Regeneron’s REGM5678 Combination Shows Positive Results for Prostate Cancer


Preliminary data from the ongoing dose-escalation portion of the clinical trial, show dose-dependent anti-tumor activity when combined with standard-dose Libtayo.

Regeneron Pharmaceuticals Inc announced initial data from an ongoing phase 1/2 trial investigating REGN5678 in combination with cemiplimab (Libtayo) in advanced metastatic castration-resistant prostate cancer (mCRPC).

REGN5678, a novel PSMAxCD28 costimulatory bispecific antibody, is one of Regeneron’s 3 clinical-stage costimulatory bispecific. The clinical-stage costimulatory bispecific candidates are designed to bridge T cells to cancer cells and increase CD28 signaling more anti-tumor activity in combination with cemiplimab, a PD-1 inhibitor, 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, associate professor of Medical Oncology at Columbia University Vagelos College of Physicians and Surgeons, said in a statement. “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.”

The phase 1/2 open-label trial is enrolling individuals with advanced mCRPC whose tumors have previously progressed on multiple anti-androgen therapies, and a majority have also received prior chemotherapy.

In phase 1, individuals were initiated on a weekly dose of REGN5678 for 3 weeks, and investigators assessed the efficacy and safety of the drug alone and then in combination with the standard dose of cemiplimab.

The primary endpoints are pharmacokinetics, safety, and tolerability. The key secondary endpoint includes objective response rate, defined as a 50% or greater decline of prostate-specific antigens (PSA) from the baseline and/or tumor shrinkage.

Preliminary data from the ongoing dose-escalation portion of the trial, across 8 cohort levels, showed dose-dependent anti-tumor activity per centrally collected PSA values, as well as investigator reports.

Not all patients have completed tumor assessments, so the data are not final.

At the lowest dose levels, cohorts 1 through 5, there was almost no evidence of anti-tumor activity, with just 1 of 17 individuals showing a decrease in PSA. There were no grade 3 or greater immune-related adverse events (irAE) at these doses.

The lack of response was consistent with the rates reported in other trials with anti-PD1 monotherapy.

At the next 3 doses levels, cohorts 6 through 8, evidence of dose-dependent anti-tumor activity was generally seen within 6 weeks of starting the combined treatment.

In cohort 6, 1 of 4 individuals experienced a 100% decrease in PSA and a complete response (CR) in target lesions based on RECIST 1.1 criteria. The patient discontinued therapy because of a grade 3 irAE of the skin. The individual maintained the 100% decrease in PSA and CR in target lesions for approximately 10 months.

In cohort 7, 3 of 8 individuals had decreases in PSA of greater than 99%, 44%, and 22%. Additionally, 2 of these individuals had a grade 3 AE.

In cohort 8, 2 of 4 individuals experienced decreases in PSA greater than 99% and another of 82%. Of the 2 individuals with a greater than 99% reduction, 1 experienced a grade 3 case of mucositis, and the other experienced a grade 3 case of acute inflammatory demyelinating polyradiculopathy.

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). News release. Regeneron. August 3, 2022. Accessed August 5, 2022.

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