Study of RP-3500, Camonsertib, in Advanced Solid Tumors

NCT ID: NCT04497116

Last Updated: 2025-10-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 276 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-22
• Study Completion Date: 2025-06-13

Brief Summary

The primary purpose of this study is to define the maximum tolerated dose (MTD) and determine a recommended Phase 2 dose (RP2D) and schedule of orally-administered RP-3500 (camonsertib) alone or in combination with talazoparib, a PARP inhibitor, or Gemcitabine in patients with advanced solid tumors with ATR inhibitor-sensitizing mutations. This study will also evaluate the safety and tolerability of RP-3500 (camonsertib) alone or in combination with talazoparib or gemcitabine, examine both the pharmacokinetics (PK)and pharmacodynamics (PD)and investigate its anti-tumor activity in solid tumors.

Detailed Description

This is a first-in-human, Phase 1/2a, multi-center, open-label, dose-escalation and expansion study to:

• Evaluate the safety profile and MTD of RP-3500 (camonsertib) when administered orally, alone and in combination with talazoparib or gemcitabine, to establish the dose and schedule recommended for the Phase 2
• Characterize the PK profile of RP-3500 (camonsertib) alone or in combination with talazoparib or gemcitabine
• Identify anti-tumor activity associated with RP-3500 (camonsertib) given alone or in combination with talazoparib or gemcitabine

The initial cohorts will test RP-3500 (camonsertib) as monotherapy. Additional cohorts will enroll with RP-3500 (camonsertib) in combination with talazoparib or gemcitabine.

After the RP2D and schedule is determined, expansion cohort(s) for RP-3500 (camonsertib) will be enrolled to study the anti-tumor effect, and further examine the safety and PK of RP-3500 (camonsertib) at the RP2D

Conditions

Advanced Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RP-3500 (camonsertib) alone

Phase 1:

Multiple doses of RP-3500 (camonsertib) for oral administration alone

Group Type: EXPERIMENTAL

RP-3500 (camonsertib)

Intervention Type: DRUG

Oral ATR inhibitor

Expansion cohorts with RP-3500 (camonsertib)

Phase 2:

Expansion cohorts with RP-3500 (camonsertib)

Group Type: EXPERIMENTAL

RP-3500 (camonsertib)

Intervention Type: DRUG

Oral ATR inhibitor

RP-3500 (camonsertib) with Talazoparib or Gemcitabine

Phase 1:

Multiple doses of RP-3500 (camonsertib) for oral administration in combination with talazoparib or gemcitabine

Group Type: EXPERIMENTAL

RP-3500 (camonsertib)

Intervention Type: DRUG

Oral ATR inhibitor

Talazoparib

Intervention Type: DRUG

Oral PARP inhibitor

Gemcitabine Injection

Intervention Type: DRUG

Gemcitabine

Interventions

RP-3500 (camonsertib)

Oral ATR inhibitor

Intervention Type: DRUG

Talazoparib

Oral PARP inhibitor

Intervention Type: DRUG

Gemcitabine Injection

Gemcitabine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Written informed consent, according to local guidelines, signed and dated by the patient or legal guardian prior to the performance of any study-specific procedures, sampling, or analyses.
• Male or female and ≥ 18 years-of-age at the time of signature of the consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
• Histologically confirmed solid tumors resistant or refractory to standard treatment and/or patients who are intolerant to standard therapy.
• Measurable disease as per RECIST v1.1
• Existing biomarker profile (tumor tissue or plasma) reported from a local test obtained in a certified lab per institutional guidelines:
• Available tumor tissue
• Ability to comply with the protocol and study procedures detailed in the Schedule of Assessments.
• Ability to swallow and retain oral medications.
• Acceptable organ function at screening
• Acceptable blood counts at screening
• Negative pregnancy test (serum) for females of childbearing potential at Screening and prior to first study drug.
• Resolution of all toxicities of prior treatment or surgery.
• Male patients with female partners of childbearing potential and females of childbearing potential must follow a contraception method (oral contraceptives allowed) during their participation in the study and for at least 6 months following last dose of study drug. Male patients must also refrain from donating sperm during their participation in the study and for 6 months following last dose of study drug.
• Life expectancy ≥12 weeks after the start of the treatment according to the investigator's judgment.
• Module 1c only: Ability to consume a high-fat meal and fast for 12 hours.

Exclusion Criteria

• Chemotherapy, small molecule anticancer or biologic anticancer therapy given within 14 days prior to first dose of study drug.
• History or current condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment.
• Prior therapy with an ATR or DNA-dependent protein kinase (DNA-PK) inhibitor.
• Known hypersensitivity to any of the ingredients of RP-3500 (camonsertib).
• Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction or other reasons which, in the investigator's opinion, could compromise the patient's safety.
• Uncontrolled, symptomatic brain metastases.
• Uncontrolled high blood pressure
• Patients with active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
• Moderate or severe hepatic impairment (ie, Child-Pugh class B or C).
• History or presence of an abnormal ECG that is clinically significant in the investigator's opinion.
• History of ventricular dysrhythmias or risk factors such as structural heart disease, coronary heart disease (clinically significant electrolyte abnormalities or family history of sudden unexplained death or long QT syndrome
• Current treatment with medications that are well-known to prolong the QT interval
• History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis
• Module 3 only: Known sensitivity to any of the ingredients of talazoparib.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Repare Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy A Yap, MBBS PhD FRCP

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

#1014, Northwestern University

Chicago, Illinois, United States

#1006, Massachusetts General Hospital

Boston, Massachusetts, United States

#1002, Dana Farber Cancer Institute

Boston, Massachusetts, United States

#1004, Memorial Sloan Kettering Cancer Institute

New York, New York, United States

#1005, Duke Cancer Institute

Durham, North Carolina, United States

#1007, Rhode Island Hospital

Providence, Rhode Island, United States

#1003, Sarah Cannon Research Institute

Nashville, Tennessee, United States

#1001, The University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

#2001, Princess Margaret Cancer Centre

Toronto, Ontario, Canada

#4001, Copenhagen University Hospital Rigshospitalet - Blegdamsvej

Copenhagen, DK, Denmark

#3003, Sarah Cannon Research Institute

London, , United Kingdom

#3001, The Christie NHS Foundation Trust

Manchester, , United Kingdom

#3002, Freeman Hospital Newcastle

Newcastle upon Tyne, , United Kingdom

Countries

United States; Canada; Denmark; United Kingdom

References

Fontana E, Rosen E, Lee EK, Hojgaard M, Mettu NB, Lheureux S, Carneiro BA, Cote GM, Carter L, Plummer R, Mahalingam D, Fretland AJ, Schonhoft JD, Silverman IM, Wainszelbaum M, Xu Y, Ulanet D, Koehler M, Yap TA. Ataxia telangiectasia and Rad3-related (ATR) inhibitor camonsertib dose optimization in patients with biomarker-selected advanced solid tumors (TRESR study). J Natl Cancer Inst. 2024 Sep 1;116(9):1439-1449. doi: 10.1093/jnci/djae098.

Reference Type: DERIVED

PMID: 38710487 (View on PubMed)

Yap TA, Fontana E, Lee EK, Spigel DR, Hojgaard M, Lheureux S, Mettu NB, Carneiro BA, Carter L, Plummer R, Cote GM, Meric-Bernstam F, O'Connell J, Schonhoft JD, Wainszelbaum M, Fretland AJ, Manley P, Xu Y, Ulanet D, Rimkunas V, Zinda M, Koehler M, Silverman IM, Reis-Filho JS, Rosen E. Camonsertib in DNA damage response-deficient advanced solid tumors: phase 1 trial results. Nat Med. 2023 Jun;29(6):1400-1411. doi: 10.1038/s41591-023-02399-0. Epub 2023 Jun 5.

Reference Type: DERIVED

PMID: 37277454 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-000301-87

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RP-3500-01

Identifier Type: -

Identifier Source: org_study_id