Recurrent Ovarian Cancer, Recurrent Fallopian Tube Cancer, Recurrent Primary Peritoneal Cancer, Recurrent Endometrial Cancer, Endometrial Cancer, Low-grade Serous Ovarian Cancer
Conditions
Brief summary
The main purpose of this study is to: * Learn about the safety of ubamatamab and to find out what dose of ubamatamab 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 ubamatamab and/or cemiplimab in the body and measure how well the body can remove the study drug(s). This is called pharmacokinetics * The study will also look at any signs that ubamatamab alone or with cemiplimab can treat recurrent advanced ovarian cancer or cancer of the uterus * To find out how safe and tolerable pretreatment is in combination with ubamatamab and to see how well it works to prevent or minimize Cytokine Release Syndrome (CRS)
Interventions
DRUGUbamatamab
Administered per the protocol
DRUGCemiplimab
Administered per the protocol
DRUGSarilumab
Administered per the protocol
DRUGTocilizumab
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 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, not required for low-grade serous carcinoma) 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 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: 1. MUC16 positivity of tumor cells ≥25% by immunohistochemistry (IHC), as defined in the protocol 2. 1-4 prior lines of systemic therapy, as described in the protocol 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 (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 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-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation Phase |
| Concentration of ubamatamab in serum over time for ubamatamab monotherapy | Up to 2 years | Dose Escalation Phase |
| Number of participants with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) for ubamatamab monotherapy | Up to 2 years | Dose Escalation Phase |
| Number of participants with SAEs for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation Phase |
| Number of deaths for ubamatamab monotherapy | Up to 2 years | Dose Escalation Phase |
| Number of deaths for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation Phase |
| Number of participants with Dose-limiting toxicity (DLTs) for ubamatamab monotherapy | From Cycle 1, Day 1 up to 35 days | Dose Escalation Phase |
| Number of participants with DLTs for ubamatamab with cemiplimab | From Cycle 2, Day 1 up to 21 days | Dose Escalation Phase |
| Number of participants with Treatment-emergent adverse event (TEAE)s (including immune-related adverse events (imAEs)) for ubamatamab monotherapy | Up to 2 years | Dose Escalation Phase |
| Number of participants with TEAEs (including imAEs) for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation Phase |
| Number of participants with serious adverse events (SAEs) for ubamatamab monotherapy | Up to 2 years | Dose Escalation Phase |
| Concentration of ubamatamab in serum over time for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation Phase |
| Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for ubamatamab monotherapy | Up to 2 years | Dose Expansion Phase |
| ORR defined by RECIST 1.1 for ubamatamab with cemiplimab | Up to 2 years | Dose Expansion Phase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR based on iRECIST for ubamatamab monotherapy | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| Disease control rate based on iRECIST for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| ORR based on RECIST 1.1 for ubamatamab monotherapy | Up to 2 years | Dose Escalation Phase |
| ORR based on RECIST 1.1 for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation Phase |
| Number of participants with TEAEs (including imAEs) for ubamatamab monotherapy | Up to 2 years | Dose Expansion Phase |
| Number of participants with TEAEs (including imAEs) for ubamatamab with cemiplimab | Up to 2 years | Dose Expansion Phase |
| Number of participants with SAEs for ubamatamab monotherapy | Up to 2 years | Dose Expansion Phase |
| Number of participants with SAEs for ubamatamab with cemiplimab | Up to 2 years | Dose Expansion Phase |
| Number of deaths for ubamatamab monotherapy | Up to 2 years | Dose Expansion Phase |
| Number of deaths for ubamatamab with cemiplimab | Up to 2 years | Dose Expansion Phase |
| Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab monotherapy | Up to 2 years | Dose Expansion Phase |
| Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab with cemiplimab | Up to 2 years | Dose Expansion Phase |
| Concentration of ubamatamab in serum over time for ubamatamab monotherapy | Up to 2 years | Dose Expansion Phase |
| Concentration of ubamatamab in serum over time for ubamatamab with cemiplimab | Up to 2 years | Dose Expansion Phase |
| 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 ubamatamab monotherapy | Baseline up to 2 years | Dose Expansion Phase The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social) , symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as not at all and 4 as very much. |
| 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 ubamatamab with cemiplimab | Baseline up to 2 years | Dose Expansion Phase |
| Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for ubamatamab monotherapy | Baseline up to 2 years | Dose Expansion Phase |
| Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for ubamatamab with cemiplimab | Baseline up to 2 years | Dose Expansion Phase |
| Change from baseline in abdominal symptoms as measured by the Measure of Ovarian Symptoms and Treatment (MOST)-Abdominal index score for ubamatamab monotherapy | Baseline up to 2 years | Dose Expansion Phase excluding the Endometrial Cancer Cohort The MOST-24 is a 24-item questionnaire used to measure the impact of chemotherapy on symptoms (21 items) and well-being (3 items). The expected questionnaire completion time is less than 5 minutes. The prevalence of each MOST item at assessment time points can be summarized by providing the mean, standard deviation and proportions based on the MOST response format, a numeric rating scale with integers from zero to 10, with five verbal anchors: 'No trouble at all' (0), 'Mild' (1-3), 'Moderate' (4-6), 'Severe' (7-10), and 'Worst I can imagine' (10). |
| Change from baseline in abdominal symptoms as measured by the MOST-Abdominal index score for ubamatamab with cemiplimab | Baseline up to 2 years | Dose Expansion Phase Not applicable to Endometrial Cancer Cohort |
| Time to deterioration in GHS/QoL for ubamatamab monotherapy | Up to 2 years | Dose Expansion Phase |
| Time to deterioration in GHS/QoL for ubamatamab with cemiplimab | Up to 2 years | Dose Expansion Phase |
| Time to deterioration in physical functioning for ubamatamab monotherapy | Up to 2 years | Dose Expansion Phase |
| Time to deterioration in physical functioning for ubamatamab with cemiplimab | Up to 2 years | Dose Expansion Phase |
| Time to deterioration in abdominal symptoms for ubamatamab monotherapy | Up to 2 years | Dose Expansion Phase |
| Time to deterioration in abdominal symptoms for ubamatamab with cemiplimab | Up to 2 years | Dose Expansion Phase |
| Change from baseline in QoL as measured by EQ-5D for ubamatamab monotherapy | Baseline up to 2 years | Dose Expansion Phase |
| Change from baseline in QoL as measured by EQ-5D for ubamatamab with cemiplimab | Baseline up to 2 years | Dose Expansion Phase |
| ORR based on iRECIST for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| Best overall response (BOR) based on RECIST 1.1 for ubamatamab monotherapy | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| BOR based on iRECIST for ubamatamab monotherapy | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| BOR based on RECIST 1.1 for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| BOR based on iRECIST for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| Duration of response (DOR) based on RECIST 1.1 for ubamatamab monotherapy | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| DOR based on iRECIST for ubamatamab monotherapy | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| DOR based on RECIST 1.1 for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| Complete response (CR) rate based on RECIST 1.1 for ubamatamab monotherapy | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| DOR based on iRECIST for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| Disease control rate based on RECIST 1.1 for ubamatamab monotherapy | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| Disease control rate based on iRECIST for ubamatamab monotherapy | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| Disease control rate based on RECIST 1.1 for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| CR rate based on iRECIST 1.1 for ubamatamab monotherapy | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| CR rate based on RECIST 1.1 for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| CR rate based on iRECIST 1.1 for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| Progression-free survival (PFS) based on RECIST 1.1 for ubamatamab monotherapy | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| PFS based on iRECIST for ubamatamab monotherapy | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| PFS based on RECIST 1.1 for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| PFS based on iRECIST for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| Cancer antigen-125 (CA-125) response for ubamatamab monotherapy | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| CA-125 response for ubamatamab with cemiplimab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| Presence or absence of anti-drug antibodies against ubamatamab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
| Presence or absence of anti-drug antibodies against cemiplimab | Up to 2 years | Dose Escalation and Dose Expansion Phases |
Countries
Australia, Belgium, France, Israel, Italy, Netherlands, South Korea, Spain, United Kingdom, United States
Contacts
Primary ContactClinical Trials Administrator
Outcome results
None listed