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NeoplasmsPhase 1NCT04544995

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

A Phase 1 study testing Niraparib (Tablet for oral suspension), Dostarlimab and Niraparib (Tablet) in people with Neoplasms, run by GlaxoSmithKline at 2 sites in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 months to 17 years
Conditions the study is for
Neoplasms
What is being tested?
Niraparib (Tablet for oral suspension), Dostarlimab and Niraparib (Tablet)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
2 sitesUnited Kingdom
Study dates
6 Oct 2020to 23 Apr 2025
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.
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  • 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.
  • 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).
  • 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.
  • Participant must confirm at screening that an archival or fresh tumor tissue sample is available for use, in retrospective exploratory biomarker analysis. Otherwise, enrolling site must discuss with Sponsor.
  • For Part 2B:
  • Participant has recurrent or refractory neuroblastoma and must not be eligible for alternative curative treatment. Documentation of BRCAness mutational signature 3 will be requested, but not required, for enrollment.
  • Participant must confirm at screening that an archival or fresh tumor tissue sample is available for use, in retrospective exploratory biomarker analysis. Otherwise, enrolling site must discuss with Sponsor.

Who cannot join

  • 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.
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  • 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.
  • Participant had treatment with systemic anticancer therapy (investigational agent or device, or approved chemotherapy, targeted therapy, immunotherapy, or other systemic therapy) within 3 weeks or 5 half-lives, whichever is shorter, 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 not recovered adequately from AEs or complications from any major surgery prior to starting 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 at screening >450 milliseconds (msec) or >480 msec for participants with bundle branch block.
  • Participant has received a solid organ transplant.
  • Participant has a documented presence of HCV antibody at Screening or within 3 months prior to first dose of study intervention. NOTE: Participants with a positive HCV antibody test result due to prior resolved disease can be enrolled, if a confirmatory HCV RNA test is negative and the participant otherwise meets entry criteria.
  • Participant has a documented presence of HCV RNA at Screening or within 3 months prior to first dose of study intervention. NOTE: The HCV RNA test is optional and participants with negative HCV antibody test are not required to undergo HCV RNA testing as well.
  • For Part 2:
  • 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).

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • GSK Investigational Site

    Birmingham, B4 6NH

  • GSK Investigational Site

    Sutton, SM2 5PT

Other trials in United Kingdom

About this study

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

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
Being tested
Niraparib (Tablet for oral suspension), Dostarlimab, Niraparib (Tablet)
Keywords
Dose escalation, Dose expansion, Dostarlimab, Niraparib, Osteosarcoma, Neuroblastoma
Medical subject headings
Neoplasms, Osteosarcoma, Neuroblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Niraparib (Tablet for oral suspension)Drug

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

  • DostarlimabDrug

    Dostarlimab will be administered as IV infusion

  • Niraparib (Tablet)Drug

    Niraparib will be administered as tablet

Study groups in NCT04544995
Study groupRoleWhat they receive
Part 1A: Dose EscalationExperimentalParticipants with body weight of ≥ 20 kilogram (kg) and who can swallow niraparib tablets will receive niraparib tablets and dostarlimab.
Receives: Drug: Dostarlimab; Drug: Niraparib (Tablet)
Part 1B: Dose EscalationExperimentalParticipants who are <8 years of age will receive niraparib TfOS and dostarlimab.
Receives: Drug: Niraparib (Tablet for oral suspension); Drug: Dostarlimab
Part 2 Safety Run-inExperimentalParticipants with osteosarcoma or neuroblastoma who are ≥8 years of age will receive niraparib TfOS and dostarlimab.
Receives: Drug: Niraparib (Tablet for oral suspension); Drug: Dostarlimab
Part 2A: Cohort Expansion for OsteosarcomaExperimentalParticipants with osteosarcoma will receive the RP2D of the combination of niraparib and dostarlimab.
Receives: Drug: Niraparib (Tablet for oral suspension); Drug: Dostarlimab; Drug: Niraparib (Tablet)
Part 2B: Cohort Expansion for NeuroblastomaExperimentalParticipants with neuroblastoma will receive the RP2D of the combination of niraparib and dostarlimab.
Receives: Drug: Niraparib (Tablet for oral suspension); Drug: Dostarlimab; Drug: Niraparib (Tablet)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 42 days

  2. 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.

    Measured: Up to 42 days

  3. 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.

    Measured: Up to 42 days

  4. 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).

    Measured: At Month 6

  5. 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%.

    Measured: Up to approximately 196 weeks

Secondary outcomes (38)

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

    ORR is the percentage of participants with a best overall response (BOR) of confirmed CR or PR using RECIST v1.1 or INRC (for neuroblastoma participants only) as determined by the Investigator. Per RECIST v1.1: CR is disappearance of all target lesions, with pathological lymph nodes <10 mm in short axis. PR is ≥30% decrease in sum of diameters of target lesions, referencing baseline sum (percent change from baseline). Per 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%.

    Measured: Up to approximately 196 weeks

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

    DOR is the time from first documented response (CR or PR) to first PD by RECIST v1.1 or INRC (neuroblastoma only), based on Investigator assessment, or death (whichever occurs first). If no PD or death occurs post-response, participants are censored at their last tumor assessment date. Per RECIST v1.1, CR is disappearance of all target lesions; PR is ≥30% decrease in lesion diameters from baseline; PD is ≥20% increase in lesion sum from nadir plus ≥5 mm absolute increase. Per INRC, CR is resolution of detectable disease, including soft tissue, bone, and bone marrow, with residual lesions <10 mm, no bone marrow infiltration, and normal MIBG/FDG uptake. PR is a ≥30% decrease in lesion size, ≥50% reduction in bone involvement (MIBG/FDG), no new lesions, and bone marrow infiltration ≤5%. PD is >20% lesion size increase, new lesions, or increased infiltration in bone marrow.

    Measured: Up to approximately 196 weeks

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

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A TEAE is any event that emerged during treatment and was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA dictionary).

    Measured: Up to approximately 196 weeks

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

    Dostarlimab-Related Immune-Mediated AEs were reported. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA dictionary).

    Measured: Up to approximately 196 weeks

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

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A TEAE is any event that emerged during treatment and was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.

    Measured: Up to approximately 196 weeks

  6. Part 1A and Part 1B: Niraparib Concentrations

    Blood samples were obtained to analyze niraparib concentration levels.

    Measured: 2.5 hours (HR) and 7 HR post-dose on Cycle 1 Week 1, 168 HR post-dose on Cycle 1 Week 2

  7. Part 1A and Part 1B: Dostarlimab Concentrations

    Blood samples were collected for PK analysis of Dostarlimab.

    Measured: Pre-dose on Day 1; 1 HR post-dose on Cycle 1 Week 1; 168 HR post-dose on Cycle 1 Week 2; 504 HR post-dose) on Cycle 2 Week 1; Pre-dose on Week 1 of Cycles 4, 6, 12, 18, 24, 30, 36; End of Treatment (Up to approximately 196 weeks)

  8. Part 1A and Part 1B: Number of Participants With Positive Anti-Drug Antibody (ADAs) to Dostarlimab

    Blood samples were collected for the analysis of the presence of ADAs using electrochemiluminescence. All samples were tested in screening and confirmatory assay, and positive samples were further characterized for antibody titers.

    Measured: Up to approximately 196 weeks

  9. Part 1A and Part 1B: Number of Participants Answered Acceptability and Palatability of Niraparib Via Questionnaires

    The acceptability and palatability for participants who received niraparib tablet or TfOS were evaluated by using a questionnaire.

    Measured: At Week 1 of Cycle 1

  10. Part 2 Safety-run in: Objective Response Rate (ORR)

    ORR is the percentage of participants with a best overall response (BOR) of confirmed CR or PR, using RECIST v1.1 or INRC (neuroblastoma only) as determined by the Investigator. Per RECIST v1.1: CR is disappearance of all target lesions, with pathological lymph nodes <10 mm in short axis. PR is ≥30% decrease in sum of diameters of target lesions, referencing baseline sum (percent change from baseline). Per 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%.

    Measured: Up to approximately 196 weeks

  11. Part 2 Safety-run in: Duration of Response (DOR)

    DOR is the time from first documented response (CR or PR) to first PD by RECIST v1.1 or INRC (neuroblastoma only), based on Investigator assessment, or death (whichever occurs first). It is calculated for participants with a BOR of confirmed CR or PR. If no PD or death occurs post-response, participants are censored at their last tumor assessment date. Per RECIST v1.1, CR is disappearance of all target lesions; PR is ≥30% decrease in lesion diameters from baseline; PD is ≥20% increase in lesion sum from nadir plus ≥5 mm absolute increase. Per INRC, CR is resolution of detectable disease, including soft tissue, bone, and bone marrow, with residual lesions <10 mm, no bone marrow infiltration, and normal MIBG/FDG uptake. PR is a ≥30% decrease in lesion size, ≥50% reduction in bone involvement (MIBG/FDG), no new lesions, and bone marrow infiltration ≤5%. PD is >20% lesion size increase, new lesions, or increased infiltration in bone marrow.

    Measured: Up to approximately 196 weeks

  12. Part 2 Safety-run in: Disease Control Rate (DCR)

    DCR is the percentage of participants achieving a BOR of confirmed CR, PR, or stable disease (SD) by RECIST v1.1 or INRC (neuroblastoma only). Per RECIST v1.1: CR is disappearance of all target lesions and pathological lymph nodes <10 mm in short axis; PR is ≥30% decrease in lesion diameters from baseline; SD is neither sufficient shrinkage for PR nor sufficient increase for PD. Per INRC: CR is resolution of all detectable disease (soft tissue, bone, marrow) with residual lesion <10 mm, no tumor infiltration in the bone marrow, and no abnormal MIBG or FDG/PET uptake. PR is ≥30% decrease in lesion size, ≥50% bone involvement reduction (MIBG/FDG uptake), no new lesions, and bone marrow infiltration ≤5%. SD was defined as neither sufficient shrinkage for PR nor sufficient increase for PD at the primary site. Bone marrow infiltration remains >5%.

    Measured: Up to approximately 196 weeks

  13. Part 2 Safety-run in: Progression-free Survival (PFS)

    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 (in participants with neuroblastoma only) based on Investigator assessment, or death from any cause (whichever occurs first). Per RECISTv1.1: 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). In addition, the sum must have an absolute increase from nadir of 5 mm. Per INRC: PD is >20% lesion size increase, new lesions, or increased marrow tumor infiltration (>5%).

    Measured: Up to approximately 196 weeks

  14. Part 2 Safety-run in: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs (SAEs)

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A TEAE is any event that emerged during treatment and was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA dictionary).

    Measured: Up to approximately 196 weeks

  15. Part 2 Safety-run in: Number of Participants With Dostarlimab-Related Immune-Mediated Adverse Events (imAEs)

    Dostarlimab-Related Immune-Mediated AEs were reported. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA dictionary).

    Measured: Up to approximately 196 weeks

  16. Part 2 Safety-run in: Number of Participants With TEAEs Leading to Death and Treatment Discontinuation

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A TEAE is any event that emerged during treatment and was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.

    Measured: Up to approximately 196 weeks

  17. Part 2 Safety-run in: Niraparib Concentrations

    Blood samples were obtained to analyze niraparib concentration levels.

    Measured: 2.5 HR and 7 HR post-dose on Cycle 1 Week 1, Pre-dose on Cycle 1 Week 2 and Pre-dose and 5 HR post-dose on Cycle 2 Week 1

  18. Part 2A: Objective Response Rate (ORR) by the Investigator Using RECIST v1.1

    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 RECIST v1.1. CR was defined as disappearance of all target and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline).

    Measured: Up to approximately 196 weeks

  19. Part 2A: Duration of Response (DOR) by the Investigator Using RECIST v1.1

    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 , based on Investigator assessment, or death (whichever occurs first). CR was defined as disappearance of all target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). 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). In addition, the sum must have an absolute increase from nadir of 5 mm.

    Measured: Up to approximately 196 weeks

  20. Part 2A: Disease Control Rate (DCR) by the Investigator Using RECIST v1.1

    DCR is defined as the percentage of participants who have achieved a BOR of confirmed CR, confirmed PR, or stable disease (SD) by RECIST v1.1. CR was defined as disappearance of all target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

    Measured: Up to approximately 196 weeks

  21. Part 2A: Progression-free Survival (PFS) by the Investigator Using RECIST v1.1

    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 , based on Investigator assessment, or death from any cause (whichever occurs first). 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).

    Measured: Up to approximately 196 weeks

  22. Part 2A: Number of Participants With of Treatment Emergent Adverse Events (TEAEs) and Serious AEs (SAEs)

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A TEAE is any event that emerged during treatment and was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA dictionary).

    Measured: Up to approximately 196 weeks

  23. Part 2A: Number of Participants With Dostarlimab-Related Immune-Mediated Adverse Events (imAEs)

    Dostarlimab-Related Immune-Mediated AEs were reported. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA dictionary).

    Measured: Up to approximately 196 weeks

  24. Part 2A: Number of Participants With TEAEs Leading to Death and Treatment Discontinuation

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A TEAE is any event that emerged during treatment and was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.

    Measured: Up to approximately 196 weeks

  25. Part 2A: Niraparib Concentrations

    Blood samples were obtained to analyze niraparib concentration levels.

    Measured: 2.5 HR and 7 HR post-dose on Cycle 1 Week 1, 168 HR post-dose on Cycle 1 Week 2

  26. Part 2A: Dostarlimab Concentrations

    Blood samples were collected for PK analysis of Dostarlimab.

    Measured: Pre-dose on Day 1; 1 HR post-dose on Cycle 1 Week 1; 168 HR post-dose on Cycle 1 Week 2; 504 HR post-dose) on Cycle 2 Week 1; Pre-dose on Week 1 of Cycles 4 and 6; End of Treatment (Up to approximately 196 weeks)

  27. Part 2A: Number of Participants With Positive Anti-Drug Antibody (ADAs) to Dostarlimab

    Blood samples were collected for the analysis of the presence of ADAs using electrochemiluminescence. All samples were tested in screening and confirmatory assay, and positive samples were further characterized for antibody titers.

    Measured: Up to approximately 196 weeks

  28. Part 2A: Number of Participants Answered Acceptability and Palatability of Niraparib Via Questionnaires

    The acceptability and palatability for participants who received niraparib tablet were evaluated by using a questionnaire.

    Measured: At Week 1 of Cycle 1

  29. Part 2B: Duration of Response (DOR) by the Investigator by INRC

    DOR is defined as the time from first documentation of response (CR or PR) until the time of first documented PD by INRC , based on Investigator assessment, or death (whichever occurs first). 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%. PD is >20% lesion size increase,new lesions or increased tumor infiltration in bone marrow.

    Measured: Up to approximately 196 weeks

  30. Part 2B: Disease Control Rate (DCR) by the Investigator by INRC

    DCR is defined as the percentage of participants who have achieved a BOR of confirmed CR, confirmed PR, or SD by INRC. CR is resolution of all detectable disease (soft tissue, bone, marrow) with residual lesion <10 mm, no tumor infiltration in the bone marrow, and no abnormal MIBG or FDG/PET uptake. PR is ≥30% decrease in lesion size, ≥50% bone involvement reduction (MIBG/FDG uptake), no new lesions, and bone marrow infiltration ≤5%. SD was defined as neither sufficient shrinkage for PR nor sufficient increase for PD at the primary site. Bone marrow infiltration remains >5%.

    Measured: Up to approximately 196 weeks

  31. Part 2B: Progression-free Survival (PFS) by the Investigator by INRC

    PFS is defined as the time from the date of the first dose of study treatment to the first documented PD, as determined by INRC , based on Investigator assessment, or death (whichever occurs first). PD is >20% lesion size increase, new lesions, or increased tumor infiltration in bone marrow.

    Measured: Up to approximately 196 weeks

  32. Part 2B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious AEs (SAEs)

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A TEAE is any event that emerged during treatment and was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA dictionary).

    Measured: Up to approximately 196 weeks

  33. Part 2B: Number of Participants With Dostarlimab-Related Immune-Mediated Adverse Events (imAEs)

    Dostarlimab-Related Immune-Mediated AEs were reported. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA dictionary).

    Measured: Up to approximately 196 weeks

  34. Part 2B: Number of Participants With TEAEs Leading to Death and Treatment Discontinuation

    A TEAE is any event that emerged during treatment and was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.

    Measured: Up to approximately 196 weeks

  35. Part 2B: Niraparib Concentrations

    Blood samples were obtained to analyze niraparib concentration levels.

    Measured: 2.5 HR and 7 HR post-dose on Cycle 1 Week 1, 168 HR post-dose on Cycle 1 Week 2

  36. Part 2B: Dostarlimab Concentrations

    Blood samples were collected for PK analysis of Dostarlimab.

    Measured: Pre-dose on Day 1; 1 HR post-dose on Cycle 1 Week 1; 168 HR post-dose on Cycle 1 Week 2; 504 HR post-dose on Cycle 2 Week 1; Pre-dose on Week 1 of Cycles 4, 6, 12 and 18; End of Treatment (Up to approximately 196 weeks)

  37. Part 2B: Number of Participants With Positive Anti-Drug Antibody (ADAs) to Dostarlimab

    Blood samples were collected for the analysis of the presence of ADAs using electrochemiluminescence. All samples were tested in screening and confirmatory assay, and positive samples were further characterized for antibody titers.

    Measured: Up to approximately 196 weeks

  38. Part 2B: Number of Participants Answered Acceptability and Palatability of Niraparib Via Questionnaires

    The acceptability and palatability for participants who received niraparib tablet were evaluated by using a questionnaire.

    Measured: At Week 1 of Cycle 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2020
  2. Study start6 Oct 2020
  3. Primary completion23 Apr 2025
  4. Study completion23 Apr 2025

Why it stopped: Sponsor Decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04544995
Sponsor's protocol ID
213406
Other IDs
2020-002359-39
Status last verified
Jan 2026
First submitted
4 Sep 2020
Last updated
21 Jan 2026
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Niraparib (Tablet for oral suspension), Dostarlimab and Niraparib (Tablet) in people with Neoplasms, run by GlaxoSmithKline at 2 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1A and Part 1B: Number of Participants With Dose-limiting Toxicities (DLT) (time frame: Up to 42 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04544995.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2026.

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