Clinical trial NCT04029922: Study of MT-5111 in HER2-positive Solid Tumors
Official title: A Phase 1 Open-label, Multicenter Dose Escalation and Expansion Study of MT-5111 in Subjects With Previously Treated Advanced HER2-positive Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: HER2-positive Solid Cancers
Lead sponsor: Molecular Templates, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-23
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: MT-5111 (active drug)
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: To evaluate safety and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
timeFrame: 21 day cycle
measure: To evaluate tolerability and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
timeFrame: 21 day cycle
Secondary outcomes:
measure: PK as measured by concentrations of free MT-5111 (Maximum Plasma Concentration [Cmax])
timeFrame: Day 1, Day 8, and Day 15 in Each 21-Day cycle
measure: PK as measured by concentrations of free MT-5111 (Time to reach maximum concentration after drug administration [Tmax])
timeFrame: Day 1, Day 8, and Day 15 in Each 21-Day cycle
measure: PK as measured by concentrations of free MT-5111 (Area Under the Curve [AUC])
timeFrame: Day 1, Day 8, and Day 15 in Each 21-Day cycle
measure: To evaluate the tumor response to MT-5111
timeFrame: Screening, approximately every 6 weeks, at End of Treatment and 30 days after the last dose
measure: To evaluate the immunogenicity of MT-5111
timeFrame: Screening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visit
measure: To evaluate the immunogenicity of MT-5111
timeFrame: Screening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visit
Other outcomes:
measure: To correlate the pharmacodynamic markers of cancer under study (for breast cancer subjects using historic data, if available)
timeFrame: Screening (baseline)
measure: To correlate the pharmacodynamic markers of cancer under study relationship for MT-5111 using the PK, pharmacodynamics, safety, and tumor response variables.
timeFrame: Screening (baseline), every 6 weeks (± 1 week) and within 7 days of the EoT Visit.
measure: If warranted by the study results, to evaluate the exposure-response relationship for MT-5111
timeFrame: Screening (baseline), every 6 weeks (± 1 week) and within 7 days of the EoT Visit.
measure: To evaluate overall Survival
timeFrame: 30 days after last dose, and every 3 months for up to 24 months
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic (Arizona)
state: Arizona
city: Fullerton
country: United States
facility: St. Joseph Heritage Healthcare
state: California
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty Clinic
state: California
city: Santa Monica
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology & Oncology
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute
state: Colorado
city: Coral Gables
country: United States
facility: Sylvester Comprehensive Cancer Center (University of Miami)
state: Florida
city: Hollywood
country: United States
facility: South Broward Hospital District d/b/a Memorial Healthcare System
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic (Florida)
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Pembroke Pines
country: United States
facility: South Broward Hospital District d/b/a Memorial Healthcare System
state: Florida
city: Plantation
country: United States
facility: BRCR Medical Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic (Minnesota)
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Charlotte
country: United States
facility: Novant Health Cancer Institute
state: North Carolina
city: Winston-Salem
country: United States
facility: Novant Health Forsyth Medical Center
state: North Carolina
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center
state: Texas
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
state: Melbourne, VIC
city: Bowral
country: Australia
facility: Southern Highlands Cancer Centre
state: New South Wales
city: Macquarie
country: Australia
facility: Macquarie University Hospital (Clinical Trials Unit)
state: New South Wales
city: Adelaide
country: Australia
facility: Cancer Research South Australia
state: South Australia
city: Saint Albans
country: Australia
facility: Sunshine Hospital - Western Health
state: Victoria
city: Shepparton
country: Australia
facility: Goulburn Valley Health
state: Victoria
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research (Christchurch)
Study officials:
References: