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

Phase 1Active Not RecruitingNCT04170153

EMD Serono Research & Development Institute, Inc.161 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

161

Conditions

Metastatic or Locally Advanced Unresectable Solid Tumors

Interventions

M1774DRUG

M1774 will be administered orally throughout the study.

NiraparibDRUG

Niraparib will be administered orally throughout the study.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 \- Other protocol defined inclusion criteria could apply 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 * Other protocol defined exclusion criteria could apply

Locations (16)

Massachusetts General Hospital

Boston, Massachusetts, United States

NEXT Oncology

Austin, Texas, United States

Outcomes

Primary Outcomes

Part A1, A4 and A5: Occurrence of Dose-Limiting Toxicities (DLTs) During the DLT Observation Period

Time frame: Day 1 to Day 21 of Cycle 1 (Each Cycle is of 21 days)

Part A1, A3, A4, A5 and B1: Occurrence of Treatment-emergent Adverse Events (TEAEs), Treatment-related Adverse Events (AEs) and Death According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

Time frame: Baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years

Part A1, A3, A4, A5 and B1: Number of Participants With Grade 3 or Higher Laboratory Findings According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

Time frame: Baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years

Part A1, A3, A4, A5 and B1: Number of Participants With Abnormalities in Vital Signs

Time frame: Baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years

Part A1, A3, A4, A5 and B1: Number of Participants With Clinical Significant Abnormalities in Electrocardiogram (ECG) Findings

Time frame: Baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years

Part A2: Area Under the Plasma Concentration Curve From Time Zero to 24 Hours Post Dose (AUC 0-24h) of Tuvusertib (M1774)

Time frame: Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

Part A2: Area Under the Plasma Concentration Curve From Time Zero to Infinity Post Dose (AUC 0-inf) of Tuvusertib (M1774)

Time frame: Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

Data from ClinicalTrials.gov

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