Carotuximab Combo Proves Safe for Advanced Prostate Cancer

Carotuximab (ENV-105) was well tolerated when combined with the standard of care hormone therapy, Erleada (apalutamide), in the first 10 patients enrolled on a phase 2 trial for metastatic castration-resistant prostate cancer in; no serious side effects were reported.

These findings were shared in a news release from Kairos Pharma.

“The favorable safety profile observed in this phase 2 study is encouraging, as it validates our belief in ENV-105’s clinical potential and supports continued development in a patient population with limited effective treatment options,” Dr. John Yu, CEO of Kairos Pharma, said in the news release.

The randomized phase 2 trial is enrolling up to 100 participants and is currently open at Cedars-Sinai Medical Center in Los Angeles, California; City of Hope in Duarte, California; and Huntsman Cancer Center in Salt Lake City, Utah. The study is evaluating the safety, tolerability and early signs of efficacy of ENV-105, a CD105-targeting therapy, in men whose prostate cancer has progressed after standard hormone treatments. Interim results are expected in September 2025, as per the news release.

Participants in the active comparator group receive standard-of-care Erleada at 240 milligrams (mg) taken orally once daily in 28-day cycles. If their disease progresses, they may cross over to the combination therapy group.

Participants in the experimental group receive the same dose of Erleada along with intravenous carotuximab. Carotuximab is administered at 3 mg per kilogram (mg/kg) on day one of cycle one, 7 mg/kg on day four, and 10 mg/kg on days eight, 15 and 22. In cycle two, participants receive 15 mg/kg on days one and 15. Beginning with cycle three, carotuximab is given at 15 mg/kg on day one of each 28-day cycle and continues on a once-every-four-weeks schedule.

To be eligible for this study, patients must have a history of castration-resistant prostate cancer with rising prostate-specific antigen (PSA) levels while receiving a contemporary androgen receptor signaling inhibitor (ARSI), such as Zytiga (abiraterone), Xtandi (enzalutamide), or Nubeqa (darolutamide). Treatments like bicalutamide, nilutamide, and flutamide are not considered contemporary ARSIs. Patients must have received one or two prior AR-targeted therapies, not including Erleada. Participants must also either decline or be considered ineligible for taxane-based chemotherapy, in the opinion of their treating physician. In addition, all participants must agree to use an adequate method of contraception during the study and for at least three months after their last dose of Erleada or carotuximab, as determined by the study doctor.

Patients cannot take part in the study if they have a form of prostate cancer that does not produce PSA, such as small cell prostate cancer or cancer that progresses on imaging without a PSA increase. Previous treatment with Erleada or any CD105-targeting antibody, including carotuximab, is also not allowed. Other exclusion criteria include having another active cancer that requires treatment, any condition that poses a high risk of bleeding, or a known diagnosis of Osler-Weber-Rendu syndrome.

With approximately one million men diagnosed with prostate cancer each year in the U.S., and millions more worldwide, resistance to hormone therapy represents a growing challenge for patients — particularly in an aging population, according to the news release. Castration-resistant prostate cancer refers to disease that progresses despite hormone-blocking treatment, and options remain limited once these therapies stop working.

Kairos Pharma is developing ENV-105 as a potential alternative and plans to meet with regulatory agencies to discuss a possible phase 3 trial based on emerging data.

Reference

“Kairos Pharma Announces Positive Safety Results from Phase 2 Trial of ENV-105 in Advanced Prostate Cancer,” July 15, 2025, Kairos Pharma.

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