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Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Patients With Recurrent Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT03564340
Recruitment Status : Recruiting
First Posted : June 20, 2018
Last Update Posted : January 29, 2021
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Recurrent Ovarian Cancer Recurrent Fallopian Tube Cancer Recurrent Primary Peritoneal Cancer Drug: REGN4018 Drug: cemiplimab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 392 participants
Allocation: Non-Randomized
Intervention Model: Parallel 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
Actual Study Start Date : May 21, 2018
Estimated Primary Completion Date : March 1, 2023
Estimated Study Completion Date : January 9, 2024


Arm Intervention/treatment
Experimental: Monotherapy
REGN4018 administration
Drug: REGN4018
REGN4018 will be administered in a series of dose escalation cohorts by a weekly intravenous (IV) infusion 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 cohorts by a weekly intravenous (IV) infusion during 6-week cycle (42 days).

Drug: cemiplimab
Cemiplimab will be administered in a series of dose escalation cohorts by IV infusion every 3 weeks over 6 week cycles.
Other Names:
  • REGN2810
  • Libtayo




Primary Outcome Measures :
  1. Number of participants with Dose-limiting toxicity (DLTs) for REGN4018 monotherapy [ Time Frame: Up to 28 days ]
    Dose Escalation Phase

  2. Number of participants with DLTs for REGN4018 with cemiplimab [ Time Frame: Up to 28 days ]
    Dose Escalation Phase

  3. Number of participants with Treatment-emergent adverse event (TEAE)s (including immune-related adverse events (irAEs)) for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase

  4. Number of participants with TEAEs (including irAEs) for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase

  5. Number of participants with serious adverse events (SAEs) for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase

  6. Number of participants with SAEs for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase

  7. Number of deaths for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase

  8. Number of deaths for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase

  9. 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

  10. 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

  11. Concentration of REGN4018 in serum over time for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase

  12. Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase

  13. Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (Eisenhauer 2009) for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase

  14. ORR defined by RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase


Secondary Outcome Measures :
  1. ORR based on RECIST 1.1 (Eisenhauer 2009) for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase

  2. ORR based on RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation Phase

  3. Number of participants with TEAEs (including irAEs) for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase

  4. Number of participants with TEAEs (including irAEs) for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase

  5. Number of participants with SAEs for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase

  6. Number of participants with SAEs for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase

  7. Number of deaths for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase

  8. Number of deaths for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase

  9. Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase

  10. 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

  11. Concentration of REGN4018 in serum over time for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase

  12. Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Expansion Phase

  13. ORR based on iRECIST (Seymour 2017) for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  14. ORR based on iRECIST for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  15. Best overall response (BOR) based on RECIST 1.1 for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  16. BOR based on iRECIST for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  17. BOR based on RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  18. BOR based on iRECIST for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  19. Duration of response (DOR) based on RECIST 1.1 for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  20. DOR based on iRECIST for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  21. DOR based on RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  22. DOR based on iRECIST for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  23. Disease control rate based on RECIST 1.1 for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  24. Disease control rate based on iRECIST for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  25. Disease control rate based on RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  26. Disease control rate based on iRECIST for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  27. Complete response (CR) rate based on RECIST 1.1 for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  28. CR rate based on iRECIST 1.1 for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  29. CR rate based on RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  30. CR rate based on iRECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  31. Progression-free survival (PFS) based on RECIST 1.1 for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  32. PFS based on iRECIST for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  33. PFS based on RECIST 1.1 for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  34. PFS based on iRECIST for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  35. Cancer antigen-125 (CA-125) response for REGN4018 monotherapy [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  36. CA-125 response for REGN4018 with cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  37. Presence or absence of anti-drug antibodies against REGN4018 [ Time Frame: Up to 62 weeks ]
    Dose Escalation and Dose Expansion Phases

  38. 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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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


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
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Contact: Clinical Trails Administrator 844-734-6643 clinicaltrials@regeneron.com

Locations
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United States, Massachusetts
Regeneron Study Site Recruiting
Boston, Massachusetts, United States, 02214
Regeneron Study Site Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Regeneron Study Site Recruiting
Buffalo, New York, United States, 14263
Regeneron Study Site Recruiting
New York, New York, United States, 10032
Regeneron Study Site Recruiting
New York, New York, United States, 10065
United States, Ohio
Regeneron Study Site Recruiting
Hilliard, Ohio, United States, 43026
United States, Oklahoma
Regeneron Study Site Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee
Regeneron Study Site Recruiting
Nashville, Tennessee, United States, 37203
Belgium
Regeneron Research Site Recruiting
Leuven, Belgium, 3000
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
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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: January 29, 2021
Last Verified: January 2021

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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
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases
Cemiplimab
Antineoplastic Agents, Immunological
Antineoplastic Agents