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.
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.
- In order to be eligible to receive the niraparib tablet formulation, participant must
be able to swallow the 100 mg niraparib tablet and have a body weight of >=20 kg.
Participants who are unable to swallow the 100 mg niraparib tablet or who have a body
weight <20 kg are eligible to receive the niraparib AAOLF only.
- Performance status must be >=70 percent on the Karnofsky scale for participants >16
years of age and >=50 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
- 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]) previously documented to have 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. 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.
- Participant has radiographically measurable disease that can be tracked as RECIST v1.1
- 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.
- 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.
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
- Participant has active autoimmune disease that has required systemic treatment in the
past 2 years (ie, with use of disease-modifying anti-rheumatic drugs, corticosteroids,
or immunosuppressive drugs). Replacement therapy (eg, 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
- 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 drug are not
eligible. 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
- 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 drug.
- Participant has a known history of human immunodeficiency virus (HIV) (type 1 or 2
- Participant has known active hepatitis B (eg, hepatitis B surface antigen reactive) or
hepatitis C (eg, 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
- Participant had treatment with prior systemic anticancer therapy within the 3 weeks
prior to the first dose of study drug, radiation therapy encompassing >20 percent of
the bone marrow within 2 weeks prior to the first dose of study drug, or any radiation
therapy within 1 week prior to the first dose of study drug.
- Participant has received a live vaccine within 14 days of planned start of study drug.
- Participant has clinically significant cardiovascular disease (eg, 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. The participant may be eligible to participate in the study following
discussion with the Sponsor's Medical Monitor.
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).