A Study to Find Out How Safe REGN5668 is and How Well it Works In Adult Women When Given with Either Cemiplimab, or Cemiplimab + Fianlimab, or Ubamatamab

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Sep 2023 → ongoing

Decision date (initial)

2023-06-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Regeneron Pharmaceuticals Inc.

External identifiers

EU CT number

2022-501904-83-00

ClinicalTrials.gov

NCT04590326

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Safety, Efficacy

In the Dose Escalation Phase:
- To assess the safety, tolerability, and pharmacokinetics (PK) of REGN5668 alone and in separate combinations with cemiplimab or ubamatamab, to determine a maximally tolerated dose(s) (MTD) or recommended phase 2 dose(s) (RP2D) for these combinations

In the Dose Expansion Phase:
- Module 1: To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or cemiplimab + fianlimab (as of PA6) as determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Module 2: To assess the preliminary efficacy of REGN5668 in combination with ubamatamab, (separately by cohort and combination) as determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Secondary objectives 7

1. In the Dose Escalation Phase: - To assess the preliminary efficacy of REGN5668 in combination with cemiplimab, or ubamatamab (separately by cohort and combination) as determined by ORR by RECIST 1.1
2. In the Dose Expansion Phase: - To characterize the safety profile in each expansion cohort
3. In both the Dose Escalation and Dose Expansion Phases: To assess preliminary efficacy of REGN5668 in combination with cemiplimab, cemiplimab + fianlimab (as of PA6 and only in Dose Expansion), or ubamatamab as measured by best overall response (BOR), duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) based on RECIST 1.1
4. In both the Dose Escalation and Dose Expansion Phases: To assess changes in CA-125 levels from baseline after treatment with REGN5668 in combinations with cemiplimab, or cemiplimab + fianlimab (as of PA6), or ubamatamab (separately by cohort and combination)
5. In both the Dose Escalation and Dose Expansion Phases: To characterize the PK of REGN5668 in combination with cemiplimab, cemiplimab + fianlimab (as of PA6), or ubamatamab (separately by cohort and combination)
6. In both the Dose escalation and Dose expansion Phases: Immunogenicity of REGN5668, alone and in combinations with cemiplimab, cemiplimab + fianlimab (as of PA6), or ubamatamab
7. All the above primary and secondary objectives will apply to each cohort (unless specified) in the study including those who receive sarilumab and those who do not receive sarilumab.

Conditions and MedDRA coding

Ovarian Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Ovarian Cancer Cohorts Only: 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. Has a serum CA-125 level ≥2x ULN (in screening, not applicable to endometrial cohorts)
3. Has adequate organ and bone marrow function as defined in the protocol
4. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Has a life expectancy of at least 3 months
6. Expansion cohorts only: Has at least 1 lesion that is measurable by RECIST 1.1 as described in the protocol.
7. Endometrial Cancer Cohorts Only: histologically confirmed endometrial cancer that has progressed or recurrent after prior anti-PD-1 therapy and platinum-based chemotherapy as described in the protocol
8. Note: Other protocol-defined inclusion criteria apply

Exclusion criteria 10

1. Current or recent (as defined in the protocol) treatment with an investigational agent, systemic biologic therapy, or anti-cancer immunotherapy
2. Has history of clinically significant cardiovascular disease as defined in the protocol
3. Has known allergy or hypersensitivity to cemiplimab and/or components of study drug(s).
4. Note: Other protocol-defined Exclusion criteria apply
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. Prior treatment with a MUC16-targeted therapy
7. Ovarian Expansion cohorts only: More than 5 prior lines of systemic therapy
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. Incidence of dose limiting toxicities (DLT), Dose escalation phase, Module 1
2. Incidence of DLTs, Dose escalation phase, Module 2
3. Incidence of treatment-emergent adverse events (TEAEs), Primary: Dose escalation phase, Secondary: Dose expansion phase
4. Incidence of serious adverse events (SAEs), Primary: Dose escalation phase; Secondary: Dose expansion phase
5. Incidence of deaths, 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]), Primary: Dose escalation phase; Secondary: Dose expansion phase
7. Concentrations of REGN5668 in serum when dosed alone and in combination with cemiplimab or ubamatamab, Primary: Dose escalation phase
8. ORR defined by RECIST 1.1 (Eisenhauer, 2009) of REGN5668 in combination with cemiplimab, cemiplimab + fianlimab, or ubamatamab (separately by cohort and combination), Primary: Dose expansion phase

Secondary endpoints 11

1. ORR based on RECIST 1.1, Dose escalation phase
2. Best Overall Response (BOR) based on RECIST 1.1, Dose escalation and expansion phases
3. Duration of Response (DOR) based on RECIST 1.1, Dose escalation and expansion phases
4. Disease Control Rate (DCR) based on RECIST 1.1, Dose escalation and expansion phases
5. Progression Free Survival (PFS) based on RECIST 1.1, Dose escalation and expansion phases
6. CA-125 change from baseline after treatment with REGN5668 in combinations with cemiplimab, cemiplimab + fianlimab, or ubamatamab (separately by cohort and combination), Dose escalation and expansion phases
7. Concentration of REGN5668 in serum over time when dosed alone and in combination with cemiplimab, cemiplimab + fianlimab, or ubamatamab, Dose escalation and expansion phases
8. Presence or absence of anti-drug antibodies against REGN5668, Dose escalation and expansion phases
9. Presence or absence of anti-drug antibodies against ubamatamab, Dose escalation and expansion phases
10. Presence or absence of anti-drug antibodies against cemiplimab, Dose escalation and expansion phases
11. Presence or absence of anti-drug antibodies against fianlimab, Dose escalation and expansion phases

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Third parties 8

Locations

3 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 37 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications