NEW YORK – Bicycle Therapeutics recently announced plans to develop the investigational agent zelenectide pevedotin in patients with NECTIN4 gene-amplified cancers, including breast and lung cancers.
The firm plans to launch several Phase I/II clinical trials throughout 2025 using a NECTIN4 gene amplification strategy to home in on patients in this biomarker-defined indication. Bicycle believes that patients with Nectin-4-associated cancers have the potential to respond better to the agent.
Zelenectide pevedotin is part of a new class of drugs that Bicycle calls a bicyclic toxin conjugate. It includes a bicyclic peptide designed to target Nectin-4 on the surface of cancer cells that is bound to the cytotoxin MMAE via a sarcosine spacer chain and a valine-citrulline cleavable linker.
News of Bicycle's development plans for the agent come after the firm reported top-line data for zelenectide pevedotin plus Merck's checkpoint inhibitor Keytruda (pembrolizumab) in first-line metastatic urothelial cancer. In these patients, the drug led to a 60 percent overall response rate.
The firm also reported data on zelenectide pevedotin's activity in heavily pretreated breast cancer and non-small cell lung cancer patients with NECTIN4 gene amplification or polysomy. There was a deeper response in these patients than in all comers.
In a post hoc analysis of 38 heavily pretreated breast cancer patients enrolled in the Phase I/II Duravelo-1 clinical trial, eight patients had NECTIN4 gene amplifications or harbored NECTIN4 polysomy. Among these patients, the overall response rate to zelenectide pevedotin monotherapy was 62.5 percent, whereas the overall response rate in the all-comer breast cancer population was 14.3 percent. None of the patients without the NECTIN4 amplifications or polysomies responded to the agent.
In a separate post hoc analysis of 40 pretreated NSCLC patients in the Duravelo-1 trial, six patients had NECTIN4 gene amplifications. Forty percent of these biomarker-positive patients responded to zelenectide pevedotin, as opposed to 8.8 percent of all efficacy-evaluable NSCLC patients.
Bicycle plans to present more data from the Duravelo-1 study at an upcoming medical conference.
"While early, the zelenectide pevedotin monotherapy data in breast cancer and NSCLC patients with NECTIN4 gene amplification underscore its promising antitumor activity and solidify our next steps for the therapy's development," Bicycle CEO Kevin Lee said in a statement. "By leveraging NECTIN4 gene amplification, we expect to be able to identify the patients who may most benefit from zelenectide pevedotin and accelerate development for solid tumor indications beyond bladder cancer."