Study of MT-5111 in HER2-positive Solid Tumors

This will be a Phase 1b, first in human, open-label, dose escalation and expansion study of MT-5111 (a recombinant fusion protein) given as monotherapy in subjects with HER2-positive solid tumors

This study will be conducted in two parts:

Part A (Dose Escalation): The purpose of Part A is to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D). Part A will include any type of HER2-positive solid cancer.

Part B (Dose Expansion): The purpose of Part B is to confirm the safety and tolerability of MT-5111 doses selected from those explored in Part A including the MTD or RP2D. Part B will include 3 types of HER2-positive solid cancers in the following 3 expansion groups: Group B1: Breast cancer; Group B2: gastric or gastroesophageal adenocarcinomas (GEA); and Group B3: Other HER2-positive solid cancers.

The Breast Cancer cohort will start enrolling in parallel to Part A.

Up to 178 eligible subjects will be identified and treated through competitive enrollment at multiple study centers globally

In Parts A and B of the study, a subject may participate for the following four periods:

Screening (up to 28 days before first dose of MT-5111)

Treatment period (active period where a subject will receive three weekly doses of MT-5111 over a 21-day treatment cycle)

Short-term Follow-up (30 days after last dose of MT-5111)

Long-term follow-up (up to 24 months after the last dose of MT-5111)

MT-5111 will be given as an intravenous (IV) infusion over about 30 minutes on the same day every week (i.e., on day 1, day 8 and day 15 of each cycle, a cycle being defined as 21 days). A subject can continue receiving MT-5111 as long as it is well-tolerated, their disease has not worsened, or until the subject decides they no longer want to participate in the study.

Eligibility Criteria:
Inclusion Criteria:

1. Histologically confirmed, unresectable, locally advanced or metastatic solid cancers:

   * Part A (Dose-Escalation): All HER2-positive solid cancers are eligible
   * Part B (Dose-Expansion): Any type of HER2-positive solid cancer, including breast cancer, and gastric or gastroesophageal adenocarcinomas (GEA).
2. HER2-positive in the latest tumor sample tested for HER2 (testing to be done on a metastatic lesion in cases of metastatic cancers).
3. Relapsed or refractory to or intolerant of existing therapy(ies)
4. At least 1 measurable or evaluable lesion according to RECIST 1.1 (Subjects with evaluable disease only may be included in the dose escalation phase)
5. ECOG performance score of ≤ 1
6. Adequate Bone marrow function as determined by:

   * Absolute neutrophil count (ANC) ≥ 1,000/mm3
   * Platelet count ≥ 75,000 mm³ and
   * Hemoglobin ≥ 8.0 g/dL
   * Red blood cell transfusion within 2 weeks of study treatment start is allowed if hemoglobin levels remain stable
7. Kidney function:

   * Creatinine clearance (CLcr) ≥ 50 mL/min either measured or estimated using the Cockcroft-Gault formula
8. Cardiac Function:

   * Left ventricular ejection fraction (LVEF) ≥ 55% on the echocardiogram (ECHO) assessment (preferred), or multigated acquisition (MUGA) scan, and QTcF ≤ 480 ms for women and QTcF ≤ 450 ms for men \[average from three QTcF values on the triplicate 12-lead electrocardiogram (ECG)\] at baseline
9. Hepatic function:

   * Total bilirubin ≤ 1.5 x ULN, or ≤ 3 x ULN for subjects with Gilbert's Syndrome and
   * AST ≤ 3 x ULN (or ≤ 5 x ULN if liver metastasis) and ALT ≤ 3 x ULN (or ≤ 5 x ULN if liver metastasis)

Exclusion Criteria:

1. History or current evidence of another tumor that is histologically distinct from the tumor under study
2. Current evidence of new or growing CNS metastases during screening

   * Subjects with known CNS metastases will be eligible if they meet protocol specified criteria
3. Evidence of CTCAE Grade \>1 toxicity before the start of treatment, except for hair loss and those Grade 2 toxicities listed as permitted in other eligibility criteria
4. History or evidence of significant cardiovascular disease
5. Current evidence of active, uncontrolled hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV) (evidenced by detectable viral load by PCR) or acquired immunodeficiency syndrome (AIDS) related illness
6. Current evidence of ≥ grade 2 underlying pulmonary disease
7. Certain exclusionary prior treatments