Carotuximab plus apalutamide demonstrates promising PFS in mCRPC

The combination of carotuximab (ENV105) plus apalutamide (Erleada) demonstrated encouraging progression-free survival (PFS) in patients with metastatic castration-resistant prostate cancer (mCRPC) whose tumors had progressed following standard hormone-based therapies, according to an interim efficacy analysis of a phase 2 trial (NCT05534646) reported by Kairos Pharma.¹

Specifically, carotuximab, an investigational CD105 antagonist, in combination with apalutamide demonstrated a median PFS of more than 13 months. Notably, the combination exceeded the threshold required to demonstrate a 45% improvement in PFS, which the trial was powered to detect.

“Our therapeutics, targeting cancer resistance, continue to showcase the potential to revolutionize the way we treat cancer patients,” said John S. Yu, MD, CEO of Kairos Pharma, in a news release from the company.¹ “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.”

A total of 10 patients were enrolled in the study, of whom 2 withdrew from the trial for unrelated events. Among the 8 patients remaining, 5 continued treatment without experiencing progression, and 7 achieved a decrease in their prostate-specific antigen level from baseline.

These efficacy findings follow favorable results from an interim safety analysis of the trial shared in July 2025, which showed that the combination of carotuximab plus apalutamide was well-tolerated in patients with mCRPC.

The interim safety analysis of the regimen included the first 10 patients enrolled in the study. Overall, no dose-limiting toxicities, unexpected adverse events (AEs), nor grade 3 or 4 toxicities were reported. According to the company, observed treatment-related AEs were manageable with standard supportive care.

The investigators plan to enroll a total of 100 adult patients in the study through clinical trial sites in the US. To be eligible for enrollment, patients need to have tumors that failed at least 1 and up to 2 prior androgen receptor-targeted therapies, with the exception of apalutamide.² Patientsalso must decline or be ineligible for taxane therapy per the opinion of the treating physician.

Patients enrolled in the study will be randomly assigned to receive standard of care (SOC) 240 mg apalutamide administered orally and daily on days 1 through 28 of every 28-day cycle or to receive SOC apalutamide plus intravenous carotuximab. Patients in the comparator arm are eligible to crossover to the experimental arm after disease progression.

The primary end point for the study is radiographic PFS. Secondary end points include the incidence of adverse events, overall radiographic response rate, biochemical PFS, and the proportion of patients in the monotherapy arm who are resistant to treatment and crossover to the combination arm and benefit from the addition of carotuximab.

In a prior news release,³ Kairos Pharma reported that they planned to initiate discussions with regulatory authorities regarding the design of a pivotal phase 3 study of the regimen, pending positive results from the phase 2 trial.

Final completion of the phase 2 study is expected in January 2027.

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, Ltd. September 18, 2025. Accessed September 18, 2025. https://investors.kairospharma.com/news-and-events/news-releases/news-details/2025/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/default.aspx

2. Study of apalutamide with carotuximab in metastatic, castration-resistant prostate cancer. ClinicalTrials.gov. Last updated June 5, 2025. Accessed September 18, 2025. https://clinicaltrials.gov/study/NCT05534646

3. Kairos Pharma announces positive safety results from phase 2 trial of ENV-105 in advanced prostate cancer. News release. Kairos Pharma, LTD. Published online and accessed July 15, 2025. https://investors.kairospharma.com/news-and-events/news-releases/news-details/2025/Kairos-Pharma-Announces-Positive-Safety-Results-from-Phase-2-Trial-of-ENV-105-in-Advanced-Prostate-Cancer/default.aspx