Study of MT-5111 in HER2-positive Solid Tumors

NCT04029922 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: MT-5111_001
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 30

Brief Summary

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

Conditions

HER2-positive Solid Cancers

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• PK as measured by concentrations of free MT-5111 (Maximum Plasma Concentration [Cmax])

  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])

  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])

  Day 1, Day 8, and Day 15 in Each 21-Day cycle

• To evaluate the tumor response to MT-5111

  Screening, approximately every 6 weeks, at End of Treatment and 30 days after the last dose

• To evaluate the immunogenicity of MT-5111

  Screening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visit

Other Outcomes (4)

• To correlate the pharmacodynamic markers of cancer under study (for breast cancer subjects using historic data, if available)

  Screening (baseline)

• To correlate the pharmacodynamic markers of cancer under study relationship for MT-5111 using the PK, pharmacodynamics, safety, and tumor response variables.

  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

  Screening (baseline), every 6 weeks (± 1 week) and within 7 days of the EoT Visit.

Study Arms (2)

Part A- Dose Escalation

EXPERIMENTAL

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)

Part B- Dose Expansion

EXPERIMENTAL

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)

Interventions

MT-5111 (experimental study drug) DRUG

Experimental treatment with MT-5111

Part A- Dose Escalation; Part B- Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• HER2-positive in the latest tumor sample tested for HER2 (testing to be done on a metastatic lesion in cases of metastatic cancers).
• Relapsed or refractory to or intolerant of existing therapy(ies)
• 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)
• ECOG performance score of ≤ 1
• 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
• Kidney function:
• Creatinine clearance (CLcr) ≥ 50 mL/min either measured or estimated using the Cockcroft-Gault formula
• Cardiac Function:

You may not qualify if:

• History or current evidence of another tumor that is histologically distinct from the tumor under study
• Current evidence of new or growing CNS metastases during screening
• Subjects with known CNS metastases will be eligible if they meet protocol specified criteria
• 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
• History or evidence of significant cardiovascular disease
• 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
• Current evidence of ≥ grade 2 underlying pulmonary disease

Sponsors & Collaborators

• Molecular Templates, Inc.: lead

Study Sites (30)

Mayo Clinic (Arizona)

Phoenix, Arizona, 85054, United States

Location

St. Joseph Heritage Healthcare

Fullerton, California, 92835, United States

Location

Cancer and Blood Specialty Clinic

Los Alamitos, California, 90720, United States

Location

Cedars-Sinai Medical Center

Santa Monica, California, 90048, United States

Location

UCLA Hematology & Oncology

Santa Monica, California, 90404, United States

Location

Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

Location

Sylvester Comprehensive Cancer Center (University of Miami)

Coral Gables, Florida, 33146, United States

Location

South Broward Hospital District d/b/a Memorial Healthcare System

Hollywood, Florida, 33021, United States

Location

Mayo Clinic (Florida)

Jacksonville, Florida, 32224, United States

Location

Orlando Health

Orlando, Florida, 32806, United States

Location

South Broward Hospital District d/b/a Memorial Healthcare System

Pembroke Pines, Florida, 33024, United States

Location

BRCR Medical Center

Plantation, Florida, 33322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic (Minnesota)

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63130, United States

Location

Novant Health Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, 27103, United States

Location

Prisma Health

Greenville, South Carolina, 29605, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75251, United States

Location

The University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

St. Vincent's Hospital Melbourne

Fitzroy, Melbourne, VIC, 3065, Australia

Location

Southern Highlands Cancer Centre

Bowral, New South Wales, 2576, Australia

Location

Macquarie University Hospital (Clinical Trials Unit)

Macquarie, New South Wales, 2109, Australia

Location

Cancer Research South Australia

Adelaide, South Australia, 5000, Australia

Location

Sunshine Hospital - Western Health

Saint Albans, Victoria, 3021, Australia

Location

Goulburn Valley Health

Shepparton, Victoria, 3630, Australia

Location

New Zealand Clinical Research (Christchurch)

Christchurch, 8011, New Zealand

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: MT-5111 (active drug)

Study Record Dates

• First Submitted: July 19, 2019
• First Posted: July 23, 2019
• Study Start: November 12, 2019
• Primary Completion: February 1, 2023
• Study Completion: April 27, 2023
• Last Updated: June 18, 2023

Record last verified: 2023-06

Locations

US (23); AU (6); NZ (1)