A Phase I/II Study of REGN4018 (Ubamatamab), a MUC16×CD3 Bispecific Antibody, Administered Alone or in Combination With Cemiplimab in Patients With Recurrent Ovarian Cancer or Other Recurrent MUC16+ Cancers

Study Identifier:
R4018-ONC-1721
CT.gov Identifier:
NCT03564340
EudraCT Identifier:
2019-003298-24
EU Trial (CTIS) Number:
2024-510783-23-00
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

To assess preliminary efficacy of REGN4018 as monotherapy and in combination with cemiplimab (separately by cohort) as measured by ORR, best overall response (BOR), duration of response (DOR), disease control rate, and progression-free survival (PFS) and to assess efficacy of REGN4018 as monotherapy and in combination with cemiplimab as measured by CA-125 level.

The impact of ubamatamab on quality of life and physical functioning will also be assessed.

To present safety, pharmacokinetics (PK) and efficacy from a first-in-human Phase 1 study of ubamatamab.

To support FIH regimen selection in dose escalation and expansion

clinical PK, cytokine, and efficacy data from dose escalation were integrated to determine regimens in dose expansion. Population PK modeling simulated regimens of interest.

To evaluate for recurrent advanced or metastatic EC that is MUC16+.

To evaluate in monotherapy and combination therapy expansion cohorts.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Ovarian
  • Fallopian Tube
  • Primary Peritoneal
  • Endometrial
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Monotherapy REGN4018 administration Drug: Ubamatamab Administered per the protocol Drug: Sarilumab Administered per the protocol Drug: Tocilizumab Administered per the protocol Experimental: Combination Therapy REGN4018 and cemiplimab administration Drug: Ubamatamab Administered per the protocol Drug: Cemiplimab Administered per the protocol EIOC 2022 Patients will be randomised to three IV arms (1:1:1) to receive ubamatamab 250 mg IV Q3W or 800 mg IV Q3W as monotherapy, or ubamatamab 250 mg IV Q3W in combination with cemiplimab 350 mg Q3W. All arms will include weekly step-up dosing of ubamatamab (1 mg week 1, 20 mg week 2, and full dose weeks 3 and 4) to limit risk of cytokine release syndrome prior to proceeding to Q3W dosing. Expansion cohorts will use a Simon 2-stage study design, with an interim analysis after the first 20 patients. Any arm with ≥3 objective responses will be expanded to 50 patients. ASCPT 2023: Ubamatamab was administered intravenously to pts with OC as monotherapy (78 pts) or in combination with anti-PD-1 cemiplimab (27 pts). ASCO 2023: Patients will be randomized to three arms (1:1:1) to receive ubamatamab 250 mg IV Q3W or 800 mg IV Q3W as monotherapy, or ubamatamab 250 mg IV Q3W in combination with cemiplimab 350 mg Q3W. All arms will include weekly step-up dosing of ubamatamab (1 mg week 1, 20 mg week 2, and full dose weeks 3 and 4) to limit risk of cytokine release syndrome prior to proceeding to Q3W dosing. Patients received weekly intravenous (IV) ubamatamab at a dose range of 1-450 mg after initial step-up dosing. Cemiplimab 350 mg IV every 3 weeks was added beginning Day 29-36. Patients will be randomized 1:1:1 to IV Q3W treatment: ubamatamab 250 mg; ubamatamab 800 mg; or ubamatamab 250 mg plus cemiplimab 350 mg. All treatment arms will include weekly step-up dosing of ubamatamab (1 mg week 1, 20 mg week 2, and full dose weeks 3 and 4) to limit risk of cytokine release syndrome before proceeding to Q3W dosing Patients with recurrent platinum-experienced OC received weekly intravenous ubamatamab 0.3-800mg after step-up dosing. Patients in combination cohorts received intravenous cemiplimab 350mg every 3 weeks beginning Day 29-36. Step-up doses of ubamatamab IV at 1 mg in W1 and 20 mg (split over 2 days) in W2 prior to full doses in ≥W3 (20-800 mg QW, N=95) were evaluated during dose escalation. A Phase 2 cohort will also be randomized 1:1:1 to receive ubamatamab 250 mg IV Q3W or 800 mg IV Q3W or ubamatamab 250 mg IV Q3W + cemiplimab 350 mg IV Q3W. The initial EC cohort will receive ubamatamab 250 mg IV Q3W. Based upon observed safety and activity, additional cohorts may be enrolled to receive ubamatamab 800 mg IV Q3W and/or ubamatamab 250 mg IV Q3W + cemiplimab 350 mg IV Q3W. To limit the risk of cytokine release syndrome, all pts will receive ubamatamab once-weekly step-up dosing prior to addition of cemiplimab and/or Q3W dosing.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • 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, not required for low-grade serous carcinoma)
    • 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 2 to 4 lines of platinum-based therapy as defined in the protocol.
    • 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), as defined in the protocol
    • 1-4 prior lines of systemic therapy, as described in the protocol
    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 (does not apply to low-grade serous ovarian cancer cohort)
    • 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 cardiovascular disease, 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-defined Inclusion/Exclusion Criteria apply

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Victor Moreno Garcia
    Status
    Recruiting
    Condition(s) Treated at Site
    Ovarian
    Fallopian Tube
    Primary Peritoneal
    Endometrial