Dose Escalation and Cohort Expansion Study of Niraparib and Dostarlimab in Paediatric Participants With Solid Tumours

Phase 1

• Conditions: Recurrent or refractory solid tumour; MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-002359-39-DE
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-23
• Last Update Posted: 18 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 116

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) and must not be
eligible for local curative treatment; a.) participants with non-CNS solid tumours other than osteosarcoma, neuroblastoma, adrenocortical carcinoma, Ewing sarcoma or rhabdomyosarcoma are required to have prior documented 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 Cycle 1 Day 1. b.) 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 mutational signature 3, and tumour mutational burden. c.) 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.
2. Participant is child or adolescent =6 months to <18 years old at the time of informed consent/assent.
3. Participant with disease other than neuroblastoma has radiologically
measurable disease that can be tracked as RECIST v1.1. Participant with
neuroblastoma has measurable/evaluable disease by International
Neuroblastoma Response Criteria (INRC) at the time of study enrolment.
Neuroblastoma participants with recurrent/relapsed bone metastasis
that is MIBG-positive (or FDG-PET positive, for MIBG-nonavid tumors) as
only site of disease are eligible.
4. 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 baseline body weight of =20 kg. Participants who are unable to swallow the 100 mg niraparib tablet or who have a baseline body weight <20 kg are eligible to receive the niraparib AAOLF only.
5. Performance status must be =60% on the Karnofsky scale for participants >16 years of age and =60% 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 enrolment. 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.
6. Participant has adequate organ function, defined as follows: Note: The participant must not have received blood transfusion, growth factors
or platelet stimulating agents in the 14 days prior to providing a sample
for haematologic analysis nor erythropoietin in the prior 6 weeks.
a. absolute neutrophil count (ANC) =1,000/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 amino

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 their 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 (i.e., with use of disease-modifying antirheumatic drugs, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or 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 treatment 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 treatment. 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 assent/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.
9. Participant is pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the Screening Visit through 180 days after the last dose of study treatment. 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 within 7 days prior to the first dose of study treatment.
11. Participant has a known history of HIV (type 1 or 2 antibodies).
12. 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).
13. Participant must not have a gastrointestina

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified