Dive Brief:

• AstraZeneca is terminating a Phase 3 study of its experimental bispecific antibody drug volrustomig, saying Monday that trial data monitors have concluded at an interim check the therapy is unlikely to improve survival in lung cancer patients compared with standard treatment.
• The trial paired volrustomig with chemotherapy against Merck & Co.’s Keytruda and chemo in people with non-small cell lung cancer whose tumors express lower levels of a protein known as PD-L1, which both drugs bind to. AstraZeneca believes acting on a second immunological target, "CTLA-4," as its drug does will provide further benefit to patients.
• Volrustomig is one in a long list of experimental medicines AstraZeneca is counting on to help it achieve $80 billion in sales by 2030. In addition to lung cancer, the U.K.-based pharmaceutical giant is running trials of the drug in mesothelioma, cervical, and head and neck cancers.

Dive Insight:

Antibody drugs blocking so-called immune checkpoints have revolutionized cancer care, helping people with more than a dozen types of cancer live longer and even eliminate their disease. Drugs targeting PD-1 and the related PD-L1 have proven most successful, but before they came on the market, a medicine named Yervoy became the first approved cancer immunotherapy by blocking another checkpoint: CTLA-4.

Bristol Myers Squibb, which developed Yervoy and, later, the PD-1-targeting drug Opdivo, has pursued the hypothesis that using the two types of therapies together will improve survival. That has yielded dual-agent approvals in melanoma, lung cancer and other types of disease.

With volrustomig, AstraZeneca is trying to show a single bispecific antibody drug that blocks both immune checkpoints — which turn off immune cell-evading proteins present on cancer cells — can perform better than a PD-1 blocker alone. Bispecific antibodies have worked their way into cancer care in recent years, primarily in hematological malignancies where they bind to diseased cells and T cells to turn on an immune response.

However, Yervoy and the CTLA-4 class have been known to come with a high side effect rate. Indeed, in its very first trial in humans, one-third of enrollees stopped taking volrustomig because of side effects. Analysts at Leerink Partners have therefore questioned whether AstraZeneca can find a “therapeutic window” where its drug achieves a sufficient tumor response without triggering excess toxicities.

AstraZeneca said it is proceeding with its other Phase 3 trials as planned. As for the lung cancer trial, the company is “disappointed” by the outcome, said Susan Galbraith, the company’s executive vice president for oncology and hematology research.

She added, “We will learn from this trial and are determined to continue pioneering new medicines from our industry-leading pipeline in our quest to improve outcomes for patients with lung cancer.”