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

NCT04497116 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: RP-3500-012020-000301-87
• Study Type: interventional
• Target: 276
• Locations: 4 countries
• Sites: 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.

Conditions

Advanced Solid Tumor

Keywords

Adult

Outcome Measures

Primary Outcomes (2)

• Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above

  Treatment-emergent adverse events (TEAEs) are those events that occur or worsen on or after the first dose of study drug up through 30 days post the last dose (or cross over to a different module) or the start of subsequent anticancer therapy. AEs are considered related to treatment if the relationship to camonsertib or the other combination drug (in the study regimen) is "Related" (include unknown relationship) as indicated on the AE eCRF page based on investigator's assessment.

  Start of treatment to 30 days post last dose, up to 1 year

• Frequency of Dose Limiting Toxicity (DLT)

  Toxicity were assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. A toxicity was considered dose-limiting if it occurred during the first cycle and was deemed at least possibly related to study treatment. If multiple toxicities occurred, the most severe toxicity was used in the assessment. The DLT Evaluable population consists of patients who received at least 80% of planned total doses of camonsertib , 80% of planned total doses of camonsertib and talazoparib, or 80% of planned total doses of camonsertib and 100% of gemcitabine; complete all required safety evaluations and are observed through the end of Cycle 1; or patients who experience a DLT qualifying event in the first cycle of treatment.

  Either 21 days or 28 days (1 cycle) from the initiation of the study treatment.

Study Arms (3)

RP-3500 (camonsertib) alone

EXPERIMENTAL

Phase 1: Multiple doses of RP-3500 (camonsertib) for oral administration alone

Drug: RP-3500 (camonsertib)

Expansion cohorts with RP-3500 (camonsertib)

EXPERIMENTAL

Phase 2: Expansion cohorts with RP-3500 (camonsertib)

Drug: RP-3500 (camonsertib)

RP-3500 (camonsertib) with Talazoparib or Gemcitabine

EXPERIMENTAL

Phase 1: Multiple doses of RP-3500 (camonsertib) for oral administration in combination with talazoparib or gemcitabine

Drug: RP-3500 (camonsertib); Drug: Talazoparib; Drug: Gemcitabine Injection

Interventions

RP-3500 (camonsertib) DRUG

Oral ATR inhibitor

Expansion cohorts with RP-3500 (camonsertib); RP-3500 (camonsertib) alone; RP-3500 (camonsertib) with Talazoparib or Gemcitabine

Talazoparib DRUG

Oral PARP inhibitor

RP-3500 (camonsertib) with Talazoparib or Gemcitabine

Gemcitabine Injection DRUG

Gemcitabine

RP-3500 (camonsertib) with Talazoparib or Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Repare Therapeutics: lead

Study Sites (13)

#1014, Northwestern University

Chicago, Illinois, 60611, United States

Location

#1006, Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

#1002, Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

#1004, Memorial Sloan Kettering Cancer Institute

New York, New York, 10065, United States

Location

#1005, Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

#1007, Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

#1003, Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

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

Houston, Texas, 77030, United States

Location

#2001, Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

#4001, Copenhagen University Hospital Rigshospitalet - Blegdamsvej

Copenhagen, DK, 2100 Ø, Denmark

Location

#3003, Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

Location

#3001, The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

#3002, Freeman Hospital Newcastle

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 38710487 DERIVED

• 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.

  PMID: 37277454 DERIVED

MeSH Terms

Interventions

talazoparib; Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

No Module 5 (pediatric cohort) study activities were initiated.

Results Point of Contact

• Title: Repare Therapeutics Medical Monitor
• Organization: Repare Therapeutics Inc

clininfo@reparerx.com

1 (857) 340-5402

Study Officials

• Timothy A Yap, MBBS PhD FRCP

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose Escalation, expansion and phase 2

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: August 4, 2020
• Study Start: July 22, 2020
• Primary Completion: June 13, 2025
• Study Completion: June 13, 2025
• Last Updated: October 21, 2025
• Results First Posted: October 21, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (8); GB (3); CA (1); DK (1)