A Study of RP-3500 in Combination With Standard Radiation Therapy in People With Solid Tumor Cancer

NCT ID: NCT05566574

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-30

Study Completion Date

2026-09-30

Brief Summary

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The purpose of this study is to test the safety of the study drug, RP-3500 when given in combination with palliative external beam radiotherapy (EBRT) to people who have metastatic solid tumor cancer with a mutation of the ATM gene. The study researchers will do tests to find the highest dose of RP3500 that causes few or mild side effects.

Detailed Description

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Conditions

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Solid Tumor Metastatic Cancer

Keywords

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Palliative treatment RP-3500 (ATRi) External Beam Radiotherapy (EBRT) 22-222

Study Design

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Allocation Method

NA

Intervention Model

PARALLEL

Single arm, phase I/II trial to assess safety and tolerability of RP-3500 and palliative RT.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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RP-3500 in Combination With Standard Radiation Therapy

Patients with metastatic cancers with identified mutations in ATM will be enrolled. All patients will receive a standard palliative RT (4Gy x 5 fractions) on Days 1-5 in combination with RP-3500 on Days 1-5. In the first phase of the study, a 3+3 study design will be used to identify a safe dose of RP-3500 (starting at 80 mg QD) in combination with palliative RT.

Group Type EXPERIMENTAL

RP-3500

Intervention Type DRUG

RP-3500 on Days 1-5.

External Beam Radiotherapy (EBRT)

Intervention Type RADIATION

Palliative radiation therapy (4Gy x 5 fractions) to a metastatic site on Days 1-5

Pilot subcohort

The primary objective is to assess 6 month local control rate of patients of new metastatic lesions with pathogenic ATM who haves received prior RP-3500 and palliative RT.

Group Type EXPERIMENTAL

RP-3500

Intervention Type DRUG

RP-3500 on Days 1-5.

External Beam Radiotherapy (EBRT)

Intervention Type RADIATION

Palliative radiation therapy (4Gy x 5 fractions) to a metastatic site on Days 1-5

Interventions

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RP-3500

RP-3500 on Days 1-5.

Intervention Type DRUG

External Beam Radiotherapy (EBRT)

Palliative radiation therapy (4Gy x 5 fractions) to a metastatic site on Days 1-5

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed malignancy with at least one metastatic lesion amenable to radiotherapy. Bone, visceral, and soft tissue are eligible.
* Mutation in ATM (deleterious or VUS; somatic or germline; monoallelic or biallelic)

* Note: Homozygous Deletion in the ATM gene will also be allowed
* ECOG performance status 0-2 or KPS equivalent
* Age ≥18 years
* Expected survival greater than 6 months
* Participant or Legally Authorized Representative (LAR) able to provide written informed consent
* Patients of reproductive potential must agree to practice an effective contraceptive method
* Ability to swallow capsules and retain oral medications
* Acceptable organ function at Screening, as evidenced by the following laboratory data:

1. Serum creatinine ≤1.5 × upper limit of normal (ULN) or calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation or by 24-hour urine collection
2. Total bilirubin ≤1.5 × ULN or \<3.0 × ULN if known Gilbert's disease
3. Serum albumin ≥2.5 g/dL
4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN unless liver metastases are present and thought to be a reason for AST/ALT elevation, in which case they must be ≤5 × ULN
* Acceptable hematologic function at Screening:

1. No red blood cell or platelet transfusions or growth factors within 7 days of the first dose of RP-3500
2. Hemoglobin ≥9.5 g/dL
3. ANC ≥1700 cells/mm\^3
4. Platelet count ≥130,000 cells/mm\^3
* Resolution of all toxicities of prior therapy or surgical procedures to baseline or Grade 1 (except for neuropathy, hypothyroidism requiring medication and alopecia can be resolved to Grade ≤2)
* Negative pregnancy test (serum or urine) for women of childbearing potential (WOCBP) at Screening and prior to first study drug. Non-WOCBP is defined as 1) adequate time of amenorrhea for \> 12 months plus adequate FSH level or 2) surgically or anatomically infertile
* Male patients with female partners of childbearing potential and WOCBP must follow a contraception method (oral contraceptives allowed) at least as conservative as Clinical Trial Facilitation Group (CTFG) recommendations during their participation in the study. WOCBP must follow the recommendations until 6 months following last dose of study drug and male patients must follow the recommendations for 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

Exclusion Criteria

* Previous radiotherapy to the intended treatment site
* Prior therapy with an ATR or DNA-dependent protein kinase (DNA-PK) inhibitor
* Serious medical co-morbidities precluding radiotherapy
* Pregnant or breast-feeding women
* No other concurrent systemic therapy during the entire duration of protocol treatment. Patients can have other systemic treatments up until the start of protocol treatment. Patients can also have other systemic treatments after the completion of protocol treatments
* Known hypersensitivity to any of the ingredients of RP-3500
* Uncontrolled hypertension (systolic blood pressure \[BP\] ≥160 mmHg; diastolic BP ≥100 mmHg) despite adequate treatment prior to first dose of RP-3500
* 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. In equivocal cases, patients whose viral load is negative, may be eligible. HIV seropositive patients who are healthy and low risk for AIDS related outcomes could be considered eligible. Eligibility criteria for HIV positive patients should be evaluated and discussed, and will be based on current and past CD4 and T-cell counts, history (if any) of AIDS-defining conditions (eg, opportunistic infections), and status of HIV treatment
* 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, including complete left bundle branch block, second- or third-degree heart block, or recent history of myocardial infarction that in the opinion of the investigator will pose an increased risk of rhythm abnormalities
* History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (eg, severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (eg, hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
* Current treatment with medications that are well-known to prolong the QT interval
* Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol
* Patients who are receiving strong CYP3A inhibitors or inducers, P-gp inhibitors and/or BCRP inhibitors
* Patients with germline homozygous ATM mutations
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Repare Therapeutics

INDUSTRY

Sponsor Role collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nancy Lee, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Memorial Sloan Kettering Basking Ridge (Limited Protocol Activites)

Basking Ridge, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center at Suffolk-Commack (All Protocol Activities)

Commack, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Nancy Lee, MD

Role: CONTACT

Phone: 212-639-3341

Email: [email protected]

Ezra Rosen, MD,PhD

Role: CONTACT

Phone: 646-888-6955

Facility Contacts

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Nancy Lee, MD

Role: primary

Nancy Lee, MD

Role: primary

Nancy Lee, MD

Role: primary

Nancy Lee, MD

Role: primary

Nancy Lee, MD

Role: primary

Nancy Lee, MD

Role: primary

Ezra Rosen, MD, PhD

Role: backup

Nancy Lee, MD

Role: primary

Related Links

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http://www.mskcc.org/mskcc/html/44.cfm

Memorial Sloan Kettering Cancer Center

Other Identifiers

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22-222

Identifier Type: -

Identifier Source: org_study_id