REGN4336 (a PSMAXCD3 Bispecific Antibody) Administered Alone or in Combination With Cemiplimab in Adult Male Patients With Metastatic Castration-Resistant Prostate Cancer
Study Details
Study Description
Brief Summary
The primary objective of the study is:
Dose Escalation:
• To assess the safety, tolerability, and pharmacokinetics (PK) and to determine recommended phase 2 dosing regimen (RP2DR) of REGN4336 separately as monotherapy or in combination with cemiplimab
Dose Expansion:
• To assess preliminary anti-tumor activity of REGN4336 as monotherapy or in combination with cemiplimab as measured by objective response rate (ORR) per modified Prostate Cancer Working Group (PCWG3) criteria
The secondary objectives of the study are:
Dose Escalation:
• To assess preliminary anti-tumor activity of REGN4336 as monotherapy or in combination with cemiplimab as measured by ORR per modified PCWG3 criteria
Dose Expansion:
-
To characterize the safety profile in each expansion cohort
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To characterize the PK of REGN4336 as monotherapy or in combination with cemiplimab
In both Dose Escalation and Dose Expansion:
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To assess preliminary anti-tumor activity of REGN4336 as monotherapy or in combination with cemiplimab as measured by prostate specific antigen (PSA) decline
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To evaluate immunogenicity of REGN4336 in Module 1 and immunogenicity of REGN4336 and cemiplimab in Module 2
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Module 1- Monotherapy REGN4336 |
Drug: REGN4336
Administered once weekly (QW) or every 3 weeks (Q3W) by subcutaneous (SC) injection.
Other: 18F-DCFPyL
Prostate-specific membrane antigen (PSMA) Positron emission tomography (PET)/Computer tomography (CT) imaging agent to be used at select sites
|
Experimental: Module 2-Combo Therapy REGN4336 + Cemiplimab |
Drug: REGN4336
Administered once weekly (QW) or every 3 weeks (Q3W) by subcutaneous (SC) injection.
Drug: Cemiplimab
Administered concomitantly every 3 weeks (Q3W) by IV infusion
Other Names:
Other: 18F-DCFPyL
Prostate-specific membrane antigen (PSMA) Positron emission tomography (PET)/Computer tomography (CT) imaging agent to be used at select sites
|
Outcome Measures
Primary Outcome Measures
- Incidence of dose-limiting toxicities (DLTs) [28 days, up to 42 days]
Dose escalation
- Incidence and severity of treatment-emergent adverse events (TEAEs) [Up to 5 years]
Dose escalation
- Incidence and severity of Immune-related Adverse Events (irAEs) [Up to 5 years]
Dose escalation
- Incidence and severity of SAEs [Up to 5 years]
Dose escalation
- Incidence and severity of adverse event of special interests (AESIs) [Up to 5 years]
Dose escalation
- Number of patients with grade ≥3 laboratory abnormalities [Up to 5 years]
Dose escalation
- REGN4336 concentrations in serum [Up to 5 years]
Dose escalation: As monotherapy or in combination with cemiplimab
- ORR per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria [Up to 5 years]
Dose expansion
Secondary Outcome Measures
- ORR per modified per modified PCWG3 criteria [Up to 5 years]
Dose Escalation:
- Incidence of dose-limiting toxicities (DLTs) [Up to 28 days]
Dose expansion
- Incidence and severity of TEAEs [Up to 5 years]
Dose expansion
- Incidence and severity of Immune-related Adverse Events [Up to 5 years]
Dose expansion
- Incidence and severity of SAEs [Up to 5 years]
Dose expansion
- Incidence and severity of adverse event of special interests (AESIs) [Up to 5 years]
Dose expansion
- Number of patients with grade ≥3 laboratory abnormalities [Up to 5 years]
Dose expansion
- REGN4336 concentrations in serum [Up to 5 years]
Dose expansion: As monotherapy or in combination with cemiplimab
- Percentage of patients with ≥50% reduction prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥4 weeks later [Up to 5 years]
Dose escalation and expansion
- Percentage of patients with ≥90% reduction prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥4 weeks later [UP to 5 years]
Dose escalation and expansion
- Anti-drug antibodies (ADA) to REGN4336 [Up to 5 years]
Module 1
- ADA to REGN4336 and cemiplimab [Up to 5 years]
Module 2
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma
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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
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Has progressed upon or intolerant to ≥2 lines prior systemic therapy approved in the metastatic and/or castration-resistant setting (in addition to androgen deprivation therapy [ADT]) including at least one second-generation anti-androgen therapy (e.g. abiraterone, enzalutamide, apalutamide, or darolutamide)
Key Exclusion Criteria:
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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
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Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy
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Has received prior PSMA-targeting therapy
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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
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Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
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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
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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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Stanford Cancer Center | Palo Alto | California | United States | 94304 |
2 | Norton Cancer Institute | Louisville | Kentucky | United States | 40207 |
3 | University of Maryland, Greenebaum Comprehensive Cancer Center | Baltimore | Maryland | United States | 21201 |
4 | Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | United States | 08901 |
5 | University of Pennsylvania Perelman Center for Advanced Medicine | Philadelphia | Pennsylvania | United States | 19104 |
6 | Thomas Jefferson University, Sidney Kimmel Center, Clinical Research Organization | Philadelphia | Pennsylvania | United States | 19107 |
7 | Froedtert and Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R4336-ONC-20104
- 2021-001104-15