Carotuximab/Radium-223 Will Be Evaluated in Bone-Involved Metastatic CRPC

Carotuximab (ENV-105), a first-in-class CD105/BMP signaling inhibitor, will be evaluated in combination with radium-223 dichloride (Xofigo) in patients with metastatic castration-resistant prostate cancer (CRPC) involving bone metastases, according to a news release from Kairos Pharma.¹

The combination will assess whether adding carotuximab to radium-223 dichloride can extend the duration and depth of response to radium-223 dichloride’s targeted alpha therapy in men with metastatic CRPC involving bone metastases. “Drug resistance remains one of the greatest challenges in advanced prostate cancer, and [radium-223 dichloride], like many standard-of-care therapies, can lose efficacy over time,” stated John Yu, MD, chief executive officer of Kairos Pharma, in the press release.¹ “[Carotuximab] has already demonstrated the ability to re-sensitize tumors to existing treatments with a strong safety profile, and this collaboration with Bayer represents a major milestone in our mission to deliver more durable and more effective treatment regimens for patients with metastatic prostate cancer.”

What data support combining carotuximab with radium-223 dichloride?

The planned evaluation follows positive interim phase 2 data (NCT05534646) showing a progression-free survival (PFS) advantage with carotuximab plus apalutamide (Erleada) vs standard hormone therapy in patients with treatment-resistant metastatic CRPC.² The trial evaluated apalutamide with or without carotuximab in men with metastatic CRPC whose disease had progressed on prior hormone-based therapy. Therein, patients received apalutamide orally at 240 mg daily for each 28-day cycle, and carotuximab was 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; and cycle 2 days 1 and 15 at 15 mg/kg. After cycle 2, patients received carotuximab every 4 weeks at 15 mg/kg.³

A previous interim efficacy analysis from this trial showed that the median PFS was 13 months among evaluable patients, compared with a historical 3.7-month median PFS reported for second- or third-line hormone therapy in the phase 4 CARD trial (NCT02485691).⁴ An earlier interim safety analysis of the same trial, which was reported in July 2025, demonstrated no dose-limiting toxicities, unexpected adverse effects, or grade 3/4 toxicities among the first 10 patients treated with carotuximab plus apalutamide.⁵

The trial's primary end point was radiographic PFS, with secondary end points including overall radiographic response rate and biochemical PFS.

How does carotuximab work to overcome treatment resistance?

CD105 is upregulated in response to standard androgen receptor inhibition and ionizing radiation, driving pro-survival BMP-SMAD signaling that underlies therapy resistance, according to the developers. By targeting CD105, carotuximab is designed to re-sensitize resistant tumors, potentially extending the duration and depth of response to therapies such as radium-223 dichloride’s targeted alpha radiation. “CD105's role as a central resistance mechanism validated now across multiple drug classes makes this collaboration scientifically compelling and clinically timely, given [radium-223 dichloride’s] recent phase 3 momentum,” stated Neil Bhowmick, PhD, chief scientific officer and principal investigator at Kairos Pharma, in the press release.¹

What is radium-223 dichloride's regulatory and clinical history in metastatic CRPC?

Radium-223 dichloride is the first and only FDA-approved alpha-emitting radiopharmaceutical for metastatic CRPC with symptomatic bone metastases, and is currently being evaluated in additional combination studies, including the phase 3 EORTC 1333/PEACE-3 trial (NCT02194842). Previous final overall survival results from PEACE-3 showed radium-223 dichloride combined with enzalutamide (Xtandi) reduced the risk of death by 24% compared with enzalutamide alone (HR, 0.76; 95% CI, 0.60-0.96; P = .0096) in patients with metastatic CRPC and bone metastases.⁶ Kairos's current carotuximab development program also includes a phase 1 trial in EGFR-driven non–small cell lung cancer, alongside the ongoing phase 2 prostate cancer trial with apalutamide.

References

1. Kairos Pharma announces strategic collaboration with Bayer to enhance XOFIGO activity in metastatic prostate cancer. News release. Kairos Pharma, Ltd. July 22, 2026. Accessed July 22, 2026. https://tinyurl.com/nzyajp24
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 July 22, 2026. https://tinyurl.com/y9tzcj2h
3. Study of apalutamide with carotuximab in metastatic, castration-resistant prostate cancer. ClinicalTrials.gov. Updated February 2, 2026. Accessed July 22, 2026. https://tinyurl.com/4mshstfc
4. de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. N Engl J Med. 2019;381(26):2506-2518. doi:10.1056/NEJMoa1911206
5. 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 22, 2026. https://tinyurl.com/mwyfrfu7
6. Bayer's XOFIGO® (radium-223 dichloride) plus enzalutamide demonstrates significant overall survival benefit in PEACE-3 trial in patients with metastatic castration-resistant prostate cancer with bone metastases. News release. Bayer AG. February 26, 2026. Accessed July 22, 2026. https://tinyurl.com/jn7ej5j6