First-in-Man, Dose-escalation Trial of C-met Kinase Inhibitor MSC2156119J in Subjects With Advanced Solid Tumors
Condition: Patients With Solid Tumors, Either Refractory to Standard Therapy or for Which no Effective Standard Therapy is Available
MeSH terms: Neoplasms
Intervention: MSC2156119J
Intervention MeSH terms: Tepotinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 149.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Phase 1; advanced solid tumors; refractory to standard therapy

Summary:

      This is a an open-label, dose-escalation, first-in-man (FIM) study designed to explore
      MSC2156119J, in subjects with advanced solid tumors who have not responded to previous
      therapies or for whom no other therapies are available.

      Subjects will be assigned one of the dosing regimens:

        -  Regimen 1: MSC2156119J once daily for 14 days, followed by 7 days with no treatment
           (21-day cycle)

        -  Regimen 2: MSC2156119J three times per week (e.g., Days 1, 3, and 5) for three weeks
           (21-day cycle)

        -  Regimen 3: MSC2156119J every day for three weeks (21-day cycle)
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject should read and fully understand the requirements of the trial, be willing to
             comply with all trial visits and assessments, and be willing and able to give informed
             consent

          2. Histologically or cytologically confirmed solid tumor, either refractory to standard
             therapy or for which no effective standard therapy is available

          3. Measurable or evaluable disease, as defined by RECIST 1.0

          4. Estimated life expectancy greater than (>) three months

          5. Men or women aged greater than or equal to (>=) 18 years

          6. Women of childbearing potential must have a negative blood pregnancy test at the
             Screening Visit. For this trial, women of childbearing potential are defined as all
             women after puberty, unless they are post-menopausal for at least 12 months, are
             surgically sterile, or are sexually inactive.

          7. Subjects and their partners must be willing to avoid pregnancy during the trial and
             until three months after the last trial treatment. Male subjects with female partners
             of childbearing potential and female subjects of childbearing potential must,
             therefore, be willing to use adequate contraception as approved by the investigator,
             such as a two-barrier method or one-barrier method with spermicide or intrauterine
             device. This requirement begins two weeks before receiving the first trial treatment
             and ends one month after receiving the last treatment.

          8. ECOG performance status of 0 to 2

          9. Adequate hematological function:

               -  Hemoglobin >= 9.0 g/dL

               -  Neutrophils > 1.5 x 109/L

               -  Platelets >= 75 x 109/L

         10. Adequate liver function:

               -  Total bilirubin less than or equal to (<=) 1.5 x ULN (upper limit to normal)

               -  AST/ ALT ≤ 2.5 x ULN

             For subjects with liver metastases:

               -  Total bilirubin ≤ 1.5 x ULN

               -  AST/ ALT ≤ 5 x ULN

         11. Adequate renal function:

               -  Serum creatinine < 1.5 x ULN, and/or

               -  Calculated creatinine clearance > 60 mL/min

         12. Resolution of all acute chemotherapy, radiotherapy or surgery-related AEs to Grade <=
             2, except for alopecia

         13. Recovery from any surgical intervention

         14. Subjects enrolling after the MTD has been determined must present specific c Met
             alterations (mutation, overexpression, amplification

        Exclusion Criteria:

          1. Received chemotherapy, immunotherapy, hormonal therapy (except subjects with prostate
             cancer), biologic therapy, or any other investigational agent or anticancer therapy
             within 28 days (or five half-lives for non-cytotoxics, whichever is shorter), of Day 1
             of trial treatment (six weeks for nitrosureas or mitomycin C)

          2. Received extensive prior radiotherapy on more than 30% of bone marrow

          3. Symptomatic primary tumors or metastasis of brain and/or central nervous system,
             uncontrolled with antiepileptics and requiring high doses of steroids

          4. Known HIV positivity, active hepatitis C, or active hepatitis B

          5. Medical history of liver fibrosis/ cirrhosis

          6. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family
             members who suffer(ed) from such

          7. Medical history of difficulty swallowing, malabsorption or other chronic
             gastrointestinal disease, or conditions that may hamper compliance and/or absorption
             of the tested product

          8. Medical history of surgery within six weeks prior to enrollment

          9. Impaired cardiac function (left ventricular ejection fraction < 45% defined by
             echocardiograph, serious arrhythmia, unstable angina pectoris, congestive heart
             failure NYHA III and IV, myocardial infarction within the last 12 months prior to
             trial entry; signs of pericardial effusion)

         10. Hypertension uncontrolled by standard therapies (not stabilized to 150/90 mm Hg)

         11. Peripheral neuropathy Grade >= 2

         12. Medical history of any other significant medical disease, major surgery, or
             psychiatric condition that might impair the subject's well being or preclude full
             participation in the trial

         13. Women who are pregnant or nursing

         14. Known drug abuse or alcohol abuse

         15. Participation in another clinical trial within the past 28 days

         16. Requires concurrent treatment with a non-permitted drug

         17. Known hypersensitivity to any of the trial treatment ingredients

         18. Legal incapacity or limited legal capacity

         19. Any other reason that, in the opinion of the principal investigator, precludes the
             subject from participating in the trial