AzTrials
AzTrials

Metastatic or Locally Advanced Unresectable Solid TumorsPhase 1NCT04170153

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

A Phase 1 study testing M1774 and Niraparib in people with Metastatic or Locally Advanced Unresectable Solid Tumors, run by EMD Serono Research & Development Institute, Inc. at 16 sites in 5 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
M1774 and Niraparib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
161 participants
Where
16 sitesin 5 countries
Study dates
20 Dec 2019to 30 Nov 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 17Show fewer
  • 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

Trial locations and contacts

16 sites in 5 countries.

16 sites in 5 countries

United States5 sites

  • NEXT Oncology

    Austin, Texas, 78758

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Mary Crowley Cancer Research Centers

    Dallas, Texas, 75230

  • The Methodist Hospital Research Institute

    Houston, Texas, 77030

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

    Houston, Texas, 77030

Other trials in United States

Spain4 sites

  • Hospital Clinic de Barcelona - Servicio de Oncologia

    Barcelona

  • Hospital Universitari Vall d'Hebron - Oncology Dept.

    Barcelona

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

    Madrid

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

    Valencia

Other trials in Spain

United Kingdom4 sites

  • Addenbrooke's Hospital - Dept of Oncology

    Cambridge

  • The Christie Hospital - Dept of Oncology

    Manchester

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

    Newcastle upon Tyne

  • Royal Marsden Hospital - Dept of Oncology

    Sutton

Other trials in United Kingdom

Japan2 sites

  • National Cancer Center Hospital - Dept of Experimental Therapeutics

    Chūōku

  • National Cancer Center Hospital East - Dept of Experimental Therapeutics

    Kashiwa-shi

Other trials in Japan

China1 site

  • Beijing Cancer Hospital

    Beijing

Other trials in China

About this study

Official title: An Open-label, Multicenter Trial of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of Tuvusertib (M1774) in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 301)

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.

Being tested
M1774, Niraparib
Keywords
Tuvusertib (M1774), ATR inhibitor, Niraparib, PARP inhibitor, Metastatic or Locally Advanced Unresectable Solid Tumors
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • M1774Drug

    Also called Tuvusertib

    M1774 will be administered orally throughout the study.

  • NiraparibDrug

    Niraparib will be administered orally throughout the study.

Study groups in NCT04170153
Study groupRoleWhat they receive
Part A1: Monotherapy Dose EscalationExperimentalParticipants will initially receive Tuvusertib (M1774) once daily under fasting conditions. Additional schedules may be evaluated if needed.
Receives: Drug: M1774
Part A2 - Preliminary Food Effect AssessmentExperimentalParticipants 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.
Receives: Drug: M1774
Part A3 - Monotherapy ExpansionExperimentalPart 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.
Receives: Drug: M1774
Part B1: Combination Therapy Dose FindingExperimentalB1a: 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.
Receives: Drug: M1774; Drug: Niraparib
Part A4: Japan Dose Confirmation MonotherapyExperimentalStarting 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.
Receives: Drug: M1774
Part A5: China Dose Confirmation MonotherapyExperimentalStarting 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.
Receives: Drug: M1774

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

  2. 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

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

  3. 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

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

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

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

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

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

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

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

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

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

  8. Part A2: Maximum Observed Plasma Concentration (Cmax) of Tuvusertib (M1774)

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

  9. Part A2: Relative Bioavailability Based on Area Under the Plasma Concentration Curve (Frel[AUC]) of Tuvusertib (M1774) Under Fed Condition as Compared to Fasting Condition

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

  10. Part A2: Relative Bioavailability Based on Maximum Observed Plasma Concentration (Frel[Cmax]) of Tuvusertib (M1774) Under Fed Condition as Compared to Fasting Condition

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

  11. Part A3: Objective Response as Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

    Measured: Baseline up to 2.2 years

  12. Part B1: Occurrence of Dose-Limiting Toxicities (DLTs) During the DLT Observation Period

    Measured: Day 1 to Day 28 of Cycle 1 (Each Cycle is of 28 days)

  13. Part A1, A4, A5 and B1: To Determine the Recommended Dose Expansion (RDE) for Tuvusertib (M1774) monotherapy globally, in Japanese and in Chinese participants With Metastatic or Locally Advanced Unresectable Solid Tumors and in combination with Niraparib

    Measured: Assessed up to approximately 2.2 years

Secondary outcomes (82)

  1. Part A1, A3, A4 and A5: Maximum Observed Plasma Concentration (Cmax) of Tuvusertib (M1774)

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  2. Part A1, A3, A4 and A5: Time to Reach Maximum Plasma Concentration (tmax) of Tuvusertib (M1774)

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  3. Part A1, A3, A4 and A5: Area Under the Plasma Concentration Curve From Time Zero to 24 Hours Post Dose (AUC0-24h) of Tuvusertib (M1774)

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  4. Part A1, A3, A4 and A5: Area Under Plasma Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of Tuvusertib (M1774)

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  5. Part A1, A3, A4 and A5: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Tuvusertib (M1774)

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  6. Part A1, A3, A4 and A5: Apparent Terminal Half-life (t1/2) of Tuvusertib (M1774)

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  7. Part A1, A3, A4 and A5: Apparent Total Body Clearance From Plasma (CL/f) of Tuvusertib (M1774)

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  8. Part A1, A3, A4 and A5: Apparent Clearance Body Clearance at Steady State Following Extravascular Administration (CLss/F) of Tuvusertib (M1774)

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  9. Part A1, A3, A4 and A5: Apparent Volume of Distribution During Terminal Phase Following Extravascular Administration (Vz/F) of Tuvusertib (M1774)

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  10. Part A1, A3, A4 and A5: Accumulation Ratio for Area Under the Plasma Concentration Concentration-Time Curve (Racc[AUC]) of Tuvusertib (M1774)

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  11. Part A1, A3, A4 and A5: Accumulation Ratio of Maximum Observed Plasma Concentration (Racc[Cmax]) of Tuvusertib (M1774)

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  12. Part A1, A3, A4 and A5: Dose Normalized Area Under Concentration-Time Curve Within One Dosing Interval (AUC0-tau/Dose) of M1774

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  13. Part A1, A3, A4 and A5: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h/Dose) Post-Dose of M1774

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  14. Part A1, A3, A4 and A5: Dose Normalized Area Under Concentration-Time Curve From Time Zero (dosing time) Extrapolated to Infinity (AUC0-inf/Dose) of M1774

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  15. Part A1, A3, A4 and A5: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M1774

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  16. Part A1, A3, A4 and A5: Area Under the Plasma Concentration Curve From Time Zero to 12 Hours (AUC0-12h) Post-Dose of M1774

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose up to 12 hours post-dose (Each Cycle is of 21 days)

  17. Part A1, A3, A4 and A5: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 12Hours (AUC0-12h/Dose) Post-dose of M1774

    Measured: Cycle 1 Day 1 and Day 8: Pre-dose upto 12 hours post-dose (Each Cycle is of 21 days)

  18. Part A1, A3, A4 and A5: Area Under the Plasma Concentration Curve From Time Zero to 10 Hours Post-dose (AUC0-10h) of M1774

    Measured: Part A1, A3, A4 and A5: Cycle 1 Day 1 and Day 8: Pre-dose up to 10 hours post-dose (Each Cycle is of 21 days)

  19. Part A1, A3, A4 and A5: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 10 Hours (AUC0-10h/Dose) Post-dose of M1774

    Measured: Part A1, A3, A4 and A5: Cycle 1 Day 1 and Day 8: Pre-dose up to 10 hours post-dose (Each Cycle is of 21 days)

  20. Part A1, A3, A4 and A5: Area Under Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-t) of M1774

    Measured: Part A1, A3, A4 and A5: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  21. Part A1, A3, A4 and A5 : Dose Normalized Area Under Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-t/Dose) of M1774

    Measured: Part A1, A3, A4 and A5: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  22. Part A1, A3, A4 and A5: Renal Clearance (CLr) of M1774

    Measured: Part A1, A3, A4 and A5: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  23. Part A1, A3, A4 and A5: Cumulative Amount Excreted From Time Zero to Infinity (Ae0-infinity) of M1774

    Measured: Part A1, A3, A4 and A5: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  24. Part A1, A3, A4 and A5: Cumulative Amount Excreted From Time Zero to Time After Dosing (Ae0-t) of M1774

    Measured: Part A1, A3, A4 and A5: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  25. Part A1, A3, A4 and A5: Cumulative Percentage of Dose Excreted From Time Zero to Time After Dosing (Ae0-t%) of M1774

    Measured: Part A1, A3, A4 and A5: Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  26. Part A2: 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

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

  27. Part A2: 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

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

  28. Part A2: Number of Participants With Abnormalities in Vital Signs

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

  29. Part A2: Number of Participants With Clinical Significant Abnormalities in Electrocardiogram (ECG) Findings

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

  30. Part A2: Time to Reach Maximum Plasma Concentration (tmax) Under Fed/Fasted Ratio of M1774

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

  31. Part A2: Area Under Plasma Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M1774

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

  32. Part A2: Apparent Terminal Half-life (t1/2) of M1774

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

  33. Part A2: Apparent Total Body Clearance From Plasma (CL/f) of M1774

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

  34. Part A2: Apparent Volume of Distribution During Terminal Phase Following Extravascular Administration (Vz/F) of M1774

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

  35. Part A2: Dose Normalized Area Under Concentration Time Curve Within One Dosing Interval (AUC0-tau/Dose) of M1774

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

  36. Part A2: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h/Dose) Post dose of M1774

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

  37. Part A2: Dose Normalized Area Under Concentration-Time Curve From Time Zero (dosing time) Extrapolated to Infinity (AUC0-inf/Dose) of M1774

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

  38. Part A2: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M1774

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

  39. Part A2: Cumulative Amount Excreted From Time Zero (dosing time) to Infinity (Ae0-inf) of M1774

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

  40. Part A2: Cumulative Amount Excreted From Time Zero to Time After Dosing (Ae0-t) of M1774

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

  41. Part A2: Cumulative Percentage of Dose Excreted From Time Zero to Time After Dosing (Ae0-t%) of M1774

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

  42. Part A2: Renal Clearance (CLr) of M1774

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

  43. Part A2: Dose Normalized Area Under Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-t/Dose) Under Fed/Fasted Ratio of M1774

    Measured: Part A2: Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  44. Part A2: Area Under the Plasma Concentration Curve From Time Zero to 12 Hours (AUC0-12h) Post-Dose Under Fed/Fasted Ratio of M1774

    Measured: Part A2: Cycle 1 Day -7 and Day 1: Pre-dose up to 12 hours post-dose (Each Cycle is of 21 days)

  45. Part A2: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 12Hours (AUC0-12h/Dose) Post-dose Under Fed/Fasted Ratio of M1774

    Measured: Part A2: Cycle 1 Day -7 and Day 1: Pre-dose up to 12 hours post-dose (Each Cycle is of 21 days)

  46. Part A2: Area Under the Plasma Concentration Curve From Time Zero to 10 Hours PostDose AUC(0-10h) Under Fed/Fasted Ratio of M1774

    Measured: Part A2: Cycle 1 Day -7 and Day 1: Pre-dose up to 10 hours post-dose (Each Cycle is of 21 days)

  47. Part A2: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 10 Hours (AUC0-10h/Dose) Post-dose Under Fed/Fasted Ratio of M1774

    Measured: Part A2: Cycle 1 Day -7 and Day 1: Pre-dose up to 10 hours post-dose (Each Cycle is of 21 days)

  48. Part A2: Area Under Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-t) Under Fed/Fasted Ratio of M1774

    Measured: Part A2: Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  49. Part A2: Apparent Clearance Body Clearance at Steady State Following Extravascular Administration (CLss/F) Under Fed/Fasted Ratio of M1774

    Measured: Part A2: Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  50. Part A2: Accumulation Ratio for Area Under the Plasma Concentration Concentration-Time Curve (Racc[AUC]) Under Fed/Fasted Ratio of M1774

    Measured: Part A2: Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  51. Part A2: Accumulation Ratio of Maximum Observed Plasma Concentration (Racc[Cmax]) Under Fed/Fasted Ratio of of M1774

    Measured: Part A2: Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)

  52. Part A2: Number of Participants With Corrected QT (QTc) Interval

    Measured: Baseline up to Day 8

  53. Part A3: Duration of Response (DOR) According to RECIST v1.1

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

  54. Part A3: Number of Participants With Clinical Benefit According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

    Participants with a clinical benefit, defined as an objective response or stable disease for at least 6 months, as determined by the Investigator through the use of RECIST version 1.1.

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

  55. Part A3: Progression-Free Survival (PFS) as Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

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

  56. Part A3: Overall Survival (OS)

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

  57. Part B1: Objective Response as Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

    Measured: Baseline up to 2.2 years

  58. Part B1: Maximum Observed Plasma Concentration (Cmax) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  59. Part B1: Time to Reach Maximum Plasma Concentration (tmax) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  60. Part B1: Area Under the Plasma Concentration Curve From Time Zero to 24 Hours Post Dose AUC(0-24h) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  61. Part B1: Area Under Plasma Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  62. Part B1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  63. Part B1: Apparent Terminal Half-life (t1/2) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  64. Part B1: Apparent Total Body Clearance From Plasma (CL/f) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  65. Part B1: Apparent Clearance Body Clearance at Steady State Following Extravascular Administration (CLss/F) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  66. Part B1: Apparent Volume of Distribution During Terminal Phase Following Extravascular Administration (Vz/F) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  67. Part B1: Accumulation Ratio for Area Under the Plasma Concentration Concentration-Time Curve (Racc[AUC]) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  68. Part B1: Accumulation Ratio of Maximum Observed Plasma Concentration (Racc[Cmax]) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  69. Part B1: Dose Normalized Area Under Concentration-Time Curve Within One Dosing Interval (AUC0-tau/Dose) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  70. Part B1: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h/Dose) Post-Dose of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  71. Part B1: Dose Normalized Area Under Concentration-Time Curve From Time Zero (dosing time) Extrapolated to Infinity (AUC0-inf/Dose) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  72. Part B1: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  73. Part B1: Area Under the Plasma Concentration Curve From Time Zero to 12 Hours (AUC0-12h) Post-Dose of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3 (each cycle is of 28 days)

  74. Part B1: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 12Hours (AUC0-12h/Dose) Post-dose of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3 (each cycle is of 28 days)

  75. Part B1: Area Under the Plasma Concentration Curve From Time Zero to 10 Hours PostDose AUC(0-10h) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  76. Part B1: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 10 Hours (AUC0-10h/Dose) Post-dose of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  77. Part B1: Area Under Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-t) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  78. Part B1: Dose Normalized Area Under Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-t/Dose) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  79. Part B1: Renal Clearance (CLr) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  80. Part B1: Cumulative Amount Excreted From Time Zero to Infinity (Ae0-infinity) of M1774 as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  81. Part B1: Cumulative Amount Excreted From Time Zero to Time After Dosing (Ae0-t) of Tuvusertib (M1774) as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

  82. Part B1: Cumulative Percentage of Dose Excreted From Time Zero to Time After Dosing (Ae0-t%) of Tuvusertib (M1774) as well as its Metabolites and Niraparib

    Measured: Part B1: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10 hours post-dose on Day 1and Day 8, Pre-dose on Day 15 of cycle 1; Pre-dose, 2, 4 hours post-dose pm Day 1 of Cycle 2; Pre-dose on Day 1 of cycle 3(each cycle is of 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Nov 2019
  2. Study start20 Dec 2019
  3. Primary completion30 Nov 2026 (estimated)
  4. Study completion30 Nov 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Open-Label
Masking
None (open label)
Enrolment
161 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04170153
Sponsor's protocol ID
MS201924_0001
Other IDs
2019-002203-18, 2024-515848-23-00, jRCT2031220326, CTR20222665, 2019
Status last verified
Aug 2026
First submitted
18 Nov 2019
Last updated
13 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: IPD will not be shared for Phase I interventional or observational studies. Further information on how to request data can be found on our website bit.ly/IPD21.

Publications

  • Mukker JK, Diderichsen PM, Hellmann F, Yap TA, Plummer R, Tolcher AW, de Bono JS, Gounaris I, Szucs Z, Zimmermann A, Kareva I, Bolleddula J, Seithel-Keuth A, Locatelli G, Enderlin M, Hicking C, Zutshi A, Gao W, Strotmann R, Benincosa L, Venkatakrishnan K. Integrated Population Pharmacokinetic, Pharmacodynamic, and Safety Analyses to Inform Dosage Selection in the Clinical Development of the ATR Inhibitor Tuvusertib. Clin Pharmacol Ther. 2026 Mar;119(3):618-628. doi: 10.1002/cpt.70029. Epub 2025 Aug 21.

    PubMed 40838864

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing M1774 and Niraparib in people with Metastatic or Locally Advanced Unresectable Solid Tumors, run by EMD Serono Research & Development Institute, Inc. at 16 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Spain, United Kingdom, Japan, China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04170153, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in