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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04544995

Collaborator

(none)

116

Enrollment

Locations

Arm

113.2

Anticipated Duration (Months)

9.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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 pediatric 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 pediatric participants with recurrent or refractory solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms	Drug: Niraparib Drug: Dostarlimab	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

116 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

In Part 1 (dose escalation phase), the RP2D of the combination of niraparib and dostarlimab will be determined. This will be followed by Part 2 (dose expansion [DE] phase), in which the RP2D established in Part 1 will be evaluated for efficacy and safety in disease-specific expansion cohorts (osteosarcoma and neuroblastoma).In Part 1 (dose escalation phase), the RP2D of the combination of niraparib and dostarlimab will be determined. This will be followed by Part 2 (dose expansion [DE] phase), in which the RP2D established in Part 1 will be evaluated for efficacy and safety in disease-specific expansion cohorts (osteosarcoma and neuroblastoma).

Masking:

None (Open Label)

Masking Description:

This will be an open-label study.

Primary Purpose:

Treatment

Official Title:

A PHASE 1, MULTICENTRE, OPEN-LABEL, DOSE-ESCALATION AND COHORT EXPANSION STUDY OF NIRAPARIB AND DOSTARLIMAB IN PAEDIATRIC PATIENTS WITH RECURRENT OR REFRACTORY SOLID TUMOURS

Actual Study Start Date :

Oct 6, 2020

Anticipated Primary Completion Date :

Sep 28, 2029

Anticipated Study Completion Date :

Mar 15, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Participants receiving Niraparib +Dostarlimab Participants will receive Niraparib and Dostarlimab.	Drug: Niraparib Niraparib will be administered Drug: Dostarlimab Dostarlimab will be administered.

Arm

Intervention/Treatment

Experimental: Participants receiving Niraparib +Dostarlimab

Participants will receive Niraparib and Dostarlimab.

Drug: Niraparib

Niraparib will be administered

Drug: Dostarlimab

Dostarlimab will be administered.

Outcome Measures

Primary Outcome Measures

Part 1A: Number of participants with dose limiting toxicities (DLTs) [Up to 42 days from start of the treatment (Day 0)]
Number of participants with DLTs will be reported.
Part 1B: Number of participants with DLTs [Up to 42 days from start of the treatment (Day 0)]
Number of participants with DLTs will be reported.
Part 2: Progression-free survival rate at 6 months (PFS6) in participants with osteosarcoma [Up to 6 months from start of the treatment (Day 0)]
PFS6 is defined as the proportion of participants without progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria or death at 6 months from the date of the first dose of study treatment.
Part 2: Overall response rate (ORR) in participants with neuroblastoma [Up to 2 years from start of the treatment (Day 0)]
ORR is defined as the proportion 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).

Secondary Outcome Measures

ORR [Up to 2 years from start of the treatment (Day 0)]
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 criteria or INRC (for participants with neuroblastoma only).
Duration of response (DOR) [Up to 2 years from start of the treatment (Day 0)]
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).
Disease control rate (DCR) in participants [Up to 2 years from start of the treatment (Day 0)]
DCR is defined as the proportion of participants who have achieved a BOR of confirmed CR, confirmed PR, or stable disease by RECIST v1.1 or INRC (for participants with neuroblastoma only) based on Investigator assessment.
PFS in participants [Up to 2 years from start of the treatment (Day 0)]
PFS is defined as the time from the date of the first dose of study treatment to the first documented PD, as determined by RECIST v1.1 or INRC (for participants with neuroblastoma only) based on Investigator assessment, or death from any cause (whichever occurs first).
Number of participants with Treatment emergent adverse events (TEAEs), adverse events (AEs, Serious AEs (SAEs), immune-related AEs (irAEs), TEAEs leading to death and AEs leading to discontinuation [Up to 5 years]
TEAEs, AEs, SAEs, irAEs, TEAEs leading to death and AEs leading to discontinuation will be collected.
Plasma concentration of niraparib [Up to Cycle 1 Week 2 (Each Cycle of 21 days)]
Blood samples will be collected for the concentrations of niraparib.
Serum concentration of dostarlimab [Up to 2 years from start of the treatment (Day 0)]
Blood samples will be collected for the concentrations of dostarlimab.
Number of participants compliant based on 'Acceptability and Palatability questionnaire' [At Cycle 1 Week 1 (Each Cycle of 21 days)]
Participants will be assessed on Acceptability and Palatability questionnaire

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

For Part 1 and Part 2 (osteosarcoma and neuroblastoma expansion cohorts):

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 will receive niraparib tablet or age-appropriate oral liquid formulation based on body weight and ability to swallow tablet.
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.

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]) 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 prior to enrolment and must not be eligible for local curative treatment. 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 BRCA1/2 and other homologous recombination DNA repair (HRR) pathway genes, mutational signatures including signature 3, and tumor mutational burden (TMB).

For Part 2 (osteosarcoma expansion cohort) only:

Participant has recurrent or refractory osteosarcoma and must not be eligible for local curative treatment.
Participant has radiographically measurable disease that can be tracked as RECIST v1.1 target lesion(s).
Participant must provide tumor tissue sample at screening for retrospective exploratory biomarker analysis.

For Part 2 (neuroblastoma expansion cohort) only:

Participant has recurrent or refractory neuroblastoma and must not be eligible for local curative treatment.
Participant has radiographically measurable disease at the time of study enrolment; participants with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine-positive (+) evaluable disease are eligible. Measurable disease in participants with CNS involvement is defined as a tumor that is measurable in 2 perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than 1 slice.
Participant must provide tumor tissue sample at screening.

Exclusion Criteria:

For Part 1 and Part 2 (osteosarcoma and neuroblastoma expansion cohorts):

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 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), 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: Participants who received a transfusion (platelets or red blood cells) within 6 weeks of the first dose of study treatment are not eligible. Participants who received colony-stimulating factors (e.g., granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior to the first dose of study treatment are not eligible.
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 known active hepatitis B (e.g., hepatitis B surface antigen reactive) or hepatitis C (e.g., hepatitis C virus ribonucleic acid [qualitative] is detected).
Participant has had any known Grade 3 or 4 anemia, neutropenia, or thrombocytopenia due to prior chemotherapy that persisted >4 weeks related to the most recent prior treatment.
Participant had treatment with prior systemic anticancer therapy within the 3 weeks prior to the first dose of study treatment, radiation therapy encompassing >20 percent of the bone marrow within 2 weeks prior to the first dose of study treatment, or any radiation therapy within 1 week prior to the first dose of study treatment.
Participant has received a live vaccine within 30 days of planned start of study treatment.
Participant has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, cardiac arrhythmia or unstable angina, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, and history of cerebrovascular accident) within 6 months of enrolment.
Participant has heart rate-corrected QT interval prolongation >480 milliseconds at screening.
For Part 2 (osteosarcoma expansion cohort and neuroblastoma expansion cohort):
Participant has received prior therapy with an anti-PD-1, anti-programmed cell death ligand 1, anti-programmed cell death-ligand 2, anti-cytotoxic T-lymphocyte-associated antigen-4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways (with the exception of participants rolling over from Part 1 of the study: these participants are allowed to have received dostarlimab).
Participant has had prior treatment with a known poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor (with the exception of participants rolling over from Part 1 of the study: these participants are allowed to have received niraparib).

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	GSK Investigational Site	Lille	France	59000
2	GSK Investigational Site	Lyon	France	69008
3	GSK Investigational Site	Marseille	France	13005
4	GSK Investigational Site	Paris cedex 05	France	75248
5	GSK Investigational Site	Paris	France	75012
6	GSK Investigational Site	Villejuif	France	94805
7	GSK Investigational Site	Barcelona	Spain	08035
8	GSK Investigational Site	Esplugues De Llobregat. Barcelona	Spain	08950
9	GSK Investigational Site	Madrid	Spain	28009
10	GSK Investigational Site	Madrid	Spain	28046
11	GSK Investigational Site	Valencia	Spain	46026
12	GSK Investigational Site	Glasgow	United Kingdom	G51 4TF