Study to Estimate Efficacy of Combining Dostarlimab and Niraparib in Relapsed EOC After Treatment With PARPi

NCT05126342 | Withdrawn Phase 2

• 2 other identifiers: AGO-OVAR 2.352021-003572-14
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multicenter, open-label, non-randomized pilot study (Phase II). The aim is to obtain evidence of efficacy of niraparib and dostarlimab (TSR-042) in patients with relapsed ovarian cancer in two experimental cohorts and to generate data on PARPi (Poly(ADP-ribose)-Polymerase inhibitor) resistance and predictive biomarkers for IO (Immuno-Oncology) and PARPi.

Conditions

Recurrent Ovarian Cancer; Recurrent Fallopian Tube Cancer; Primary Peritoneal Cancer

Keywords

Recurrent Ovarian Cancer; Niraparib; Dostarlimab

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Defined as Complete Response rate (CR) plus Partial Response Rate (PR) according to RECIST 1.1 assessments

  At week 16 of treatment

Secondary Outcomes (6)

• Response Rate

  At week 16 of treatment

• Median Progression Free Survival (PFS)

  At 6 months

• 6 months Progression Free Survival (PFS) rate

  At 6 months

• Disease Control Rate (DCR)

  At 16 weeks

• Overall Survival (OS)

  At 12 months

Study Arms (2)

Cohort A

EXPERIMENTAL

Recurrent ovarian-, fallopian tube, or primary peritoneal cancer with relapse after more than 6 months of PARPi maintenance therapy.

Drug: Niraparib; Drug: Dostarlimab

Cohort B

EXPERIMENTAL

Recurrent ovarian-, fallopian tube, or primary peritoneal cancer with relapse within 6 months of PARPi maintenance therapy.

Drug: Niraparib; Drug: Dostarlimab

Interventions

Niraparib DRUG

Niraparib starting dose of study treatment will be based upon the patient's baseline body weight and baseline platelet count. Patients with a baseline body weight ≥77 kg and baseline platelet count ≥150 x 10\^9/L may start with niraparib 300 mg (3 x 100 mg capsules) daily unless the dose has not already been reduced to 200 mg in a prior treatment line. Patients with a baseline body weight \<77 kg or a baseline platelet count \<150 x 10\^9/L will be administered niraparib 200 mg (2 x 100 mg capsules) daily.

Also known as: Zejula

Cohort A; Cohort B

Dostarlimab DRUG

Dostarlimab (TSR-042) is administered 500 mg iv Q3W for the first 12 weeks. For the remainder of the study dostarlimab (TSR-042) is administered 1000 mg iv Q6W.

Also known as: TSR-042

Cohort A; Cohort B

Eligibility Criteria

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

You may qualify if:

• Cohort A
• Patients with secondary PARPi resistance, i.e. those whose disease has first relapsed more than 6 months after PARPi maintenance therapy
• a. Criterion for relapse can be according to RECIST 1.1, CA-125 (GCIG) or clinical symptoms
• Cohort B
• Patients with primary PARPi resistance, i.e. those whose disease has relapsed within 6 months of PARPi maintenance therapy.
• a. Criterion for relapse can be according to RECIST 1.1, CA-125 (GCIG) or clinical symptoms
• Both cohorts
• Patients with relapsed serous, endometrioid or clear cell epithelial ovarian cancer.
• Histologically confirmed diagnosis (cytology alone excluded) of high-grade serous, endometrioid or clear cell ovarian carcinoma.
• Patients with one or two prior lines of chemotherapy. The last line of chemotherapy should have included platinum.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Estimated life expectancy of at least 3 months.
• Measurable disease according to RECIST or evaluable disease (GCIG CA-125 criteria and other).
• Urgent chemotherapy not clinically needed according to physicians estimation.
• Formalin fixed, paraffin-embedded archival tumor available from the primary or recurrent cancer required for all patients.

You may not qualify if:

• Highly symptomatic disease according to physician´s discretion, i.e. rapid remission is required.
• Patients with mucinous endothelial ovarian cancer.
• Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (e.g. germ cell tumors).
• Ovarian tumors of low malignant potential (e.g. borderline tumors).
• Malignancies other than ovarian cancer (EOC) within 5 years prior to registration, with the exception of those with a negligible risk of metastasis or death (e.g. 5-year OS rate \>90%) and treated with expected curative outcome (such as adequately treated non melanoma skin carcinoma, ductal carcinoma in situ, or stage I low grade uterine cancer).
• More than two prior systemic anticancer regimens; maintenance therapies (e.g. with bevacizumab or PARPi) are not calculated as separate line.
• More than two lines of PARPi therapies.
• Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted).
• The following washout requirements for prior therapies/procedures must be observed:
• g. surgery: ≥3 weeks prior to therapy
• h. investigational therapy: within 4 weeks or within less than at least 5 half-lives, whichever is shorter, prior to therapy
• i. radiation: radiation encompassing \>20% of bone marrow ≤2 weeks prior to therapy
• Patient has any known history or current diagnosis of MDS or AML.
• Prior treatment with immune checkpoint blockade therapies, anti-PD1, or anti-PD-L1 therapeutic antibodies or anti-CTLA4 or anti-TIM-3, or participating in AGO-OVAR 2.29 trial.
• Treatment with systemic immunostimulatory agents (including but not limited to interferon-alpha (IFN-α) and interleukin-2 (IL-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to cycle 1, day 1.

Sponsors & Collaborators

• AGO Research GmbH: lead
• GlaxoSmithKline: collaborator

Related Links

• Homepage of AGO Research GmbH

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

niraparib; dostarlimab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study population will be divided into 2 cohorts: Cohort A: Recurrent ovarian-, fallopian tube, or primary peritoneal cancer with relapse after more than 6 months of PARPi maintenance therapy. Cohort B: Recurrent ovarian-, fallopian tube, or primary peritoneal cancer with relapse within 6 months of PARPi mainte-nance therapy. Both cohorts will receive the selective PARP 1/2 inhibitor niraparib in combination with the anti-PD-1 checkpoint inhibitor dostarlimab (TSR-042).

Study Record Dates

• First Submitted: October 18, 2021
• First Posted: November 19, 2021
• Study Start: November 1, 2023
• Primary Completion: November 1, 2024
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 6, 2025

Record last verified: 2025-04