Study of M4344 in Combination With Niraparib

Sponsor
EMD Serono Research & Development Institute, Inc.
Study ID
NCT04655183
Phase
PHASE1/PHASE2
Status
Withdrawn

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Niraparib — DRUG
    Niraparib will be administered orally, once daily.
  • M4344 — DRUG
    M4344 will be administered once daily or on an intermittent schedule in combination with niraparib.
  • Niraparib — DRUG
    Niraparib will be administered orally once daily at the RDE as determined in Part 1 of this study.
  • M4344 — DRUG
    M4344 will be administered at a dose and schedule that was determined as RDE in Part 1A in combination with niraparib.
  • Niraparib — DRUG
    Niraparib will be administered orally, once daily. Dose of niraparib will be escalated beyond the dose in Part 1A.
  • Niraparib — DRUG
    Niraparib will be administered as single agent at the approved dose.

Study Details

Study will include 3 parts. Aim of Part 1 of this study is to establish the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) for M4344 (is an Ataxia Telangiectasia Mutated and Rad3-related \[ATR\] inhibitors) in combination with niraparib in participants with advanced solid tumors. Aim of Parts 2 and 3 of the study is to provide clinical proof-of-concept for the preclinically predicted synergistic efficacy of ATR and poly(ADP-Ribose) polymerase (PARP) inhibitors (PARPi) in defined populations of participants with advanced breast cancer (aBC) with DDR mutations with an unmet medical need.

Key Dates

Start date
Dec 1, 2020
Status verified
Jun 2021
Primary completion
Sep 1, 2023
Completion
Sep 1, 2023

Study Design

Enrollment
0 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Part 1A (Dose escalation): Niraparib plus M4344 once daily
    Participants with baseline body weight \< 77 kilograms (kg) or baseline platelet count \< 150, 000 per cubic millimeter will be included in this Part. Dose escalation of M4344 administered along with niraparib.
  • Experimental: Part 1B (Dose escalation): Niraparib plus M4344 once daily
    Participants with baseline body weight \> =77 kilograms (kg) and baseline platelet count \>=150, 000 per cubic millimeter will be included in this Part. M4344 will be administered at a dose and schedule that was determined as the recommended dose for expansion (RDE) in Part 1A. Dose of niraparib will be escalated to the next higher dose level.
  • Experimental: Part 2 (Dose expansion): PARPi resistant, Niraparib plus M4344
    Participants with Poly(ADP-ribose) polymerase inhibitor (PARPi) resistant, germline breast cancer 1/2 mutated (gBRCA1/2m) human epidermal growth factor receptor 2 (HER2) negative advanced Breast Cancer (aBC) will receive the combination of niraparib and M4344 at the RDE which was determined in Part 1.
  • Experimental: Part 3 (Dose expansion): PARPi-naive, Niraparib
    Participants with PARPi-naive germline BRCA1/2 wild type (gBRCAwt) homologous recombination repair gene mutated (HRRm) advanced breast cancer (aBC) will be randomized to receive niraparib as a single agent.
  • Experimental: Part 3 (Dose expansion): PARPi-naive, Niraparib plus M4344
    Participants with PARPi-naive germline BRCA1/2 wild type (gBRCAwt) homologous recombination repair gene mutated (HRRm) advanced breast cancer (aBC) will be randomized to receive the combination of niraparib and M4344 at the RDE as determined in Part 1 of this study.

Primary Outcome Measure

Part 1 A and B: Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Day 1 up to Day 28 ]

Related Studies