M8891 First in Human in Solid Tumors
Condition: Advanced Solid Tumors; Metastatic Renal Cell Carcinoma
MeSH terms: Carcinoma, Renal Cell
Intervention: Part 1: M8891
Intervention description: Participants receives M8891 orally once daily at escalated dose levels under fasting condition for consecutive 21-day cycles of continuous treatment until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Solid Tumors; Metastatic Renal Cell Carcinoma; M8891; Methionine Aminopeptidase 2 Inhibitor

Summary:

      The purpose of this study was to determine the maximum tolerated dose (MTD), safety,
      tolerability, Pharmacokinetic (PK), pharmacodynamic and clinical activity of M8891 as single
      agent in participants with advanced solid tumors in Part 1.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must be refractory to or intolerant of existing cancer therapy(ies) known
             to provide clinical benefit.

          -  Histologically confirmed advanced solid tumors with no clear curative treatment
             options available after at least 1 prior systemic anticancer therapy.

          -  Tumor accessible for biopsies and agreement to conduct pre-dose and post-dose fresh
             tumor biopsies.

          -  Male or female subjects at least 18 years of age

          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at Screening

          -  Histologic or cytologic evidence/proven of metastatic renal cell carcinoma (mRCC) with
             clear cell component

          -  Part 2A: Participants should have progressed to 1 or more previous lines of systemic
             anticancer therapy, excluding treatment with cabozantinib

          -  Part 2B: Participants should have progressed to 1 or 2 previous lines of systemic
             anticancer therapy, excluding treatment with cabozantinib. Participants should have
             failed to only 1 previous TKI for metastatic disease. Adjuvant therapy with sunitinib
             will be considered as 1 line of therapy for metastatic disease in the case that
             disease progression occurs during or within 3 months of the completion of the
             treatment.

          -  Other protocol defined inclusion criteria could apply

        Exclusion Criteria:

          -  ECOG PS >= 2

          -  Extensive prior radiotherapy on more than 30% of bone marrow reserves, or prior bone
             marrow/stem cell transplantation within 5 years of study start.

          -  Severe bone marrow, renal or liver impairment.

          -  Tumor in contact with, invading or encasing major blood vessels or radiographic
             evidence of significant cavitary pulmonary lesions

          -  Uncontrolled hypertension defined as sustained Blood Pressure (BP) > 150 millimeters
             of mercury (mm Hg) systolic or > 100 mm Hg diastolic despite optimal antihypertensive
             treatment

          -  Participant is pregnant or breastfeeding

          -  Part 2A and 2B: Previous use of cabozantinib or a MetAP2 inhibitor, tumor in contact
             with invading or encasing major blood vessels or radiographic evidence of significant
             cavitary pulmonary lesions

          -  Other protocol defined exclusion criteria could apply