First in Human Study of M6223 in Participants With Metastatic or Locally Advanced Solid Unresectable Tumors
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ClinicalTrials.gov Identifier: NCT04457778 |
Recruitment Status :
Recruiting
First Posted : July 7, 2020
Last Update Posted : February 23, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Metastatic Solid Tumors | Drug: M6223 Drug: Bintrafusp alfa | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 35 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | July 10, 2020 |
Estimated Primary Completion Date : | September 14, 2022 |
Estimated Study Completion Date : | September 14, 2022 |
Arm | Intervention/treatment |
---|---|
Experimental: Part 1A: M6223 Monotherapy |
Drug: M6223
Participants will receive an intravenous (IV) infusion of M6223 at escalated doses every 2 weeks on Day 1 of each Cycle (Each cycle is of 14 days) according to the recommendation of the SMC (Safety Monitoring Committee) until the maximum tolerated dose (MTD) has been reached or confirmed disease progression. |
Experimental: Part1B: M6223 + Bintrafusp alfa |
Drug: M6223
Participants will receive an intravenous (IV) infusion of M6223 at escalated doses every 2 weeks on Day 1 of each Cycle (Each cycle is of 14 days) according to the recommendation of the SMC (Safety Monitoring Committee) until the maximum tolerated dose (MTD) has been reached or confirmed disease progression. Drug: Bintrafusp alfa Participants will receive an IV infusion of bintrafusp alfa every 2 weeks on Day 1 of each Cycle (Cycle is 14 days) until confirmed disease progression. |
- Part 1A and 1B: Occurrence of Dose Limiting Toxicities (DLTs) During the DLT Observation Period (28 Days) [ Time Frame: Day 1 to Day 28 ]
- 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 [ Time Frame: Time from first study drug administration to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years) ]
- Part IA and IB: Occurrence of Treatment-Emergent Adverse Events (TEAEs) as per Severity and Deaths [ Time Frame: Time from first study drug administration to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years) ]
- Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Clinical Laboratory Measures [ Time Frame: Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years) ]
- Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Electrocardiogram Findings [ Time Frame: Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years) ]
- Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Vital Signs [ Time Frame: Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years) ]
- Part IA and IB: Occurrence of Change From Baseline in Eastern Cooperative Oncology Group Performance Status [ Time Frame: Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years) ]
- 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 post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days) ]
- 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 post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days) ]
- 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 post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days) ]
- Part 1A and Part 1B: Maximum Observed Serum Concentration (Cmax) of M6223 [ Time Frame: Pre-dose up to 14 days post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days) ]
- Part 1A and Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of M6223 [ Time Frame: Pre-dose up to 14 days post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days) ]
- Part 1A and Part 1B: Time to Reach Maximum Serum Concentration (Tmax) of M6223 [ Time Frame: Pre-dose up to 14 days post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days) ]
- Part 1A and Part 1B: Apparent Terminal Half-Life (t1/2) of M6223 [ Time Frame: Pre-dose up to 14 days post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days) ]
- Part 1A and Part 1B: Elimination Rate Constant (Lambda z) of M6223 [ Time Frame: Pre-dose up to 14 days post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days) ]
- Part 1B: Maximum Observed Serum Concentration (Cmax) of Bintrafusp alfa [ Time Frame: Pre-dose up to 14 days post-dose of Cycles 1 and 4 (Each cycle is of 14 days) ]
- Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Bintrafusp alfa [ Time Frame: Pre-dose up to 14 days post-dose of Cycles 1 and 4 (Each cycle is of 14 days) ]
- Part IA and 1B: Immunogenicity of M6223 Measured by Antidrug Antibody (ADA) Assays [ Time Frame: Pre-dose of Day 1 Cycle 1 (Cycle is 14 days) up to end of safety follow-up visit (up to a maximum of 2 years) ]
- Part 1B: Immunogenicity of Bintrafusp alfa Measured by Antidrug Antibody (ADA) Assays [ Time Frame: Pre-dose of Day 1 Cycle 1 (Cycle is 14 days) up to end of safety follow-up visit (up to a maximum of 2 years) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- 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) ]
- Part 1A and 1B: Overall Survival [ Time Frame: Time from first treatment to end of study (planned 12 months after last patient started treatment) ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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) 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04457778
Contact: US Medical Information | 888-275-7376 | eMediUSA@emdserono.com | |
Contact: Communication Center | 49 6151 72 5200 | service@emdgroup.com |
United States, Tennessee | |
Sarah Cannon Research Institute | Recruiting |
Nashville, Tennessee, United States, 37203 | |
Contact j.bendell@tnonc.com | |
Principal Investigator: Johanna Bendell | |
United States, Texas | |
MD Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact anaing@mdanderson.org | |
Principal Investigator: Aung Naing | |
Next Oncology | Recruiting |
San Antonio, Texas, United States, 78229 | |
Contact atolcher@nextoncology.com | |
Principal Investigator: Anthony Tolcher | |
Canada | |
Princess Margaret Cancer Centre | Recruiting |
Toronto, Canada | |
Contact lillian.siu@uhn.on.ca | |
Principal Investigator: Lillian Sui |
Study Director: | Medical Responsible | Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany |
Responsible Party: | EMD Serono Research & Development Institute, Inc. |
ClinicalTrials.gov Identifier: | NCT04457778 |
Other Study ID Numbers: |
MS201430_0001 |
First Posted: | July 7, 2020 Key Record Dates |
Last Update Posted: | February 23, 2021 |
Last Verified: | February 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Plan Description: | Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be is found on our website https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
M6223 Bintrafusp alfa Metastatic Solid Tumors |
Neoplasms |