Clinical Trials /

Study of MT-5111 in HER2-positive Solid Tumors

NCT04029922

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: MT-5111_001
  • NCT ID: NCT04029922

Conditions

  • HER2-positive Solid Cancers

Interventions

DrugSynonymsArms
MT-5111 (experimental study drug)Arm 1- Dose Escalation

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1- Dose EscalationExperimentalThe 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).
  • MT-5111 (experimental study drug)
Arm 1- Dose ExpansionExperimentalThe 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).
  • MT-5111 (experimental study drug)

Eligibility Criteria

        Inclusion Criteria:

          1. 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).

          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

          5. ECOG performance score of ≤ 1

          6. 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

          7. 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

          8. 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

          9. 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)

        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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To evaluate safety and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
Time Frame:21 day cycle
Safety Issue:
Description: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

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Evaluation of the pharmacokinetic profile of MT-5111
Measure: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
Safety Issue:
Description:Evaluation of the pharmacokinetic profile of MT-5111
Measure: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
Safety Issue:
Description:Evaluation of the pharmacokinetic profile of MT-5111
Measure: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
Safety Issue:
Description:Objective response rate (ORR) defined as the proportion of subjects with either a complete response or a partial response as determined by investigator assessment
Measure: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
Safety Issue:
Description:Immunogenicity as measured by MT-5111 (anti-drug antibody [ADA] titer)
Measure: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
Safety Issue:
Description:Immunogenicity as measured by MT-5111 (neutralizing antibody [NAb])

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Molecular Templates, Inc.

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