Study of MT-5111 in HER2-positive Solid Tumors (MT-5111)

A Phase 1 Open-label, Multicenter Dose Escalation and Expansion Study of MT-5111 in Subjects With Previously Treated Advanced 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

Study Overview

• Status: Terminated
• Conditions: HER2-positive Solid Cancers
• Intervention / Treatment: Drug: MT-5111 (experimental study drug)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Joshua Pelham; Phone Number: (415) 378-4738; Email: joshua.pelham@mtem.com
• Study Contact Backup: Name: Amanda Keaton; Phone Number: 859-354-7222; Email: Amanda.Keaton@mtem.com

Study Locations

• Australia
  • Melbourne, VIC
    • Fitzroy, Melbourne, VIC, Australia, 3065
      • St. Vincent's Hospital Melbourne
  • New South Wales
    • Bowral, New South Wales, Australia, 2576
      • Southern Highlands Cancer Centre
    • Macquarie, New South Wales, Australia, 2109
      • Macquarie University Hospital (Clinical Trials Unit)
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Cancer Research South Australia
  • Victoria
    • Saint Albans, Victoria, Australia, 3021
      • Sunshine Hospital - Western Health
    • Shepparton, Victoria, Australia, 3630
      • Goulburn Valley Health
• New Zealand
  • Christchurch, New Zealand, 8011
    • New Zealand Clinical Research (Christchurch)
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic (Arizona)
  • California
    • Fullerton, California, United States, 92835
      • St. Joseph Heritage Healthcare
    • Los Alamitos, California, United States, 90720
      • Cancer and Blood Specialty Clinic
    • Santa Monica, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Santa Monica, California, United States, 90404
      • UCLA Hematology & Oncology
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Sylvester Comprehensive Cancer Center (University of Miami)
    • Hollywood, Florida, United States, 33021
      • South Broward Hospital District d/b/a Memorial Healthcare System
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic (Florida)
    • Orlando, Florida, United States, 32806
      • Orlando Health
    • Pembroke Pines, Florida, United States, 33024
      • South Broward Hospital District d/b/a Memorial Healthcare System
    • Plantation, Florida, United States, 33322
      • BRCR Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic (Minnesota)
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Cancer Institute
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health Forsyth Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75251
      • Mary Crowley Cancer Research
    • San Antonio, Texas, United States, 78229
      • The University of Texas Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A- Dose Escalation; Part A- Dose Escalation in patients with previously treated advanced HER2-positive solid tumors. 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: Part B- Dose Expansion; Part B - Dose Expansion in previously treated HER2-positive breast, GEA and other HER2-positive solid cancers Part B will include 3 expansion groups: Group B1 (Breast Cancer) will begin enrolling while Part A is being conducted following the completion of Cohort 7 and Subsequent cohort of subjects in group B1 may enroll into higher doses that are tolerated in Part A. Group B2 (GEA) and Group B3 (Other HER-2 positive solid cancer groups) will begin enrollment after the MTD or RP2D is determined in Part A. 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate safety and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)	Evaluation of safety of MT-5111 as measured by number of subjects with adverse events using Common Terminology Criteria for Adverse Events (CTCAE) v 5.0	21 day cycle
To evaluate tolerability and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)	Evaluation of tolerability of MT-5111 as measured by number of subjects with dose limiting toxicities (DLTs)	21 day cycle

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK as measured by concentrations of free MT-5111 (Maximum Plasma Concentration [Cmax])	Evaluation of the pharmacokinetic profile of MT-5111	Day 1, Day 8, and Day 15 in Each 21-Day cycle
PK as measured by concentrations of free MT-5111 (Time to reach maximum concentration after drug administration [Tmax])	Evaluation of the pharmacokinetic profile of MT-5111	Day 1, Day 8, and Day 15 in Each 21-Day cycle
PK as measured by concentrations of free MT-5111 (Area Under the Curve [AUC])	Evaluation of the pharmacokinetic profile of MT-5111	Day 1, Day 8, and Day 15 in Each 21-Day cycle
To evaluate the tumor response to MT-5111	Objective response rate (ORR) defined as the proportion of subjects with either a complete response or a partial response as determined by investigator assessment	Screening, approximately every 6 weeks, at End of Treatment and 30 days after the last dose
To evaluate the immunogenicity of MT-5111	Immunogenicity as measured by MT-5111 (anti-drug antibody [ADA] titer)	Screening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visit
To evaluate the immunogenicity of MT-5111	Immunogenicity as measured by MT-5111 (neutralizing antibody [NAb])	Screening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To correlate the pharmacodynamic markers of cancer under study (for breast cancer subjects using historic data, if available)	The expression of HER2, Estrogen Receptor (ER), Progesterone Receptor (PgR) and Ki67 (exploratory) on the tumor cell analyzed by immunohistochemistry	Screening (baseline)
To correlate the pharmacodynamic markers of cancer under study relationship for MT-5111 using the PK, pharmacodynamics, safety, and tumor response variables.	Serum-HER2 (s-HER2)	Screening (baseline), every 6 weeks (± 1 week) and within 7 days of the EoT Visit.
If warranted by the study results, to evaluate the exposure-response relationship for MT-5111	Analyze data collected for all primary, secondary and exploratory endpoints using the PK, pharmacodynamics, safety, and tumor response variables	Screening (baseline), every 6 weeks (± 1 week) and within 7 days of the EoT Visit.
To evaluate overall Survival		30 days after last dose, and every 3 months for up to 24 months

Collaborators and Investigators

• Sponsor: Molecular Templates, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2019
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): April 27, 2023

Study Registration Dates

• First Submitted: July 19, 2019
• First Submitted That Met QC Criteria: July 19, 2019
• First Posted (Actual): July 23, 2019

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 15, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: MT-5111_001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No