Description:
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 tumors.
Title
- Brief Title: 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 Tumors
Clinical Trial IDs
- ORG STUDY ID:
MS201430_0001
- NCT ID:
NCT04457778
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| M6223 | | Part 1A: M6223 Monotherapy |
| Bintrafusp alfa | | Part1B: M6223 + Bintrafusp alfa |
| M6223 | | Part1B: M6223 + Bintrafusp alfa |
Purpose
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 tumors.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Part 1A: M6223 Monotherapy | Experimental | | |
| Part1B: M6223 + Bintrafusp alfa | Experimental | | |
Eligibility Criteria
Inclusion Criteria:
- Participants have histologically or cytologically proven locally advanced or advanced
solid malignancies who are refractory to or have progressed under standard treatment
and have no other treatment options known to confer clinical benefit
- Participants with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0
to 1 at Screening
- Participant has a formalin-fixed paraffin-embedded block containing tumor tissue or a
minimum of 15 (preferably 25) unstained tumor slides suitable for
immunohistochemistry-based staining of protein expression
- Participants with life expectancy of at least 12 weeks
- Participants with measurable disease according to Response Evaluation Criteria in
Solid Tumors version 1.1 (RECIST 1.1)
- Adequate hematological, hepatic and renal function as defined in the protocol
- Other protocol defined inclusion criteria may apply
Exclusion Criteria:
- Participants with persisting toxicity related to prior therapy Grade greater than (>)
1 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Version 5.0, however, alopecia, sensory neuropathy Grade less than or equal to (<=) 2,
or other non-immune-related Grade <= 2 not constituting a safety risk
- Participants with prior organ transplantation including allogeneic stem cell
transplantation
- Participants with prior toxicity related to an immune checkpoint inhibitor Grade
greater than equal to (>=) 3 NCI-CTCAE Version 5.0 unless resolved to Grade <= 1 prior
to study inclusion
- Participants with current significant cardiac conduction abnormalities, including
corrected QT interval (QTcF, corrected with Fridericia formula) prolongation of > 450
milli seconds (ms) on triplicate 12-lead ECG or impaired cardiovascular function,
ventricular tachycardia, hypokalemia or a history of paroxysmal atrial fibrillation,
serious cardiac arrhythmia and family history of sudden death or long QT syndrome
- A history of vascular, cardiovascular or cerebrovascular disease like, cerebral
vascular accident/stroke (less than [<] 6 months prior to enrollment), myocardial
infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure
(New York Heart Association Classification Class >= II), deep vein thrombosis (< 3
months prior to enrollment) or pulmonary thrombosis/embolism (< 3 months prior to
enrollment)
- Other protocol defined exclusion criteria may apply
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Part 1A and 1B: Occurrence of Dose Limiting Toxicities (DLTs) During the DLT Observation Period (28 Days) |
| Time Frame: | Day 1 to Day 28 |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | 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 |
| Time Frame: | Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC 0-inf) of M6223 |
| Time Frame: | Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and Part 1B: Area Under Serum Concentration-Time Curve Over a Dosing Interval From Time Zero to Tau (τ) (AUCτ) of M6223 |
| Time Frame: | Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and Part 1B: Maximum Observed Serum Concentration (Cmax) of M6223 |
| Time Frame: | Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of M6223 |
| Time Frame: | Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and Part 1B: Time to Reach Maximum Serum Concentration (Tmax) of M6223 |
| Time Frame: | Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and Part 1B: Apparent Terminal Half-Life (t1/2) of M6223 |
| Time Frame: | Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and Part 1B: Elimination Rate Constant (Lambda z) of M6223 |
| Time Frame: | Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1B: Maximum Observed Serum Concentration (Cmax) of Bintrafusp alfa |
| Time Frame: | Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Bintrafusp alfa |
| Time Frame: | Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen) |
| Safety Issue: | |
| Description: | |
| Measure: | Part IA and 1B: Immunogenicity of M6223 Measured by Antidrug Antibody (ADA) Assays |
| Time Frame: | Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen) up to end of safety follow-up visit (up to a maximum of 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1B: Immunogenicity of Bintrafusp alfa Measured by Antidrug Antibody (ADA) Assays |
| Time Frame: | Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen) up to end of safety follow-up visit (up to a maximum of 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and 1B: Change from Baseline in QT Interval |
| Time Frame: | From Day 1 Cycle 1 (Baseline) up to Day 1 Cycle 7 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and IB: Best Overall Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator |
| Time Frame: | From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and 1B: Duration of Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator |
| Time Frame: | From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and 1B: Time to Tumor Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator |
| Time Frame: | From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and 1B: Disease Control According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator |
| Time Frame: | From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and 1B: Progression-free Survival Time According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator |
| Time Frame: | From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Part 1A and 1B: Overall Survival |
| Time Frame: | Time from first treatment to end of study (planned 12 months after last patient started treatment) |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | EMD Serono Research & Development Institute, Inc. |
Trial Keywords
- M6223
- Bintrafusp alfa
- Metastatic Solid Tumors
Last Updated
July 7, 2021
