Overview

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) in participants with metastatic or locally advanced solid unresectable tumors.

Eligibility

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