Tuvusertib (M1774) in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 301)

NCT ID: NCT04170153

Last Updated: 2026-01-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 161 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-20
• Study Completion Date: 2027-01-30

Brief Summary

This is an open-label, Phase I, first-in-human (FIH) multicenter, clinical study conducted in multiple parts to establish the safety, tolerability and pharmacokinetic/pharmacodynamic (PK/PD) profile (with and without food) and early signs of efficacy of Tuvuseritib (M1774) as monotherapy and in combination with the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib.

Conditions

Metastatic or Locally Advanced Unresectable Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A1: Monotherapy Dose Escalation

Participants will initially receive Tuvusertib (M1774) once daily under fasting conditions. Additional schedules may be evaluated if needed.

Group Type: EXPERIMENTAL

M1774

Intervention Type: DRUG

M1774 will be administered orally throughout the study.

Part A2 - Preliminary Food Effect Assessment

Participants in the food effect assessment will receive Tuvusertib (M1774) at the dose and schedule determined as recommended dose for expansion (RDE) in Part A1. A single dose of Tuvusertib (M1774) will be administered on Day -7 under a fed (low-fat meal) or fasted condition, followed by a 1-week washout period. After completion of the scheduled food effect assessments, participants will follow the same schedule as participants in Part A1.

Group Type: EXPERIMENTAL

M1774

Intervention Type: DRUG

M1774 will be administered orally throughout the study.

Part A3 - Monotherapy Expansion

Part A3 is an expansion of Part A1 where Tuvusertib (M1774) will be administered as a single agent at the RDE established in Part A1. Participants with defined loss-of-function mutation in ARID1A, ATRX and/or DAXX, and ATM will be enrolled.

Group Type: EXPERIMENTAL

M1774

Intervention Type: DRUG

M1774 will be administered orally throughout the study.

Part B1: Combination Therapy Dose Finding

B1a: Participants with baseline body weight less than (<) 77 kilogram (kg) or platelets <150,000 cubic per millimeter (mm^3) will receive Niraparib once daily combined with different doses of Tuvusertib (M1774).

B1b: Participants with baseline body weight greater than or equal to (>=) 77 kg and or platelets >= 150,000 mm^3 will receive Niraparib once daily combined with different doses of Tuvusertib (M1774) and schedule determined as recommended dose for expansion (RDE) in Part B1a.

Group Type: EXPERIMENTAL

M1774

Intervention Type: DRUG

M1774 will be administered orally throughout the study.

Niraparib

Intervention Type: DRUG

Niraparib will be administered orally throughout the study.

Part A4: Japan Dose Confirmation Monotherapy

Starting at global RDE from Part A1, in Japan. Participants will initially receive Tuvusertib (M1774) once daily under fasting conditions. Additional schedules may be evaluated if needed.

Group Type: EXPERIMENTAL

M1774

Intervention Type: DRUG

M1774 will be administered orally throughout the study.

Part A5: China Dose Confirmation Monotherapy

Starting at global RDE from Part A1, in China. Participants will initially receive Tuvusertib (M1774) once daily under fasting conditions. Additional schedules may be evaluated if needed.

Group Type: EXPERIMENTAL

M1774

Intervention Type: DRUG

M1774 will be administered orally throughout the study.

Interventions

M1774

M1774 will be administered orally throughout the study.

Intervention Type: DRUG

Niraparib

Niraparib will be administered orally throughout the study.

Intervention Type: DRUG

Other Intervention Names

Tuvusertib

Eligibility Criteria

Inclusion Criteria

• Participants with locally advanced or metastatic disease that is refractory to standard therapy or for which no standard therapy is judged appropriate by the Investigator which may convey clinical benefit
• Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (<=) 1
• Participants with clinically controlled brain metastases, which is defined as individuals with central nervous system metastases that have been treated for, are asymptomatic, and have discontinued steroids (for the treatment of brain metastases) for greater than (>) 28 days may be enrolled
• Participants with meningeal carcinomatosis are excluded
• In Part A3, measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
• Part A3: Participants with presence of loss of function mutations in the genes for ARID1A, ATRX and /or DAXX and ATM
• Contraceptive use by males or females will be consistent with local regulations on contraception methods for those participating in clinical studies
• Adequate hematological, hepatic, and renal function as defined in the protocol
• Female participants are not pregnant or breastfeeding
• Part B1:

Subpart B1a: Participants with Baseline Body weight < 77 kg or platelets <150,000 cubic per millimeter (mm^3) Subpart B1b: Participants with Baseline Body weight >= 77 kg and platelets >=150,000 mm^3 will be included

Exclusion Criteria

• Participants with major surgery (as deemed by the Investigator) for any reason, except diagnostic biopsy, within 4 weeks of the study intervention and/or if the participant has not fully recovered from the surgery within 4 weeks of the study intervention
• Presence of toxicities due to prior anticancer therapies (example, radiotherapy, chemotherapy, immunotherapies, et cetera [etc]) that do not recover to <= Grade 1 with the exception of toxicities that do not pose a safety risk to the participant in the judgment of the Investigator (example: ongoing Grade 2 alopecia)
• Part B1 only: Uncontrolled arterial hypertension which is systolic blood pressure >140 millimeter of mercury (mmHg); Diastolic blood pressure >90mmHg
• Unstable angina, myocardial infarction, congestive heart failure >= II or a coronary revascularization procedure within 180 days of study entry. Calculated QTc average (using the Fridericia correction calculation) of > 450 msec for males and > 470 msec for females that does not resolve with correction of electrolyte abnormalities
• Participants with active and/or uncontrolled infection. The following exceptions apply:
• Participants with human immunodeficiency virus (HIV) infection are eligible if they are on effective antiretroviral therapy with undetectable viral load within 6 months, provided there is no expected drug-drug interaction
• Participants with evidence of chronic hepatitis B virus (HBV) infection are eligible if the HBV viral load is undetectable on suppressive therapy (if indicated), and if they have alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels < upper limit of normal (ULN), and provided there is no expected drug-drug interaction
• Participants with a history of hepatitis C virus (HCV) infection are eligible if they have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load, and if they have ALT, AST, and total bilirubin levels < ULN
• Treatment with live or live attenuated vaccine within 30 days of dosing (non-replicating vector vaccines are permitted)
• Part B1 only: participants diagnosed with hereditary diseases characterized by genetic defects of DNA repair mechanisms, including ataxia telangiectasia, Nijmegen breakage syndrome, Werner syndrome, Bloom Syndrome, Fanconi anemia, xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy
• Any other clinical condition, uncontrolled concurrent illness, or other situation which in the Investigator's opinion would not make the participant a good candidate for the clinical study including or may potentially impact the absorption of M1774, such as (but not limiting to) significant small bowel resection or gastric surgery and exocrine pancreatic insufficiency requiring pancreatic enzyme replacement therapy
• Prohibited concomitant medication, as per Protocol
• Another investigational drug within 28 days or 5 half-lives, whichever is shorter, prior to start of administration of study intervention
• Prior use of Ataxia telangiectasia mutated and Rad3-related (ATR) inhibitor and/or Checkpoint kinase 1 (CHK1) inhibitor
• Participants who cannot comply with restrictions for medications or food
• Part B1 only: Participants with a known history of acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), and prostate cancer

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

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

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

NEXT Oncology

Austin, Texas, United States

Mary Crowley Cancer Research Centers

Dallas, Texas, United States

The Methodist Hospital Research Institute

Houston, Texas, United States

University of Texas M. D. Anderson Cancer Center - Investigational Cancer Therapeutics

Houston, Texas, United States

Beijing Cancer Hospital

Beijing, , China

National Cancer Center Hospital - Dept of Experimental Therapeutics

Chūōku, , Japan

National Cancer Center Hospital East - Dept of Experimental Therapeutics

Kashiwa-shi, , Japan

Hospital Clinic de Barcelona - Servicio de Oncologia

Barcelona, , Spain

Hospital Universitari Vall d'Hebron - Oncology Dept.

Barcelona, , Spain

Centro Integral Oncologico Clara Campal - Unidad de Fase I-Oncologica

Madrid, , Spain

Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica

Valencia, , Spain

Addenbrooke's Hospital - Dept of Oncology

Cambridge, , United Kingdom

The Christie Hospital - Dept of Oncology

Manchester, , United Kingdom

Northern Centre for Cancer Care - Sir Bobby Robson Cancer Trials Research Centre

Newcastle upon Tyne, , United Kingdom

Royal Marsden Hospital - Dept of Oncology

Sutton, , United Kingdom

Countries

United States; China; Japan; Spain; United Kingdom

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS201924_0001

Trial Awareness and Transparency website

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

US Medical Information website, Medical Resources

http://www.DDRiver-trials.com

DDRiver website

Other Identifiers

2019-002203-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-515848-23-00

Identifier Type: CTIS

Identifier Source: secondary_id

MS201924_0001

Identifier Type: -

Identifier Source: org_study_id