Phase 2 Data Show PFS Benefit With Carotuximab Combo in mCRPC

The addition of carotuximab (ENV-105) to apalutamide (Erleada) significantly improved progression-free survival (PFS) compared with apalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC), as observed in interim data from an ongoing phase 2 trial (NCT05534646).¹

At the interim analysis, median PFS was 17.7 months with carotuximab plus apalutamide compared with 2.0 months with apalutamide alone, representing a statistically significant difference (P =.0008).

"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, CEO of Kairos Pharma, 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."

The rationale for carotuximab centers on CD105, a target associated with treatment resistance and disease relapse. Rather than replacing androgen receptor–directed therapy, carotuximab is being investigated as a combination strategy intended to target resistance mechanisms that may limit the durability of standard treatment. In the current phase 2 study, this approach is being evaluated alongside androgen receptor–directed therapy.

Phase 2 Study Design

The open-label, randomized phase 2 study is evaluating carotuximab in combination with androgen receptor–directed therapy in patients with mCRPC.² The trial was initially designed to compare apalutamide alone with apalutamide plus carotuximab.

The study enrolled patients with mCRPC whose disease had demonstrated resistance to standard hormone therapy. Patients were randomly assigned to receive either apalutamide monotherapy or apalutamide in combination with carotuximab.

The trial is being conducted at 3 US sites, including Cedars-Sinai Medical Center, City of Hope, and Huntsman Cancer Institute at the University of Utah.

Clinical Development: Prior Data and Next Steps

The current findings build on earlier data from the phase 2 study. In an initial cohort of 10 evaluable patients, carotuximab plus apalutamide produced a median PFS of 13 months, while 7 of 9 patients had a decrease in prostate-specific antigen levels from baseline. In a separate safety analysis of the initial cohort, the combination was not associated with dose-limiting toxicities or unexpected adverse events, and no grade 3 or 4 toxicities were reported.

Following the interim efficacy analysis, the study protocol was modified to evaluate carotuximab earlier in the course of disease progression and broaden eligibility. Under the amended protocol, patients will be eligible after experiencing a prostate-specific antigen increase following upfront treatment with an androgen signaling inhibitor.

The treatment regimen will also change under the amended study design. Patients will be randomly assigned to receive enzalutamide (Xtandi) alone or enzalutamide in combination with carotuximab. The sponsor expects to complete the phase 2 study in or before the fourth quarter of 2027.

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 7, 2026. https://tinyurl.com/3bnmu9ae

2. Study of AR Suppression With Carotuximab in Metastatic, Castration-Resistant Prostate Cancer. ClinicalTrials.gov. Updated October 5, 2026. Accessed October 7, 2026. https://clinicaltrials.gov/study/NCT05534646