Study of MT-5111 in HER2-positive Solid Tumors

NCT ID: NCT04029922

Last Updated: 2023-06-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-12
• Study Completion Date: 2023-04-27

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

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.

Conditions

HER2-positive Solid Cancers

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

MT-5111 (experimental study drug)

Intervention Type: DRUG

Experimental treatment with MT-5111

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).

Group Type: EXPERIMENTAL

MT-5111 (experimental study drug)

Intervention Type: DRUG

Experimental treatment with MT-5111

Interventions

MT-5111 (experimental study drug)

Experimental treatment with MT-5111

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Molecular Templates, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Mayo Clinic (Arizona)

Phoenix, Arizona, United States

St. Joseph Heritage Healthcare

Fullerton, California, United States

Cancer and Blood Specialty Clinic

Los Alamitos, California, United States

Cedars-Sinai Medical Center

Santa Monica, California, United States

UCLA Hematology & Oncology

Santa Monica, California, United States

Sarah Cannon Research Institute

Denver, Colorado, United States

Sylvester Comprehensive Cancer Center (University of Miami)

Coral Gables, Florida, United States

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

Hollywood, Florida, United States

Mayo Clinic (Florida)

Jacksonville, Florida, United States

Orlando Health

Orlando, Florida, United States

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

Pembroke Pines, Florida, United States

BRCR Medical Center

Plantation, Florida, United States

Northwestern University

Chicago, Illinois, United States

University of Chicago Medical Center

Chicago, Illinois, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Clinic (Minnesota)

Rochester, Minnesota, United States

Washington University

St Louis, Missouri, United States

Novant Health Cancer Institute

Charlotte, North Carolina, United States

Novant Health Forsyth Medical Center

Winston-Salem, North Carolina, United States

Prisma Health

Greenville, South Carolina, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Mary Crowley Cancer Research

Dallas, Texas, United States

The University of Texas Health Science Center

San Antonio, Texas, United States

St. Vincent's Hospital Melbourne

Fitzroy, Melbourne, VIC, Australia

Southern Highlands Cancer Centre

Bowral, New South Wales, Australia

Macquarie University Hospital (Clinical Trials Unit)

Macquarie, New South Wales, Australia

Cancer Research South Australia

Adelaide, South Australia, Australia

Sunshine Hospital - Western Health

Saint Albans, Victoria, Australia

Goulburn Valley Health

Shepparton, Victoria, Australia

New Zealand Clinical Research (Christchurch)

Christchurch, , New Zealand

Countries

United States; Australia; New Zealand

Other Identifiers

MT-5111_001

Identifier Type: -

Identifier Source: org_study_id