M1774 for Metastatic or Locally Advanced Unresectable Solid Tumors

Phase-Based Progress Estimates
1
Effectiveness
1
Safety
Metastatic or Locally Advanced Unresectable Solid TumorsM1774 - Drug
Eligibility
18+
All Sexes
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Study Summary

This trial is testing a new drug, M1774, to see if it is safe and effective when used alone or with another drug, niraparib.

Eligible Conditions
  • Metastatic or Locally Advanced Unresectable Solid Tumors

Treatment Effectiveness

Effectiveness Progress

1 of 3

Similar Trials

Study Objectives

12 Primary · 84 Secondary · Reporting Duration: Baseline up to 2.2 years

Year 2
Part A1 and B1: To Determine the Recommended Dose Expansion (RDE) for M1774 in Combination With Niraparib in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors
Year 2
Part A3: Objective Response as Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Part B1: Objective Response as Assessed by Investigator According to Response Evaluation Criteriain Solid Tumors Version (RECIST) 1.1
Year 2
Part A1, A3 and B1: Number of Participants With Abnormalities in Vital Signs
Part A1, A3 and B1: Number of Participants With Clinical Significant Abnormalities in Electrocardiogram(ECG) Findings
Part A1, A3 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
Part A1, A3 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
Part A2: Number of Participants With Abnormalities in Vital Signs
Part A2: Number of Participants With Clinical Significant Abnormalities in Electrocardiogram (ECG) Findings
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
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
Part A3: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Part A3: Number of Participants With Clinical Benefit According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Part A3: Overall Survival (OS) According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Part A3: Progression-Free Survival (PFS) as Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Day 8
Part A1 and A3: Number of Participants With Corrected QT (QTc) Interval
Part A2: Number of Participants With Corrected QT (QTc) Interval
Day 21
Part A2: Apparent Terminal Half-life (t1/2) of M1774
Part A2: Apparent Total Body Clearance From Plasma (CL/f) of M1774
Part A2: Apparent Volume of Distribution During Terminal Phase Following Extravascular Administration (Vz/F) of M1774
Part A2: Area Under Plasma Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M1774
Part A2: Area Under the Plasma Concentration Curve From Time Zero to 24 Hours Post Dose (AUC 0-24h) of M1774
Part A2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of M1774
Part A2: Dose Normalized Area Under Concentration Time Curve Within One Dosing Interval (AUC0-tau/Dose) of M1774
Part A2: Dose Normalized Area Under Concentration-Time Curve From Time Zero (dosing time) Extrapolated to Infinity (AUC0-inf/Dose) of M1774
Part A2: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h/Dose) Post dose of M1774
Part A2: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M1774
Part A2: Maximum Observed Plasma Concentration (Cmax) of M1774
Part A2: Relative Bioavailability Based on Area Under the Plasma Concentration Curve (Frel[AUC]) of M1774 Under Fed Condition as Compared to Fasting Condition
Part A2: Relative Bioavailability Based on Maximum Observed Plasma Concentration (Frel[Cmax]) of M1774 Under Fed Condition as Compared to Fasting Condition
Part A2: Time to Reach Maximum Plasma Concentration (tmax) Under Fed/Fasted Ratio of M1774
Day 21
Part A2: Cumulative Amount Excreted From Time Zero (dosing time) to Infinity (Ae0-inf) of M1774
Part A2: Cumulative Amount Excreted From Time Zero to Time After Dosing (Ae0-t) of M1774
Part A2: Cumulative Percentage of Dose Excreted From Time Zero to Time After Dosing (Ae0-t%) of M1774
Part A2: Renal Clearance (CLr) of M1774
Day 21
Part A1 and A3: Area Under the Plasma Concentration Curve From Time Zero to 12 Hours (AUC0-12h) Post-Dose of M1774
Day 21
Part A1 and A3: Accumulation Ratio for Area Under the Plasma Concentration Concentration-Time Curve (Racc[AUC]) of M1774
Part A1 and A3: Accumulation Ratio of Maximum Observed Plasma Concentration (Racc[Cmax]) of M1774
Part A1 and A3: Apparent Clearance Body Clearance at Steady State Following Extravascular Administration (CLss/F) of M1774
Part A1 and A3: Apparent Terminal Half-life (t1/2) of M1774
Part A1 and A3: Apparent Total Body Clearance From Plasma (CL/f) of M1774
Part A1 and A3: Apparent Volume of Distribution During Terminal Phase Following Extravascular Administration (Vz/F) of M1774
Part A1 and A3: Area Under Plasma Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M1774
Part A1 and A3: Area Under the Plasma Concentration Curve From Time Zero to 24 Hours Post Dose (AUC0-24h) of M1774
Part A1 and A3: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of M1774
Part A1 and A3: Dose Normalized Area Under Concentration-Time Curve From Time Zero (dosing time) Extrapolated to Infinity (AUC0-inf/Dose) of M1774
Part A1 and A3: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h/Dose) Post-Dose of M1774
Part A1 and A3: Dose Normalized Area Under Concentration-Time Curve Within One Dosing Interval (AUC0-tau/Dose) of M1774
Part A1 and A3: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M1774
Part A1 and A3: Maximum Observed Plasma Concentration (Cmax) of M1774
Part A1 and A3: Time to Reach Maximum Plasma Concentration (tmax) of M1774
Day 21
Part A1 and A3: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 12Hours (AUC0-12h/Dose) Post-dose of M1774
Day 21
Part A1: Occurrence of Dose-Limiting Toxicities (DLTs) During the DLT Observation Period
Day 28
Part B1: Occurrence of Dose-Limiting Toxicities (DLTs) During the DLT Observation Period
Day 21
Part A1 and A3: Area Under the Plasma Concentration Curve From Time Zero to 10 Hours Post-dose (AUC0-10h) of M1774
Part A1 and A3: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 10 Hours (AUC0-10h/Dose) Post-dose of M1774
Day 21
Part A1 and A3: Area Under Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-t) of M1774
Part A1 and A3: Cumulative Amount Excreted From Time Zero to Infinity (Ae0-infinity) of M1774
Part A1 and A3: Cumulative Amount Excreted From Time Zero to Time After Dosing (Ae0-t) of M1774
Part A1 and A3: Cumulative Percentage of Dose Excreted From Time Zero to Time After Dosing (Ae0-t%) of M1774
Part A1 and A3: Dose Normalized Area Under Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-t/Dose) of M1774
Part A1 and A3: Renal Clearance (CLr) of M1774
Day 21
Part A2: Area Under the Plasma Concentration Curve From Time Zero to 10 Hours PostDose AUC(0-10h) Under Fed/Fasted Ratio of M1774
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
Day 21
Part A2: Area Under the Plasma Concentration Curve From Time Zero to 12 Hours (AUC0-12h) Post-Dose Under Fed/Fasted Ratio of M1774
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
Day 21
Part A2: Accumulation Ratio for Area Under the Plasma Concentration Concentration-Time Curve (Racc[AUC]) Under Fed/Fasted Ratio of M1774
Part A2: Accumulation Ratio of Maximum Observed Plasma Concentration (Racc[Cmax]) Under Fed/Fasted Ratio of of M1774
Part A2: Apparent Clearance Body Clearance at Steady State Following Extravascular Administration (CLss/F) Under Fed/Fasted Ratio of M1774
Part A2: Area Under Concentration-Time Curve From Time Zero to Last Sampling Time (AUC0-t) Under Fed/Fasted Ratio of M1774
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
Day 28
Part B1: Accumulation Ratio for Area Under the Plasma Concentration Concentration-Time Curve (Racc[AUC]) of M1774 as well as its Metabolites and Niraparib
Part B1: Accumulation Ratio of Maximum Observed Plasma Concentration (Racc[Cmax]) of M1774 as well as its Metabolites and Niraparib
Part B1: Apparent Clearance Body Clearance at Steady State Following Extravascular Administration (CLss/F) of M1774 as well as its Metabolites and Niraparib
Part B1: Apparent Terminal Half-life (t1/2) of M1774 as well as its Metabolites and Niraparib
Part B1: Apparent Total Body Clearance From Plasma (CL/f) of M1774 as well as its Metabolites and Niraparib
Part B1: Apparent Volume of Distribution During Terminal Phase Following Extravascular Administration (Vz/F) of M1774 as well as its Metabolites and Niraparib
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
Part B1: Area Under Plasma Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M1774 as well as its Metabolites and Niraparib
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
Brain Diseases, Metabolic
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
Part B1: Cumulative Amount Excreted From Time Zero to Infinity (Ae0-infinity) of M1774 as well as its Metabolites and Niraparib
Part B1: Cumulative Amount Excreted From Time Zero to Time After Dosing (Ae0-t) of M1774 as well as its Metabolites and Niraparib
Part B1: Cumulative Percentage of Dose Excreted From Time Zero to Time After Dosing (Ae0-t%) of M1774 as well as its Metabolites and Niraparib
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
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
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
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
Part B1: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M1774 as well as its Metabolites and Niraparib
Part B1: Maximum Observed Plasma Concentration (Cmax) of M1774 as well as its Metabolites and Niraparib
Part B1: Renal Clearance (CLr) of M1774 as well as its Metabolites and Niraparib
Part B1: Time to Reach Maximum Plasma Concentration (tmax) of M1774 as well as its Metabolites and Niraparib
Day 28
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
Day 28
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
Day 28
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

Trial Safety

Safety Progress

1 of 3

Similar Trials

Side Effects for

FE Niraparib Fasted
6%Anaemia
6%Urinary tract infection
6%Diarrhoea
6%Blood creatinine increased
6%Decreased appetite
6%Hypokalaemia
6%Hypomagnesaemia
6%Cough
6%Catheter site pain
6%Atrial fibrillation
6%Dry eye
This histogram enumerates side effects from a completed 2021 Phase 3 trial (NCT01847274) in the FE Niraparib Fasted ARM group. Side effects include: Anaemia with 6%, Urinary tract infection with 6%, Diarrhoea with 6%, Blood creatinine increased with 6%, Decreased appetite with 6%.

Trial Design

5 Treatment Groups

Part A1: Monotherapy Dose Escalation
1 of 5
Part A3 - Monotherapy Expansion
1 of 5
Part B1b: Combination Therapy Dose Finding
1 of 5
Part A2 - Preliminary Food Effect Assessment
1 of 5
Part B1a: Combination Therapy Dose Finding
1 of 5

Experimental Treatment

130 Total Participants · 5 Treatment Groups

Primary Treatment: M1774 · No Placebo Group · Phase 1

Part A1: Monotherapy Dose Escalation
Drug
Experimental Group · 1 Intervention: M1774 · Intervention Types: Drug
Part A3 - Monotherapy Expansion
Drug
Experimental Group · 1 Intervention: M1774 · Intervention Types: Drug
Part B1b: Combination Therapy Dose FindingExperimental Group · 2 Interventions: M1774, Niraparib · Intervention Types: Drug, Drug
Part A2 - Preliminary Food Effect Assessment
Drug
Experimental Group · 1 Intervention: M1774 · Intervention Types: Drug
Part B1a: Combination Therapy Dose FindingExperimental Group · 2 Interventions: M1774, Niraparib · Intervention Types: Drug, Drug
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Niraparib
FDA approved

Trial Logistics

Trial Timeline

Screening: ~3 weeks
Treatment: Varies
Reporting: baseline up to 2.2 years

Who is running the clinical trial?

Merck KGaA, Darmstadt, GermanyIndustry Sponsor
429 Previous Clinical Trials
112,909 Total Patients Enrolled
3 Trials studying Metastatic or Locally Advanced Unresectable Solid Tumors
117 Patients Enrolled for Metastatic or Locally Advanced Unresectable Solid Tumors
EMD Serono Research & Development Institute, Inc.Lead Sponsor
74 Previous Clinical Trials
29,877 Total Patients Enrolled
3 Trials studying Metastatic or Locally Advanced Unresectable Solid Tumors
117 Patients Enrolled for Metastatic or Locally Advanced Unresectable Solid Tumors
Medical ResponsibleStudy DirectorMerck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
279 Previous Clinical Trials
67,213 Total Patients Enrolled
3 Trials studying Metastatic or Locally Advanced Unresectable Solid Tumors
117 Patients Enrolled for Metastatic or Locally Advanced Unresectable Solid Tumors

Eligibility Criteria

Age 18+ · All Participants · 10 Total Inclusion Criteria

Mark “Yes” if the following statements are true for you:
You have 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.
You have a meningeal carcinomatosis.
The disease must be measurable according to RECIST Version 1.1.
You have loss of function mutation in the gene for ARIDIA, ATRX and /or DAXX and ATM.