Carotuximab Plus Apalutamide Improves PFS in mCRPC

Carotuximab (ENV-105) plus apalutamide (Erleada) demonstrated a statistically significant progression-free survival (PFS) improvement vs apalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC), according to interim findings from an ongoing phase 2 trial (NCT05534646).¹

Findings announced by Kairos Pharma showed the median PFS was 17.7 months with the combination vs 2.0 months with apalutamide monotherapy (P = .0008). The analysis included all trial patients treated with these regimens.

Based on the interim efficacy signal, the trial protocol is being amended to enroll patients earlier after a prostate-specific antigen (PSA) increase on initial androgen receptor (AR) pathway inhibition, where patients will be randomly assigned to enzalutamide (Xtandi) with or without carotuximab. The company is targeting study completion by the fourth quarter of 2027.

"These interim results provide an important clinical signal for [carotuximab] and support our strategy of targeting the mechanisms underlying drug resistance," said John Yu, MD, chief executive officer of Kairos Pharma, stated in a news release. "The protocol modification will allow more patients to be eligible for the potential benefits of [carotuximab] treatment while evaluating the therapy earlier in disease progression."

How was the ENV-105 Trial Designed?

The open-label, multicenter study is evaluating AR blockade with or without carotuximab—a first-in-class anti-CD105 antibody—following progression on an AR pathway inhibitor. Its design includes an initial safety assessment in 10 patients, followed by the phase 2 portion if the combination is considered safe. Estimated enrollment is 116 patients.²

Eligible patients are men at least 18 years of age with a history of mCRPC and rising prostate-specific antigen (PSA) during treatment with a contemporary AR signaling inhibitor. The protocol defines a qualifying PSA rise as an increase of at least 0.2 ng/mL on 2 separate occasions more than 1 week apart. Patients must have an ECOG performance status of 0 or 1 and adequate organ function, and they must decline docetaxel or be ineligible in the opinion of the treating physician. Prior chemotherapy is excluded except for docetaxel administered for castration-sensitive disease.

The protocol required 1 to 2 prior AR-targeted agents, with prior enzalutamide exposure restricting enrollment to the exposed combination group. Exclusion criteria include non–PSA-producing tumors, prior carotuximab or another CD105-targeted antibody, uncontrolled hypertension, and active bleeding or a medical condition associated with a high bleeding risk.

The updated protocol lists 3 treatment groups: the control arm of enzalutamide or apalutamide monotherapy for enzalutamide-naive patients; enzalutamide or apalutamide plus carotuximab for enzalutamide-naive patients; and apalutamide plus carotuximab for patients previously exposed to enzalutamide. Patients assigned to monotherapy can cross over to the combination after progression.

AR blockade is administered each day orally in 28-day cycles, using apalutamide at 240 mg or enzalutamide at 160 mg. Intravenous carotuximab dosing is escalated during the first cycle, followed by 15 mg/kg on days 1 and 15 of cycle 2 and every 4 weeks thereafter.

The primary end point is radiographic PFS, assessed using RECIST 1.1 and Prostate Cancer Working Group 3 criteria. Secondary end points include the incidence of grade 3 or higher treatment-related adverse effects, radiographic response, activity after crossover, and radiographic and biochemical PFS in the overall population.

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. 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 cancer. ClinicalTrials.gov. Updated October 5, 2026. Accessed October 6, 2026. https://clinicaltrials.gov/study/NCT05534646