A Molecularly Driven Phase 1b Dose Escalation and Dose Expansion Study of the DNA-PK Inhibitor Peposertib (M3814) in Combination With the ATR Inhibitor M1774
National Cancer Institute (NCI)
Summary
This phase I trial tests the safety, side effects and best dose of peposertib (M3814) in combination with tuvusertib (M1774) in treating patients with solid tumors that have spread to other places in the body (advanced). Peposertib and tuvusertib stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Description
PRIMARY OBJECTIVES: I. To determine the safety and tolerability of peposertib (M3814) in combination with tuvusertib (M1774). (DOSE ESCALATION AND EXPANSION COHORT) II. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of peposertib (M3814) and tuvusertib (M1774). (DOSE ESCALATION COHORT) SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To determine the pharmacokinetic (PK) profiles of peposertib (M3814) and tuvusertib (M1774) when administered in combination. EXPLORATORY OBJECTIVES: I. To explore correlations betwe…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients must have histologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. * For the dose escalation and dose expansion phases, patients must have genomic (tumor next-generation sequencing \[NGS\], circulating tumor deoxyribonucleic acid \[ctDNA\], fluorescence in situ hybridization \[FISH\], etc.) or immunohistochemical evidence of inactivating ATM mutations, MYC amplification, mutation of FBXW7, CCNE1 amplification, SWI/SNF member mutation (ARID1A, PBRM1…
Interventions
- ProcedureBiopsy Procedure
Undergo tissue biopsy
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureComputed Tomography
Undergo CT
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- DrugPeposertib
Given PO
- ProcedurePositron Emission Tomography
Undergo PET
- DrugTuvusertib
Given PO
Locations (6)
- National Cancer Institute Developmental Therapeutics ClinicBethesda, Maryland
- National Institutes of Health Clinical CenterBethesda, Maryland
- Massachusetts General Hospital Cancer CenterBoston, Massachusetts
- Dana-Farber Cancer InstituteBoston, Massachusetts
- NYU Langone Hospital - Long IslandMineola, New York
- Laura and Isaac Perlmutter Cancer Center at NYU LangoneNew York, New York