MT-5111 in HER2-positive Solid Tumors

Trial Summary

Official Title

A Phase 1 Open-label, Multicenter Dose Escalation Study of MT-5111 in Subjects With Previously Treated Advanced HER2-positive Solid Tumors

Status

Recruiting

Condition

HER2-positive Solid Cancers

About the Trial

Study of MT-5111 in HER2-positive Solid Tumors

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.

Detailed Info

Brief Summary

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.

Study Phase

Phase 1

Estimated Enrollment

140

Study Type

Interventional

Interventions

Drug: MT-5111 (experimental study drug)

Sponsor

Molecular Templates, Inc.

Eligibility

Inclusion Criteria Exclusion Criteria

Gender

Male & Female

Age

18 Years and older

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).
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
ECOG performance score of ≤ 1
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
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
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
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)

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 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
Certain exclusionary prior treatments

Location

The following cities have clinical trial sites. Please check back often as locations will be updated.

Mayo Clinic (Arizona)
Phoenix, Arizona 85054
United States
Recruiting

Cedars-Sinai Medical Center
Santa Monica, California 90048
United States
Recruiting

UCLA Hematology & Oncology
Santa Monica, California 90404
United States
Recruiting

Sylvester Comprehensive Cancer Center (University of Miami)
Coral Gables, Florida 33146
United States
Recruiting

Mayo Clinic (Florida)
Jacksonville, Florida 32224
United States
Recruiting

Mayo Clinic (Minnesota)
Rochester, Minnesota 55905
United States
Recruiting

Washington University
Saint Louis, Missouri 63130
United States
Recruiting

Sarah Cannon Research Institute
Nashville, Tennessee 37203
United States
Recruiting

Mary Crowley Cancer Research
Dallas, Texas 75251
United States
Recruiting

The University of Texas Health Science Center
San Antonio, Texas 78229
United States
Recruiting

Enrollment

For more information on enrollment in our current clinical trials, please visit clinicaltrials.gov for location information.

Visit clinicaltrials.gov

About HER2-positive Solid Tumors

The human epidermal growth factor receptor 2, also known as HER2, is a gene that can play a vital role in the development of breast cancer. This gene is responsible for making HER2 proteins, which serve as receptors on breast cells.

Healthy HER2 receptors help oversee and control how a healthy breast cell grows, divides, and repairs itself. In approximately 25 percent of breast cancers, however, the HER2 gene does not work correctly and makes too many copies of itself (this is as known as HER2 gene amplification). These extra HER2 genes tell breast cells to make too many HER2 receptors, resulting in HER2 protein overexpression, which makes breast cells grow and divide uncontrollably. Breast cancers featuring HER2 gene amplification or HER2 protein overexpression are called HER2-positive.