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Testing RP-3500 with radiation therapy for metastatic solid tumors

RP-3500 (ATRi) + External Beam Radiotherapy (EBRT) for the Palliative Treatment of Metastatic Disease

Phase1; Phase2 Interventional Memorial Sloan Kettering Cancer Center · NCT05566574

This study is testing a new drug called RP-3500 combined with radiation therapy to see if it can safely help people with advanced solid tumors that have a specific gene mutation.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment84 (estimated)
Ages18 Years and up
SexAll
SponsorMemorial Sloan Kettering Cancer Center Academic / other
Locations7 sites (Basking Ridge, New Jersey and 6 other locations)
Trial IDNCT05566574 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety of RP-3500, a drug targeting the ATM gene mutation, when combined with palliative external beam radiotherapy (EBRT) in patients with metastatic solid tumor cancer. Researchers will determine the maximum tolerated dose of RP-3500 that results in minimal side effects. The trial focuses on individuals with confirmed malignancies and specific genetic mutations, providing a targeted approach to treatment.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with metastatic solid tumors and a confirmed mutation in the ATM gene.

Not a fit: Patients without ATM gene mutations or those with conditions not amenable to radiotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with metastatic solid tumors and ATM gene mutations.

How similar studies have performed: While this approach is novel in combining RP-3500 with EBRT, similar studies targeting genetic mutations in cancer have shown promise.

Eligibility criteria

Show full inclusion / exclusion criteria 
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
* 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

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Solid TumorMetastatic CancerPalliative treatmentRP-3500External Beam Radiotherapy22-222
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.