Carotuximab plus apalutamide demonstrates safety, tolerability in mCRPC

The combination of carotuximab (ENV-105) plus apalutamide (Erleada) was well-tolerated in patients with metastatic castration-resistant prostate cancer (mCRPC), according to data from the safety lead-in portion of an ongoing phase 2 trial (NCT05534646)of the regimen.¹

Carotuximab is an investigational, first-in-class CD105 antagonist.

Carotuximab is an investigational, first-in-class CD105 antagonist. According to Kairos Pharma, “Elevation of CD105 in response to standard therapy results in resistance and disease relapse. ENV-105 aims to reverse drug resistance by targeting CD105 and restore the effectiveness of standard therapies across multiple cancer types.”

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), or grade 3 or 4 toxicities have been reported. According to the company, observed treatment-related AEs were manageable with standard supportive care.

“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,” said John Yu, MD, CEO of Kairos Pharma, in a news release on the findings.¹

Based on these positive findings, the study will now proceed with the phase 2 portion of the trial.

In total, the open-label, phase 2 trial plans to enroll 100 adult patients through clinical trial sites across the US. The study is enrolling patients with mCRPC whose disease has progressed following 1 to 2 prior androgen receptor targeted therapies, with the exclusion of apalutamide. Patients must also decline or be ineligible for taxane therapy per the discretion of the treating physician.²

Patients are not eligible for the study if they have non–prostate-specific antigen producing prostate cancers, have received prior treatment with apalutamide, have had prior exposure to carotuximab or any CD105 targeted antibody, have active bleeding or a condition with a high bleeding risk, or have a known diagnosis of Osler-Weber-Rendu syndrome.

Participants in the study will be randomly assigned to receive 240 mg apalutamide daily with or without intravenous carotuximab. Patients in the apalutamide monotherapy arm are eligible to crossover to the experimental arm following disease progression.

The primary end point for the study is radiographic progression-free survival. Secondary end points include the incidence of AEs, overall radiographic response rate, and biochemical progression-free survival. According to a prior news release from Kairos, “The company is also validating biomarkers throughout the study to best identify those patients believed to have the most benefit for the combination therapy.”³

The company said it plans to report interim efficacy data from the trial in September 2025. Pending positive results, Kairos then plans to initiate discussions with regulatory authorities regarding the design of a pivotal phase 3 study of the regimen in mCRPC.

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

REFERENCES

1. 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

2. Study of apalutamide with carotuximab in metastatic, castration-resistant prostate cancer. ClinicalTrials.gov. Last updated June 5, 2025. Accessed July 15, 2025. https://clinicaltrials.gov/study/NCT05534646

3. Kairos Pharma Ltd. announces completed enrollment of the safety arm of its phase 2 clinical trial of ENV105 in metastatic, castration-resistant prostate cancer. News release. March 31, 2025. Accessed July 15, 2025. https://investors.kairospharma.com/news-and-events/news-releases/news-details/2025/Kairos-Pharma-Ltd--Announces-Completed-Enrollment-of-the-Safety-Arm-of-Its-Phase-2-Clinical-Trial-of-ENV105-in-Metastatic-Castration-Resistant-Prostate-Cancer/default.aspx