Description:
The primary objectives of the Dose Escalation Phase are to assess the safety and
pharmacokinetics (PK) in order to determine a maximally tolerated dose (MTD) or recommended
phase 2 dose (RP2D) of REGN4018 as monotherapy and in combination with cemiplimab. In the
Dose Expansion Phase, the primary objectives are to assess the preliminary efficacy of
REGN4018 as monotherapy and in combination with cemiplimab, (separately by cohort) as
determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1.
The secondary objectives of the Dose Escalation Phase are to assess the preliminary efficacy
of REGN4018 as monotherapy and in combination with cemiplimab (separately by cohort) as
determined by ORR by RECIST 1.1. In the Dose Expansion Phase, the secondary objectives are to
characterize the safety profile in each expansion cohort and characterize the PK of REGN4018
as monotherapy and in combination with cemiplimab. In both the Dose Escalation and Dose
Expansion Phases, secondary objectives are to assess preliminary efficacy of REGN4018 as
monotherapy and in combination with cemiplimab (separately by cohort) as measured by ORR
based on immune based therapy RECIST (iRECIST), best overall response (BOR), duration of
response (DOR), disease control rate, complete response (CR) rate and progression-free
survival (PFS) based on RECIST 1.1 and iRECIST, to assess efficacy of REGN4018 as monotherapy
and in combination with cemiplimab as measured by CA-125 level and immunogenicity of REGN4018
and cemiplimab.
Title
- Brief Title: Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Patients With Recurrent Ovarian Cancer
- Official Title: A Phase 1/2 Study of REGN4018 (A MUC16xCD3 Bispecific Antibody) Administered Alone or in Combination With Cemiplimab in Patients With Recurrent Ovarian Cancer
Clinical Trial IDs
- ORG STUDY ID:
R4018-ONC-1721
- SECONDARY ID:
2019-003298-24
- NCT ID:
NCT03564340
Conditions
- Recurrent Ovarian Cancer
- Recurrent Fallopian Tube Cancer
- Recurrent Primary Peritoneal Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| REGN4018 | | Combination Therapy |
| cemiplimab | REGN2810, Libtayo | Combination Therapy |
Purpose
The primary objectives of the Dose Escalation Phase are to assess the safety and
pharmacokinetics (PK) in order to determine a maximally tolerated dose (MTD) or recommended
phase 2 dose (RP2D) of REGN4018 as monotherapy and in combination with cemiplimab. In the
Dose Expansion Phase, the primary objectives are to assess the preliminary efficacy of
REGN4018 as monotherapy and in combination with cemiplimab, (separately by cohort) as
determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid
Tumors (RECIST) 1.1.
The secondary objectives of the Dose Escalation Phase are to assess the preliminary efficacy
of REGN4018 as monotherapy and in combination with cemiplimab (separately by cohort) as
determined by ORR by RECIST 1.1. In the Dose Expansion Phase, the secondary objectives are to
characterize the safety profile in each expansion cohort and characterize the PK of REGN4018
as monotherapy and in combination with cemiplimab. In both the Dose Escalation and Dose
Expansion Phases, secondary objectives are to assess preliminary efficacy of REGN4018 as
monotherapy and in combination with cemiplimab (separately by cohort) as measured by ORR
based on immune based therapy RECIST (iRECIST), best overall response (BOR), duration of
response (DOR), disease control rate, complete response (CR) rate and progression-free
survival (PFS) based on RECIST 1.1 and iRECIST, to assess efficacy of REGN4018 as monotherapy
and in combination with cemiplimab as measured by CA-125 level and immunogenicity of REGN4018
and cemiplimab.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Monotherapy | Experimental | REGN4018 administration | |
| Combination Therapy | Experimental | REGN4018 and cemiplimab administration | |
Eligibility Criteria
Key Inclusion Criteria:
- Patients with histologically or cytologically confirmed diagnosis of advanced,
epithelial ovarian cancer (except carcinosarcoma), primary peritoneal, or fallopian
tube cancer who have all of the following:
- serum CA-125 level ≥2x upper limit of normal (ULN) (in screening)
- has received at least 1 line of platinum-containing therapy or must be
platinum-intolerant
- documented relapse or progression on or after the most recent line of therapy
- no standard therapy options likely to convey clinical benefit
- Adequate organ and bone marrow function as defined in the protocol
- Adequately controlled blood pressure
- Life expectancy of at least 3 months
Key Exclusion Criteria:
- Recent treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy
- Expansion cohort only: More than 3 prior lines of cytotoxic chemotherapy for
platinum-experienced and/or intolerant disease
- Expansion cohort only: prior treatment with a Mucin 16 (MUC16)-targeted therapy
- Untreated or active primary brain tumor, central nervous system (CNS) metastases, or
spinal cord compression
- History of clinically significant cardiac disease, myocarditis, presence of moderate
to large pericardial effusion and other measures of cardiac health as defined in the
protocol
- Moderate to large pleural effusion as defined in the protocol
Note: Other protocol Inclusion/Exclusion Criteria apply
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Number of participants with Dose-limiting toxicity (DLTs) for REGN4018 monotherapy |
| Time Frame: | Up to 28 days |
| Safety Issue: | |
| Description: | Dose Escalation Phase |
Secondary Outcome Measures
| Measure: | ORR based on RECIST 1.1 (Eisenhauer 2009) for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation Phase |
| Measure: | ORR based on RECIST 1.1 for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation Phase |
| Measure: | Number of participants with TEAEs (including irAEs) for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Expansion Phase |
| Measure: | Number of participants with TEAEs (including irAEs) for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Expansion Phase |
| Measure: | Number of participants with SAEs for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Expansion Phase |
| Measure: | Number of participants with SAEs for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Expansion Phase |
| Measure: | Number of deaths for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Expansion Phase |
| Measure: | Number of deaths for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Expansion Phase |
| Measure: | Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Expansion Phase |
| Measure: | Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Expansion Phase |
| Measure: | Concentration of REGN4018 in serum over time for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Expansion Phase |
| Measure: | Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Expansion Phase |
| Measure: | ORR based on iRECIST (Seymour 2017) for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | ORR based on iRECIST for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | Best overall response (BOR) based on RECIST 1.1 for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | BOR based on iRECIST for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | BOR based on RECIST 1.1 for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | BOR based on iRECIST for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | Duration of response (DOR) based on RECIST 1.1 for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | DOR based on iRECIST for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | DOR based on RECIST 1.1 for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | DOR based on iRECIST for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | Disease control rate based on RECIST 1.1 for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | Disease control rate based on iRECIST for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | Disease control rate based on RECIST 1.1 for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | Disease control rate based on iRECIST for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | Complete response (CR) rate based on RECIST 1.1 for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | CR rate based on iRECIST 1.1 for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | CR rate based on RECIST 1.1 for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | CR rate based on iRECIST 1.1 for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | Progression-free survival (PFS) based on RECIST 1.1 for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | PFS based on iRECIST for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | PFS based on RECIST 1.1 for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | PFS based on iRECIST for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | Cancer antigen-125 (CA-125) response for REGN4018 monotherapy |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | CA-125 response for REGN4018 with cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | Presence or absence of anti-drug antibodies against REGN4018 |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
| Measure: | Presence or absence of anti-drug antibodies against cemiplimab |
| Time Frame: | Up to 62 weeks |
| Safety Issue: | |
| Description: | Dose Escalation and Dose Expansion Phases |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Regeneron Pharmaceuticals |
Last Updated
January 29, 2021
