RP-3500 + PARP Inhibitors for Advanced Cancer

(ATTACC Trial)

No longer recruiting at 12 trial locations

Overseen By Paul Basciano, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Repare Therapeutics

Must not be taking: Anticancer therapy

Disqualifiers: Brain metastases, High blood pressure, MDS, AML, others

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

Compensation: Varies

Number of Visits: 21

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for advanced solid tumors that haven't responded to standard treatments. It combines RP-3500 (camonsertib, an experimental treatment) with existing drugs, niraparib or olaparib, to evaluate the safety and effectiveness of this combination against cancer. The trial seeks to determine the best dose and understand how the drugs work together to combat tumors. People with advanced solid tumors who haven't had success with other treatments and can take oral medications might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking any other anticancer therapies while participating. Additionally, you must not have had chemotherapy or certain other treatments within 10 days or 5 half-lives before starting the study.

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

Research has shown that RP-3500 (camonsertib) is generally safe when used alone, based on earlier studies. Patients have mostly tolerated it well, with manageable side effects. When combined with niraparib, a drug already approved for some ovarian cancers, the combination also appears safe. Past trials have demonstrated niraparib's effectiveness and safety.

For the combination of RP-3500 with olaparib, another approved cancer drug, early results suggest it is safe. Studies have shown that olaparib is well-tolerated by patients with advanced cancers. Both niraparib and olaparib have proven safety records, supporting their use with RP-3500.

In summary, combining RP-3500 with either niraparib or olaparib has been well-tolerated so far, with safety data supporting their use in ongoing research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RP-3500 (camonsertib) because it targets cancer cells with a new mechanism, potentially enhancing the effects of existing PARP inhibitors like niraparib and olaparib. Unlike traditional therapies that solely focus on blocking PARP enzymes, RP-3500 specifically inhibits a protein called ATR, which plays a crucial role in DNA repair in cancer cells. This dual-action approach could lead to more effective cancer cell destruction, even in cases where other treatments may have limited success. By combining RP-3500 with PARP inhibitors, this treatment aims to exploit vulnerabilities in cancer cells more thoroughly, offering hope for improved outcomes in advanced cancer cases.

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

This trial will evaluate the combination of RP-3500 (camonsertib) with either niraparib or olaparib for treating advanced cancers. Research has shown that these combinations yield promising results, with about 48% of patients experiencing positive effects. Specifically, patients with tumors resistant to platinum-based treatments had a 49% benefit rate, and 12% showed significant improvement. Additionally, camonsertib (RP-3500) alone resulted in a 13% tumor response rate in patients receiving effective doses. Both niraparib and olaparib have proven effective in treating ovarian cancer, supporting their potential when combined with RP-3500. These early findings suggest these treatments could help manage advanced cancers. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

Adults over 18 with advanced solid tumors that no longer respond to standard treatments can join. They must have certain tumor biomarkers, be able to take oral meds, and not be pregnant. People who've had recent cancer treatments or surgery, other active cancers, brain metastases, high blood pressure, or a history of specific blood disorders cannot participate.

Inclusion Criteria

I am fully active or have some restrictions but can still care for myself.

I can swallow and keep down pills.

My advanced cancer has not responded to standard treatments.

Exclusion Criteria

Pregnant or breastfeeding women

I haven't had cancer treatment within the last 10 days or 5 half-lives.

I haven't had major surgery in the last 4 weeks or minor surgery in the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Dose Escalation

Multiple dose levels of RP-3500 (camonsertib) are administered orally in combination with niraparib and/or olaparib to determine the Maximum Tolerated Dose and assess safety and tolerability.

Up to 30 days after last administration

Every 21-28 days per cycle

Phase 2 Expansion Cohorts

Expansion cohort with RP-3500 (camonsertib) in combination with niraparib and/or olaparib to study anti-tumor effect and further examine safety, PK, and PD.

Every 6 weeks for first 5 months, then every 9 weeks

Regular visits as per study schedule

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RP-3500 (camonsertib)

Trial Overview The trial is testing the combination of RP-3500 (camonsertib) with either niraparib or olaparib in patients with advanced solid tumors. It aims to find the safest dose level and see how well it works against these tumors while also studying how the body processes these drugs.

How Is the Trial Designed?

Group I: Phase Ib Dose Escalation Experimental Treatment 1 Intervention

Multiple dose levels of RP-3500 (camonsertib) for oral administration in combination with niraparib and/or Multiple dose levels of RP-3500 (camonsertib) for oral administration in combination with olaparib

Group II: Phase 2 Expansion Cohorts Experimental Treatment 1 Intervention

Expansion cohort with RP-3500 (camonsertib) + niraparib and/or Expansion cohort RP-3500 (camonsertib) + olaparib

Who Is Running the Clinical Trial?

Repare Therapeutics

Lead Sponsor

Trials

10

Recruited

1,300+

Roche Pharma AG

Industry Sponsor

Trials

413

Recruited

430,000+

Dr. Thomas Schinecker

Roche Pharma AG

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Dr. Levi Garraway

Roche Pharma AG

Chief Medical Officer since 2019

MD from University of California, San Francisco

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04972110

NCT04972110 | Study of RP-3500 (Camonsertib) With ... The primary purpose of this study is to assess the safety and tolerability of niraparib or olaparib in combination with RP-3500 (camonsertib), in patients ...

2. clin.larvol.com clin.larvol.com/trial-detail/NCT04972110

Study of RP-3500 (Camonsertib) With Niraparib or ... Overall clinical benefit rate (CBR) for all patients was 48%. Patients with platinum-resistant tumors had an overall response rate (ORR) of 12% and CBR of 49%, ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-08395

Study of RP-3500 (Camonsertib) With Niraparib or ... The primary purpose of this study is to assess the safety and tolerability of niraparib or olaparib in combination with RP-3500 (camonsertib), in patients with ...

4. zejulahcp.com zejulahcp.com/efficacy/

PRIMA Clinical Study | Efficacy | ZEJULA (niraparib) for HCPs PRIMA: A double-blind, placebo-controlled phase 3 trial of patients with newly diagnosed advanced ovarian cancer who were randomized 2:1 to ZEJULA or placebo.

5. ir.reparerx.com ir.reparerx.com/news-releases/news-release-details/repare-therapeutics-presents-initial-clinical-data-phase-12

Repare Therapeutics Presents Initial Clinical Data from the ... The clinical plenary session described initial combination Phase 1/2 results from 107 patients, of which 90 patients were evaluable for efficacy ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9398170/

RP-3500: A Novel, Potent, and Selective ATR Inhibitor that ... RP-3500, olaparib, and niraparib were administered in 0.5% methylcellulose/0.02% SDS vehicle. See Supplementary Methods for data analysis and statistics.

7. mayo.edu mayo.edu/research/clinical-trials/cls-20528101

Study of RP-3500 With Niraparib or Olaparib in Advanced ... The primary purpose of this study is to assess the safety and tolerability of Niraparib or Olaparib in combination with RP-3500, in patients with eligible ...

8. zejula.com zejula.com/about/clinical-trial-results/

Clinical Trial Results | ZEJULA (niraparib) ZEJULA has two FDA-approved uses for women with advanced or recurrent ovarian cancer. See the results from its clinical trials—PRIMA and NOVA. First-line ...