Recurrent or refractory solid tumour MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864
Conditions
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant has recurrent or refractory osteosarcoma, neuroblastoma, adrenocortical carcinoma, Ewing sarcoma, rhabdomyosarcoma, or any other solid tumour (excluding tumours of the CNS) previously documented to have BRCAness mutational signature (mutational signature 3) on DNA sequencing of tumour obtained in the relapsed/recurrent disease setting, within 6 (preferably 3) months prior to enrolment. For participants with documented BRCAness mutational signature: Existing information on molecular profiling of the participant’s tumour tissue must be through a molecular profiling platform such as Individualized Therapy for Relapsed Malignancies in Childhood (INFORM). Molecular profile information must contain information from whole exome sequencing or whole genome sequencing, including the mutation status of breast cancer susceptibility gene (BRCA) 1 and BRCA2 and other homologous recombination DNA repair pathway genes, mutational signatures including signature 3, and tumour mutational burden. 2. Participant is child or adolescent =6 months to 16 years of age and =50% on the Lansky scale for participants =16 years of age. Note: Neurologic deficits in participants with brain metastases must have been stable for at least 7 days prior to study enrollment. Participants who are unable to walk because of paralysis, but who are upright in a wheelchair, will be considered ambulatory for the purpose of assessing the performance status. 5. Participant has adequate organ function, defined as follows: Note: CBC should be obtained without transfusion or receipt of colony-stimulating factors in the 2 weeks before obtaining sample. a. absolute neutrophil count (ANC) =1,500/µL b. platelets =100,000/µL c. haemoglobin =9 g/dL or =5.6 mmol/L d. serum creatinine =1.5 × upper limit of normal (ULN) for age or calculated creatinine clearance or radioisotope glomerular filtration rate =60 mL/min/1.73 m2 e. total bilirubin =1.5 × ULN or direct bilirubin =1 × ULN f. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × ULN unless liver metastases are present, in which case AST and ALT must be =5 × ULN g. international normalised ratio or prothrombin time (PT) =1.5 × ULN unless the participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants h. activated PTT =1.5 × ULN unless the participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants 6. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: a. Is not a woman of childbearing potential (WOCBP). OR b. Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, as described in Appendix 3, from the Screening Visit through at least 180 days after the last dose of study drug and agrees not to dona
Exclusion criteria
Exclusion criteria: 1.Participation presents unacceptable risk to the prospective participant based on the Investigator’s judgment. 2.Participant has known hypersensitivity to dostarlimab or niraparib, their components or excipients. 3.Participant has a known history of myelodysplastic syndrome (MDS) or AML. 4.Participant has active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying antirheumatic drugs, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal/pituitary insufficiency) is not considered a form of systemic treatment. 5.Participant has known active CNS metastases, carcinomatous meningitis, or both. Note: Participants with previously treated brain metastases may participate provided they are clinically stable (without evidence of progression by imaging [using the identical imaging modality for each assessment, either MRI or CT scan] for at least 4 weeks prior to the first dose of study drug and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and have not been using steroids for at least 7 days prior to the first dose of study drug. Carcinomatous meningitis precludes a participant from study participation regardless of clinical stability. 6.Participant had a known additional malignancy that progressed or required active treatment within the last 2 years. 7.Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active infection that requires systemic therapy. Specific examples include but are not limited to, history of (noninfectious) pneumonitis that required steroids or current pneumonitis, uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining consent). 8.Participant has a condition (such as transfusion-dependent anaemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results or interfere with the participant’s participation for the full duration of the study treatment including the following: a.Participants who received a transfusion (platelets or red blood cells) within 6 weeks of the first dose of study drug are not eligible. b.Participants who received colony-stimulating factors (eg, granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior to the first dose of study drug are not eligible. 9.Participant is expecting to conceive within the projected duration of the study, starting with the Screening Visit through 180 days after the last dose of study drug. No data are available regarding the presence of dostarlimab or niraparib or its metabolites in human milk or on its effects on the breastfed infant or milk production. Because of the potential for serious adverse reactions in breastfed infants from dostarlimab and/or niraparib, female participants should not breastfeed during treatment with dostarlimab and/or niraparib and for 1 month after receiving the final dose. 10.Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy withi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Part 1A: to establish the recommended Phase 2 dose (RP2D) of the combination of niraparib tablet and dostarlimab in paediatric participants • Part 1B: to establish the RP2D of the combination of niraparib age-appropriate oral liquid formulation (AAOLF) and dostarlimab in paediatric participants;Secondary Objective: Secondary objectives for Part 1 of this study: • to evaluate additional measures of anticancer activity including objective response rate (ORR) and duration of response (DOR) • to evaluate the safety and tolerability of the combination of niraparib (tablet or AAOLF) and dostarlimab in paediatric participants • to characterise the pharmacokinetics (PK) of the combination of niraparib and dostarlimab in paediatric participants • to assess the acceptability and palatability of niraparib tablets and AAOLF in paediatric participants;Primary end point(s): Part 1A and 1B: Assess the incidence of DLTs by study part and cohort for the DLT-evaluable population to establish the RP2D of the combination of niraparib (both tablet in Part 1a and age-appropriate oral formulation AAOF in Part 1b) and dostarlimab. Part 2: Please refer to the separate cohort-specific supplements for this information.;Timepoint(s) of evaluation of this end point: The DLT observation period is 42 days following the initiation of study drugs (ie, the first 2 treatment cycles) in Part 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • ORR based on Investigator assessment is defined as the proportion of participants with a BOR of confirmed CR or PR as determined by the Investigator using RECIST v1.1 or INRC (for participants with neuroblastoma only). • DOR is defined as the time from first documentation of response (CR or PR) until the time of first documented PD by RECIST v1.1 or INRC (for participants with neuroblastoma only) based on Investigator assessment or death (whichever occurs first). Part 1: Please refers to main study protocol for further Endpoints Part 2: Please refer to the separate cohort-specific supplements for this information.;Timepoint(s) of evaluation of this end point: Timepoint is included in each Endpoint | — |
Countries
Spain, United Kingdom
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Limited
Outcome results
None listed