Dose Escalation and Cohort Expansion Study of Niraparib and Dostarlimab in Paediatric Participants With Solid Tumors (SCOOP)

NCT04544995 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 2134062020-002359-39
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

Brief Summary

This study will evaluate the combination of a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor, niraparib, with the programmed cell death protein 1 (PD-1) inhibitor, dostarlimab in the paediatric population. This study will be conducted to determine the recommended Phase 2 dose (RP2D) and evaluate the pharmacokinetics (PK), safety, and efficacy of niraparib in combination with dostarlimab in paediatric participants with recurrent or refractory solid tumors.

Conditions

Neoplasms

Keywords

Dose escalation; Dose expansion; Dostarlimab; Niraparib; Osteosarcoma; Neuroblastoma

Outcome Measures

Primary Outcomes (5)

• Part 1A and Part 1B: Number of Participants With Dose-limiting Toxicities (DLT)

  DLT referred to adverse effects within the first 42 days of treatment, indicating the maximum tolerated dose. DLTs included treatment-related Grade (G) 4 non-haematologic AEs or G3 AEs unresolved to G≤1 within 48 hours. G3/4 non-haematologic lab abnormalities were DLTs if causing hospitalization or persisting ≥7 days with symptoms or requiring intervention. Haematologic DLTs included prolonged G4 thrombocytopenia, G3/4 thrombocytopenia with bleeding or transfusion needs, prolonged G4 neutropenia, G3/4 neutropenia with infection, and G3/4 anemia requiring transfusion. Other criteria included Cycle 2 delays \>2 weeks, unresolved G≥2 uveitis/endocrine toxicity, persistent colitis/diarrhea, unresolved G3/4 immune-related AEs, G≥3 infusion reactions, hemophagocytic lymphohistiocytosis, posterior reversible encephalopathy syndrome, and treatment-related G5 AE. DLT-evaluable participants completed ≥2 cycles with ≥80% of planned niraparib and ≥2 dostarlimab infusions or had a DLT.

  Up to 42 days

• Part 2 Safety-run in: Number of Participants With Dose-limiting Toxicities (DLT)

  DLT referred to adverse effects within the first 42 days of treatment, indicating the maximum tolerated dose. DLTs included treatment-related Grade (G) 4 non-haematologic AEs or G3 AEs unresolved to G≤1 within 48 hours. G3/4 non-haematologic lab abnormalities were DLTs if causing hospitalization or persisting ≥7 days with symptoms or requiring intervention. Haematologic DLTs included prolonged G4 thrombocytopenia, G3/4 thrombocytopenia with bleeding or transfusion needs, prolonged G4 neutropenia, G3/4 neutropenia with infection, and G3/4 anemia requiring transfusion. Other criteria included Cycle 2 delays \>2 weeks, unresolved G≥2 uveitis/endocrine toxicity, persistent colitis/diarrhea, unresolved G3/4 immune-related AEs, G≥3 infusion reactions, hemophagocytic lymphohistiocytosis, posterior reversible encephalopathy syndrome, and treatment-related G5 AE. DLT-evaluable participants completed ≥2 cycles with ≥80% of planned niraparib and ≥2 dostarlimab infusions or had a DLT.

  Up to 42 days

• Part 2 Safety-run in: Number of Participants With Grade ≥3 Thrombocytopenia Adverse Events

  Thrombocytopenia events were defined as treatment-related toxicities of Grade 3 or Grade 4 thrombocytopenia occurring within the first 42 days of study treatment. AEs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0.

  Up to 42 days

• Part 2A: Progression-Free Survival at 6 Months Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1

  PFS6 is defined as the percentage of participants without progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 or death at 6 months from the date of the first dose of study treatment. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start).

  At Month 6

• Part 2B: Objective Response Rate (ORR) by the Investigator Using International Neuroblastoma Response Criteria (INRC)

  ORR is defined as the percentage of participants who have a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) as determined by the Investigator using International Neuroblastoma Response Criteria (INRC). CR is resolution of all detectable disease, including soft tissue, bone, and bone marrow, with residual lesion measurements \<10 mm and no tumor infiltration in the bone marrow or abnormal MIBG/FDG uptake. PR: Significant reduction in tumor burden, including a ≥30% decrease in primary or metastatic lesion size and ≥50% reduction in bone involvement (MIBG/FDG), with no new lesions and bone marrow infiltration ≤5%.

  Up to approximately 196 weeks

Secondary Outcomes (38)

• Part 1A and Part 1B: Objective Response Rate (ORR)

  Up to approximately 196 weeks

• Part 1A and Part 1B: Duration of Response (DOR)

  Up to approximately 196 weeks

• Part 1A and Part 1B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs (SAEs)

  Up to approximately 196 weeks

• Part 1A and Part 1B: Number of Participants With Dostarlimab-Related Immune-Mediated Adverse Events (imAEs)

  Up to approximately 196 weeks

• Part 1A and Part 1B: Number of Participants With TEAEs Leading to Death and Treatment Discontinuation

  Up to approximately 196 weeks

Study Arms (5)

Part 1A: Dose Escalation

EXPERIMENTAL

Participants with body weight of ≥ 20 kilogram (kg) and who can swallow niraparib tablets will receive niraparib tablets and dostarlimab.

Drug: Dostarlimab; Drug: Niraparib (Tablet)

Part 1B: Dose Escalation

EXPERIMENTAL

Participants who are \<8 years of age will receive niraparib TfOS and dostarlimab.

Drug: Niraparib (Tablet for oral suspension); Drug: Dostarlimab

Part 2 Safety Run-in

EXPERIMENTAL

Participants with osteosarcoma or neuroblastoma who are ≥8 years of age will receive niraparib TfOS and dostarlimab.

Drug: Niraparib (Tablet for oral suspension); Drug: Dostarlimab

Part 2A: Cohort Expansion for Osteosarcoma

EXPERIMENTAL

Participants with osteosarcoma will receive the RP2D of the combination of niraparib and dostarlimab.

Drug: Niraparib (Tablet for oral suspension); Drug: Dostarlimab; Drug: Niraparib (Tablet)

Part 2B: Cohort Expansion for Neuroblastoma

EXPERIMENTAL

Participants with neuroblastoma will receive the RP2D of the combination of niraparib and dostarlimab.

Drug: Niraparib (Tablet for oral suspension); Drug: Dostarlimab; Drug: Niraparib (Tablet)

Interventions

Niraparib (Tablet for oral suspension) DRUG

Niraparib will be administered as TfOS (Tablet for oral suspension)

Part 1B: Dose Escalation; Part 2 Safety Run-in; Part 2A: Cohort Expansion for Osteosarcoma; Part 2B: Cohort Expansion for Neuroblastoma

Dostarlimab DRUG

Dostarlimab will be administered as IV infusion

Part 1A: Dose Escalation; Part 1B: Dose Escalation; Part 2 Safety Run-in; Part 2A: Cohort Expansion for Osteosarcoma; Part 2B: Cohort Expansion for Neuroblastoma

Niraparib (Tablet) DRUG

Niraparib will be administered as tablet

Part 1A: Dose Escalation; Part 2A: Cohort Expansion for Osteosarcoma; Part 2B: Cohort Expansion for Neuroblastoma

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• For Part 1 and Part 2:
• Participant is a child or an adolescent greater than or equal to (\>=) 6 months to less than (\<) 18 years old at the time of informed consent/assent.
• Participant with disease other than neuroblastoma has radiologically measurable disease at screening that can be tracked as RECIST v1.1 target lesion(s).
• Participant with neuroblastoma has measurable/evaluable target and/or non-target disease by INRC at screening. Neuroblastoma participants with recurrent/relapsed bone metastasis that is metaiodobenzylguanidine (MIBG)-positive (or FDG-PET positive, for MIBG-nonavid tumors) as only site of disease are eligible.
• Performance status must be \>=60 percent on the Karnofsky scale for participants \>16 years of age and \>=60 percent on the Lansky scale for participants less than or equal to (\<=) 16 years of age.
• Participant has adequate organ function.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) or Is a WOCBP and using a contraceptive method that is highly effective.
• A male participant of reproductive potential is eligible to participate if he agrees to refrain from donating sperm plus, either be abstinent from heterosexual intercourse or must agree to use a male condom starting with the first dose of study treatment through at least 90 days after the last dose of study treatment.
• For Part 1 only:
• Participant has recurrent or refractory osteosarcoma, neuroblastoma, adrenocortical carcinoma, Ewing sarcoma, rhabdomyosarcoma, or any other solid tumor (excluding tumors of the central nervous system \[CNS\]) and must not be eligible for alternative curative treatment: i. Participants with non-CNS solid tumours other than osteosarcoma, neuroblastoma, adrenocortical carcinoma, Ewing sarcoma or rhabdomyosarcoma are required to have prior documented breast cancer susceptibility gene (BRCAness) mutational signature (mutational signature 3) on deoxyribonucleic acid (DNA) sequencing of tumor obtained in the relapsed/recurrent disease setting, within 6 (preferably 3) months of Cycle 1 Day 1.
• ii. For participants with documented BRCAness mutational signature: Existing information on molecular profiling of the participant's tumor 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 BRCA1 and BRCA 2 and other homologous recombination DNA repair (HRR) pathway genes, mutational signatures including mutational signature 3, and tumor mutational burden (TMB).
• iii. NOTE: Participants with recurrent or refractory osteosarcoma, neuroblastoma, adrenocortical carcinoma, Ewing sarcoma, or rhabdomyosarcoma are asked to provide documentation, if available, of the BRCAness mutational signature analysis on DNA sequencing of their tumour.
• For Part 2A:
• Participant has recurrent or refractory osteosarcoma and must not be eligible for alternative curative treatment.
• Documentation of BRCAness mutational signature 3 will be requested, but not required, for enrollment.

You may not qualify if:

• For Part 1 and Part 2:
• Participant has known hypersensitivity to dostarlimab or niraparib, their components, or their excipients.
• Participant has a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• Participant has active autoimmune disease that has required systemic treatment in the past 2 years (that is \[i.e.\], with use of disease-modifying anti-rheumatic drugs, corticosteroids, or immunosuppressive drugs). Replacement therapy (for example \[e.g.\], thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Participant has known active CNS metastases, carcinomatous meningitis, or both. Carcinomatous meningitis precludes a participant from study participation regardless of clinical stability.
• Participant had a known additional (second primary) malignancy that progressed or required active treatment within the last 2 years.
• Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active infection that requires systemic therapy.
• Participant has a condition (such as transfusion-dependent anemia or thrombocytopenia), requirement for 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.
• Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
• Participant has a known history of human immunodeficiency virus (HIV) (type 1 or 2 antibodies).
• Participant has documented presence of HbsAg and/or HBcAb at Screening or within 3 months prior to first dose of study intervention. Participants with a negative HbsAg and positive HbcAb result are eligible only if HBV DNA is negative.
• Participant must not have a gastrointestinal condition, such as bowel obstruction, that can impact absorption of oral medications and is identified by clinical symptoms or CT scan, etc.
• Participant has had any known Grade 3 or 4 anemia, neutropenia, and/or thrombocytopenia that was related to the most recent prior anti-cancer treatment and that persisted \>4 weeks (28 days).
• Participant has not recovered (i.e., to Grade ≤1 or to baseline) from prior systemic anticancer therapy-induced AEs. Note: Participants with alopecia, hearing impairment, Grade ≤2 neuropathy, Grade ≤2 fatigue, Grade ≤ 2 anaemia, and/or Grade ≤2 neutropenia are an exception to this criterion and may qualify for participation in the study.
• Participant had toxicity related to prior immunotherapy that led to study treatment discontinuation.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Birmingham, B4 6NH, United Kingdom

Location

GSK Investigational Site

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms; Osteosarcoma; Neuroblastoma

Interventions

niraparib; Tablets; Suspensions; dostarlimab

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Sarcoma; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Colloids; Complex Mixtures

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This will be an open-label study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2020
• First Posted: September 10, 2020
• Study Start: October 6, 2020
• Primary Completion: April 23, 2025
• Study Completion: April 23, 2025
• Last Updated: January 21, 2026
• Results First Posted: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

GB (2)