What is the mechanism of action of this treatment?

PARP inhibitors such as Niraparib and Olaparib work by inhibiting the enzyme poly (ADP-ribose) polymerase (PARP), which plays a crucial role in repairing DNA damage in cells. By blocking PARP, these drugs prevent cancer cells from repairing their DNA, leading to cell death, particularly in cells with existing DNA repair deficiencies like BRCA mutations. RP-3500 (camonsertib) targets DNA damage response pathways, potentially enhancing the effects of PARP inhibitors. This combination is important for solid tumor patients as it offers a targeted treatment strategy that exploits specific weaknesses in cancer cell DNA repair mechanisms, potentially improving treatment efficacy and reducing side effects compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

The most common side effects of PARP inhibitors such as Niraparib and Olaparib, especially when used in combination with RP-3500 (camonsertib), include hematologic toxicities like anemia, neutropenia, and thrombocytopenia. Non-hematologic side effects often reported are nausea, fatigue, and anorexia. These adverse effects are generally manageable with dose modifications and supportive care.

What prior FDA approvals exist?

The FDA has approved several PARP inhibitors, such as Niraparib and Olaparib, for the treatment of solid tumors, particularly in ovarian and prostate cancers. These approvals are often based on the presence of specific genetic mutations like BRCA1/2. For instance, Olaparib has been approved for use in BRCA-mutated ovarian cancer and metastatic castration-resistant prostate cancer. Similarly, Niraparib has been approved for maintenance treatment in recurrent ovarian cancer. These treatments are now being studied in combination with other agents, such as RP-3500 (camonsertib), to potentially enhance their efficacy in advanced solid tumors.

What other types of research exist?

Promising novel alternatives to Niraparib or Olaparib in combination with RP-3500 (camonsertib) for solid tumors include the combination of HMA (hypomethylating agents) with venetoclax or ivosidenib. These combinations have shown benefits in other cancer types and may offer potential for solid tumors as well. Additionally, the combination of lenvatinib plus pembrolizumab has demonstrated significant efficacy in renal cell carcinoma and could be considered for solid tumors.

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Protein Kinase Inhibitor

RP-3500 + PARP Inhibitors for Advanced Cancer (ATTACC Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by Repare Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

Ability to swallow and retain oral medications

Must not have

Chemotherapy, small molecule anticancer or biologic anticancer therapy given within 10 days or 5 half-lives (whichever is longer), prior to first dose of study drug

Major surgery ≤28 days or minor surgical procedures ≤7 days prior to first study treatment dose

Timeline

Screening 3 weeks

Treatment Varies

Follow Up while on study therapy, every 6 weeks for first 5 months and then every 9 weeks thereafter

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include issues related to organ function such as blood cell counts and digestive health; however, specific side effects will depend on individual patient reactions and which drug combination they receive.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I can swallow and keep down pills.

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My advanced cancer has not responded to standard treatments.

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My tumor has specific markers identified by a certified lab test.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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

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I have previously been treated with an ATR or DNA-PK inhibitor.

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I have been diagnosed with MDS or AML.

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I am not receiving any other cancer treatments while on this study.

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I have brain metastases that are not under control and cause symptoms.

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I do not have any other active invasive cancers.

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My high blood pressure is not under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ while on study therapy, every 6 weeks for first 5 months and then every 9 weeks thereafter

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~while on study therapy, every 6 weeks for first 5 months and then every 9 weeks thereafter

This trial's timeline: 3 weeks for screening, Varies for treatment, and while on study therapy, every 6 weeks for first 5 months and then every 9 weeks thereafter for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase Ib - Safety and Tolerability of niraparib or olaparib in combination with RP-3500 (camonsertib) by assessing the grade and frequency of adverse events and serious adverse events.

Primary Phase 1b - Define Maximum Tolerated Dose of RP-3500-03 (camonsertib) in combination with niraparib or olaparib and Recommended Phase 2 Dose and preferred schedule by assessing frequency of Dose Limiting Toxicities observed at each dose level

Primary Phase 2 - Assess preliminary anti-tumor activity of RP-3500 (camonsertib) with niraparib or olaparib in patients with eligible advanced solid tumors

Secondary study objectives

To assess PK parameters of RP-3500 (camonsertib) in combination with niraparib or olaparib - AUC

To assess PK parameters of RP-3500 (camonsertib) in combination with niraparib or olaparib -Cmax

To assess PK parameters of RP-3500 (camonsertib) in combination with niraparib or olaparib -Tmax

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Phase Ib Dose EscalationExperimental Treatment1 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 CohortsExperimental Treatment1 Intervention

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

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

PARP inhibitors such as Niraparib and Olaparib work by inhibiting the enzyme poly (ADP-ribose) polymerase (PARP), which plays a crucial role in repairing DNA damage in cells. By blocking PARP, these drugs prevent cancer cells from repairing their DNA, leading to cell death, particularly in cells with existing DNA repair deficiencies like BRCA mutations. RP-3500 (camonsertib) targets DNA damage response pathways, potentially enhancing the effects of PARP inhibitors. This combination is important for solid tumor patients as it offers a targeted treatment strategy that exploits specific weaknesses in cancer cell DNA repair mechanisms, potentially improving treatment efficacy and reducing side effects compared to traditional chemotherapy.