First-in-Human Study of MS201408-0005A as Single Agent and in Combinations
Condition: Metastatic or Locally Advanced Unresectable Solid Tumors
Intervention: M4112
Intervention description: All participants who received M4112 100,200,400,600 and 800 mg twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MS201408-0005A; MS201408-0005B; MS201408-0005C; First-in-Human; Advanced solid tumors

Summary:

      This is a Phase I, open-label study to determine the safety, tolerability, pharmacokinetic
      (PK), pharmacodynamics (PD), and preliminary antitumor activity of MS201408-0005A as single
      agent (Part IA only) and in combination with MS201408-0005C or MS201408-0005B (Part IB, Part
      IC).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with histologically or cytologically proven advanced or metastatic solid
             malignancies for whom no effective standard therapy exists or has failed or subjects
             who are intolerant to established therapy known to provide clinical benefit for their
             condition (dose escalation cohorts; Part I).

          -  An eastern cooperative oncology group performance status (ECOG PS) of 0 to 1 at
             screening and adequate hematological, renal and hepatic function as defined by
             protocol specified criteria.

          -  Other protocol defined inclusion criteria could apply.

        Exclusion Criteria:

          -  Intolerance to immune checkpoint inhibitor therapy as defined by the occurrence of an
             adverse drug reaction requiring drug discontinuation (dose escalation cohorts),
             concurrent anticancer treatment or immunosuppressive agents.

          -  Prior organ transplantation including allogeneic stem cell transplantation, brain
             metastases (except those meeting certain protocol specified criteria which are
             acceptable), significant acute or chronic infections, a history of
             cardiovascular/cerebrovascular disease.

          -  Current significant cardiac conduction abnormalities and hypokalemia as specified in
             the protocol.

          -  Warfarin or other Vitamin K antagonists treatment, strong inhibitors or inducers of
             cytochrome P450 (CYP)3A4, and drugs with a narrow therapeutic index, which are
             predominantly metabolized by CYP3A4 and drugs known to have a high risk to prolong QTc
             as per label.

          -  Pregnancy or lactation.

          -  Severe hypersensitivity reactions to monoclonal antibodies, known hypersensitivity to
             the investigational medicinal products or to one or more of the excipients, autoimmune
             diseases (inflammatory bowel diseases, interstitial lung disease, or pulmonary
             fibrosis), and live vaccines within 28 days prior to study entry.

          -  Pneumonitis and history of pneumonitis.

          -  Other protocol defined exclusion criteria could apply.