Bispecific Antibody, PD-1 Combo Maintenance Had Activity in mCRPC

By Leah Lawrence - Last Updated: August 18, 2022

Newly released data shows that the combination of an investigational bispecific antibody with a PD-1 inhibitor had encouraging anti-tumor activity in advanced metastatic castration-resistant prostate cancer (mCRPC).

A phase 1/2 trial was testing REGN5678, a novel PSMAxCD28 costimulatory bispecific antibody, in combination with cemiplimab. The costimulatory bispecific antibody is designed to bridge T cells to cancer cells and augment CD28 signaling to increase anti-tumor activity in combination with cemiplimab or a CD3 bispecific.

“In past clinical trials, metastatic castration-resistant prostate cancer has been largely unresponsive to PD-1 inhibition and immunotherapy in general, leaving patients with inadequate treatment options, a poor prognosis and an expected survival of 1 to 2 years depending on the treatment history,” Mark Stein, MD, a trial investigator and associate professor of medical oncology at Columbia University Vagelos College of Physicians and Surgeons, said in a press release. “These initial data provide the first clinical evidence indicating that a costimulatory bispecific antibody may synergistically combine with an anti-PD-1 agent such as [cemiplimab] to enable activity against a tumor class previously resistant to anti-PD-1 immunotherapy. We look forward to further investigating the safety and efficacy of this combination.”

In the study’s phase 1 dose-escalation portion, patients were given weekly doses of REGN5678 for three weeks to assess safety and efficacy of monotherapy. After that the patients continued on REGN5678 plus cemiplimab.

Preliminary data showed that across 8 dose level cohorts and 33 patients there was dose-dependent anti-tumor activity per centrally collected prostate-specific antigen (PSA) values, as well as investigators reports. Data are not yet final.

At the lowest levels, there was almost no evidence of anti-tumor activity; only 1 patient showed a decrease in PSA. There were no grade 3 or worse immune-related adverse events at these low doses.

At the next 3 dose levels, anti-tumor activity was observed within 6 weeks of starting combination therapy. In cohort 6 of the study, 1 of 4 patients experienced a 100% decrease in PSA and a complete response in target lesions. The patient discontinued treatment due to a grade 3 immune-related adverse event of the skin, but has maintained the decreased PSA and complete response in target lesions for 10 months.

In cohort 7 of the study, 3 of 8 patients experienced decreases in PSA of >99%, 44%, and 22%. In cohort 8 of the study, 3 of 4 patients had decreases in PSA of >99%, >99%, and 82%.

Additional data are planned for presentation at an upcoming medical meeting.


Novel costimulatory bispecific antibody shows encouraging anti-tumor activity when combined with PD-1 inhibitor Libtayo® (cemiplimab) in advanced metastatic castration-resistant prostate cancer (mCRPC)

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