RP-3500 + PARP Inhibitors for Advanced Cancer

(ATTACC Trial)

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

196 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug combination to treat advanced cancers. It combines camonsertib with existing drugs niraparib or olaparib to see if it is safe and effective. The goal is to make it harder for cancer cells to fix themselves, which could help stop the cancer from growing. Olaparib and niraparib have shown effectiveness in treating ovarian cancer.

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.

What data supports the effectiveness of the drug RP-3500 (camonsertib) combined with PARP inhibitors for advanced cancer?

Research shows that PARP inhibitors, when used in prostate cancer, have improved survival rates and slowed disease progression, especially in patients with specific genetic mutations. This suggests that combining PARP inhibitors with other treatments like RP-3500 could potentially enhance effectiveness in treating advanced cancers. ^{1 2 3 4 5}

What is known about the safety of RP-3500 (camonsertib) and PARP inhibitors in humans?

PARP inhibitors, which are sometimes used with other treatments, can cause blood-related side effects that might require changes to the treatment plan. This is a known issue for people with advanced prostate cancer, but specific safety data for RP-3500 (camonsertib) is not provided in the available research. ^{1 2 6 7 8}

How is the drug RP-3500 + PARP Inhibitors unique for advanced cancer?

The combination of RP-3500 (camonsertib) with PARP inhibitors is unique because it targets DNA damage repair pathways, potentially offering a new treatment option for cancers that have developed resistance to existing therapies. This approach may be particularly beneficial for patients with specific genetic mutations that affect DNA repair. ^{1 9 10 11 12}

Eligibility Criteria

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.

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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

References

1. United States pubmed.ncbi.nlm.nih.gov

PARP inhibitors on the move in prostate cancer: spotlight on Niraparib & update on PARP inhibitor combination trials. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Differential Activity of PARP Inhibitors in BRCA1- Versus BRCA2-Altered Metastatic Castration-Resistant Prostate Cancer. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Application of Poly(ADP-ribose) Polymerase (PARP) Inhibitors in Prostate Cancer. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

PARP Inhibitors as Monotherapy in Daily Practice for Advanced Prostate Cancers. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

A Meta-Analysis of Randomized Clinical Trials Assessing the Efficacy of PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Emergence of BRCA Reversion Mutations in Patients with Metastatic Castration-resistant Prostate Cancer After Treatment with Rucaparib. [2023]

7. France pubmed.ncbi.nlm.nih.gov

Hematological Toxicity of PARP Inhibitors in Metastatic Prostate Cancer Patients with Mutations of BRCA or HRR Genes: A Systematic Review and Safety Meta-analysis. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Homologous Recombination Repair Gene Variants and Outcomes Among Patients With Prostate Cancer Treated With Poly (ADP-ribose) Polymerase Inhibitors. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

PARP inhibitors in breast and ovarian cancer with BRCA mutations: a meta-analysis of survival. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Hematological Toxicities with PARP Inhibitors in Prostate Cancer: A Systematic Review and Meta-Analysis of Phase II/III Randomized Controlled Trials. [2023]

11. England pubmed.ncbi.nlm.nih.gov

PARP inhibitors in castration-resistant prostate cancer. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

CX-5461 Sensitizes DNA Damage Repair-proficient Castrate-resistant Prostate Cancer to PARP Inhibition. [2022]