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

Primary Purpose

Metastatic or Locally Advanced Unresectable Solid Tumors

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

M1774

M4076

Avelumab

About this trial

This is an interventional treatment trial for Metastatic or Locally Advanced Unresectable Solid Tumors focused on measuring ATR inhibitor, ATM inhibitor, Immunotherapy, M1774, M4076, Avelumab, Metastatic or Locally Advanced Unresectable Solid Tumors, DNA Damage Response Inhibitor, Immune Checkpoint Inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Texas M. D. Anderson Cancer Center - PartnerRecruiting
NEXT OncologyRecruiting
Princess Margaret Cancer CentreRecruiting
Hospital QuironSalud Barcelona - Next OncologyRecruiting
Hospital Universitario Quironsalud Madrid - NEXT OncologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Part A1: M1774 and M4076

Part B1: M1774 and Avelumab

Arm Description

Outcomes

Primary Outcome Measures

Part A1: Number of Participants with Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period

Part A1: Number of Participants with Adverse Events (AEs) and Treatment-Related AEs

Part B1: Number of Participants with Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period

Part B1: Number of Participants with Adverse Events (AEs) and Treatment-Related AEs

Part A1: Change from Baseline in Pharmacodynamic (PD) Biomarker

The PD biomarker of histone variant will be measured by flow cytometry.

Part B1: Change from Baseline in Pharmacodynamic (PD) Biomarker

The PD biomarker of histone variant will be measured by flow cytometry.

Secondary Outcome Measures

Part A1: Pharmacokinetic (PK) Plasma Concentration of M1774 and M4076

Part B1: Pharmacokinetic (PK) Plasma Concentration of M1774

Part B1: Pharmacokinetic (PK) Serum Concentration of Avelumab

Part A1 and B1: Number of Participants with Clinically Significant Abnormalities in Digital Electrocardiogram (ECG) Measures

Part A1 and B1: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1

Part B1: Number of Participants with Any Positive Anti-Drug Antibody (ADA) of Avelumab

Full Information

NCT ID

NCT05396833

First Posted

May 24, 2022

Last Updated

September 19, 2023

Sponsor

EMD Serono Research & Development Institute, Inc.

Collaborators

Merck KGaA, Darmstadt, Germany

1. Study Identification

Unique Protocol Identification Number

NCT05396833

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 7, 2022 (Actual)

Primary Completion Date

December 12, 2023 (Anticipated)

Study Completion Date

December 12, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

EMD Serono Research & Development Institute, Inc.

Collaborators

Merck KGaA, Darmstadt, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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 M4076 (in Part A1) and in combination with avelumab (in Part B1) in participants with metastatic or locally advanced unresectable solid tumors who are intolerant or have no standard therapy available.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic or Locally Advanced Unresectable Solid Tumors

Keywords

ATR inhibitor, ATM inhibitor, Immunotherapy, M1774, M4076, Avelumab, Metastatic or Locally Advanced Unresectable Solid Tumors, DNA Damage Response Inhibitor, Immune Checkpoint Inhibitor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Part A1: M1774 and M4076

Arm Type

Experimental

Arm Title

Part B1: M1774 and Avelumab

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

M1774

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

M4076

Intervention Description

M4076 will be administered orally once daily over a defined period of time in Part A1 until disease progression, death, discontinuation, or end of study.

Intervention Type

Drug

Intervention Name(s)

Avelumab

Intervention Description

Avelumab 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.

Primary Outcome Measure Information:

Title

Part A1: Number of Participants with Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period

Time Frame

Day 1 up to Day 28

Title

Part A1: Number of Participants with Adverse Events (AEs) and Treatment-Related AEs

Time Frame

Baseline up to 18 months

Title

Part B1: Number of Participants with Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period

Time Frame

Day 1 up to Day 28

Title

Part B1: Number of Participants with Adverse Events (AEs) and Treatment-Related AEs

Time Frame

Baseline up to 18 months

Title

Part A1: Change from Baseline in Pharmacodynamic (PD) Biomarker

Description

The PD biomarker of histone variant will be measured by flow cytometry.

Time Frame

Pre-dose up to approximately 1 month

Title

Part B1: Change from Baseline in Pharmacodynamic (PD) Biomarker

Description

The PD biomarker of histone variant will be measured by flow cytometry.

Time Frame

Pre-dose up to approximately 1 month

Secondary Outcome Measure Information:

Title

Part A1: Pharmacokinetic (PK) Plasma Concentration of M1774 and M4076

Time Frame

Pre-dose up to approximately 6 months

Title

Part B1: Pharmacokinetic (PK) Plasma Concentration of M1774

Time Frame

Pre-dose up to approximately 6 months

Title

Part B1: Pharmacokinetic (PK) Serum Concentration of Avelumab

Time Frame

Pre-dose up to approximately 18 months

Title

Part A1 and B1: Number of Participants with Clinically Significant Abnormalities in Digital Electrocardiogram (ECG) Measures

Time Frame

Baseline up to 18 months

Title

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

Title

Part B1: Number of Participants with Any Positive Anti-Drug Antibody (ADA) of Avelumab

Time Frame

Baseline up to 18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

US Medical Information

Phone

888-275-7376

eMediUSA@emdserono.com

First Name & Middle Initial & Last Name or Official Title & Degree

Communication Center

Phone

+49 6151 72 5200

service@emdgroup.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Responsible

Organizational Affiliation

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Official's Role

Study Director

Facility Information:

Facility Name

University of Texas M. D. Anderson Cancer Center - Partner

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Name

NEXT Oncology

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Individual Site Status

Recruiting

Facility Name

Princess Margaret Cancer Centre

City

Toronto

ZIP/Postal Code

M5G 2C1

Country

Canada

Individual Site Status

Recruiting

Facility Name

Hospital QuironSalud Barcelona - Next Oncology

City

Barcelona

ZIP/Postal Code

08023

Country

Spain

Individual Site Status

Recruiting

Facility Name

Hospital Universitario Quironsalud Madrid - NEXT Oncology

City

Madrid

ZIP/Postal Code

28223

Country

Spain

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing 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

Links:

URL

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS201924_0020

Description

Trial Awareness and Transparency website

URL

https://medical.emdserono.com/en_US/home.html

Description

US Medical Information website, Medical Resources

URL

http://www.DDRiver-trials.com

Description

DDRiver website

Learn more about this trial

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

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