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Study of M1774 in Combination With DNA Damage Response Inhibitor or Immune Checkpoint Inhibitor (DDRiver Solid Tumors 320)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05396833
Recruitment Status : Recruiting
First Posted : May 31, 2022
Last Update Posted : October 24, 2022
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Tracking Information
First Submitted Date  ICMJE May 24, 2022
First Posted Date  ICMJE May 31, 2022
Last Update Posted Date October 24, 2022
Actual Study Start Date  ICMJE June 7, 2022
Estimated Primary Completion Date December 12, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 27, 2022)
  • Part A1: Number of Participants with Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period [ Time Frame: Day 1 up to Day 28 ]
  • Part A1: Number of Participants with Adverse Events (AEs) and Treatment-Related AEs [ Time Frame: Baseline up to 18 months ]
  • Part B1: Number of Participants with Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period [ Time Frame: Day 1 up to Day 28 ]
  • Part B1: Number of Participants with Adverse Events (AEs) and Treatment-Related AEs [ Time Frame: Baseline up to 18 months ]
  • Part A1: Change from Baseline in Pharmacodynamic (PD) Biomarker [ Time Frame: Pre-dose up to approximately 1 month ]
    The PD biomarker of histone variant will be measured by flow cytometry.
  • Part B1: Change from Baseline in Pharmacodynamic (PD) Biomarker [ Time Frame: Pre-dose up to approximately 1 month ]
    The PD biomarker of histone variant will be measured by flow cytometry.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2022)
  • Part A1: Pharmacokinetic (PK) Plasma Concentration of M1774 and Drug A [ Time Frame: Pre-dose up to approximately 6 months ]
  • Part B1: Pharmacokinetic (PK) Plasma Concentration of M1774 [ Time Frame: Pre-dose up to approximately 6 months ]
  • Part B1: Pharmacokinetic (PK) Serum Concentration of Drug B [ Time Frame: Pre-dose up to approximately 18 months ]
  • Part A1 and B1: Number of Participants with Clinically Significant Abnormalities in Digital Electrocardiogram (ECG) Measures [ Time Frame: Baseline up to 18 months ]
  • Part A1 and B1: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 [ Time Frame: Up to 18 months after first dose administration ]
  • Part B1: Number of Participants with Any Positive Anti-Drug Antibody (ADA) of Drug B [ Time Frame: Baseline up to 18 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of M1774 in Combination With DNA Damage Response Inhibitor or Immune Checkpoint Inhibitor (DDRiver Solid Tumors 320)
Official Title  ICMJE An Open-label, Multicenter Phase Ib Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of the ATR Inhibitor M1774 in Combination With DNA Damage Response Inhibitors or Immune Checkpoint Inhibitors in Patients With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 320)
Brief Summary This is an open-label, multicenter, clinical study conducted in multiple parts to establish the safety, tolerability, Pharmacokinetic/Pharmacodynamic (PK/PD) profile, maximum tolerated dose (MTD) combinations (if observed) and recommended dose for expansion (RDE) combination for M1774 in combination with Drug A (DNA Damage Response Inhibitor - in Part A1) and in combination with Drug B (Immune Checkpoint Inhibitor - in Part B1) in participants with metastatic or locally advanced unresectable solid tumors who are intolerant or have no standard therapy available.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic or Locally Advanced Unresectable Solid Tumors
Intervention  ICMJE
  • Drug: M1774
    M1774 will be administered orally once daily over a defined period of time in Part A1 and Part B1 until disease progression, death, discontinuation, or end of study.
  • Drug: Drug A (DNA Damage Response Inhibitor)
    Drug A will be administered orally once daily over a defined period of time in Part A1 until disease progression, death, discontinuation, or end of study.
  • Drug: Drug B (Immune Checkpoint Inhibitor)
    Drug B will be administered by intravenous infusion once a day over a defined period of time in Part B1 until disease progression, death, discontinuation, or end of study.
Study Arms  ICMJE
  • Experimental: Part A1: M1774 and Drug A
    Interventions:
    • Drug: M1774
    • Drug: Drug A (DNA Damage Response Inhibitor)
  • Experimental: Part B1: M1774 and Drug B
    Interventions:
    • Drug: M1774
    • Drug: Drug B (Immune Checkpoint Inhibitor)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 27, 2022)		 72
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 12, 2023
Estimated Primary Completion Date December 12, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants with metastatic or locally advanced unresectable solid tumors refractory to standard therapy or for which no standard therapy is judged appropriate by the Investigator, which may convey clinical benefit, or who cannot tolerate standard of care treatment
  • Participants with eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, with estimated life expectancy of at least 3 months
  • Adequate hematological, hepatic, and renal function as defined in the protocol
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Participants with any condition, including any uncontrolled disease state other than with metastatic or locally advanced unresectable solid tumors, that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation
  • Participants with a known additional malignancy that is progressing and/or requires active treatment
  • Participants with carcinomatous meningitis are excluded regardless of clinical stability
  • Participants with serious gastrointestinal bleeding within 3 months, refractory nausea and vomiting, uncontrolled diarrhea, known malabsorption, significant small bowel resection or gastric bypass surgery, use of feeding tubes, other chronic gastrointestinal disease, and/or other situations that may preclude adequate absorption of oral medications
  • Participants with organ transplantation, including allogeneic stem cell transplant
  • Other protocol defined exclusion criteria could apply
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US Medical Information 888-275-7376 eMediUSA@emdserono.com
Contact: Communication Center +49 6151 72 5200 service@emdgroup.com
Listed Location Countries  ICMJE Canada,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05396833
Other Study ID Numbers  ICMJE MS201924_0020
2022-500287-35 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
Current Responsible Party EMD Serono ( EMD Serono Research & Development Institute, Inc. )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE EMD Serono Research & Development Institute, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Merck KGaA, Darmstadt, Germany
Investigators  ICMJE
Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
PRS Account EMD Serono
Verification Date October 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP