Key Takeaways

  • AstraZeneca announced on Monday that it is terminating the Phase III study of its experimental bispecific antibody drug, volrustomig,the company said, after the data monitoring committee concluded at an interim review that the drug was unlikely to improve survival compared to standard care in lung cancer patients.
  • The trial compared volrustomig plus chemotherapy against Merck's Keytruda plus chemotherapy in patients with non-small cell lung cancer whose tumors expressed low levels of the PD-L1 protein, which both drugs target. AstraZeneca believed that its drug, which also targets a second immune checkpoint called CTLA-4, would provide additional benefits for patients.
  • Volrustomig is one of the many experimental drugs AstraZeneca hopes will help itachieve $80 billion in sales by 2030. In addition to lung cancer, the UK-based pharmaceutical giant is also testing the drug in mesothelioma, cervical cancer, and head and neck cancer.

Deep Dive

Antibody drugs targeting so-called immune checkpoints haverevolutionized cancer treatment, helping patients with more than a dozen types of cancer live longer or even eliminating the disease. Drugs targeting PD-1 and its related PD-L1 have proven most successful, but before these drugs came to market,a drug called Yervoybecame the first approved cancer immunotherapy by blocking another checkpoint, CTLA-4.

Bristol Myers Squibb, which developed Yervoy and later the PD-1-targeting Opdivo, has worked to validate the hypothesis that combining the two therapies improves survival. This strategy has led to approvals of the dual-drug combination in melanoma, lung cancer, and other cancer types.

With volrustomig, AstraZeneca sought to prove that a bispecific antibody drug that simultaneously blocks two immune checkpoints—which shut down immune-evasion proteins present on cancer cells—could perform better than a PD-1 blocker alone. In recent years, bispecific antibodies have entered cancer treatment, primarily for blood cancers, where they bind to both diseased cells and T cells to activate an immune response.

However, Yervoy and CTLA-4-class drugs are known to havehigh rates of side effects. In fact, in volrustomig's first human trial,one-third of participants stopped treatment due to side effects. Therefore, analysts at Leerink Partners questioned whether AstraZeneca could find a "therapeutic window" that allows the drug to achieve sufficient tumor response without causing excessive toxicity.

AstraZeneca said its other ongoing Phase III trials will continue as planned. As for the lung cancer trial, Susan Galbraith, the company's executive vice president of oncology and hematology research, said the company is "disappointed" with the results.

She added: "We will take the learnings from this trial and are determined to continue to advance new medicines from our industry-leading pipeline to improve outcomes for patients with lung cancer."