The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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
Recruitment Status : Recruiting
First Posted : June 20, 2018
Last Update Posted : April 15, 2024
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE May 17, 2018
First Posted Date  ICMJE June 20, 2018
Last Update Posted Date April 15, 2024
Actual Study Start Date  ICMJE May 21, 2018
Estimated Primary Completion Date June 21, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 13, 2023)
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: June 8, 2018)
  • Number of participants with Dose-limiting toxicity (DLTs) [ Time Frame: Up to 28 days ]
    Dose Escalation Phase
  • Number of participants with Treatment-emergent adverse event (TEAE)s (including immune (iAEs)) [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase
  • Number of participants with serious adverse events (SAEs) [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase
  • Number of deaths [ 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]) [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase
  • Concentration in serum at end of infusion (Ceoi) of REGN4018 in monotherapy and in combination with cemiplimab during the dose escalation phase [ Time Frame: Up to 62 weeks ]
  • Concentration in serum at pre-infusion (Ctrough) of REGN4018 in monotherapy and in combination with cemiplimab during the dose escalation phase. [ Time Frame: Up to 62 weeks ]
  • Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (Eisenhauer 2009) for monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase
  • ORR defined by RECIST 1.1 (Eisenhauer 2009) in combination with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2023)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 8, 2018)
  • ORR based on RECIST 1.1 (Eisenhauer 2009) [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase
  • Number of participants with TEAEs (including immune-related) [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase
  • Number of participants with SAEs [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase
  • Number of deaths [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase
  • Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase
  • Concentration in serum at end of infusion (Ceoi) of REGN4018 in monotherapy and in combination with cemiplimab during the dose expansion phase [ Time Frame: Up to 62 weeks ]
  • Concentration in serum at pre-infusion (Ctrough) of REGN4018 in monotherapy and in combination with cemiplimab during the dose expansion phase. [ Time Frame: Up to 62 weeks ]
  • ORR based on Immune-based therapy Response Evaluation Criteria in Solid Tumors (iRECIST) (Seymour 2017) [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases
  • Best overall response (BOR) [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases
  • Duration of response (DOR) [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases
  • Disease control rate [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases
  • Progression-free survival (PFS) based on RECIST 1.1 [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases
  • PFS based on iRECIST [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases
  • Cancer antigen-125 (CA-125) response [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Ovarian Cancer
  • Recurrent Fallopian Tube Cancer
  • Recurrent Primary Peritoneal Cancer
  • Recurrent Endometrial Cancer
Intervention  ICMJE
  • 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
  • Drug: Sarilumab
    Sarilumab will be administered by IV, one-time-only, prior to IV/SC REGN4018.
Study Arms  ICMJE
  • Experimental: Monotherapy
    REGN4018 administration
    Interventions:
    • Drug: REGN4018
    • Drug: Sarilumab
  • Experimental: Combination Therapy
    REGN4018 and cemiplimab administration
    Interventions:
    • Drug: REGN4018
    • Drug: cemiplimab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 13, 2023)		 690
Original Estimated Enrollment  ICMJE
 (submitted: June 8, 2018)		 264
Estimated Study Completion Date  ICMJE June 21, 2026
Estimated Primary Completion Date June 21, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. 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:

    1. serum CA-125 level ≥2 x upper limit of normal (ULN) (in screening)
    2. 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)
    3. documented relapse or progression on or after the most recent line of therapy
    4. no standard therapy options likely to convey clinical benefit
  2. Adequate organ and bone marrow function as defined in the protocol
  3. Life expectancy of at least 3 months
  4. 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.

  5. 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:

    1. MUC16 positivity of tumor cells ≥25% by immunohistochemistry (IHC)
    2. 1-2 prior lines of systemic therapy

Key Exclusion Criteria:

  1. Prior treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy, as described in the protocol
  2. Ovarian Cancer Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy
  3. Prior treatment with a MUC16 - targeted therapy
  4. Untreated or active primary brain tumor, central nervous system (CNS) metastases, or spinal cord compression, as described in the protocol
  5. History and/or current cardiac findings as defined in the protocol
  6. 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com
Listed Location Countries  ICMJE Australia,   Belgium,   France,   Israel,   Italy,   Korea, Republic of,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03564340
Other Study ID Numbers  ICMJE R4018-ONC-1721
2019-003298-24 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Regeneron Pharmaceuticals
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Regeneron Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trial Management Regeneron Pharmaceuticals
PRS Account Regeneron Pharmaceuticals
Verification Date December 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP