Study of REGN4018 (Ubamatamab) Administered Alone or in Combination with Cemiplimab in Adult Patients with Recurrent Ovarian Cancer or Other Recurrent Mucin-16 expressing (MUC16+) Cancers

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

29 Oct 2020 → ongoing

Decision date (initial)

2024-06-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Regeneron Pharmaceuticals Inc.

External identifiers

EU CT number

2024-510783-23-00

EudraCT number

2019-003298-24

ClinicalTrials.gov

NCT03564340

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Pharmacokinetic, Efficacy

In the Dose Escalation Phase:
• To assess the safety and pharmacokinetics (PK) in order to determine a maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of ubamatamab as monotherapy and in combination with cemiplimab
In the Dose Expansion Phase:
• To assess the preliminary efficacy of ubamatamab 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

Secondary objectives 7

1. In the Dose Escalation Phase: To assess the preliminary efficacy of ubamatamab as monotherapy and in combination with cemiplimab (separately by cohort) 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 the Dose Expansion Phase: To characterize the PK of ubamatamab as monotherapy and in combination with cemiplimab
4. In the Dose Expansion Phase: To assess the effect of ubamatamab as monotherapy and in combination with cemiplimab on patient-reported outcomes (PROs), including health-related quality of life (HRQoL), functioning, and symptoms
5. In both the Dose Escalation and Dose Expansion Phases: To assess preliminary efficacy of ubamatamab 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, CR rate, and progression-free survival (PFS) based on RECIST 1.1 and iRECIST
6. In both the Dose Escalation and Dose Expansion Phases: To assess efficacy of ubamatamab as monotherapy and in combination with cemiplimab as measured by CA-125 level
7. In both the Dose Escalation and Dose Expansion Phases: Immunogenicity of ubamatamab and cemiplimab

Conditions and MedDRA coding

Fallopian Tube Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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: a. serum CA-125 level ≥2 x upper limit of normal (ULN) (in screening), not required for low-grade serous carcinoma); b. 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
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 2 to 4 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: a. MUC16 positivity of tumor cells ≥25% by immunohistochemistry (IHC), as defined in the protocol; b. 1-4 prior lines of systemic therapy, as described in the protocol
6. Other protocol-defined inclusion criteria apply

Exclusion criteria 7

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 (does not apply to low-grade serous ovarian cancer cohort)
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 cardiac findings 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
7. Other protocol-defined exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. In the Dose Escalation Phase: Number of participants with Dose-limiting toxicity (DLTs) for ubamatamab monotherapy and in combination with cemiplimab
2. In the Dose Escalation Phase: Number of participants with Treatment-emergent adverse event (TEAE)s (including immune (imAEs)) for ubamatamab monotherapy and in combination with cemiplimab
3. In the Dose Escalation Phase: Number of participants with serious adverse events (SAEs) for ubamatamab monotherapy and in combination with cemiplimab
4. In the Dose Escalation Phase: Number of deaths for ubamatamab monotherapy and in combination with cemiplimab
5. In the Dose Escalation Phase: Number of participants with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) for ubamatamab monotherapy and in combination with cemiplimab
6. In the Dose Escalation Phase: Concentration of REGN4018 in serum over time for ubamatamab monotherapy and in combination with cemiplimab
7. In the Dose Expansion Phase: Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for ubamatamab monotherapy and in combination with cemiplimab

Secondary endpoints 19

1. In the Dose Escalation Phase: ORR based on RECIST 1.1 for ubamatamab monotherapy and in combination with cemiplimab
2. In the Dose Expansion Phase: Number of participants with TEAEs (including imAEs) for ubamatamab monotherapy and in combination with cemiplimab
3. In the Dose Expansion Phase: Number of participants with SAEs for ubamatamab monotherapy and in combination with cemiplimab
4. In the Dose Expansion Phase: Number of deaths for ubamatamab monotherapy and in combination with cemiplimab
5. In the Dose Expansion Phase: Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab monotherapy and in combination with cemiplimab
6. In the Dose Expansion Phase: Concentration of ubamatamab in serum over time for ubamatamab monotherapy and in combination with cemiplimab
7. In the Dose Expansion Phase: Change from baseline in QoL as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 GHS/QoL score for ubamatamab monotherapy and in combination with cemiplimab
8. In the Dose Expansion Phase: Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for ubamatamab monotherapy and in combination with cemiplimab
9. In the Dose Expansion Phase: Change from baseline in abdominal symptoms as measured by the Measure of Ovarian Symptoms and Treatment (MOST)-Abdominal index score (Not applicable to Endometrial Cancer Cohort) for ubamatamab monotherapy and in combination with cemiplimab
10. In the Dose Expansion Phase: Time to deterioration in GHS/QoL, physical functioning, and abdominal symptoms for ubamatamab monotherapy and in combination with cemiplimab
11. In the Dose Expansion Phase: Change from baseline in QoL as measured by EQ-5D for ubamatamab monotherapy and in combination with cemiplimab
12. In the Dose Escalation and Dose Expansion Phase: ORR based on iRECIST for ubamatamab monotherapy and with cemiplimab
13. In the Dose Escalation and Dose Expansion Phase: Best overall response (BOR) based on RECIST 1.1 and iRECIST for ubamatamab monotherapy and in combination with cemiplimab
14. In the Dose Escalation and Dose Expansion Phase: Duration of response (DOR) based on RECIST 1.1 and iRECIST for ubamatamab monotherapy and in combination with cemiplimab
15. In the Dose Escalation and Dose Expansion Phase: Disease control rate based on RECIST 1.1 and iRECIST for ubamatamab monotherapy and in combination with cemiplimab
16. In the Dose Escalation and Dose Expansion Phase: Progression-free survival (PFS) based on RECIST 1.1 and iRECIST for ubamatamab monotherapy and in combination with cemiplimab
17. In the Dose Escalation and Dose Expansion Phase: Complete Response (CR) rate for ubamatamab monotherapy and in combination with cemiplimab
18. In the Dose Escalation and Dose Expansion Phase: Cancer antigen-125 (CA-125) response for ubamatamab monotherapy and in combination with cemiplimab
19. In the Dose Escalation and Dose Expansion Phase: Presence or absence of anti-drug antibodies against ubamatamab and cemiplimab

Investigational products

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

Test 6

Auxiliary 1

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 7

Locations

5 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 53 files

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

Application history

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