NCT05687136

Testing the Combination of Two Anti-cancer Drugs, Peposertib (M3814) and Tuvusertib (M1774) for Advanced Solid Tumors

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 66 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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 between pharmacodynamic (PD) and predictive biomarkers (gammaH2AX, phospho-KAP1 and phospho-RPA) with clinical outcomes. II. To explore correlations between baseline genomic alterations of ataxia-telangiectasia mutated (ATM) or markers of replicative stress, ATM expression by immunohistochemistry (IHC), RAD5' foci formation with clinical outcomes. III. To determine metrics of anticancer activity including the objective response rate (ORR) and progression-free survival (PFS). OUTLINE: This a dose-escalation study of peposertib and tuvusertib, followed by a dose-expansion study. Patients receive peposertib orally (PO) once (QD) or twice (BID) daily on days 2-14 of cycle 1 and days 1-14 of subsequent cycles in combination with tuvusertib PO QD or BID daily on days 1-14 of each cycle. Cycles repeat every 28 days in the absence of disease progression, pregnancy, non-compliance, unacceptable toxicity, termination of the study or the study drug is no longer available. Patients also undergo tumor biopsy, blood sample collection, positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging (MRI) throughout the study. After completion of study treatment, patients are followed up for a minimum of 30 days after removal from treatment or until initiating a new anticancer therapy or until death, whichever occurs first.

Conditions

• Advanced Malignant Solid Neoplasm
• Metastatic Malignant Solid Neoplasm
• Unresectable Malignant Solid Neoplasm

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo tissue biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	Peposertib	Given PO
PROCEDURE	Positron Emission Tomography	Undergo PET
DRUG	Tuvusertib	Given PO

Timeline

• Start date: 2024-06-07
• Primary completion: 2026-08-31
• Completion: 2026-08-31
• First posted: 2023-01-18
• Last updated: 2026-04-13

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study