E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent Ovarian Cancer Recurrent Fallopian Tube Cancer Recurrent Primary Peritoneal Cancer Recurrent Endometrial Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer Endometrial Cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014736 |
E.1.2 | Term | Endometrial cancer recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 REGN4018 as monotherapy and in combination with cemiplimab
In the Dose Expansion Phase: To assess the preliminary efficacy of REGN4018 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 |
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E.2.2 | Secondary objectives of the trial |
Dose Escalation Phase To assess the preliminary efficacy of REGN4018 as monotherapy and in combination with cemiplimab (separately by cohort) as determined by ORR by RECIST 1.1 Dose Expansion Phase •To characterize the safety profile in each expansion cohort •To characterize the PK of REGN4018 as monotherapy and in combination with cemiplimab •To assess the effect of REGN4018 as monotherapy and in combination with cemiplimab on patient-reported outcomes, including health-related quality of life, functioning, and symptoms In both Dose Escalation and Dose Expansion Phases •To assess preliminary efficacy of REGN4018 as monotherapy and in combination with cemiplimab (separately by cohort) as measured by ORR based on immune based therapy RECIST, BOR, DOR, disease control rate, CR rate and PFS based on RECIST 1.1 and iRECIST •To assess efficacy of REGN4018 as monotherapy and in combination with cemiplimab as measured by CA-125 level •Immunogenicity of REGN4018 and cemiplimab |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Genomics sub-study - Optional Germ-line DNA will be collected as optional to enable analysis of tumor mutational burden as well as exploratory analysis of variants potentially associated with efficacy and/or safety signals. |
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E.3 | Principal 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: a. serum CA-125 level ≥2 x upper limit of normal (ULN) (in screening) 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) c. documented relapse or progression on or after the most recent line of therapy d. 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 (supersedes criterion 2): histologically confirmed endometrial cancer that has progressed or recurrent after prior anti-PD-1 therapy and platinum-based chemotherapy
Note: Other protocol Inclusion Criteria apply |
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E.4 | Principal exclusion criteria |
1. Recent treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy 2. Ovarian Cancer Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy 3. Prior treatment with a Mucin 16 (MUC16)-targeted therapy 4. Untreated or active primary brain tumor, central nervous system (CNS) metastases, or spinal cord compression 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
Note: Other protocol Exclusion Criteria apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Dose Escalation Phase: 1. Number of participants with Dose-limiting toxicity (DLTs) 2. Number of participants with Treatment-emergent adverse event (TEAE)s (including immune (imAEs)) 3. Number of participants with serious adverse events (SAEs) 4. Number of deaths 5. Number of participants with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) 6. Concentration of REGN4018 in serum over time for monotherapy and in combination with cemiplimab Dose Expansion Phase: 7. Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for monotherapy and with cemiplimab |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 28 days 2 - 7. Up to 62 weeks |
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E.5.2 | Secondary end point(s) |
Dose Escalation Phase: 1. ORR based on RECIST 1.1 for monotherapy and with cemiplimab Dose Expansion Phase: 2. Number of participants with TEAEs (including imAEs) 3. Number of participants with SAEs 4. Number of deaths 5. Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) 6. Concentration of REGN4018 in serum over time for monotherapy and in combination with cemiplimab 7. 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 8. Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score 9. 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) 10. Time to deterioration in GHS/QoL, physical functioning, and abdominal symptoms 11. Change from baseline in QoL as measured by EQ-5D
Dose Escalation and Dose Expansion Phases: 12. ORR based on iRECIST for monotherapy and with cemiplimab 13. Best overall response (BOR) based on RECIST 1.1 and iRECIST for monotherapy and with cemiplimab 14. Duration of response (DOR) based on RECIST 1.1 and iRECIST for monotherapy and with cemiplimab 15. Disease control rate based on RECIST 1.1 and iRECIST for monotherapy and with cemiplimab 16. Progression-free survival (PFS) based on RECIST 1.1 and iRECIST for monotherapy and with cemiplimab 17. Complete Response (CR) rate 18. Cancer antigen-125 (CA-125) response 19. Presence or absence of anti-drug antibodies against REGN4018 and cemiplimab |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Israel |
Korea, Republic of |
United Kingdom |
United States |
Belgium |
France |
Italy |
Netherlands |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 22 |