Carotuximab/Apalutamide Further Extends PFS in Metastatic CRPC

Carotuximab (ENV-105) plus apalutamide (Erleada) produced a statistically significant improvement in progression-free survival (PFS) vs apalutamide alone in patients with metastatic castration-resistant prostate cancer (CRPC), according to interim efficacy data from a phase 2 trial (NCT05534646) reported in a news release from the developer, Kairos Pharma.¹

What did the interim efficacy analysis show?

The interim analysis compared all patients in the trial treated with carotuximab plus apalutamide with those treated with apalutamide alone. The median PFS was 17.7 months with the combination vs 2 months with apalutamide monotherapy (P = .0008). The release did not report the number of patients included in the analysis, a hazard ratio, or confidence intervals.

The findings build on an earlier interim efficacy analysis reported in September 2025.² At that time, 8 patients were evaluable for efficacy. At the time of the analysis, the median PFS was 13 months, 5 patients remained on treatment without progression, and 7 had a decrease in prostate-specific antigen (PSA) from baseline. All patients had experienced disease progression on at least 1 prior androgen receptor (AR) inhibitor.

An interim safety analysis of the first 10 patients enrolled, reported in July 2025, showed no dose-limiting toxicities, unexpected adverse effects (AEs), or grade 3/4 AEs.³ Treatment-related AEs were manageable with supportive care.

“These interim results provide an important clinical signal for ENV-105 and support our strategy of targeting the mechanisms underlying drug resistance,” John Yu, MD, chief executive officer of Kairos Pharma, said in the press release.¹

How is the phase 2 protocol changing?

Based on the interim efficacy signal, the developers have modified the phase 2 protocol to enroll patients earlier in the course of disease progression. Under the original protocol, patients enrolled after 1 or 2 prior antiandrogen agents. The trial will now enroll patients who experience a PSA increase following upfront treatment with an AR signaling inhibitor. These patients will be randomly assigned to enzalutamide (Xtandi) alone or enzalutamide plus carotuximab.

The modification is intended to expand the eligible patient population and facilitate enrollment. Kairos Pharma is targeting completion of the phase 2 trial in or before the fourth quarter of 2027.

What is the design of the phase 2 trial?

The trial was designed to enroll up to 100 patients at Cedars-Sinai Medical Center, City of Hope, and Huntsman Cancer Institute at the University of Utah.⁴ Under the original protocol, eligible patients:

• had a rising PSA level on a contemporary AR signaling inhibitor
• had received 1 or 2 prior AR-targeted therapies other than apalutamide
• had declined or were ineligible for taxane therapy

Key exclusion criteria were:

• non-PSA–producing prostate cancer
• prior apalutamide or CD105-targeting therapy
• active bleeding or high bleeding risk
• Osler-Weber-Rendu syndrome

Patients received oral apalutamide at 240 mg daily in 28-day cycles. Carotuximab was administered intravenously with step-up dosing during the first 2 cycles. Doses increased from 3 mg/kg on cycle 1 day 1 to 15 mg/kg on cycle 2 days 1 and 15, followed by 15 mg/kg every 4 weeks thereafter.

The primary end point is radiographic PFS. Secondary end points include the incidence of AEs and overall radiographic response rate. Patients who progressed on apalutamide monotherapy were permitted to cross over to the combination.

How does carotuximab work?

Carotuximab is a first-in-class antibody targeting CD105, a protein the developer has identified as a key driver of resistance and disease relapse following standard cancer therapy. By targeting CD105, the agent is intended to reverse drug resistance and restore the effectiveness of standard therapies. That mechanism provides the rationale for combining it with hormone therapy in prostate cancer.

In addition to the phase 2 prostate cancer trial, the developers are evaluating carotuximab in a phase 1 trial in lung cancer. The agent is not approved by the FDA for any indication.

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 8, 2026. https://tinyurl.com/3adtmfb7
2. 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 October 8, 2026. https://tinyurl.com/4x8tdmzx
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 8, 2026. https://tinyurl.com/survv5nv
4. Study of AR suppression with carotuximab in metastatic, castration-resistant prostate canc. ClinicalTrials.gov. Updated October 5, 2026. Accessed October 7, 2026. https://tinyurl.com/ejf7j3fh