Niraparib and Dostarlimab for Patients With MMR-D/MSI-H Colorectal Cancers

NCT06365970 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HCC 23-056
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The second line of therapy for patients with MSI-H CRC who experience disease progression on anti-PD1 based therapies is not well defined and there is an unmet need for research for patients with anti-PD1 refractory MSI-H CRC. This study will examine the combination of niraparib and dostarlimab for a synergistic antitumor effect for patients with MSI-H CRC.

Conditions

MMR-D/MSI-H Colorectal Cancers

Keywords

PARP inhibitor; MRE11 deficiency; Immune checkpoint inhibitor; Homologous recombination defect; HRD; MSI-H/MMR-D Colorectal cancer; Niraparib; Dostarlimab

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Percentage of evaluable patients that experience an objective response (Complete Response (CR) or Partial Response (PR)), per RECISIT v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm. PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Up to 12 months

Secondary Outcomes (4)

• Adverse Events Related to Treatment

  Up to 12 months

• Progression-free Survival (PFS)

  Up to 36 months

• Duration of Response (DoR)

  Up to 36 months

• Overall Survival (OS)

  Up to 36 months

Study Arms (1)

Niraparib + Dostarlimab

EXPERIMENTAL

Niraparib: 300/200 mg daily (weight-based dosing\*) Dostarlimab: 500 mg Q3 weeks \*Weight-based dosing: Patients weighing ≥77 kg (≥170 lbs) AND a platelet count ≥150,000/mcL, the niraparib dose is determined to be 300 mg taken orally once daily continuously in combination with dostarlimab 500 mg every 3 weeks. Patients weighing \<77 kg (\<170 lbs) OR with a platelet count \<150,000/mcL, the niraparib dosage will be 200 mg taken orally, once daily continuously in combination with dostarlimab 500 mg every 3 weeks (Q3W)

Drug: Niraparib; Drug: Dostarlimab

Interventions

Niraparib DRUG

An anti-cancer medication that helps to repair DNA when it becomes damaged, known as a PARP inhibitor.

Also known as: Zejula

Niraparib + Dostarlimab

Dostarlimab DRUG

An anti-cancer medication that is a programmed death receptor-1 -blocking monoclonal antibody.

Also known as: Jemperli

Niraparib + Dostarlimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed mismatch repair deficient or microsatellite instability high advanced stage colorectal cancer
• Measurable disease per RECIST v1.1
• ECOG 0 to 2
• Age ≥ 18 years
• Able to swallow oral medication (tablets).
• Progression on prior anti-PD1 ± anti-CTLA4 therapy.
• Adequate organ function based on the following lab assessments:
• ANC must be ≥ 1500/mm3.
• Platelet count must be ≥ 100,000/mm3.
• WBC count ≥ 2.5 × 109 /L
• Hemoglobin must be ≥ 9 g/dL.
• Alkaline phosphatase ≤ 2.5× upper limit of normal (ULN) with the exception of patients with documented liver or bone metastases who should have ALP ≤ 5.0× ULN.
• AST and ALT≤ 2.5× ULN with the exception of patients with documented liver metastases who may have AST and/or ALT ≤ 5.0× ULN.
• International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation.
• Total bilirubin ≤ 1.5× ULN (≤3× ULN if Gilbert syndrome present)

You may not qualify if:

• More than 2 lines of systemic therapy (excluding adjuvant therapy)
• Prior oxaliplatin based chemotherapy for metastatic disease. This excludes adjuvant oxaliplatin. Patients who received oxaliplatin based chemotherapy for metastatic disease before determination of MMR-D/MSI-H status (due to test turn-around time) can be enrolled if they received 4 or less cycle of oxaliplatin treatment (each cycle is one dose).
• More than 1 line of anti-PD1 based therapy.
• History of severe hypersensitivity to anti-PD1 monoclonal antibodies
• Prior PARPi
• Progression on platinum-based chemotherapy
• Active autoimmune disease requiring immune suppression except following conditions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone without an active complication are eligible for the study.
• Patients with well controlled Type 1 diabetes mellitus who are actively on an insulin regimen are eligible for the study.
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Disease is well controlled at baseline and requires only topical corticosteroids. - No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• Active untreated brain metastasis (patients treated brain metastasis within 4 weeks can be enrolled)
• Any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
• Received colony-stimulating factors (e.g., granulocyte macrophage colony-stimulating factor or recombinant erythropoietin) within 4 weeks.
• Previously or are currently participating in a treatment study of an investigational agent within 4 weeks of the first dose of therapy preceding the study.

Sponsors & Collaborators

• Ibrahim Halil Sahin: lead
• GlaxoSmithKline: collaborator

MeSH Terms

Interventions

niraparib; dostarlimab

Study Officials

• Ibrahim H Sahin, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medical oncology

Study Record Dates

• First Submitted: March 29, 2024
• First Posted: April 15, 2024
• Study Start: January 31, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: February 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share