A Phase 1/2 Study of REGN5678 (Anti-PSMAxCD28) With or Without Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-Resistant Prostate Cancer and Other Tumors Associated With PSMA Expression

Condition: Metastatic Castration-resistant Prostate Cancer (mCRPC), Clear Cell Renal Cell Carcinoma (ccRCC)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03972657

Sponsor: Regeneron Pharmaceuticals

Phase: Phase 1/Phase 2


  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Key Inclusion Criteria:

  1. Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma (mCRPC cohorts).
  2. Metastatic, castration-resistant prostate cancer (mCRPC) with PSA value at screening ≥4 ng/mL that has progressed within 6 months prior to screening as defined in the protocol (mCRPC cohorts).
  3. (mCRPC cohorts) Has received ≥2 lines prior systemic therapy approved in the metastatic and/or castration-resistant setting (in addition to androgen deprivation therapy [ADT]) including at least:
  4. one second-generation anti-androgen therapy (eg, abiraterone, enzalutamide, apalutamide, or darolutamide)
  5. (post-177Lu-PSMA-617 radiotherapy expansion cohort only) Has received at least 2 doses of 177Lu-PSMA-6
  6. Prior therapy 177Lu-PSMA-617 is not permitted in other cohorts
  7. Histologically or cytologically confirmed RCC with a clear-cell component.
  8. Diagnosis of metastatic ccRCC with at least one measurable lesion via RECIST 1.1 criteria
  9. Tumor PSMA expression via PSMA-positron emission tomography (PET), as defined by at least one PSMA-PET positive lesion with signal above liver background via visual assessment per central review
  10. Has progressed on or after ≥1 line prior systemic therapy approved in the metastatic setting. Prior treatment must include an anti-programmed death-1 (receptor) [PD-1]/programmed death-ligand 1 (PD-L1) therapy and either ipilimumab and/or a tyrosine kinase inhibitor

Key Exclusion Criteria:

  1. Has received treatment with an approved systemic therapy within 3 weeks of dosing or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities
  2. Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy
  3. Has received prior PSMA-targeting therapy
  4. Dose Expansion (mCRPC only): Has had prior anti-cancer immunotherapy
  5. Any condition that requires ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study therapy
  6. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
  7. Encephalitis, meningitis, neurodegenerative disease (with the exception of mild dementia that does not interfere with activities of daily living [ADLs]) or uncontrolled seizures in the year prior to first dose of study therapy
  8. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency NOTE: Other protocol defined Inclusion/

Exclusion Criteria:

  • apply
  • At this time, we are only enrolling the REGN5678 monotherapy expansion cohort

View trial on ClinicalTrials.gov