Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Adult Patients With Recurrent Ovarian Cancer
Study Details
Study Description
Brief Summary
Primary Objectives
In the Dose Escalation Phase:
• 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:
• 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
Secondary Objectives
In the Dose Escalation Phase:
• 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:
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To characterize the safety profile in each expansion cohort
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To characterize the PK of REGN4018 as monotherapy and in combination with cemiplimab.
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To assess the effects of REGN4018 as monotherapy and in combination with cemiplimab on patient-reported outcomes (PROs), including health-related quality of life (HRQoL), functioning, and symptoms
In both the Dose Escalation and Dose Expansion Phases:
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To assess preliminary efficacy of REGN4018 as monotherapy and in combination with cemiplimab (separately by cohort) as measured by ORR based on 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
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To assess efficacy of REGN4018 as monotherapy and in combination with cemiplimab as measured by CA-125 level.
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Immunogenicity of REGN4018 and cemiplimab
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Monotherapy REGN4018 administration |
Drug: REGN4018
REGN4018 will be administered in a series of dose escalation and dose expansion cohorts by intravenous (IV) infusion and/or subcutaneous (SC) as described in the protocol during 6-week cycle (42 days).
|
| Experimental: Combination Therapy REGN4018 and cemiplimab administration |
Drug: REGN4018
REGN4018 will be administered in a series of dose escalation and dose expansion cohorts by intravenous (IV) infusion and/or subcutaneous (SC) as described in the protocol during 6-week cycle (42 days).
Drug: cemiplimab
Cemiplimab will be administered by IV infusion once a REGN4018 monotherapy dose has been selected.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of participants with Dose-limiting toxicity (DLTs) for REGN4018 monotherapy [From Cycle 1, Day 1 up to 35 days]
Dose Escalation Phase
- Number of participants with DLTs for REGN4018 with cemiplimab [From Cycle 2, Day 1 up to 21 days]
Dose Escalation Phase
- Number of participants with Treatment-emergent adverse event (TEAE)s (including immune-related adverse events (irAEs)) for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation Phase
- Number of participants with TEAEs (including irAEs) for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation Phase
- Number of participants with serious adverse events (SAEs) for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation Phase
- Number of participants with SAEs for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation Phase
- Number of deaths for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation Phase
- Number of deaths for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation Phase
- Number of participants with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation Phase
- Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation Phase
- Concentration of REGN4018 in serum over time for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation Phase
- Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation Phase
- Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (Eisenhauer 2009) for REGN4018 monotherapy [Up to 62 weeks]
Dose Expansion Phase
- ORR defined by RECIST 1.1 for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Expansion Phase
Secondary Outcome Measures
- ORR based on RECIST 1.1 (Eisenhauer 2009) for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation Phase
- ORR based on RECIST 1.1 for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation Phase
- Number of participants with TEAEs (including irAEs) for REGN4018 monotherapy [Up to 62 weeks]
Dose Expansion Phase
- Number of participants with TEAEs (including irAEs) for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Expansion Phase
- Number of participants with SAEs for REGN4018 monotherapy [Up to 62 weeks]
Dose Expansion Phase
- Number of participants with SAEs for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Expansion Phase
- Number of deaths for REGN4018 monotherapy [Up to 62 weeks]
Dose Expansion Phase
- Number of deaths for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Expansion Phase
- Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 monotherapy [Up to 62 weeks]
Dose Expansion Phase
- Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Expansion Phase
- Concentration of REGN4018 in serum over time for REGN4018 monotherapy [Up to 62 weeks]
Dose Expansion Phase
- Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Expansion Phase
- Change from baseline in quality of life (QoL) as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 GHS/QoL score for REGN4018 monotherapy [Baseline up to 62 weeks]
Dose Expansion Phase The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social) , symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."
- Change from baseline in quality of life (QoL) as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 GHS/QoL score for REGN4018 with cemiplimab [Baseline up to 62 weeks]
Dose Expansion Phase
- Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for REGN4018 monotherapy [Baseline up to 62 weeks]
Dose Expansion Phase
- Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for REGN4018 with cemiplimab [Baseline up to 62 weeks]
Dose Expansion Phase
- Change from baseline in abdominal symptoms as measured by the Measure of Ovarian Symptoms and Treatment (MOST)-Abdominal index score for REGN4018 monotherapy [Baseline up to 62 weeks]
Dose Expansion Phase MOST-T24 (MOST v2) (King et al. 2018) contains 24 of the original 35 items, focusing on symptoms (21 items) and well-being (3 items). The prevalence of each MOST item at assessment time points can be summarized by providing the mean, standard deviation and proportions based on the MOST response format, a numeric rating scale with integers from zero to 10, with five verbal anchors: 'No trouble at all' (0), 'Mild' (1-3), 'Moderate' (4-6), 'Severe' (7-10), and 'Worst I can imagine' (10). For all multi-item indexes, except the MOST-well-being index, compute the average of the component items (range 0-10) and then multiply this score by 10 (0-100 range). Thus, a higher score is equal to higher symptom burden. To calculate the MOST-Well-being index, repeat these same steps (i.e. take the average of the component items and multiply this score by 10) and then subtract this score from 100 so that a higher score is equal to greater well-being.
- Change from baseline in abdominal symptoms as measured by the Measure of Ovarian Symptoms and Treatment (MOST)-Abdominal index score for REGN4018 with cemiplimab [Baseline up to 62 weeks]
Dose Expansion Phase
- Time to deterioration in GHS/QoL for REGN4018 monotherapy [Up to 62 weeks]
Dose Expansion Phase
- Time to deterioration in GHS/QoL for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Expansion Phase
- Time to deterioration in physical functioning for REGN4018 monotherapy [Up to 62 weeks]
Dose Expansion Phase
- Time to deterioration in physical functioning for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Expansion Phase
- Time to deterioration in abdominal symptoms for REGN4018 monotherapy [Up to 62 weeks]
Dose Expansion Phase
- Time to deterioration in abdominal symptoms for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Expansion Phase
- Change from baseline in QoL as measured by EQ-5D for REGN4018 monotherapy [Baseline up to 62 weeks]
Dose Expansion Phase
- Change from baseline in QoL as measured by EQ-5D for REGN4018 with cemiplimab [Baseline up to 62 weeks]
Dose Expansion Phase
- ORR based on iRECIST (Seymour 2017) for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- ORR based on iRECIST for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- Best overall response (BOR) based on RECIST 1.1 for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- BOR based on iRECIST for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- BOR based on RECIST 1.1 for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- BOR based on iRECIST for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- Duration of response (DOR) based on RECIST 1.1 for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- DOR based on iRECIST for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- DOR based on RECIST 1.1 for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- DOR based on iRECIST for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- Disease control rate based on RECIST 1.1 for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- Disease control rate based on iRECIST for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- Disease control rate based on RECIST 1.1 for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- Disease control rate based on iRECIST for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- Complete response (CR) rate based on RECIST 1.1 for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- CR rate based on iRECIST 1.1 for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- CR rate based on RECIST 1.1 for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- CR rate based on iRECIST 1.1 for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- Progression-free survival (PFS) based on RECIST 1.1 for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- PFS based on iRECIST for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- PFS based on RECIST 1.1 for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- PFS based on iRECIST for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- Cancer antigen-125 (CA-125) response for REGN4018 monotherapy [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- CA-125 response for REGN4018 with cemiplimab [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- Presence or absence of anti-drug antibodies against REGN4018 [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
- Presence or absence of anti-drug antibodies against cemiplimab [Up to 62 weeks]
Dose Escalation and Dose Expansion Phases
Eligibility Criteria
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:
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serum CA-125 level ≥2x upper limit of normal (ULN) (in screening)
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has received at least 1 line of platinum-containing therapy or must be platinum-intolerant (applicable for dose escalation and non-randomized dose expansion cohorts)
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documented relapse or progression on or after the most recent line of therapy
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no standard therapy options
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Adequate organ and bone marrow function as defined in the protocol
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Life expectancy of at least 3 months
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Randomized phase 2 expansion cohorts only: Platinum resistant ovarian cancer patients who have only had 1 to 3 lines of platinum-based therapy prior treatment with poly ADP-ribose polymerase (PARP) inhibitor or bevacizumab as defined in the protocol.
Key Exclusion Criteria:
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Recent treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy
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Expansion cohort only: More than 4 prior lines of cytotoxic chemotherapy
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Prior treatment with a Mucin 16 (MUC16)-targeted therapy
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Untreated or active primary brain tumor, central nervous system (CNS) metastases, or spinal cord compression
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History and/or current cardiac findings as defined in the protocol
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Severe and/or uncontrolled hypertension at screening. Patients taking anti-hypertensive medication must be on a stable anti-hypertensive regimen
Note: Other protocol Inclusion/Exclusion Criteria apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The General Hospital Corporation d/b/a Massachusetts General Hospital | Boston | Massachusetts | United States | 02214 |
| 2 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 3 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 4 | Columbia University Irving Medical Center | New York | New York | United States | 10032 |
| 5 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 6 | James Care Gynecologic Oncology at Mill Run | Hilliard | Ohio | United States | 43026 |
| 7 | Stephenson Cancer Center | Oklahoma City | Oklahoma | United States | 73104 |
| 8 | Sarah Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
| 9 | Peter MacCallum Cancer Center | Melbourne | Victoria | Australia | 3000 |
| 10 | Universitair Ziekenhuis Antwerpen | Edegem | Antwerp | Belgium | 2650 |
| 11 | Grand Hôpital de Charleroi | Charleroi | Hainaut | Belgium | 6000 |
| 12 | UZLeuven | Leuven | Vlaams Brabant | Belgium | 3000 |
Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R4018-ONC-1721
- 2019-003298-24