Description:
The primary objectives of the study are:
In the Dose Escalation Phase:
- To assess the safety, tolerability, and pharmacokinetics (PK) of REGN5668 alone and in
separate combinations with cemiplimab or REGN4018, in order to determine a maximally
tolerated dose(s) (MTD) or recommended phase 2 dose(s) (RP2D) of these combinations
In the Dose Expansion Phase:
- To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or
REGN4018, (separately by cohort and combination) as determined by the objective response
rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
The secondary objectives of the study are:
In the Dose Escalation Phase:
- To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or
REGN4018 (separately by cohort and combination) as determined by ORR by RECIST 1.1
In the Dose Expansion Phase:
- To characterize the safety profile in each expansion cohort
- To characterize the PK of REGN5668 in combination with cemiplimab or REGN4018
(separately by cohort and combination)
In both the Dose Escalation and Dose Expansion Phases:
- To assess preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018
(separately by cohort and combination) as measured by ORR based on immune based therapy
RECIST (iRECIST), best overall response (BOR), duration of response (DOR), disease
control rate (DCR), and progression-free survival (PFS) based on RECIST 1.1 and iRECIST
- To assess changes in CA-125 levels from baseline after treatment with REGN5668 in
combinations with cemiplimab or REGN4018 (separately by cohort and combination)
- Immunogenicity of REGN5668, alone and in combinations with cemiplimab or REGN4018
Title
- Brief Title: Study of REGN5668 Administered in Combination With Cemiplimab or REGN4018 in Adult Women With Recurrent Ovarian Cancer.
- Official Title: Phase 1/2 Study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific) Administered in Combination With Cemiplimab or REGN4018 (MUC16xCD3)
Clinical Trial IDs
- ORG STUDY ID:
R5668-ONC-1938
- SECONDARY ID:
2020-000063-23
- NCT ID:
NCT04590326
Conditions
- Ovarian Cancer
- Fallopian Tube Cancer
- Primary Peritoneal Cancer
Interventions
Drug | Synonyms | Arms |
---|
REGN5668 | | Module 1 |
Cemiplimab | REGN2810, Libtayo | Module 1 |
REGN4018 | | Module 2 |
Purpose
The primary objectives of the study are:
In the Dose Escalation Phase:
- To assess the safety, tolerability, and pharmacokinetics (PK) of REGN5668 alone and in
separate combinations with cemiplimab or REGN4018, in order to determine a maximally
tolerated dose(s) (MTD) or recommended phase 2 dose(s) (RP2D) of these combinations
In the Dose Expansion Phase:
- To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or
REGN4018, (separately by cohort and combination) as determined by the objective response
rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
The secondary objectives of the study are:
In the Dose Escalation Phase:
- To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or
REGN4018 (separately by cohort and combination) as determined by ORR by RECIST 1.1
In the Dose Expansion Phase:
- To characterize the safety profile in each expansion cohort
- To characterize the PK of REGN5668 in combination with cemiplimab or REGN4018
(separately by cohort and combination)
In both the Dose Escalation and Dose Expansion Phases:
- To assess preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018
(separately by cohort and combination) as measured by ORR based on immune based therapy
RECIST (iRECIST), best overall response (BOR), duration of response (DOR), disease
control rate (DCR), and progression-free survival (PFS) based on RECIST 1.1 and iRECIST
- To assess changes in CA-125 levels from baseline after treatment with REGN5668 in
combinations with cemiplimab or REGN4018 (separately by cohort and combination)
- Immunogenicity of REGN5668, alone and in combinations with cemiplimab or REGN4018
Trial Arms
Name | Type | Description | Interventions |
---|
Module 1 | Experimental | REGN5668 and cemiplimab | |
Module 2 | Experimental | REGN5668 and REGN4018 | |
Eligibility Criteria
Key Inclusion Criteria:
1. Has histologically or cytologically confirmed diagnosis of advanced epithelial ovarian
cancer (except carcinosarcoma), primary peritoneal, or fallopian tube cancer that has
received at least 1 line of platinum-based systemic therapy as defined in the protocol
2. In dose escalation, patients will provide either newly obtained biopsy (newly obtained
biopsies at screening are required unless medically inappropriate and discussed with
medical monitor. If fresh biopsies are not appropriate, and after sponsor approval,
archived tumor tissue in dose escalation is acceptable. In dose expansion, patients
will provide a fresh tumor biopsy in screening and on treatment. Hence, in expansion
cohorts, only patients who (in the opinion of the investigator) have accessible
lesions that can be biopsied without significant risk to the patient are eligible.
3. Expansion cohorts only: Has at least 1 lesion that is measurable by RECIST 1.1. Tumor
lesions in a previously irradiated area are considered measurable if progression has
been demonstrated in such lesions after radiation.
4. Has a serum CA-125 level ≥2x ULN (in screening)
5. Has adequate organ and bone marrow function as defined in the protocol
6. Has a life expectancy of at least 3 months
Key Exclusion Criteria:
1. Has participated in a study of an investigational agent (except biologics and/or
immunotherapy) or an investigational device within 4 weeks of first dose of study drug
2. Has received treatment with an approved systemic therapy (except biologics and/or
immunotherapy) within 3 weeks or has not yet recovered as defined in the protocol
3. Prior anti-cancer immunotherapy as defined in the protocol
4. Has received radiation therapy or major surgery within 14 days of first administration
of study drug as defined in the protocol
5. Has had another malignancy within the last 5 years that is progressing, requires
active treatment, or has a high likelihood of recurrence as defined in the protocol
6. Prior treatment with a MUC16-targeted therapy
7. Expansion cohorts only: More than 3 prior lines of cytotoxic chemotherapy for
platinum-experienced and/or intolerant disease
8. Has any condition that requires ongoing/continuous corticosteroid therapy as defined
in the protocol within 1 week prior to the first dose of study drug
9. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that
required treatment with systemic immunosuppressive treatments as defined in the
protocol
10. Has untreated or active primary brain tumor, CNS metastases, leptomeningeal disease,
or spinal cord compression as defined in the protocol
11. Has encephalitis, meningitis, organic brain disease (eg, Parkinson's disease) or
uncontrolled seizures in the year prior to first dose of study drug
12. Has history of clinically significant cardiovascular disease as defined in the
protocol
Note: Other protocol-defined Inclusion/Exclusion criteria apply
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of dose limiting toxicities (DLT) |
Time Frame: | 42 days |
Safety Issue: | |
Description: | Dose escalation phase, Module 1 |
Secondary Outcome Measures
Measure: | Concentration of REGN4018 in serum over time |
Time Frame: | Up to 62 weeks |
Safety Issue: | |
Description: | Dose expansion phase |
Measure: | Concentration of cemiplimab in serum over time |
Time Frame: | Up to 62 weeks |
Safety Issue: | |
Description: | Dose expansion phase |
Measure: | ORR based on iRECIST |
Time Frame: | Up to 62 weeks |
Safety Issue: | |
Description: | Dose escalation and expansion phases |
Measure: | BOR based on RECIST 1.1 and iRECIST |
Time Frame: | Up to 62 weeks |
Safety Issue: | |
Description: | Dose escalation and expansion phases |
Measure: | DOR based on RECIST 1.1 and iRECIST |
Time Frame: | Up to 62 weeks |
Safety Issue: | |
Description: | Dose escalation and expansion phases |
Measure: | DCR based on RECIST 1.1 and iRECIST |
Time Frame: | Up to 62 weeks |
Safety Issue: | |
Description: | Dose escalation and expansion phases |
Measure: | PFS based on RECIST 1.1 and iRECIST |
Time Frame: | Up to 62 weeks |
Safety Issue: | |
Description: | Dose escalation and expansion phases |
Measure: | CA-125 change from baseline after treatment with REGN5668 in combinations with cemiplimab or REGN4018 (separately by cohort and combination) |
Time Frame: | Up to 62 weeks |
Safety Issue: | |
Description: | Dose escalation and expansion phases |
Measure: | Presence or absence of anti-drug antibodies against REGN5668 |
Time Frame: | Up to 62 weeks |
Safety Issue: | |
Description: | Dose escalation and expansion phases |
Measure: | Presence or absence of anti-drug antibodies against REGN4018 |
Time Frame: | Up to 62 weeks |
Safety Issue: | |
Description: | Dose escalation and expansion phases |
Measure: | Presence or absence of anti-drug antibodies against cemiplimab |
Time Frame: | Up to 62 weeks |
Safety Issue: | |
Description: | Dose escalation and expansion phases |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Regeneron Pharmaceuticals |
Trial Keywords
- Progressive
- Recurrent
- Refractory
- Serum CA-125 levels >2x ULN
Last Updated
July 29, 2021