Carotuximab/Apalutamide Improves PFS in Previously Treated Metastatic CRPC
In an interim safety analysis, no dose-limiting toxicities, unexpected AEs, or grade 3/4 AEs were reported in 10 patients treated for metastatic CRPC.
In an interim safety analysis, no dose-limiting toxicities, unexpected AEs, or grade 3/4 AEs were reported in 10 patients treated for metastatic CRPC.
Promising progression-free survival (PFS) was observed in a small cohort of patients with metastatic castration-resistant prostate cancer treated with carotuximab (ENV105) plus apalutamide (Erleda), according to results from a phase 2 trial (NCT05534646) published in a press release from Kairos Pharma.1
Of 8 patients evaluable for efficacy, the median PFS was 13 months, demonstrating a 45% improvement vs standard hormone therapy, and 5 patients continued treatment without progression. Additionally, 7 patients had a decrease in prostate-specific antigen (PSA) from baseline. At least 1 androgen receptor (AR) inhibitor hormone therapy had previously failed all patients enrolled in the trial.
“Our therapeutics, targeting cancer resistance, continue to showcase the potential to revolutionize the way we treat [patients with] cancer,” John Yu, MD, chief executive officer of Kairos Pharma, said in the press release. “While this is only interim data, we are excited to bring together the principal investigators and other industry experts for an important event this afternoon to lay out the primary benefits of our compound and demonstrate the clinical need filled by [carotuximab].”
The trial aimed to enroll 100 patients at Cedars-Sinai Medical Center, City of Hope, and the Huntsman Cancer Center, with 10 currently being assessed as part of the safety lead-in portion of the study.2 Of note, 2 patients withdrew from the trial due to unrelated events. Patients will receive apalutamide orally at 240 mg daily on for each 28-day cycle. Carotuximab will be given intravenously during cycle 1 day 1 at 3 mg/kg; cycle 1 day 4 at 7 mg/kg; cycle 1 days 8, 15, and 22 at 10 mg/kg; cycle 2 days 1 and 15 at 15 mg/kg. After cycle 2, patients will receive carotuximab every 4 weeks at the 15 mg/kg dose.
The primary end point was radiographic PFS, and secondary end points included the incidence of adverse effects (AEs) and the overall radiographic response rate. If patients progressed on apalutamide monotherapy, they were permitted to crossover to the combination therapy.
In July 2025, interim safety data were announced.3 This included the 10 patients enrolled, and there were no dose-limiting toxicities, unexpected AEs, or grade 3/4 AEs observed. Of note, treatment-related AEs were manageable with supportive care.
“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,” Yu said in a press release on the safety data.3
Patients were included in the trial if they had a history of prostate cancer with rising PSA on a contemporary AR signaling inhibitor; had between 1 and 2 prior AR-targeted therapies with the exception of apalutamide; had declined or were ineligible for taxane therapy; and used an adequate method of contraception.
Exclusion criteria included having non-PSA producing prostate cancer, prior use of apalutamide, a prior malignancy requiring active anti-cancer therapy, prior exposure to carotuximab or a CD105 targeting antibody, active bleeding or pathologic medical conditions of high bleeding risk, or a known diagnosis of Osler-Weber-Rendu syndrome.
The developers engineered carotuximab as an antibody targeting CD105, which was identified as a protein that is a driver of resistance to numerous cancer therapies. The investigational agent is being evaluated for its ability to reverse CD105-related drug resistance, as well as restore the efficacy of standard therapies across a variety of disease states.
References
- 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. September 18, 2025. Accessed September 23, 2025. https://tinyurl.com/4x8tdmzx
- Study of apalutamide with carotuximab in metastatic, castration-resistant prostate cancer. ClinicalTrials.gov. Updated June 5, 2025. Accessed September 23, 2025. https://tinyurl.com/ejf7j3fh
- Kairos Pharma announces positive safety results from phase 2 trial of ENV-105 in advanced prostate cancer. News release. July 15, 2025. Accessed September 23, 2025. https://tinyurl.com/survv5nv
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