Purpose

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

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Histologically confirmed, unresectable, locally advanced or metastatic solid cancers: - Part 1 (Dose-Escalation): All HER2-positive solid cancers are eligible - Part 2 (Dose-Expansion): Any type of HER2-positive solid cancer, including breast cancer, 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 5. ECOG performance score of ≤ 1 6. Bone marrow function: - Absolute neutrophil count (ANC) ≥ 1,000/mm3 - Platelet count ≥ 75,000 mm³ and - Hemoglobin ≥ 8.0 g/dL - No red blood cell transfusion within 4 weeks of study treatment start is allowed 7. Kidney function: - (eGFR) ≥ 50 mL/min calculated by the Cockcroft-Gault formula - Subjects with CLcr ≥ 50 mL/min will be eligible irrespective of the eGFR result 8. Cardiac Function: - Left ventricular ejection fraction (LVEF) ≥ 55% on the multigated acquisition (MUGA) scan (preferred) or echocardiogram (ECHO) assessment, 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: 1. Total bilirubin ≤ 1.5 x ULN, and 2. AST ≤ 3 x ULN and ALT ≤ 3 x ULN - < 5 x ULN (if hepatic metastases)

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 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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
MT-5111 (active drug)
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm 1- Dose Escalation
The dose escalation part of the study is aimed at determining the Recommended Phase 2 Dose (RP2D) of MT-5111. The assigned dose level of 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).
  • Drug: MT-5111 (experimental study drug)
    Experimental treatment with MT-5111
Experimental
Arm 1- Dose Expansion
The dose expansion part of the study will begin after completion of the dose escalation phase to confirm the safety and tolerability of the RP2D. The RP2D dose level of 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).
  • Drug: MT-5111 (experimental study drug)
    Experimental treatment with MT-5111

Recruiting Locations

The University of Texas Health Science Center
San Antonio, Texas 78229
Contact:
Maggie Tomasini
210-450-5962
tomasinim@uthscsa.edu

More Details

Status
Recruiting
Sponsor
Molecular Templates, Inc.

Study Contact

Joshua Pelham
(415) 378-4738
joshua.pelham@mtem.com

Detailed Description

This study will be conducted in two sequential parts: - Part 1 (Dose Escalation): The purpose of Part 1 is to determine the Phase 2 dose (RP2D) to be used in Part 2. Part 1 will include any type of HER2-positive solid cancer. - Part 2 (Dose Expansion): The purpose of Part 2 is to confirm the safety and tolerability of the RP2D of MT-5111. Part 2 will include any type of HER2-positive solid cancer, including breast cancer, gastric or gastroesophageal adenocarcinomas (GEA). Up to 140 eligible subjects will be identified and treated through competitive enrollment at multiple study centers. In Parts 1 and 2 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 doses of MT-5111 over a 21-day treatment cycle) - 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.