Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Adult Patients With Recurrent Ovarian Cancer or Other Recurrent Mucin-16 Expressing (MUC16+) Cancers
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03564340 |
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Recruitment Status :
Recruiting
First Posted : June 20, 2018
Last Update Posted : April 15, 2024
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Sponsor:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Regeneron Pharmaceuticals
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Brief Summary:
The main purpose of this study is to:
- Learn about the safety of REGN4018 and to find out what dose of REGN4018 can be given alone or with cemiplimab to patients with ovarian cancer or cancer of the uterus
- The study will also look at the levels of REGN4018 and/or cemiplimab in your body and measure how well your body can remove the study drug(s). This is called pharmacokinetics
- The study will also look at any signs that REGN4018 alone or with cemiplimab can treat recurrent advanced ovarian cancer or cancer of the uterus
- To find out how safe and tolerable the sarilumab pretreatment is, in combination with REGN4018 and cemiplimab
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Recurrent Ovarian Cancer Recurrent Fallopian Tube Cancer Recurrent Primary Peritoneal Cancer Recurrent Endometrial Cancer | Drug: REGN4018 Drug: cemiplimab Drug: Sarilumab | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 690 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 or Other Recurrent MUC16+ Cancers |
| Actual Study Start Date : | May 21, 2018 |
| Estimated Primary Completion Date : | June 21, 2026 |
| Estimated Study Completion Date : | June 21, 2026 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Ovarian cancer
MedlinePlus related topics:
Ovarian Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Monotherapy
REGN4018 administration
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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.
Other Name: Ubamatamab® Drug: Sarilumab Sarilumab will be administered by IV, one-time-only, prior to IV/SC REGN4018. |
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Experimental: Combination Therapy
REGN4018 and cemiplimab administration
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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.
Other Name: Ubamatamab® Drug: cemiplimab Cemiplimab will be administered by IV infusion after REGN4018 monotherapy lead-in phase.
Other Name: REGN2810 |
Primary Outcome Measures :
- Number of participants with Dose-limiting toxicity (DLTs) for REGN4018 monotherapy [ Time Frame: From Cycle 1, Day 1 up to 35 days ]Dose Escalation Phase
- Number of participants with DLTs for REGN4018 with cemiplimab [ Time Frame: 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 (imAEs)) for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation Phase
- Number of participants with TEAEs (including imAEs) for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation Phase
- Number of participants with serious adverse events (SAEs) for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation Phase
- Number of participants with SAEs for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation Phase
- Number of deaths for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation Phase
- Number of deaths for REGN4018 with cemiplimab [ Time Frame: 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 [ Time Frame: Up to 62 weeks ]Dose Escalation Phase
- Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation Phase
- Concentration of REGN4018 in serum over time for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation Phase
- Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation Phase
- Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- ORR defined by RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
Secondary Outcome Measures :
- ORR based on RECIST 1.1 for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation Phase
- ORR based on RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation Phase
- Number of participants with TEAEs (including imAEs) for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Number of participants with TEAEs (including imAEs) for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Number of participants with SAEs for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Number of participants with SAEs for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Number of deaths for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Number of deaths for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Concentration of REGN4018 in serum over time for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline up to 62 weeks ]
Dose Expansion Phase excluding the Endometrial Cancer Cohort
The MOST-24 is a 24-item questionnaire used to measure the impact of chemotherapy on symptoms (21 items) and well-being (3 items). The expected questionnaire completion time is less than 5 minutes.
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).
- Change from baseline in abdominal symptoms as measured by the MOST-Abdominal index score for REGN4018 with cemiplimab [ Time Frame: Baseline up to 62 weeks ]Dose Expansion Phase Not applicable to Endometrial Cancer Cohort
- Time to deterioration in GHS/QoL for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Time to deterioration in GHS/QoL for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Time to deterioration in physical functioning for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Time to deterioration in physical functioning for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Time to deterioration in abdominal symptoms for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Time to deterioration in abdominal symptoms for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Expansion Phase
- Change from baseline in QoL as measured by EQ-5D for REGN4018 monotherapy [ Time Frame: Baseline up to 62 weeks ]Dose Expansion Phase
- Change from baseline in QoL as measured by EQ-5D for REGN4018 with cemiplimab [ Time Frame: Baseline up to 62 weeks ]Dose Expansion Phase
- ORR based on iRECIST for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- ORR based on iRECIST for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- Best overall response (BOR) based on RECIST 1.1 for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- BOR based on iRECIST for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- BOR based on RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- BOR based on iRECIST for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- Duration of response (DOR) based on RECIST 1.1 for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- DOR based on iRECIST for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- DOR based on RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- DOR based on iRECIST for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- Disease control rate based on RECIST 1.1 for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- Disease control rate based on iRECIST for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- Disease control rate based on RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- Disease control rate based on iRECIST for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- Complete response (CR) rate based on RECIST 1.1 for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- CR rate based on iRECIST 1.1 for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- CR rate based on RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- CR rate based on iRECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- Progression-free survival (PFS) based on RECIST 1.1 for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- PFS based on iRECIST for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- PFS based on RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- PFS based on iRECIST for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- Cancer antigen-125 (CA-125) response for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- CA-125 response for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- Presence or absence of anti-drug antibodies against REGN4018 [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
- Presence or absence of anti-drug antibodies against cemiplimab [ Time Frame: Up to 62 weeks ]Dose Escalation and Dose Expansion Phases
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
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Ovarian Cancer Cohorts Only: 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 ≥2 x upper limit of normal (ULN) (in screening)
- 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)
- 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
- Life expectancy of at least 3 months
- Randomized phase 2 expansion cohort (Ovarian Cancer only): Platinum-resistant ovarian cancer patients who have had 1 to 3 lines of platinum-based therapy as defined in the protocol.
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Endometrial Cancer Cohorts Only: histologically confirmed endometrial cancer that has progressed or recurrent after prior anti-Programmed Cell Death Ligand 1 (PD-1) therapy and platinum-based chemotherapy:
- MUC16 positivity of tumor cells ≥25% by immunohistochemistry (IHC)
- 1-2 prior lines of systemic therapy
Key Exclusion Criteria:
- Prior treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy, as described in the protocol
- Ovarian Cancer Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy
- Prior treatment with a MUC16 - targeted therapy
- Untreated or active primary brain tumor, central nervous system (CNS) metastases, or spinal cord compression, as described in the protocol
- History and/or current cardiac findings as defined in the protocol
- 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03564340
Contacts
| Contact: Clinical Trials Administrator | 844-734-6643 | clinicaltrials@regeneron.com |
Locations
Show 47 study locations
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
| Study Director: | Clinical Trial Management | Regeneron Pharmaceuticals |
| Responsible Party: | Regeneron Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT03564340 |
| Other Study ID Numbers: |
R4018-ONC-1721 2019-003298-24 ( EudraCT Number ) |
| First Posted: | June 20, 2018 Key Record Dates |
| Last Update Posted: | April 15, 2024 |
| Last Verified: | December 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Ovarian Neoplasms Carcinoma, Ovarian Epithelial Endometrial Neoplasms Fallopian Tube Neoplasms Recurrence Disease Attributes Pathologic Processes Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications |
Urogenital Diseases Genital Neoplasms, Female Urogenital Neoplasms Genital Diseases Endocrine System Diseases Gonadal Disorders Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Uterine Neoplasms Uterine Diseases Fallopian Tube Diseases Cemiplimab Antineoplastic Agents, Immunological Antineoplastic Agents |