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

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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. )

Study Description
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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.

Condition or disease Intervention/treatment Phase
Metastatic or Locally Advanced Unresectable Solid Tumors Drug: M1774 Drug: Drug A (DNA Damage Response Inhibitor) Drug: Drug B (Immune Checkpoint Inhibitor) Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : June 7, 2022
Estimated Primary Completion Date : December 12, 2023
Estimated Study Completion Date : December 12, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Part A1: M1774 and Drug A 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.
Experimental: Part B1: M1774 and Drug B 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 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.


Outcome Measures
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Primary Outcome Measures :
  1. Part A1: Number of Participants with Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period [ Time Frame: Day 1 up to Day 28 ]
  2. Part A1: Number of Participants with Adverse Events (AEs) and Treatment-Related AEs [ Time Frame: Baseline up to 18 months ]
  3. Part B1: Number of Participants with Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period [ Time Frame: Day 1 up to Day 28 ]
  4. Part B1: Number of Participants with Adverse Events (AEs) and Treatment-Related AEs [ Time Frame: Baseline up to 18 months ]
  5. 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.

  6. 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.


Secondary Outcome Measures :
  1. Part A1: Pharmacokinetic (PK) Plasma Concentration of M1774 and Drug A [ Time Frame: Pre-dose up to approximately 6 months ]
  2. Part B1: Pharmacokinetic (PK) Plasma Concentration of M1774 [ Time Frame: Pre-dose up to approximately 6 months ]
  3. Part B1: Pharmacokinetic (PK) Serum Concentration of Drug B [ Time Frame: Pre-dose up to approximately 18 months ]
  4. Part A1 and B1: Number of Participants with Clinically Significant Abnormalities in Digital Electrocardiogram (ECG) Measures [ Time Frame: Baseline up to 18 months ]
  5. 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 ]
  6. Part B1: Number of Participants with Any Positive Anti-Drug Antibody (ADA) of Drug B [ Time Frame: Baseline up to 18 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05396833


Contacts
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Contact: US Medical Information 888-275-7376 eMediUSA@emdserono.com
Contact: Communication Center +49 6151 72 5200 service@emdgroup.com

Locations
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United States, Texas
University of Texas M. D. Anderson Cancer Center - Partner Recruiting
Houston, Texas, United States, 77030
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78229
Canada
Princess Margaret Cancer Centre Recruiting
Toronto, Canada, M5G 2C1
Spain
Hospital QuironSalud Barcelona - Next Oncology Recruiting
Barcelona, Spain, 08023
Hospital Universitario Quironsalud Madrid - NEXT Oncology Recruiting
Madrid, Spain, 28223
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
More Information
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Additional Information:

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Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT05396833    
Other Study ID Numbers: MS201924_0020
2022-500287-35 ( EudraCT Number )
First Posted: May 31, 2022    Key Record Dates
Last Update Posted: October 24, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
ATR inhibitor
ATM inhibitor
Immunotherapy
M1774
 Metastatic or Locally Advanced Unresectable Solid Tumors
DNA Damage Response Inhibitor
Immune Checkpoint Inhibitor
Additional relevant MeSH terms:
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Neoplasms
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents