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

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

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 M1774 as monotherapy and in combination with the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborator: Merck KGaA, Darmstadt, Germany
• Treatments: Niraparib

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 mutation in the gene for ARIDIA, 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

• Female participants are not pregnant or breastfeeding

• Not a women of childbearing potential (WOCBP)

• 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 or platelets >=150,000 mm^3

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• 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)

• 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

• Active fungal, bacterial and/or viral infection. Individuals with known human immunodeficiency virus and/or viral hepatitis (B and/or C) are excluded. However, individual with hepatitis C treated with curative therapy are not considered actively infected

• 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 pigmentosae, Cockayne syndrome, and trichothiodystrophy

• Any other clinical condition or uncontrolled concurrent illness which in the Investigator's opinion would not make the participant a good candidate for the clinical study

• 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 CHK1 inhibitor

• Participants who cannot comply with restrictions for medications or food. Participants B1: Participants with a known history of acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) Participants B1: Participants with prostrate cancer

• Other protocol defined exclusion criteria could apply