Combination Drug Therapy for Cancer

(DIDO Trial)

Overseen By Amanda Fletcher, RN

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: West Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Prostate cancer, Ovarian cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, niraparib (a PARP inhibitor) and dostarlimab (an immunotherapy), to evaluate their effectiveness against certain advanced cancers. It targets solid tumors with specific gene mutations affecting DNA repair. Suitable candidates for this trial include individuals whose cancer has spread, recurred, or cannot be surgically removed, and who have a gene mutation related to DNA repair issues. The trial aims to assess both the effectiveness and safety of this drug combination for these cancer types. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

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, certain conditions like recent surgery, radiation, or investigational therapy might require a waiting period before starting the trial. 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 niraparib and dostarlimab has been studied before, with no major safety concerns identified. One study with ovarian cancer patients demonstrated some benefits without significant safety issues. Another study on the same drug combination confirmed that the safety results aligned with existing knowledge, indicating no unexpected problems.

In simpler terms, available data suggests that niraparib and dostarlimab are generally well-tolerated. While every treatment can have side effects, evidence so far does not indicate any serious safety risks with this combination. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for cancer?

Researchers are excited about using niraparib and dostarlimab in combination for cancer treatment because these drugs work in a novel way compared to traditional therapies. Niraparib is a PARP inhibitor, which helps prevent cancer cells from repairing their DNA, making them more vulnerable to damage. Dostarlimab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. By combining these two mechanisms, the treatment has the potential to be more effective than standard options, which often focus on chemotherapy or single-agent therapies.

What evidence suggests that this combination drug therapy could be effective for cancer?

Research has shown that using niraparib and dostarlimab together may help treat certain cancers with specific genetic traits. In one study, 17.1% of patients experienced tumor shrinkage or halted growth with this combination. Another study found that this treatment could extend patients' lives, with an average of 3.8 months before cancer progression and a total survival time of 10.1 months. While niraparib alone did not perform as well as expected, combining it with dostarlimab proved more effective. These results suggest potential benefits for patients with specific genetic changes in their tumors. ^{4 6 7 8 9}

Who Is on the Research Team?

Gregory Vidal, MD

Principal Investigator

West Cancer Center

Are You a Good Fit for This Trial?

Adults with certain unresectable or metastatic solid tumors containing specific HRD gene mutations, who are in good physical condition (ECOG ≤ 1), and have proper organ function. Participants must agree to use effective contraception and not donate blood during the study. HIV-positive patients on successful treatment can join. Those with recent major surgery, other cancer treatments, or certain medical conditions are excluded.

Inclusion Criteria

I am not pregnant and agree to use effective birth control during the study.

My cancer has spread, can't be removed by surgery, and has specific genetic changes.

My blood tests show my organs are working well.

Exclusion Criteria

I have active hepatitis B or C.

I haven't had a blood transfusion in the last 4 weeks.

I do not have brain metastases or any signs of bleeding in the brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive niraparib and dostarlimab combination therapy

16 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Niraparib and Dostarlimab

Trial Overview The trial is testing a combination of niraparib and dostarlimab for effectiveness and safety in treating solid tumors with HRD gene mutations. It's an open-label, single-arm Phase 2 study where all participants receive the same drug combo without a comparison group.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

niraparib and dostarlimab

Who Is Running the Clinical Trial?

West Cancer Center

Lead Sponsor

Trials

5

Recruited

600+

Published Research Related to This Trial

Niraparib significantly prolongs progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer, with a median PFS of 18.3 months compared to 5.4 months for placebo, indicating a 68% reduction in the risk of disease progression or death.

The treatment was generally safe, though 50.8% of patients experienced grade ≥3 adverse events, with the most common being decreased neutrophil count and anemia, highlighting the importance of monitoring for side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial☆. Wu, XH., Zhu, JQ., Yin, RT., et al.[2021]

In a clinical trial involving 55 patients with advanced solid tumors, the PD-1 inhibitor dostarlimab was found to be well tolerated in both doublet and triplet combination therapies, with no new safety concerns arising.

The triplet combinations showed higher disease control rates compared to doublets, with preliminary antitumor activity observed in various combinations, indicating potential for improved efficacy in treating advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IOLite: phase 1b trial of doublet/triplet combinations of dostarlimab with niraparib, carboplatin-paclitaxel, with or without bevacizumab in patients with advanced cancer. Yap, TA., Bessudo, A., Hamilton, E., et al.[2022]

Niraparib (NIRA) is an effective treatment for patients with metastatic castration-resistant prostate cancer who have specific genetic alterations, showing promising results in a Phase II study.

When combined with abiraterone acetate and prednisone, NIRA demonstrated a manageable safety profile while effectively disrupting cancer cell signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niraparib with Abiraterone Acetate and Prednisone for Metastatic Castration-Resistant Prostate Cancer: Phase II QUEST Study Results. Chi, KN., Fleshner, N., Chiuri, VE., et al.[2023]

The combination of everolimus and niraparib in a Phase 1 trial showed significant toxicity, particularly severe hypertension and thrombocytopenia, leading to the conclusion that this treatment regimen is not feasible for patients with advanced ovarian and breast cancers.

Despite the high toxicity, the treatment resulted in a modest progression-free survival (PFS) of 6 months and an overall survival (OS) of approximately 18 months, with three patients still alive, suggesting that further research into this combination therapy may be warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 evaluation of the safety and tolerability of niraparib in combination with everolimus in advanced ovarian and breast cancers. Starks, D., Rojas-Espaillat, L., Meissner, T., et al.[2023]

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]

The study investigates the safety and effectiveness of combining niraparib, a PARP inhibitor, with dostarlimab, an immune checkpoint inhibitor, in treating advanced non-small-cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) in patients with homologous recombination deficiency (HRD) and PD-L1 expression of 1% or higher.

A total of 700 to 1000 patients will be screened to find 70 eligible participants, with the primary goal of assessing progression-free survival, while also evaluating overall survival and safety, highlighting the potential for this combination therapy to enhance cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prospective Phase II Single-arm Study of Niraparib Plus Dostarlimab in Patients With Advanced Non-small-cell Lung Cancer and/or Malignant Pleural Mesothelioma, Positive for PD-L1 Expression and Germline or Somatic Mutations in the DNA Repair Genes: Rationale and Study Design. Passiglia, F., Bironzo, P., Righi, L., et al.[2021]

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]

Niraparib, a PARP inhibitor for recurrent ovarian cancer, showed no significant changes in its pharmacokinetics when taken with a high-fat meal compared to fasting, indicating it can be safely taken with or without food.

The study demonstrated that niraparib was well-tolerated and had similar adverse events regardless of the meal condition, confirming its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of food on the pharmacokinetics of niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, in patients with recurrent ovarian cancer. Moore, K., Zhang, ZY., Agarwal, S., et al.[2019]

Niraparib, a PARP inhibitor, significantly improves progression-free survival in patients with advanced epithelial ovarian cancer, but nearly all patients (≥99%) experience treatment-emergent adverse events, with 51-74% experiencing severe (grade ≥3) events.

An individualized starting dose of niraparib based on body weight and platelet count leads to fewer severe adverse events and dose modifications, suggesting a tailored approach can enhance safety while maintaining treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and management of niraparib monotherapy in ovarian cancer clinical trials. Monk, BJ., González-Martin, A., Buckley, L., et al.[2023]

In a Phase 2 study involving 20 Japanese women with heavily pretreated ovarian cancer, niraparib demonstrated an objective response rate of 35%, indicating that it can effectively reduce tumor size in some patients.

The treatment was generally well-tolerated, with a high disease control rate of 90%, although common side effects included anemia and nausea, and 70% of patients experienced dose reductions or interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 single-arm study on the efficacy and safety of niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer. Okamoto, A., Kondo, E., Nakamura, T., et al.[2021]

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]

Niraparib, a treatment for recurrent ovarian cancer, has a high dose reduction rate of 68.9% due to treatment-emergent adverse events, with thrombocytopenia being a notable cause for 3.3% of patients.

Baseline body weight and platelet count are significant predictors for the risk of severe thrombocytopenia, suggesting that patients with a body weight under 77 kg or platelet count below 150,000/µl may benefit from starting at a lower dose of 200 mg/day without compromising progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and dose modification for patients receiving niraparib. Berek, JS., Matulonis, UA., Peen, U., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12146980/

Phase II Study Evaluating the Efficacy of Niraparib and ... At a median follow-up of 10.13 months, the median progression-free survival was 3.8 months, and the median overall survival was 10.1 months. The ...

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

Dostarlimab and niraparib in primary advanced ovarian ... Patient-reported outcomes ... Completion rates for EQ-5D-5L and EORTC QLQ-C30 were >85% in both treatment arms, with most visits remaining >80% ...

3. ascopubs.org ascopubs.org/doi/10.1200/PO.23.00693

Findings From Cohort A of the OPAL Phase II Trial In this phase II study, the triplet combination of niraparib-dostarlimab-bevacizumab resulted in a confirmed investigator-assessed 17.1% ORR.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05870761

Study Details | NCT05870761 | Combination Niraparib and ... Giving niraparib and dostarlimab may work better in treating patients with uterine serous carcinoma. Detailed Description. PRIMARY OBJECTIVE: I. To evaluate the ...

5. nature.com nature.com/articles/s41467-023-37084-w

Clinical outcome and biomarker assessments of a multi ... In conclusion, niraparib monotherapy did not meet the efficacy threshold. Niraparib in combination with dostarlimab showed modest activity.

6. 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 ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38754056/

Findings From Cohort A of the OPAL Phase II Trial - PubMed Conclusion: Results demonstrated modest activity of niraparib, dostarlimab, and bevacizumab in participants with PROC, many of whom had prognostic factors for ...

8. 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 ...

9. 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 ...