Platinum-based Therapy + Dostarlimab + Niraparib for Ovarian Cancer

(FIRST Trial)

Recruiting at 270 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Tesaro, Inc.

Must be taking: Platinum-based chemotherapy

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Pregnancy, CNS metastases, Cardiovascular disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 15 weeks

1402 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for advanced or metastatic ovarian cancer using a combination of drugs, including dostarlimab (an immunotherapy drug) and niraparib (a PARP inhibitor), alongside standard chemotherapy. The goal is to determine if this combination can extend the time patients live without their cancer worsening. Individuals diagnosed with stage III or IV high-grade non-mucinous epithelial ovarian cancer, who have not received prior treatment for this condition, may be suitable candidates. Participants will receive either the new drug combination or standard treatment to compare effectiveness. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or have received a live vaccine recently, you may need to adjust your treatment. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of dostarlimab and niraparib is generally safe for patients. Most individuals can take these treatments without major issues. Specifically, one study found no serious safety concerns when using these two drugs together. Some patients experienced side effects, but they were mostly mild. Common side effects included fatigue and nausea, which are typical for cancer treatments.

Since this trial is in a late phase, extensive safety information is already available. This indicates that the treatment has been tested in many people before and is considered safe enough for a larger group. Prospective participants might find this information reassuring regarding the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of dostarlimab and niraparib for ovarian cancer because it offers a novel approach beyond the standard of care, which typically includes chemotherapy agents like carboplatin and paclitaxel, sometimes with bevacizumab. Dostarlimab is a type of immunotherapy known as a PD-1 inhibitor, which helps the immune system recognize and attack cancer cells more effectively. Niraparib is a PARP inhibitor that targets cancer cell DNA repair mechanisms, potentially enhancing the effects of chemotherapy. This combination aims to improve patient outcomes by leveraging both immune system activation and disrupting cancer cell repair processes, offering hope for more effective treatment options.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

Research has shown that combining dostarlimab and niraparib may be promising for treating advanced ovarian cancer. In this trial, some participants will receive the combination of dostarlimab and niraparib alongside standard of care (SOC), while others will receive SOC with niraparib or SOC with a placebo. One study found that the combination of dostarlimab and niraparib helped patients live longer without their cancer worsening compared to standard treatments. Dostarlimab aids the immune system in identifying and attacking cancer cells. Niraparib, a PARP inhibitor, prevents cancer cells from repairing themselves, leading to their death. Together, these treatments attack cancer from different angles, offering a potentially more effective approach. ^{2 3 4 6 7}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

This trial is for women aged 18+ with advanced non-mucinous epithelial ovarian cancer (Stage III/IV). They must be postmenopausal, surgically sterilized, or use contraception. Eligible participants should have an ECOG score of 0 or 1, can take oral meds, and have normal blood pressure or controlled hypertension. They cannot join if they've had recent major surgery, uncontrolled medical issues, immunodeficiency, certain past cancers within specific time frames, active hepatitis B/C or autoimmune diseases.

Inclusion Criteria

I can provide a specific tissue sample for cancer testing.

I have Stage IV cancer and may have surgery or chemotherapy planned.

I have advanced ovarian, fallopian tube, or peritoneal cancer.

Exclusion Criteria

You have active hepatitis B or C.

My cancer is of a specific type (mucinous, germ cell, transitional cell, or undifferentiated).

My ovarian cancer is at an early stage (low-grade or Grade 1).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy Run-In

Participants receive SOC during the chemotherapy Run-In period (cycle 1) before randomization to study treatment

3 weeks

1 visit (in-person)

Treatment

Participants receive randomized treatment with SOC chemotherapy +/- bevacizumab followed by niraparib and dostarlimab maintenance +/- bevacizumab

15 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

What Are the Treatments Tested in This Trial?

Interventions

• Dostarlimab (TSR-042)
• Niraparib
• Standard of care

Trial Overview The study compares the effectiveness of platinum-based therapy combined with TSR-042 (dostarlimab) and niraparib versus standard chemotherapy in treating ovarian cancer. It's a global Phase 3 trial focusing on progression-free survival rates. Participants will receive standard care initially before being randomly assigned to either the new drug combination or continued standard treatment.

How Is the Trial Designed?

Group I: Participants receiving SOC+dostarlimab+niraparib Experimental Treatment 3 Interventions

Participants in this arm will receive SOC in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment dostarlimab, and maintenance treatment of +/-bevacizumab with niraparib and dostarlimab

Group II: Participants receiving SOC+niraparib Active Control 3 Interventions

Participants in this arm will receive SOC in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment dostarlimab placebo from cycles 2 to 6 and maintenance treatment of +/- bevacizumab with niraparib and dostarlimab placebo

Group III: Participants receiving SOC+placebo Placebo Group 3 Interventions

Participants in this arm will receive SOC (carboplatin+paclitaxel+/-bevacizumab) in cycle 1 (each cycle is of 21 days) followed by SOC with chemotherapy treatment with dostarlimab placebo from cycles 2 to 6 and maintenance treatment of +/-bevacizumab along with niraparib placebo and dostarlimab placebo

Dostarlimab (TSR-042) is already approved in European Union, United States for the following indications:

Approved in European Union as Jemperli for:

• Endometrial cancer

Approved in United States as Jemperli for:

• Mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer
• Solid tumors with dMMR

Who Is Running the Clinical Trial?

Tesaro, Inc.

Lead Sponsor

Trials

57

Recruited

10,600+

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

Published Research Related to This Trial

Recent advancements in ovarian cancer treatment have introduced several new options that show improved survival rates compared to historical data, marking a significant progress after decades of stagnation.

Three new PARP inhibitors (olaparib, rucaparib, niraparib) have been approved for ovarian cancer, providing new maintenance and recurrence treatment options, alongside expanded uses for bevacizumab in combination chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Therapies for Ovarian Cancer. O'Malley, DM.[2020]

In a study of 105 patients with newly diagnosed advanced ovarian cancer, the combination of niraparib and bevacizumab as first-line maintenance therapy resulted in a promising progression-free survival (PFS) rate of 62% at 18 months, with even higher rates in patients with homologous recombination deficiency (76%).

The safety profile of this combination therapy was consistent with the known side effects of the individual drugs, with common treatment-related adverse events including thrombocytopenia, fatigue, and anemia, indicating that the treatment is manageable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab. Hardesty, MM., Krivak, TC., Wright, GS., et al.[2022]

Niraparib significantly extends progression-free survival in patients with newly diagnosed advanced ovarian cancer, showing efficacy in both homologous-recombination deficiency positive (HRd) and negative (HRp) populations, based on a phase III trial.

The treatment has a manageable safety profile, with myelosuppression as the main concern, which can be effectively managed through monitoring and individualized dosing based on weight and platelet count.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in First-Line Maintenance Therapy in Advanced Ovarian Cancer. Lee, A.[2022]

Niraparib significantly improves progression-free survival and other key outcomes in patients with recurrent, platinum-sensitive ovarian cancer, based on the phase III NOVA trial involving a randomized, double-blind, placebo-controlled design.

The treatment has a manageable safety profile, with most serious side effects being blood-related issues, which can be effectively managed through dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib: A Review in Ovarian Cancer. Heo, YA., Duggan, ST.[2019]

Niraparib is an FDA and EMA-approved oral PARP inhibitor for maintenance treatment in women with recurrent ovarian cancer who have responded to platinum-based chemotherapy, showing efficacy in both BRCA mutated and wild-type cancers.

While niraparib is effective, it can cause significant hematologic toxicities, such as thrombocytopenia and anemia, necessitating dose adjustments for certain patients to minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The poly (ADP ribose) polymerase inhibitor niraparib: Management of toxicities. Moore, KN., Mirza, MR., Matulonis, UA.[2019]

In a study of 94 patients with non-gBRCA1/2 mutated recurrent ovarian cancer, niraparib maintenance treatment demonstrated effectiveness similar to phase III trials, with a median time to first subsequent treatment of 10.7 months.

Individualized dosing based on patient weight and platelet counts led to fewer dose reductions and interruptions, highlighting the importance of personalized treatment to enhance safety and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data on niraparib maintenance treatment in patients with non-gBRCA mutated platinum-sensitive recurrent ovarian cancer. Vilming, B., Fallås Dahl, J., Bentzen, AG., et al.[2023]

The combination treatment of dostarlimab and niraparib in patients with recurrent platinum-resistant ovarian cancer showed a low objective response rate of only 7.3%, leading to the early termination of the study due to insufficient efficacy.

Despite the treatment being generally safe with no new safety issues identified, 95.1% of patients experienced treatment-related adverse events, and health-related quality of life worsened over time, indicating a need for more effective therapies for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib and dostarlimab for the treatment of recurrent platinum-resistant ovarian cancer: results of a Phase II study (MOONSTONE/GOG-3032). Randall, LM., O'Malley, DM., Monk, BJ., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40461381/

Dostarlimab and niraparib in primary advanced ovarian ... Results: From 14 November 2018 to 5 January 2021, 1138 patients were randomized to arms 2 (n = 385) and 3 (n = 753) and included in efficacy ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00201-7/fulltext

Dostarlimab and niraparib in primary advanced ovarian ... Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05126342

Study to Estimate Efficacy of Combining Dostarlimab and ... 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 ...

4. aacrjournals.org aacrjournals.org/cancerrescommun/article/5/6/939/762896/Phase-II-Study-Evaluating-the-Efficacy-of

Phase II Study Evaluating the Efficacy of Niraparib and ... We designed a single-arm, open-label, phase II clinical trial to evaluate the combination of niraparib and dostarlimab in patients with R/M HNSCC.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA5506

FIRST/ENGOT-OV44: A phase 3 clinical trial of dostarlimab ... Niraparib efficacy and safety in patients with BRCA mutated (BRCAm) ovarian cancer: Results from three phase 3 niraparib trials. Antonio ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03955471

NCT03955471 | Study to Evaluate the Efficacy and Safety ... This is an open-label, single-arm Phase 2 study to evaluate the efficacy and safety of combination of niraparib and dostarlimab (TSR-042) in participants ...

7. targetedonc.com targetedonc.com/view/first-trial-no-safety-interaction-between-dostarlimab-and-niraparib

FIRST Trial: No Safety Interaction Between Dostarlimab ... A recent trial evaluates the impact of dostarlimab on ovarian cancer treatment, revealing modest benefits and no significant safety concerns ...