keytruda (pembrolizumab).

The EAGLE results will likely have the same effect, as Keytruda is already approved as a monotherapy for the same HNSCC setting. So too is Bristol-Myers Squibb’s Opdivo (nivolumab). In addition, Opdivo is approved for several indications – metastatic melanoma, kidney cancer, and certain patients with colorectal cancer – in combination with Bristol’s own CTLA-4 inhibitor, Yervoy (ipilimumab).

With ClinicalTrials.gov listing 15 Phase III trials of tremelimumab, it nevertheless still has opportunities for success.

One of those trials is KESTREL, which compares Imfinzi with or without tremelimumab against standard of care chemotherapy in patients who have not yet received prior systemic chemotherapy for recurrent or metastatic disease, and thus an earlier setting than the one for which Keytruda and Opdivo are approved. In a statement, AstraZeneca Chief Medical Officer Sean Bohen said results for KESTREL are expected in the first half of next year.

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