| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Recurrent ovarian, fallopian tube or primary peritoneal cancer. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Ovarian, fallopian tube or primary peritoneal cancer. |
|
| 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 | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061344 |
| E.1.2 | Term | Peritoneal neoplasm |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10016180 |
| E.1.2 | Term | Fallopian tube cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the overall survival (OS) |
|
| E.2.2 | Secondary objectives of the trial |
To assess progression free survival
To assess the time to first subsequent therapy
To assess the response rate
To assess the safety and tolerability of patients receiving chemotherapy or TSR 042 + Niraparib
To assess patient-reported outcome (PRO) of patients receiving chemotherapy vs the combination of TSR 042 and Niraparib |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Participant must have recurrent ovarian, Fallopian tube or primary peritoneal cancer not candidate for platinum retreatment;
2. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of <= 1
3. Participants must have measurable disease or evaluable based on RECIST 1.1 (patients with only CA 125 increase without evidence of disease are not included).
4. Participant must be >= 18 years of age
5. Participant must have adequate organ function, defined as follows:
• Absolute neutrophil count >= 1,500/µL
• Platelets >= 100,000/µL
• Hemoglobin >= 9 g/dL
• Serum creatinine <= 1.5 x upper limit of normal (ULN) or calculated creatinine clearance >= 60mL/min using the Cockcroft-Gault equation
• Total bilirubin <= 1.5 x ULN (<=2.0 in patients with known Gilberts syndrome) OR direct bilirubin <= 1 x ULN
• Aspartate aminotransferase and alanine aminotransferase <= 2.5 x ULN unless liver metastases are present, in which case they must be <= 5 x ULN
• International normalized ratio (INR) or prothrombin time (PT) <=1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants. Activated partial thromboplastin time (aPTT) <=1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
6. Pre-existing hypertension should be adequately controlled before starting niraparib treatment.
7. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
8. Participants must agree to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen.
9. Female participant has a negative urine or serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential. Nonchildbearing potential is defined as follows (by other than medical reasons):
•>=45 years of age and has not had menses for >1 year nd has a high follicle-stimulating hormone (FSH) level in the postmenopausal ranges confirmed by two FSH measurements
•Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
•Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. Information must be captured appropriately within the site’s source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
10. Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
11. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent |
|
| E.4 | Principal exclusion criteria |
1. Participant must not be simultaneously enrolled in any interventional clinical trial
2. Participants have received >2 previous CHT lines
3. Participant must not have had major surgery <= 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
4. Participant must not have received investigational therapy <= 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
5. Participant has had radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
6. Participant has not recovered to Grade 1 or baseline from all toxicities associated with previous therapy.
7. Participant must not have a known hypersensitivity to niraparib and Dostarlimab components or excipients and must not have any
hypersensitivity to the treatment used as standard of care in the control arm.
8. Participant must not show contra indications to other agents (including chemotherapy) used in this study
9. Participant must not have received a transfusion (platelets or red blood cells) <= 4 weeks prior to initiating protocol therapy.
10. Participant must not have received colony-stimulating factors within 4 weeks prior initiating protocol therapy.
11. Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment.
12. Participant must not have a diagnosis of Sars-CoV-2 infections at the time of screening
13. Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
14. Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
15. Participant must not have had diagnosis, detection, or treatment of another type of cancer <= 3 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated)
16. Participant must not have known, symptomatic brain or leptomeningeal metastases
17. Patient experienced >= Grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
18. Participant has a diagnosis of immunodeficiency or has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) or has received systemic steroid therapy at a dose > 10 mg/day or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy. Local or systemic corticosteroid treatment at a dosage less or equal than 10 mg/day is allowed. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
19. Participant has a known history of human immunodeficiency virus (type 1 or 2 antibodies).
20. Participant has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [qualitative] is detected).
21. Participant has an active infection requiring systemic therapy
22. Participant must not have a history of interstitial lung disease.
23. Participant has had an allogenic tissue/solid organ transplant
24. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
25. Has received a live vaccine within 30 days of planned start of study therapy while participating in the trial and within 90 days of the last
dose of study medication.
26. Women with childbearing potential if they do not agree with the use of highly effective contraceptive methods with low user dependency, or to be abstinent from heterosexual intercourse during the treatment period and at least 180 days following the last dose of dostarlimab or niraparib and at least 210 days following the last dose of chemotherapy
27. Participant who may be dependent on the sponsor, CRO, study center, or investigator.
28. Participant who have been arrested or otherwise taken into custody by court order or by the authorities, in accordance with Section 40 Paragraph 1 Sentence 3 No. 4 AMG. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall survival (OS) defined as the time fromrandomization to the date of death by any cause |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| Progression-free survival (PFS); Time to first subsequent therapy (TFST); ORR per RECIST 1.1; AE (Adverse Events)/ treatment-emergent (TEAEs) and laboratory abnormalities evaluated according to CTCAE version 5.0; Quality of life and Patient-reported outcome (PRO) with EORTC QLQC30, EORTC QLQOV28, and EQ-5DL |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 4 years; 4 years; 4 years; 4 years; 4 years |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 16 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 45 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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