Carotuximab plus apalutamide shows interim PFS benefit in mCRPC

An interim analysis of an ongoing phase 2 trial found that the investigational CD105-targeting antibody carotuximab (ENV-105) combined with apalutamide (Erleada) was associated with significantly longer progression-free survival (PFS) than apalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC), according to Kairos Pharma.¹

At the time of the interim analysis, the median PFS was 17.7 months with the combination vs 2 months with apalutamide alone (P = .0008).

The findings provide an early clinical signal for targeting CD105 in the setting of androgen receptor signaling inhibitor (ARSI) resistance. Based on these results, the phase 2 study has subsequently undergone a protocol modification that changes the treatment strategy and moves enrollment earlier in the course of ARSI resistance.

Trial overview

The phase 2 study (NCT05534646) is an open-label, multicenter trial evaluating androgen receptor blockade with or without carotuximab in adult patients with mCRPC whose disease has progressed while receiving an ARSI.² Patients were enrolled in the study through Cedars-Sinai Medical Center, City of Hope, and Huntsman Cancer Institute at the University of Utah.

The trial initially included a safety lead-in, followed by randomized treatment. The original study compared PFS between patients receiving apalutamide alone and those receiving apalutamide plus carotuximab. The trial's primary PFS assessment incorporates RECIST 1.1 and Prostate Cancer Working Group 3 criteria, with overall response rate, biochemical PFS, radiographic PFS, and the incidence of adverse events included as secondary end points.

Based on interim results from the study, the protocol has since been amended. According to the company, the revised study will enroll patients who experience a prostate-specific antigen (PSA) increase after upfront treatment with an androgen signaling inhibitor, rather than after treatment with 1 or 2 anti-androgen agents. These patients will be randomly assigned to enzalutamide (Xtandi) alone or enzalutamide plus carotuximab.

"We believe the interim results provide an important clinical signal for ENV-105 and support our strategy of targeting the mechanisms underlying drug resistance," said John S. Yu, MD, CEO and chairman of Kairos Pharma, in the news release from the company.¹ "The protocol modification will allow more patients to be eligible for the potential benefits of ENV-105 treatment while evaluating the therapy earlier in disease progression."

Kairos Pharma previously reported data from the safety lead in portion of the trial in July 2025.³ At that interim assessment, the first 10 patients treated with carotuximab plus apalutamide had no dose-limiting toxicities, unexpected adverse events, or grade 3 or 4 toxicities reported.

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REFERENCES

1. Kairos Pharma reports positive, statistically significant interim efficacy data from phase 2 trial of ENV-105 in metastatic prostate cancer. News release. Kairos Pharma, Ltd. October 6, 2026. Accessed October 6, 2026. https://investors.kairospharma.com/news-and-events/news-releases/news-details/2026/Kairos-Pharma-Reports-Positive-Statistically-Significant-Interim-Efficacy-Data-from-Phase-2-Trial-of-ENV-105-in-Metastatic-Prostate-Cancer/default.aspx

2. Study of AR Suppression With Carotuximab in Metastatic, Castration-Resistant Prostate Canc. ClinicalTrials.gov. Last updated October 5, 2026. Accessed October 6, 2026. 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. July 15, 2025. Accessed October 6, 2026. 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