Carotuximab Shows Promising Early Efficacy in Advanced Prostate Cancer

Carotuximab (ENV105) plus standard-of-care hormone therapy apalutamide (Erleada) demonstrated a progression-free survival (PFS) of 13 months in patients with advanced prostate cancer, according to an interim analysis from a phase 2 study (NCT05534646).¹

Additionally, the trial is powered to show a 45% improvement in PFS, translating to an increase from 3.7 to 6.7 months. Further, 7 of 9 evaluable patients had a decrease in their prostate-specific antigen (PSA) level from baseline.

“Our therapeutics, targeting cancer resistance, continue to showcase the potential to revolutionize the way we treat cancer patients,” said John Yu, MD, CEO of Kairos Pharma, in a press release. “While this is only interim data, we are excited to bring together the principal investigators and other industry experts for an important event this afternoon to lay out the primary benefits of our compound, and demonstrate the clinical need filled by ENV105.”

All patients in the study had previously failed at least 1 hormone therapy modality. This interim analysis featured data from 10 patients who were also assessed in the safety stage of the trial. Data from the safety analysis were announced in July 2025 and showed that carotuximab plus apalutamide was well tolerated with no dose-limiting toxicities or unexpected adverse events (AEs). Additionally, there were no grade 3 or 4 toxicities reported.²

The randomized phase 2 study plans to enroll 100 patients.¹ The study is accruing at City of Hope and Cedars-Sinai Medical Center in California and the Huntsman Cancer Institute and Hospital at the University of Utah in Salt Lake City. The study’s primary end point is radiographic PFS, and secondary end points include incidence of AEs, overall radiographic response rate, and biochemical PFS.³

Patients are randomized to receive apalutamide with or without carotuximab. Patients are required to have a history of castration-resistant prostate cancer with rising PSA levels on a contemporary androgen receptor (AR) signaling inhibitor, received up to 2 prior AR targeted therapies excepting apalutamide, and be ineligible for taxane therapy. Those with non-PSA–producing prostate cancers, who previously received apalutamide, who have another prior malignancy requiring active anticancer therapy, who have a pathologic medical condition that carries a high risk of bleeding events, or who have prior exposure to carotuximab or another CD105-targeted antibody are not eligible for enrollment in the study.

Carotuximab, by targeting CD105, aims to offer a new mechanism of action to address castration-resistant disease. CD105, also known as endoglin, is a cell surface glycoprotein that plays a crucial role in angiogenesis, the formation of new blood vessels that supply tumors. By antagonizing CD105, carotuximab is hypothesized to inhibit tumor angiogenesis and potentially enhance the efficacy of co-administered therapies.⁴

REFERENCES:

1. Kairos Pharma Announces Positive Interim Efficacy Analysis of Phase 2 Trial of ENV105 in Advanced Prostate Cancer with Median Progression Free Survival of Over One Year. News release. Kairos Pharma. September 18, 2025. Accessed September 18, 2025. https://tinyurl.com/5n7knfjx

2. Kairos Pharma Announces Positive Safety Results from Phase 2 Trial of ENV-105 in Advanced Prostate Cancer. News release. Kairos Pharma. July 15, 2025. Accessed September 18, 2025. https://tinyurl.com/bp6kd9m7

3. Study of Apalutamide With Carotuximab in Metastatic, Castration-Resistant Prostate Cancer. ClinicalTrials.gov. Updated June 5, 2025. Accessed September 18, 2025. https://clinicaltrials.gov/study/NCT05534646

4. Carotuximab. NCI Drug Dictionary. Accessed September 18, 2025. https://tinyurl.com/mr3b58ut