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Study of MT-5111 in HER2-positive Solid Tumors (MT-5111)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04029922
Recruitment Status : Recruiting
First Posted : July 23, 2019
Last Update Posted : April 15, 2022
Sponsor:
Information provided by (Responsible Party):
Molecular Templates, Inc.

Tracking Information
First Submitted Date  ICMJE July 19, 2019
First Posted Date  ICMJE July 23, 2019
Last Update Posted Date April 15, 2022
Actual Study Start Date  ICMJE November 12, 2019
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 22, 2019)
  • To evaluate safety and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) [ Time Frame: 21 day cycle ]
    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
  • To evaluate tolerability and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) [ Time Frame: 21 day cycle ]
    Evaluation of tolerability of MT-5111 as measured by number of subjects with dose limiting toxicities (DLTs)
Original Primary Outcome Measures  ICMJE
 (submitted: July 19, 2019)
  • To evaluate safety and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) [ Time Frame: 21 day cycle ]
    Evaluation of safety of MT-5111 measured by number of subjects with adverse events using Common Terminology Criteria for Adverse Events (CTCAE) v 5.0
  • To evaluate tolerability and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) [ Time Frame: 21 day cycle ]
    Evaluation of tolerability of MT-5111 measured by number of subjects with dose limiting toxicities (DLTs)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2019)
  • PK as measured by concentrations of free MT-5111 (Maximum Plasma Concentration [Cmax]) [ Time Frame: Day 1, Day 8 (cycle 1 only), and Day 15 (cycle 1 only) in Each 21-Day cycle ]
    Evaluation of the pharmacokinetic profile of MT-5111
  • PK as measured by concentrations of free MT-5111 (Time to reach maximum concentration after drug administration [Tmax]) [ Time Frame: Day 1, Day 8 (cycle 1 only), and Day 15 (cycle 1 only) in Each 21-Day cycle ]
    Evaluation of the pharmacokinetic profile of MT-5111
  • PK as measured by concentrations of free MT-5111 (Area Under the Curve [AUC]) [ Time Frame: Day 1, Day 8 (cycle 1 only), and Day 15 (cycle 1 only) in Each 21-Day cycle ]
    Evaluation of the pharmacokinetic profile of MT-5111
  • To evaluate the tumor response to MT-5111 [ Time Frame: Screening, approximately every 6 weeks, at End of Treatment and 30 days after the last dose ]
    Objective response rate (ORR) defined as the proportion of subjects with either a complete response or a partial response as determined by investigator assessment
  • To evaluate the immunogenicity of MT-5111 [ Time Frame: Screening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visit ]
    Immunogenicity as measured by MT-5111 (anti-drug antibody [ADA] titer)
  • To evaluate the immunogenicity of MT-5111 [ Time Frame: Screening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visit ]
    Immunogenicity as measured by MT-5111 (neutralizing antibody [NAb])
Original Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2019)
  • PK as measured by concentrations of free MT-5111 (Maximum Plasma Concentration [Cmax]) [ Time Frame: Day 1, Day 8 (cycle 1 only), and Day 15 (cycle 1 only) in Each 21-Day cycle ]
    Evaluation of the pharmacokinetic profile of MT-5111
  • PK as measured by concentrations of free MT-5111 (Time to reach maximum concentration after drug administration [Tmax]) [ Time Frame: Day 1, Day 8 (cycle 1 only), and Day 15 (cycle 1 only) in Each 21-Day cycle ]
    Evaluation of the pharmacokinetic profile of MT-5111
  • PK as measured by concentrations of free MT-5111 (Area Under the Curve [AUC]) [ Time Frame: Day 1, Day 8 (cycle 1 only), and Day 15 (cycle 1 only) in Each 21-Day cycle ]
    Evaluation of the pharmacokinetic profile of MT-5111
  • To evaluate the tumor response to MT-5111 [ Time Frame: Screening, approximately every 6 weeks, at End of Treatment and 30 days after the last dose ]
    Objective response rate (ORR) defined as the proportion of subjects with either a complete response or a partial response as determined by investigator assessment
  • To evaluate the immunogenicity of MT-5111 [ Time Frame: Sreening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visit ]
    Immunogenicity as measured by MT-5111 (anti-drug antibody [ADA] titer)
  • To evaluate the immunogenicity of MT-5111 [ Time Frame: Sreening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visi ]
    Immunogenicity as measured by MT-5111 (neutralizing antibody [NAb)
Current Other Pre-specified Outcome Measures
 (submitted: July 22, 2019)
  • To correlate the pharmacodynamic markers of cancer under study (for breast cancer subjects using historic data, if available) [ Time Frame: Screening (baseline) ]
    The expression of HER2, Estrogen Receptor (ER), Progesterone Receptor (PgR) and Ki67 (exploratory) on the tumor cell analyzed by immunohistochemistry
  • To correlate the pharmacodynamic markers of cancer under study relationship for MT-5111 using the PK, pharmacodynamics, safety, and tumor response variables. [ Time Frame: Screening (baseline), every 6 weeks (± 1 week) and within 7 days of the EoT Visit. ]
    Serum-HER2 (s-HER2)
  • If warranted by the study results, to evaluate the exposure-response relationship for MT-5111 [ Time Frame: Screening (baseline), every 6 weeks (± 1 week) and within 7 days of the EoT Visit. ]
    Analyze data collected for all primary, secondary and exploratory endpoints using the PK, pharmacodynamics, safety, and tumor response variables
Original Other Pre-specified Outcome Measures
 (submitted: July 19, 2019)
  • To correlate the pharmacodynamic markers of cancer under study (for breast cancer subjects using historic data, if available) [ Time Frame: Sreening (baseline) ]
    The expression of HER2, Estrogen Receptor (ER), Progesterone Receptor (PgR) and Ki67 (exploratory) on the tumor cell analyzed by immunohistochemistry
  • To correlate the pharmacodynamic markers of cancer under study relationship for MT-5111 using the PK, pharmacodynamics, safety, and tumor response variables. [ Time Frame: Sreening (baseline), every 6 weeks (± 1 week) and within 7 days of the EoT Visit. ]
    Serum-HER2 (s-HER2)
  • If warranted by the study results, to evaluate the exposure-response relationship for MT-5111 [ Time Frame: Sreening (baseline), every 6 weeks (± 1 week) and within 7 days of the EoT Visit. ]
    Analyze data collected for all primary, secondary and exploratory endpoints using the PK, pharmacodynamics, safety, and tumor response variables
 
Descriptive Information
Brief Title  ICMJE Study of MT-5111 in HER2-positive Solid Tumors
Official Title  ICMJE A Phase 1 Open-label, Multicenter Dose Escalation and Expansion Study of MT-5111 in Subjects With Previously Treated Advanced HER2-positive Solid Tumors
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) in subjects with HER2-positive solid tumors
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
MT-5111 (active drug)
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HER2-positive Solid Cancers
Intervention  ICMJE Drug: MT-5111 (experimental study drug)
Experimental treatment with MT-5111
Study Arms  ICMJE
  • Experimental: Arm 1- Dose Escalation

    The dose escalation part of the study is aimed at determining the Recommended Phase 2 Dose (RP2D) of MT-5111.

    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).

    Intervention: Drug: MT-5111 (experimental study drug)
  • Experimental: Arm 1- Dose Expansion

    The dose expansion part of the study will begin after completion of the dose escalation phase to confirm the safety and tolerability of the RP2D.

    The RP2D 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).

    Intervention: Drug: MT-5111 (experimental study drug)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 8, 2022)
178
Original Estimated Enrollment  ICMJE
 (submitted: July 19, 2019)
140
Estimated Study Completion Date  ICMJE May 2025
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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, 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 2weeks 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 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

Hepatic function:

Total bilirubin ≤ 1.5 x ULN, and AST ≤ 3 x ULN and ALT ≤ 3 x ULN

< 5 x ULN (if hepatic metastases)

Exclusion Criteria:

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Joshua Pelham (415) 378-4738 joshua.pelham@mtem.com
Contact: Kristen Quigley (862) 203-7537 kristen.quigley@mtem.com
Listed Location Countries  ICMJE Australia,   New Zealand,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04029922
Other Study ID Numbers  ICMJE MT-5111_001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Molecular Templates, Inc.
Study Sponsor  ICMJE Molecular Templates, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Molecular Templates, Inc.
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP