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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04029922




Registration number
NCT04029922
Ethics application status
Date submitted
19/07/2019
Date registered
23/07/2019
Date last updated
18/06/2023

Titles & IDs
Public title
Study of MT-5111 in HER2-positive Solid Tumors
Scientific 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
Secondary ID [1] 0 0
MT-5111_001
Universal Trial Number (UTN)
Trial acronym
MT-5111
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HER2-positive Solid Cancers 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - MT-5111 (experimental study drug)

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).

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).


Treatment: Drugs: MT-5111 (experimental study drug)
Experimental treatment with MT-5111
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To evaluate safety and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
Timepoint [1] 0 0
21 day cycle
Primary outcome [2] 0 0
To evaluate tolerability and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
Timepoint [2] 0 0
21 day cycle
Secondary outcome [1] 0 0
PK as measured by concentrations of free MT-5111 (Maximum Plasma Concentration [Cmax])
Timepoint [1] 0 0
Day 1, Day 8, and Day 15 in Each 21-Day cycle
Secondary outcome [2] 0 0
PK as measured by concentrations of free MT-5111 (Time to reach maximum concentration after drug administration [Tmax])
Timepoint [2] 0 0
Day 1, Day 8, and Day 15 in Each 21-Day cycle
Secondary outcome [3] 0 0
PK as measured by concentrations of free MT-5111 (Area Under the Curve [AUC])
Timepoint [3] 0 0
Day 1, Day 8, and Day 15 in Each 21-Day cycle
Secondary outcome [4] 0 0
To evaluate the tumor response to MT-5111
Timepoint [4] 0 0
Screening, approximately every 6 weeks, at End of Treatment and 30 days after the last dose
Secondary outcome [5] 0 0
To evaluate the immunogenicity of MT-5111
Timepoint [5] 0 0
Screening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visit
Secondary outcome [6] 0 0
To evaluate the immunogenicity of MT-5111
Timepoint [6] 0 0
Screening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visit

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/11/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/04/2023
Sample size
Target
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
Melbourne, VICNSW,SA,VIC
Recruitment hospital [1] 0 0
St. Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [2] 0 0
Southern Highlands Cancer Centre - Bowral
Recruitment hospital [3] 0 0
Macquarie University Hospital (Clinical Trials Unit) - Macquarie
Recruitment hospital [4] 0 0
Cancer Research South Australia - Adelaide
Recruitment hospital [5] 0 0
Sunshine Hospital - Western Health - Saint Albans
Recruitment hospital [6] 0 0
Goulburn Valley Health - Shepparton
Recruitment postcode(s) [1] 0 0
3065 - Fitzroy
Recruitment postcode(s) [2] 0 0
2576 - Bowral
Recruitment postcode(s) [3] 0 0
2109 - Macquarie
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3021 - Saint Albans
Recruitment postcode(s) [6] 0 0
3630 - Shepparton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
New Zealand
State/province [13] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Molecular Templates, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT04029922
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04029922