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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03564340




Registration number
NCT03564340
Ethics application status
Date submitted
17/05/2018
Date registered
20/06/2018
Date last updated
3/06/2024

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2019-003298-24
Secondary ID [2] 0 0
R4018-ONC-1721
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent Ovarian Cancer 0 0
Recurrent Fallopian Tube Cancer 0 0
Recurrent Primary Peritoneal Cancer 0 0
Recurrent Endometrial Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - REGN4018
Treatment: Drugs - cemiplimab
Treatment: Drugs - Sarilumab

Experimental: Monotherapy - REGN4018 administration

Experimental: Combination Therapy - REGN4018 and cemiplimab administration


Treatment: Drugs: 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.

Treatment: Drugs: cemiplimab
Cemiplimab will be administered by IV infusion after REGN4018 monotherapy lead-in phase.

Treatment: Drugs: Sarilumab
Sarilumab will be administered by IV, one-time-only, prior to IV/SC REGN4018.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with Dose-limiting toxicity (DLTs) for REGN4018 monotherapy
Timepoint [1] 0 0
From Cycle 1, Day 1 up to 35 days
Primary outcome [2] 0 0
Number of participants with DLTs for REGN4018 with cemiplimab
Timepoint [2] 0 0
From Cycle 2, Day 1 up to 21 days
Primary outcome [3] 0 0
Number of participants with Treatment-emergent adverse event (TEAE)s (including immune-related adverse events (imAEs)) for REGN4018 monotherapy
Timepoint [3] 0 0
Up to 62 weeks
Primary outcome [4] 0 0
Number of participants with TEAEs (including imAEs) for REGN4018 with cemiplimab
Timepoint [4] 0 0
Up to 62 weeks
Primary outcome [5] 0 0
Number of participants with serious adverse events (SAEs) for REGN4018 monotherapy
Timepoint [5] 0 0
Up to 62 weeks
Primary outcome [6] 0 0
Number of participants with SAEs for REGN4018 with cemiplimab
Timepoint [6] 0 0
Up to 62 weeks
Primary outcome [7] 0 0
Number of deaths for REGN4018 monotherapy
Timepoint [7] 0 0
Up to 62 weeks
Primary outcome [8] 0 0
Number of deaths for REGN4018 with cemiplimab
Timepoint [8] 0 0
Up to 62 weeks
Primary outcome [9] 0 0
Number of participants with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) for REGN4018 monotherapy
Timepoint [9] 0 0
Up to 62 weeks
Primary outcome [10] 0 0
Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab
Timepoint [10] 0 0
Up to 62 weeks
Primary outcome [11] 0 0
Concentration of REGN4018 in serum over time for REGN4018 monotherapy
Timepoint [11] 0 0
Up to 62 weeks
Primary outcome [12] 0 0
Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab
Timepoint [12] 0 0
Up to 62 weeks
Primary outcome [13] 0 0
Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for REGN4018 monotherapy
Timepoint [13] 0 0
Up to 62 weeks
Primary outcome [14] 0 0
ORR defined by RECIST 1.1 for REGN4018 with cemiplimab
Timepoint [14] 0 0
Up to 62 weeks
Secondary outcome [1] 0 0
ORR based on RECIST 1.1 for REGN4018 monotherapy
Timepoint [1] 0 0
Up to 62 weeks
Secondary outcome [2] 0 0
ORR based on RECIST 1.1 for REGN4018 with cemiplimab
Timepoint [2] 0 0
Up to 62 weeks
Secondary outcome [3] 0 0
Number of participants with TEAEs (including imAEs) for REGN4018 monotherapy
Timepoint [3] 0 0
Up to 62 weeks
Secondary outcome [4] 0 0
Number of participants with TEAEs (including imAEs) for REGN4018 with cemiplimab
Timepoint [4] 0 0
Up to 62 weeks
Secondary outcome [5] 0 0
Number of participants with SAEs for REGN4018 monotherapy
Timepoint [5] 0 0
Up to 62 weeks
Secondary outcome [6] 0 0
Number of participants with SAEs for REGN4018 with cemiplimab
Timepoint [6] 0 0
Up to 62 weeks
Secondary outcome [7] 0 0
Number of deaths for REGN4018 monotherapy
Timepoint [7] 0 0
Up to 62 weeks
Secondary outcome [8] 0 0
Number of deaths for REGN4018 with cemiplimab
Timepoint [8] 0 0
Up to 62 weeks
Secondary outcome [9] 0 0
Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 monotherapy
Timepoint [9] 0 0
Up to 62 weeks
Secondary outcome [10] 0 0
Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab
Timepoint [10] 0 0
Up to 62 weeks
Secondary outcome [11] 0 0
Concentration of REGN4018 in serum over time for REGN4018 monotherapy
Timepoint [11] 0 0
Up to 62 weeks
Secondary outcome [12] 0 0
Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab
Timepoint [12] 0 0
Up to 62 weeks
Secondary outcome [13] 0 0
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
Timepoint [13] 0 0
Baseline up to 62 weeks
Secondary outcome [14] 0 0
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
Timepoint [14] 0 0
Baseline up to 62 weeks
Secondary outcome [15] 0 0
Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for REGN4018 monotherapy
Timepoint [15] 0 0
Baseline up to 62 weeks
Secondary outcome [16] 0 0
Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for REGN4018 with cemiplimab
Timepoint [16] 0 0
Baseline up to 62 weeks
Secondary outcome [17] 0 0
Change from baseline in abdominal symptoms as measured by the Measure of Ovarian Symptoms and Treatment (MOST)-Abdominal index score for REGN4018 monotherapy
Timepoint [17] 0 0
Baseline up to 62 weeks
Secondary outcome [18] 0 0
Change from baseline in abdominal symptoms as measured by the MOST-Abdominal index score for REGN4018 with cemiplimab
Timepoint [18] 0 0
Baseline up to 62 weeks
Secondary outcome [19] 0 0
Time to deterioration in GHS/QoL for REGN4018 monotherapy
Timepoint [19] 0 0
Up to 62 weeks
Secondary outcome [20] 0 0
Time to deterioration in GHS/QoL for REGN4018 with cemiplimab
Timepoint [20] 0 0
Up to 62 weeks
Secondary outcome [21] 0 0
Time to deterioration in physical functioning for REGN4018 monotherapy
Timepoint [21] 0 0
Up to 62 weeks
Secondary outcome [22] 0 0
Time to deterioration in physical functioning for REGN4018 with cemiplimab
Timepoint [22] 0 0
Up to 62 weeks
Secondary outcome [23] 0 0
Time to deterioration in abdominal symptoms for REGN4018 monotherapy
Timepoint [23] 0 0
Up to 62 weeks
Secondary outcome [24] 0 0
Time to deterioration in abdominal symptoms for REGN4018 with cemiplimab
Timepoint [24] 0 0
Up to 62 weeks
Secondary outcome [25] 0 0
Change from baseline in QoL as measured by EQ-5D for REGN4018 monotherapy
Timepoint [25] 0 0
Baseline up to 62 weeks
Secondary outcome [26] 0 0
Change from baseline in QoL as measured by EQ-5D for REGN4018 with cemiplimab
Timepoint [26] 0 0
Baseline up to 62 weeks
Secondary outcome [27] 0 0
ORR based on iRECIST for REGN4018 monotherapy
Timepoint [27] 0 0
Up to 62 weeks
Secondary outcome [28] 0 0
ORR based on iRECIST for REGN4018 with cemiplimab
Timepoint [28] 0 0
Up to 62 weeks
Secondary outcome [29] 0 0
Best overall response (BOR) based on RECIST 1.1 for REGN4018 monotherapy
Timepoint [29] 0 0
Up to 62 weeks
Secondary outcome [30] 0 0
BOR based on iRECIST for REGN4018 monotherapy
Timepoint [30] 0 0
Up to 62 weeks
Secondary outcome [31] 0 0
BOR based on RECIST 1.1 for REGN4018 with cemiplimab
Timepoint [31] 0 0
Up to 62 weeks
Secondary outcome [32] 0 0
BOR based on iRECIST for REGN4018 with cemiplimab
Timepoint [32] 0 0
Up to 62 weeks
Secondary outcome [33] 0 0
Duration of response (DOR) based on RECIST 1.1 for REGN4018 monotherapy
Timepoint [33] 0 0
Up to 62 weeks
Secondary outcome [34] 0 0
DOR based on iRECIST for REGN4018 monotherapy
Timepoint [34] 0 0
Up to 62 weeks
Secondary outcome [35] 0 0
DOR based on RECIST 1.1 for REGN4018 with cemiplimab
Timepoint [35] 0 0
Up to 62 weeks
Secondary outcome [36] 0 0
DOR based on iRECIST for REGN4018 with cemiplimab
Timepoint [36] 0 0
Up to 62 weeks
Secondary outcome [37] 0 0
Disease control rate based on RECIST 1.1 for REGN4018 monotherapy
Timepoint [37] 0 0
Up to 62 weeks
Secondary outcome [38] 0 0
Disease control rate based on iRECIST for REGN4018 monotherapy
Timepoint [38] 0 0
Up to 62 weeks
Secondary outcome [39] 0 0
Disease control rate based on RECIST 1.1 for REGN4018 with cemiplimab
Timepoint [39] 0 0
Up to 62 weeks
Secondary outcome [40] 0 0
Disease control rate based on iRECIST for REGN4018 with cemiplimab
Timepoint [40] 0 0
Up to 62 weeks
Secondary outcome [41] 0 0
Complete response (CR) rate based on RECIST 1.1 for REGN4018 monotherapy
Timepoint [41] 0 0
Up to 62 weeks
Secondary outcome [42] 0 0
CR rate based on iRECIST 1.1 for REGN4018 monotherapy
Timepoint [42] 0 0
Up to 62 weeks
Secondary outcome [43] 0 0
CR rate based on RECIST 1.1 for REGN4018 with cemiplimab
Timepoint [43] 0 0
Up to 62 weeks
Secondary outcome [44] 0 0
CR rate based on iRECIST 1.1 for REGN4018 with cemiplimab
Timepoint [44] 0 0
Up to 62 weeks
Secondary outcome [45] 0 0
Progression-free survival (PFS) based on RECIST 1.1 for REGN4018 monotherapy
Timepoint [45] 0 0
Up to 62 weeks
Secondary outcome [46] 0 0
PFS based on iRECIST for REGN4018 monotherapy
Timepoint [46] 0 0
Up to 62 weeks
Secondary outcome [47] 0 0
PFS based on RECIST 1.1 for REGN4018 with cemiplimab
Timepoint [47] 0 0
Up to 62 weeks
Secondary outcome [48] 0 0
PFS based on iRECIST for REGN4018 with cemiplimab
Timepoint [48] 0 0
Up to 62 weeks
Secondary outcome [49] 0 0
Cancer antigen-125 (CA-125) response for REGN4018 monotherapy
Timepoint [49] 0 0
Up to 62 weeks
Secondary outcome [50] 0 0
CA-125 response for REGN4018 with cemiplimab
Timepoint [50] 0 0
Up to 62 weeks
Secondary outcome [51] 0 0
Presence or absence of anti-drug antibodies against REGN4018
Timepoint [51] 0 0
Up to 62 weeks
Secondary outcome [52] 0 0
Presence or absence of anti-drug antibodies against cemiplimab
Timepoint [52] 0 0
Up to 62 weeks

Eligibility
Key inclusion criteria
Key

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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
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 cardiovascular disease, 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/05/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
21/06/2026
Actual
Sample size
Target
690
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Center - Melbourne
Recruitment postcode(s) [1] 0 0
NSW 2031 - Randwick
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Oklahoma
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Belgium
State/province [9] 0 0
Antwerp
Country [10] 0 0
Belgium
State/province [10] 0 0
Hainaut
Country [11] 0 0
Belgium
State/province [11] 0 0
Vlaams Brabant
Country [12] 0 0
France
State/province [12] 0 0
Bourgogne
Country [13] 0 0
France
State/province [13] 0 0
Cedex 2
Country [14] 0 0
France
State/province [14] 0 0
Lyon
Country [15] 0 0
France
State/province [15] 0 0
Bordeaux
Country [16] 0 0
France
State/province [16] 0 0
Caen cedex 5
Country [17] 0 0
France
State/province [17] 0 0
Villejuif Cedex
Country [18] 0 0
Israel
State/province [18] 0 0
Haifa
Country [19] 0 0
Israel
State/province [19] 0 0
Tel Hashomer
Country [20] 0 0
Italy
State/province [20] 0 0
Lazio
Country [21] 0 0
Italy
State/province [21] 0 0
Milano
Country [22] 0 0
Italy
State/province [22] 0 0
Naples
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seoul
Country [24] 0 0
Netherlands
State/province [24] 0 0
Gelderland
Country [25] 0 0
Netherlands
State/province [25] 0 0
Zuid Holland
Country [26] 0 0
Netherlands
State/province [26] 0 0
Groningen
Country [27] 0 0
Spain
State/province [27] 0 0
Navarra
Country [28] 0 0
Spain
State/province [28] 0 0
Navarre
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Spain
State/province [31] 0 0
Santiago de Compostela
Country [32] 0 0
United Kingdom
State/province [32] 0 0
England
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Greater Manchester
Country [34] 0 0
United Kingdom
State/province [34] 0 0
London
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Oxfordshire
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Regeneron Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT03564340
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Management
Address 0 0
Regeneron Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Trials Administrator
Address 0 0
Country 0 0
Phone 0 0
844-734-6643
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03564340