Ended Therapeutic exploratory (Phase II) DNA repair-deficient or platinum-sensitive solid tumors

An open label phase II basket trial exploring the efficacy and safety of the combination of Niraparib and Dostarlimab in patients with DNA repair-deficient or platinum-sensitive solid tumors (NIRADO)

EU CTIS ID: 2024-514855-13-00

What this study is testing

The primary objective of the trial is to evaluate the antitumor activity of Dostarlimab (TSR-042) and niraparib in patients with selected advanced solid tumors as measured by the Overall Response Rate at 15 weeks according to RECIST v1.1.

Therapeutic exploratory (Phase II)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Age ≥ 18 years.
10. 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) (describes in the protocol and synopsis)
11. 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.
12. 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.
13. Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
14. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.

You likely can't join if

1. Participation in another clinical study with an investigational product simultaneously and/or during the last 4 weeks (excepting observational or noninterventional clinical studies).
10. 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.
11. Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
12. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
13. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the TSR-042 formulation, or to niraparib or its components.
14. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis. o Patients with autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible. o Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible.

See the full eligibility criteria

Who can join

1. Age ≥ 18 years.
10. 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) (describes in the protocol and synopsis)
11. 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.
12. 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.
13. Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
14. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
15. 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.
16. Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed.
17. Patient should be able and willing to comply with study visits and procedures as per protocol.
18. Patients must be affiliated to a social security system or beneficiary of an equivalent system.
2. 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.
3. Evidence of disease progression prior to trial entry.
To be enrolled in this study, only the tumor types and settings described in the protocol and synopsis
5. Patients must have progressed following standard of care or not eligible to effective standard therapy.
6. 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).
7. 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.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration from registration date.
9. Estimated life expectancy of greater than 12 weeks.

What rules you out

1. Participation in another clinical study with an investigational product simultaneously and/or during the last 4 weeks (excepting observational or noninterventional clinical studies).
10. 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.
11. Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
12. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
13. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the TSR-042 formulation, or to niraparib or its components.
14. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis. o Patients with autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible. o 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: o ongoing or active infection or severe infection requiring hospitalization or IV antibiotics within 2 weeks of starting treatment (with the exception of prophylactic antibiotics). o symptomatic congestive heart failure > NYHA II, superior vena cava syndrome, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, pericardial effusion, myocardial infarction within 90 days. o active peptic ulcer disease or gastritis. o active bleeding diatheses. o 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.
2. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 28 days prior to the first dose of study drug, or five half lives of the previous agent, whichever is the shorter.
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. o 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. o Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while on study.
3. Participant has had radiation therapy encompassing >20% of the bone marrow within 2 weeks prior to Cycle 0 Day 1; or any radiation therapy within 1 week prior to Cycle 0 Day 1.
30. History of leptomeningeal disease o Symptomatic CNS metastasis or uncontrolled CNS metastasis, requiring increasing doses of steroids or stable dose of steroids > 10mg prednisone qd. o 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.
4. History of another primary malignancy within 5 years prior to Cycle 0 Day 1 except for: o 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. o Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. o 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: o The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids for patients with orthostatic hypotension, low-dose supplemental corticosteroids for adrenocortical insufficiency and topical steroids for cutaneous diseases are allowed.
6. Acute toxicities from previous therapies that have not resolved to Grade ≤ 1, with the exception of alopecia.
7. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > Grade 1.
8. Participant must not have received a platelet transfusion ≤ 4 weeks prior to Cycle 0 Day 1.
9. Participants must not have received colony stimulating factors (eg, granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior to Cycle 0 Day 1.

The study team makes the final eligibility decision.

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.