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Study of REGN5668 Administered in Combination With Cemiplimab or REGN4018 in Adult Women With Recurrent Ovarian Cancer.

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: NCT04590326
Recruitment Status : Not yet recruiting
First Posted : October 19, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Brief Summary:

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

Condition or disease Intervention/treatment Phase
Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer Drug: REGN5668 Drug: Cemiplimab Drug: REGN4018 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 290 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 Study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific) Administered in Combination With Cemiplimab or REGN4018 (MUC16xCD3)
Estimated Study Start Date : November 20, 2020
Estimated Primary Completion Date : February 26, 2026
Estimated Study Completion Date : February 26, 2026


Arm Intervention/treatment
Experimental: Module 1
REGN5668 and cemiplimab
Drug: REGN5668
REGN5668 will be administered by once weekly intravenous (IV) infusion.

Drug: Cemiplimab
For Module 1, after a minimum of a 3-week monotherapy lead-in of REGN5668, cemiplimab will be administered concomitantly every 3 weeks (Q3W) by IV infusion.
Other Names:
  • REGN2810
  • Libtayo

Experimental: Module 2
REGN5668 and REGN4018
Drug: REGN5668
REGN5668 will be administered by once weekly intravenous (IV) infusion.

Drug: REGN4018
For Module 2, a 4-week monotherapy lead-in of REGN4018 will be administered by once weekly IV infusion. After lead-in, REGN5668 and REGN4018 will be administered concomitantly.




Primary Outcome Measures :
  1. Incidence of dose limiting toxicities (DLT) [ Time Frame: 42 days ]
    Dose escalation phase, Module 1

  2. Incidence of DLTs [ Time Frame: 21 days post combination administration ]
    Dose escalation phase, Module 2

  3. Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Through study completion, up to 5 years ]
    Primary: Dose escalation phase Secondary: Dose expansion phase

  4. Incidence of serious adverse events (SAEs) [ Time Frame: Through study completion, up to 5 years ]
    Primary: Dose escalation phase Secondary: Dose expansion phase

  5. Incidence of deaths [ Time Frame: Through study completion, up to 5 years ]
    Primary: Dose escalation phase Secondary: Dose expansion phase

  6. Incidence of laboratory abnormalities (Grade 3 or higher per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0 [v5.0]) [ Time Frame: Through study completion, up to 5 years ]
    Primary: Dose escalation phase Secondary: Dose expansion phase

  7. Concentrations of REGN5668 in serum when dosed alone and in combinations with cemiplimab or REGN4018 [ Time Frame: Up to 62 weeks ]
    Primary: Dose escalation phase Secondary: Dose expansion phase

  8. ORR defined by RECIST 1.1 (Eisenhauer, 2009) in combination with cemiplimab or REGN4018 (separately by cohort and combination) [ Time Frame: Up to 62 weeks ]
    Primary: Dose expansion phase Secondary: Dose escalation phase


Secondary Outcome Measures :
  1. Concentration of REGN4018 in serum over time [ Time Frame: Up to 62 weeks ]
    Dose expansion phase

  2. Concentration of cemiplimab in serum over time [ Time Frame: Up to 62 weeks ]
    Dose expansion phase

  3. ORR based on iRECIST [ Time Frame: Up to 62 weeks ]
    Dose escalation and expansion phases

  4. BOR based on RECIST 1.1 and iRECIST [ Time Frame: Up to 62 weeks ]
    Dose escalation and expansion phases

  5. DOR based on RECIST 1.1 and iRECIST [ Time Frame: Up to 62 weeks ]
    Dose escalation and expansion phases

  6. DCR based on RECIST 1.1 and iRECIST [ Time Frame: Up to 62 weeks ]
    Dose escalation and expansion phases

  7. PFS based on RECIST 1.1 and iRECIST [ Time Frame: Up to 62 weeks ]
    Dose escalation and expansion phases

  8. 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 ]
    Dose escalation and expansion phases

  9. Presence or absence of anti-drug antibodies against REGN5668 [ Time Frame: Up to 62 weeks ]
    Dose escalation and expansion phases

  10. Presence or absence of anti-drug antibodies against REGN4018 [ Time Frame: Up to 62 weeks ]
    Dose escalation and expansion phases

  11. Presence or absence of anti-drug antibodies against cemiplimab [ Time Frame: Up to 62 weeks ]
    Dose escalation and 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
Accepts Healthy Volunteers:   No
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) or archived tumor tissue. In 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. Expansion cohorts only: 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


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): NCT04590326


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

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: NCT04590326    
Other Study ID Numbers: R5668-ONC-1938
2020-000063-23 ( EudraCT Number )
First Posted: October 19, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regeneron Pharmaceuticals:
Progressive
Recurrent
Refractory
Serum CA-125 levels >2x ULN
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