Carotuximab/Apalutamide Shows Tolerability in Metastatic CRPC

In the first 10 patients enrolled in the phase 2 study, the combination elicited no dose-limiting toxicities or unexpected adverse effects.

Carotuximab (ENV-105) in combination with standard-of-care hormone therapy apalutamide (Erleada) exhibited tolerability as a treatment for a small cohort of patients with metastatic castration-resistant prostate cancer (CRPC) in a phase 2 trial (NCT05534646), according to a news release from the drug’s developer, Kairos Pharma.1

In the first 10 patients enrolled in the phase 2 study, the combination elicited no dose-limiting toxicities (DLTs) or unexpected adverse effects (AEs). Furthermore, all treatment-related AEs were managed with supportive care, and no grade 3 or 4 toxicities were observed in the study.

"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," John Yu, MD, chief executive officer of Kairos Pharma, said in the news release.1

The part 1 safety lead-in portion of the trial enrolled 10 patients, with a procession to the phase 2 stage if the combination is deemed safe. Patients in the trial will be randomly assigned 1:1 to receive either apalutamide monotherapy or with carotuximab.

Treatment in both arms of the study include 240 mg of oral apalutamide daily for 28-day cycles.2 Intravenous carotuximab will be given at 3 mg/kg on cycle 1, day 1; 7 mg/kg on cycle 1, day 4; and 10 mg/kg on cycle 1, days 8, 15, and 22. During cycle 2, carotuximab will be given at a dose of 15 mg/kg on days 1 and 15; on day 1 of subsequent cycles, 15 mg/kg of carotuximab will be given at the start of 28-day cycles.

The primary end point of the study is radiographic progression-free survival (PFS) per RECIST v1.1 criteria and Prostate Cancer Working Group 3. Overall radiographic response rate, biochemical PFS, and safety were among the secondary end points. The proportion of patients who are resistant to the benefit of apalutamide from the addition of carotuximab is an additional secondary end point. Grade 3 or higher treatment-related AEs will be assessed per NCI CTCAE v5.0 guidelines.

The multi-site, open-label phase 2 trial aims to enroll 100 patients, and investigators are accruing patients at Cedars-Sinai Medical Center, City of Hope, and Huntsman Cancer Center, according to the news release. Interim efficacy data are expected to be reported in September 2025, and developers plan to discuss the design of a potential pivotal phase 3 trial with regulatory authorities based on emergent data.

Citing an unmet need of resistance to current hormone therapies among patients with prostate cancer, developers designed the study to evaluate carotuximab, a CD105 antagonist, in male patients whose disease has progressed following standard hormone therapies.

Adult patients 18 years and older are eligible for enrollment on the phase 2 trial if they have a history of CRPC with rising prostate-specific antigen (PSA) on a contemporary androgen receptor signaling inhibitor, between 1 and 2 prior androgen receptor-targeted therapy except apalutamide, and had declined or were ineligible for taxane therapy.

Those ineligible for trial enrollment include patients with non-PSA producing prostate cancers, those who were previously treated with apalutamide, and those with other prior malignancies requiring active anticancer therapy. Furthermore, patients who are previously exposed to carotuximab or any CD105-targeted antibody, those with active bleeding or pathologic medical conditions that confer a high bleeding risk, and those with a known diagnosis of Osler-Weber-Rendu syndrome are ineligible for trial enrollment.

The study has an estimated completion date of 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. July 15, 2025. Accessed July 16, 2025. https://tinyurl.com/5e6dwb37
2. Study of apalutamide with carotuximab in metastatic, castration-resistant prostate cancer. ClinicalTrials.gov. Updated June 5, 2025. Accessed July 16, 2025. https://tinyurl.com/4t3b9t6n