First in Human Study of M6223

Official Title

Phase I, First-in-Human, Open-Label, Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of M6223, an Inhibitor of TIGIT, as Single Agent and in Combination With Bintrafusp Alfa, Anti-PDL1/ TGFß Trap in, Participants With Metastatic or Locally Advanced Solid Unresectable Tumours

Summary:

The main purpose of this study is to determine the safety, tolerability, pharmacokinetics (PK), immunogenicity and (if observed) the maximum tolerated dose (MTD) of M6223 as a single agent (Part 1A) and of M6223 combined with bintrafusp alfa [Part 1B, for both the every 2 weeks (Q2W) regimen and the every 3 weeks (Q3W) regimen] in participants with metastatic or locally advanced solid unresectable tumours.

Trial Description

Primary Outcome:

• Part 1A and 1B: Occurrence of Dose Limiting Toxicities (DLTs) During the DLT Observation Period (28 Days)
• Part IA and IB: Occurrence of Treatment-Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events (TRAEs) According to the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) version 5
• Part IA and IB: Occurrence of Treatment-Emergent Adverse Events (TEAEs) as per Severity and Deaths
• Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Clinical Laboratory Measures
• Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Electrocardiogram Findings
• Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Vital Signs
• Part IA and IB: Occurrence of Change From Baseline in Eastern Cooperative Oncology Group Performance Status

• Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M6223
• Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC 0-inf) of M6223
• Part 1A and Part 1B: Area Under Serum Concentration-Time Curve Over a Dosing Interval From Time Zero to Tau (τ) (AUCτ) of M6223
• Part 1A and Part 1B: Maximum Observed Serum Concentration (Cmax) of M6223
• Part 1A and Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of M6223
• Part 1A and Part 1B: Time to Reach Maximum Serum Concentration (Tmax) of M6223
• Part 1A and Part 1B: Apparent Terminal Half-Life (t1/2) of M6223
• Part 1A and Part 1B: Elimination Rate Constant (Lambda z) of M6223
• Part 1B: Maximum Observed Serum Concentration (Cmax) of Bintrafusp alfa
• Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Bintrafusp alfa
• Part IA and 1B: Immunogenicity of M6223 Measured by Antidrug Antibody (ADA) Assays
• Part 1B: Immunogenicity of Bintrafusp alfa Measured by Antidrug Antibody (ADA) Assays
• Part 1A and 1B: Change from Baseline in QT Interval
• Part 1A and IB: Best Overall Response According to Response Criteria in Solid Tumours Version 1.1 (RECIST 1.1) Assessed as per Investigator
• Part 1A and 1B: Duration of Response According to Response Criteria in Solid Tumours Version 1.1 (RECIST 1.1) Assessed as per Investigator
• Part 1A and 1B: Time to Tumour Response According to Response Criteria in Solid Tumours Version 1.1 (RECIST 1.1) Assessed as per Investigator
• Part 1A and 1B: Disease Control According to Response Criteria in Solid Tumours Version 1.1 (RECIST 1.1) Assessed as per Investigator
• Part 1A and 1B: Progression-free Survival Time According to Response Criteria in Solid Tumours Version 1.1 (RECIST 1.1) Assessed as per Investigator
• Part 1A and 1B: Overall Survival

View this trial on ClinicalTrials.gov