Basket Trial Exploring The Efficacy And Safety Of The Combination Of Niraparib And Dostarlimab

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-02-26	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-03-25
First Submitted that Met QC Criteria 2021-02-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-03-26
First Posted (ACTUAL) 2021-03-03	Results First Posted N/A	Last Verified 2024-03

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 1.A - Urothelial Bladder Cancer	DRUG: Dostarlimab Substance: immunoglobulin G4 (IgG4) humanized monoclonal antibody (mAb) that binds with high affinity to PD-1 Manufacturer: Tesaro Inc. Dose: 500 mg every 21 days for the first 4 cycles, followed by 1,000 mg every 42 days cycle (ie, Q6W) DRUG: Niraparib Substance: Inhibitor of poly-adenosine diphosphate [ADP] ribose polymerase (PARP) Manufacturer: Tesaro Inc. Dose: Flat-fixed dose (if <77kg or platelets <150,000 μL: 200mg; if >/=77kg and platelets >/= 150,000μL: 300mg)
EXPERIMENTAL: 1.B - Gastric or gastro-esophageal junction adenocarcinoma	DRUG: Dostarlimab Substance: immunoglobulin G4 (IgG4) humanized monoclonal antibody (mAb) that binds with high affinity to PD-1 Manufacturer: Tesaro Inc. Dose: 500 mg every 21 days for the first 4 cycles, followed by 1,000 mg every 42 days cycle (ie, Q6W) DRUG: Niraparib Substance: Inhibitor of poly-adenosine diphosphate [ADP] ribose polymerase (PARP) Manufacturer: Tesaro Inc. Dose: Flat-fixed dose (if <77kg or platelets <150,000 μL: 200mg; if >/=77kg and platelets >/= 150,000μL: 300mg)
EXPERIMENTAL: 1.C - Head and Neck Cancer	DRUG: Dostarlimab Substance: immunoglobulin G4 (IgG4) humanized monoclonal antibody (mAb) that binds with high affinity to PD-1 Manufacturer: Tesaro Inc. Dose: 500 mg every 21 days for the first 4 cycles, followed by 1,000 mg every 42 days cycle (ie, Q6W) DRUG: Niraparib Substance: Inhibitor of poly-adenosine diphosphate [ADP] ribose polymerase (PARP) Manufacturer: Tesaro Inc. Dose: Flat-fixed dose (if <77kg or platelets <150,000 μL: 200mg; if >/=77kg and platelets >/= 150,000μL: 300mg)
EXPERIMENTAL: 1.D - Biliary Tract Cancer and pancreatic ductal adenocarcinoma (PDAC)	DRUG: Dostarlimab Substance: immunoglobulin G4 (IgG4) humanized monoclonal antibody (mAb) that binds with high affinity to PD-1 Manufacturer: Tesaro Inc. Dose: 500 mg every 21 days for the first 4 cycles, followed by 1,000 mg every 42 days cycle (ie, Q6W) DRUG: Niraparib Substance: Inhibitor of poly-adenosine diphosphate [ADP] ribose polymerase (PARP) Manufacturer: Tesaro Inc. Dose: Flat-fixed dose (if <77kg or platelets <150,000 μL: 200mg; if >/=77kg and platelets >/= 150,000μL: 300mg)
EXPERIMENTAL: 1.E - Others: any histology, excepted breast cancer, prostate cancer or serous ovarian cancer
EXPERIMENTAL: Cohort 2 - Platinum-sensitive urothelial bladder cancer
EXPERIMENTAL: Cohort 3 - Clear Cell Renal Cell Carcinoma

Primary Outcome Measures	Measure Description	Time Frame
Overall Response Rate (ORR)	according to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)	at 15 weeks

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Age ≥ 18 years.
Patients must have histologically or cytologically confirmed progressive metastatic or recurrent solid tumor (as defined below for each tumor type). Diagnosis must be stated in a pathology report and confirmed by the physician investigator.
Evidence of disease progression prior to trial entry.
To be enrolled in this study, only the tumor types and settings described below are allowed:

Patients must have received at least one line of prior platinum - based systemic therapy. No more than 3 lines of previous systemic therapy for metastatic disease are allowed.

Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy containing platinum-based regimen is considered as first-line therapy.
Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the first-line therapy.
Patients must have platinum-sensitive disease defined as disease which reaches at least partial response after the last platinum chemotherapy line and the patient must have progressed at least 3 months after the last cycle of chemotherapy.
Previous exposure to one line of anti-PD-1 or anti-PD-L1 is allowed, unless hyperprogression (Appendix 6) occurred on immunotherapy

Metastatic or recurrent gastric or gastro-esophageal junction adenocarcinoma that has progressed following at least 1 and maximum 2 prior therapies, by imaging modalities.
Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy is considered as first-line therapy.
Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the first-line therapy.
HER2-positive and -negative amplified patients are both eligible for entry into this study.
Patients with HER2-positive gastric cancer must have received trastuzumab-containing regimen prior to study entry.
Previous exposure to anti-PD-1 or anti-PD-L1 is not allowed

Histologically or cytologically confirmed carcinoma of the head and neck.
Subjects are eligible regardless of HPV status
Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy or chemo-radiotherapy regimen is considered as first-line therapy
In case of previous platinum-based therapy, tumor progression or recurrence within 6 months of last dose of platinum-based therapy is not allowed.
Previous exposure to one line of anti-PD-1 or anti-PD-L1 is allowed, unless hyperprogression (Appendix 6) occurred on immunotherapy
Patients must have received at last one prior line of therapy in the advanced / metastatic setting
No more than 2 lines of previous systemic therapy for metastatic disease are allowed.

Histologically or cytologically confirmed carcinoma of the biliary tract or PDAC that has progressed following at least 1 and maximum 2 prior therapies, by imaging modalities.
Previous exposure to anti-PD-1 or anti-PD-L1 is not allowed

Patients must have received at least 16 weeks of continuous first-line platinum-based chemotherapy without evidence of progression during that period
Maximum of 1 prior line of therapy is allowed

Any histology, excepted breast cancer, prostate cancer or serous ovarian cancer (Appendix 7).
Previous exposure to one line of anti-PD-1 or anti-PD-L1 is allowed, unless hyperprogression (Appendix 6) occurred on immunotherapy 4.2 - Cohorts 2: Platinum-sensitive urothelial bladder cancer
Patients must have received at least one line of prior platinum - based systemic therapy. No more than 3 lines of previous systemic therapy for metastatic disease are allowed.
Platinum-sensitive disease is defined as disease which reached at least partial response after the last platinum chemotherapy line and progressed at least 3 months after the last cycle of chemotherapy
Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy containing platinum-based regimen is considered as first-line therapy.
Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the first-line therapy.
Previous exposure to one line of anti-PD-1 or anti-PD-L1 is allowed, unless hyperprogression (Appendix 6) occurred on immunotherapy 4.3 - Cohort 3: Clear cell Renal Cell Carcinoma
Patients must have received at least one line of previous therapy. No more than 4 previous lines of therapy are allowed.
Patients must have received anti-PD-1 (or anti-PD-L1) in combination with an anti-CTLA-4 or an anti-angiogenic agent, and an antiangiogenic agent.
Previous exposure to one line of anti-PD-1 or anti-PD-L1 is allowed unless hyperprogression (Appendix 6) occurred on immunotherapy For all cohorts: Representative archival formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (preferred) or 20 (ideally) freshly cut and unstained slides, with an associated pathology report, for ancillary studies and/or central testing. If less than 20 slides are available, inclusion must be discussed with the Coordinating Investigator. In all cases, recovery of the most recent tumor block or biopsy is encouraged. If no material is available (blocks or slides), a biopsy will be mandatory at baseline (before the start of the treatment).

For patients with DNA repair gene mutation already identified by local testing, mutational testing must have been done less than one year prior to inclusion in the trial (i.e. signing of informed consent). Tumor block should correspond to the one that has been used for the original testing. If no archival tissue available feasibility of a fresh tumor biopsy at baseline should be ensured and mutation confirmed on that tissue. Only tissue from core needle, punch or excisional biopsy sample collection will be accepted. Other methods such as fine-needle aspiration, brushing, bone tissue or lavage samples are not acceptable.
For patients whose tissue will be evaluated by the Gustave Roussy DNA repair gene panel, original or more recent tumor blocks can be used.

At least one lesion, not previously irradiated, measurable according to RECIST v1.1) as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and suitable for repeated assessment.
Patients must have progressed following standard of care or not eligible to effective standard therapy
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration from registration date.
Estimated life expectancy of greater than 12 weeks.
Adequate hematologic and organ function, defined by the following laboratory results obtained within 3 days prior to the first study treatment (Cycle 0 Day 1):
Absolute neutrophil count (ANC) ≥ 1500 cells/μL (without granulocyte colony-stimulating factor support within 2 weeks before cycle 0 day 1).
Lymphocyte count ≥ 500/μL.
Platelet count ≥ 100.000/μL (without platelets transfusion within 2 weeks before Cycle 0 Day 1).
Hemoglobin ≥ 9g/dL (patients are not allowed to be transfused with RBC or receive erythropoietic treatment to meet this criterion).
Total bilirubin ≤ 1.5 ULN (subjects with documented/suspected Gilbert's disease or liver metastases may be enrolled with bilirubin ≤ 3 × ULN).
Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≤ 2.5 x upper normal limit (ULN) or ≤ 5 × ULN in case of liver involvement.
Albumin ≥ 28g/L.
Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 40 mL/min (according to Cockroft and Gault formula).
International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN. This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular weight heparin or warfarin) should be on stable dose.
Women of childbearing potential must have a negative serum β-HCG pregnancy test within 14 days prior to the administration of the first study treatment.Pregnancy testing must be repeated within 72 hours prior to the first dose and while on study.
Sexually active women of childbearing potential must agree to use a highly effective method of contraception supplemented by a barrier method, or to abstain from sexual activity during the study and for at least 180 days after the last study treatment administration.
Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
Sexually active males patients must agree to use condom during the study and for at least 180 days after the last study treatment administration. Also, it is recommended their women of childbearing potential partner use a highly effective method of contraception for the same duration.
Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed.
Patient should be able and willing to comply with study visits and procedures as per protocol.
Patients must be affiliated to a social security system or beneficiary of an equivalent system.

Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence.
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
Adequately treated carcinoma in situ without evidence of disease (eg, carcinoma in situ of the cervix, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent). 5. Treatment with systemic corticosteroids or other immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor agents) within 2 weeks prior to Cycle 0 Day 1, or anticipated requirements for systemic immunosuppressive medications during the trial:

Patients with autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible. 15. Active or prior documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis). 16. History of interstitial lung disease, idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia or evidence of active pneumonitis on screening chest CT scan. 17. History of allogeneic organ transplant or prior bone marrow transplantation of double umbilical cord blood transplantation. 18. Uncontrolled intercurrent illness including, but not limited to:

ongoing or active infection or severe infection requiring hospitalization or IV antibiotics within 2 weeks of starting treatment (with the exception of prophylactic antibiotics).
symptomatic congestive heart failure > NYHA II, superior vena cava syndrome, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, pericardial effusion, myocardial infarction within 90 days.
active peptic ulcer disease or gastritis.
active bleeding diatheses.
major seizure disorder 19. Psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent. 20. Patients with known left ventricular ejection fraction (LVEF) < 40%; patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF < 50% must be on a stable cardiologic treatment. 21. Known positive test for HIV. 22. Patients with active hepatitis B (defined as positive HBsAg test at screening) or hepatitis C (HCV).Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen anti-HBc) are eligible. 23. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. 24. Active tuberculosis. 25. Administration of attenuated or live vaccine within 4 weeks prior to Cycle 0 Day 1 or anticipation that such a live attenuated vaccine will be required during the study. 26. Major surgical procedure within 20 days prior ty Cycle 0 Day 1 or anticipation of need for a major surgical procedure during the course of the study. 27. Uncontrolled tumor-related pain: patients requiring pain medication must be on a stable regimen at study entry and symptomatic lesions amenable to palliative radiotherapy should be treated prior to enrolment. 28. Uncontrolled effusion (pleural, pericardial or ascites) requiring recurrent drainage procedures (once a month or more frequently); patients with indwelling catheters (e.g. PleurX) are allowed. 29. Uncontrolled hypercalcemia (>1.5mmol/L ionized calcium or Ca > 12mg/dL or corrected serum calcium >ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.

Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history or clinically significant hypercalcemia are eligible.
Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while on study. 30. History of leptomeningeal disease

Symptomatic CNS metastasis or uncontrolled CNS metastasis, requiring increasing doses of steroids or stable dose of steroids > 10mg prednisone qd.
Spinal cord compression without evidence that disease has been clinically stable for ≥ 2 weeks prior to Cycle 0 Day 1. 31. Previous treatment with PARP inhibitors. 32. Treatment with systemic immunostimulatory agents (e.g. INF-a and IL-2) within 4 weeks prior to Cycle 0 Day 1. 33. Patients with rare hereditary problems of galactose intolerance, the lapp lactase deficiency or glucose galactose malabsorption 34. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study result. 35. Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent.

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