Niraparib + Dostarlimab for Colorectal Cancer

Overseen By Debra Diecks, MSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ibrahim Halil Sahin

Must not be taking: Oxaliplatin, PARPi, others

Disqualifiers: Autoimmune, Brain metastasis, Pneumonitis, 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

Compensation: Varies

Number of Visits: 3

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for colorectal cancer that hasn't responded well to previous therapies. Researchers are testing niraparib (a PARP inhibitor) and dostarlimab (an anti-PD-1 therapy) together to determine if they can more effectively target tumors in patients with MSI-H colorectal cancer. Individuals with this condition, whose cancer has progressed despite anti-PD1 therapies, might be suitable candidates. This study provides an opportunity to try a new approach when other options have failed. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

Is there any evidence suggesting that the combination of niraparib and dostarlimab is likely to be safe for humans?

Research has shown that the combination of niraparib and dostarlimab is generally safe and well-tolerated. A recent study on ovarian cancer found no major safety issues when these two drugs were used together. Another study aimed to determine the safest dose of these drugs, emphasizing that safety remains a key concern in ongoing research.

Although these studies focus on different types of cancer, they provide some reassurance about the safety of this drug combination. When these treatments are tested in people, they have typically passed initial safety checks. However, individual experiences may vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Niraparib and Dostarlimab for colorectal cancer because they bring a fresh approach to treatment. Unlike traditional chemotherapy that attacks fast-growing cells indiscriminately, Dostarlimab is an immunotherapy that helps the immune system recognize and destroy cancer cells by blocking the PD-1 pathway. Niraparib, on the other hand, is a PARP inhibitor that targets cancer cells' ability to repair their DNA, which can enhance the effectiveness of the immune response. Together, these drugs may offer a more targeted and potentially less toxic treatment option for patients, which is a big step forward from the current standard of care.

What evidence suggests that the combination of niraparib and dostarlimab could be an effective treatment for colorectal cancer?

Research has shown that using niraparib and dostarlimab together may help treat microsatellite instability-high colorectal cancer (MSI-H CRC). In one study, 13% of patients experienced complete cancer remission, and 30% saw a significant reduction in their cancer. Although niraparib alone hasn't met expectations, its combination with dostarlimab has demonstrated positive effects on tumors. This suggests that these drugs might be more effective together in combating this cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Ibrahim H. Sahin

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with a specific type of colorectal cancer that has high microsatellite instability (MSI-H) or matches Lynch syndrome criteria. It's aimed at those whose cancer progressed despite anti-PD1 therapy and are looking for new treatment options.

Inclusion Criteria

I am a man and will use contraception and not donate sperm.

I can care for myself and am up and about more than 50% of my waking hours.

Women of childbearing potential must use highly effective contraception

Exclusion Criteria

Active autoimmune disease requiring immune suppression

Participation in a treatment study of an investigational agent within 4 weeks

Presence of hepatitis B surface antigen or positive hepatitis C virus antibody test result

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 for MSI-H colorectal cancer

12 months

Dostarlimab administered every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Dostarlimab
• Niraparib

Trial Overview The study is testing the combination of two drugs, Niraparib and Dostarlimab, to see if they work better together in treating MSI-H colorectal cancers. The goal is to find an effective second-line therapy for these patients.

How Is the Trial Designed?

Group I: Niraparib + Dostarlimab Experimental Treatment 2 Interventions

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)

Dostarlimab is already approved in European Union, United States for the following indications:

Approved in European Union as Jemperli for:

• Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer
• dMMR/MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen

Approved in United States as Jemperli for:

• Adults with dMMR recurrent or advanced solid tumors who have progressed on or following prior treatment and lack satisfactory alternative treatment options
• Primary advanced or recurrent dMMR endometrial cancer in combination with carboplatin and paclitaxel

Who Is Running the Clinical Trial?

Ibrahim Halil Sahin

Lead Sponsor

Trials

2

Recruited

150+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06365970

Niraparib and Dostarlimab for Patients With MMR-D/MSI-H ... This study will examine the combination of niraparib and dostarlimab for a synergistic antitumor effect for patients with MSI-H CRC. Detailed Description. In ...

2. 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 ...

3. clin.larvol.com clin.larvol.com/trial-detail/NCT02715284

garnet / nct02715284 Overall, 13% of patients had a complete response and 30% of patients had a partial response...Data accepted as a late-breaking abstract and presented as a ...

4. onclive.com onclive.com/view/data-for-first-line-dostarlimab-and-niraparib-in-advanced-ovarian-cancer-the-first-trial

Data for First-Line Dostarlimab and Niraparib in Advanced ... Tara Berman, MD, MS, and Gottfried E. Konecny, MD, discuss data for dostarlimab plus niraparib in advanced ovarian cancer.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10017680/

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. clinicaltrials.gov clinicaltrials.gov/study/NCT04926324

NCT04926324 | A Safety Study Adding Niraparib and ... This clinical trial is designed to determine the maximum tolerated dose of niraparib when combined with dostarlimab and hypofractionated radiation for ...

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 ...

8. gsk.com gsk.com/en-gb/media/press-releases/gsk-announces-first-trial-met-its-primary-endpoint-of-progression-free-survival-in-first-line-advanced-ovarian-cancer/

GSK announces FIRST trial met its primary endpoint of ... The trial met its primary endpoint of PFS demonstrating a statistically significant difference with the addition of dostarlimab to both standard of care ...

9. cancernetwork.com cancernetwork.com/view/dostarlimab-chemo-maintenance-niraparib-show-modest-improvements-in-ovarian-cancer

Dostarlimab/Chemo, Maintenance Niraparib Show Modest ... The median PFS with dostarlimab plus niraparib was 20.6 months vs 19.2 months with niraparib alone in patients with treatment-naive advanced ...