AstraZeneca has advanced its push to make camizestrant a blockbuster, reporting a phase 3 win for the oral SERD at an interim analysis. The trial hit on progression-free survival (PFS), its primary endpoint, but is yet to show patients live longer on the drug candidate.
Racing rivals including Eli Lilly and Roche, AstraZeneca is striving to establish the endocrine therapy as a backbone drug in hormone receptor-positive, HER2-negative breast cancer. AstraZeneca’s rivals have similar ambitions, with multiple companies claiming their molecules could be best in class, and the field is now nearing the publication of the hard evidence that will help settle the debate.
AstraZeneca landed an early blow Wednesday. At a planned interim phase 3 analysis, the drugmaker found PFS improved when breast cancer patients switched from a standard-of-care aromatase inhibitor to camizestrant.
The study has a novel design that reflects an unmet need in the indication. All patients received an aromatase inhibitor and a CDK4/6 inhibitor—either Lilly’s Verzenio, Novartis’ Kisqali or Pfizer’s Ibrance—as their first-line treatment. Physicians monitored circulating tumour DNA to spot ESR1 mutations. If a mutation was found before disease progression, patients switched to camizestrant and stayed on the CDK4/6 drug.
ESR1 mutations are found in about 5% of patients at the time of metastatic diagnosis, Susan Galbraith, Ph.D., executive vice president of oncology R&D at AstraZeneca, said on an earnings call this month. The figure rises to around 40% by the time of disease progression at the end of first-line treatment. AstraZeneca designed the trial to show whether camizestrant can extend the benefit of first-line therapy for those patients.
The primary endpoint hit suggests that goal is within reach, but questions remain. The data on time to second disease progression (PFS2) and overall survival (OS) were immature at the time of the interim analysis. AstraZeneca noted a trend toward improvement in PFS2 but made no further comment on its OS data. No new safety concerns were seen, and discontinuations were very low, AstraZeneca said.
The PFS endpoint is the first of a series of milestones for the program. AstraZeneca is running another trial in a broader first-line population and two adjuvant studies. Through the program, the company is aiming to establish camizestrant as a new backbone therapy and hit a peak sales target that AstraZeneca CEO Pascal Soriot has set at more than $5 billion.
AstraZeneca could face competition. Lilly reported phase 3 data on its oral SERD imlunestrant in patients who progressed on an aromatase inhibitor late last year. Roche is aiming to have data on giredestrant, its challenger for the market, sometime from mid-2025 onward. AstraZeneca sees the safety profile of its candidate and ability to combine it with a range of other drugs as differentiators.
“The safety profile that we're seeing with camizestrant leads to an extremely low discontinuation rate, very low rates of these GI side effects, which I think is important, particularly when you go into the earlier lines of therapy. People want to stay on the drug for a long period of time,” Galbraith said. “I think the overall profile that we have with this drug is really looking best in class from our perspective.”
AstraZeneca plans to share the interim phase 3 data with global regulatory authorities.