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Study of MT-5111 in HER2-positive Solid Tumors

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

Status
Terminated
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04029922
Acronym
MT-5111
Enrollment
50
Registered
2019-07-23
Start date
2019-11-12
Completion date
2023-04-27
Last updated
2023-06-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HER2-positive Solid Cancers

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.

Interventions

DRUGMT-5111 (experimental study drug)

Experimental treatment with MT-5111

Sponsors

Molecular Templates, Inc.
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE

Intervention model description

MT-5111 (active drug)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
To evaluate safety and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)21 day cycleEvaluation 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)21 day cycleEvaluation of tolerability of MT-5111 as measured by number of subjects with dose limiting toxicities (DLTs)

Secondary

MeasureTime frameDescription
PK as measured by concentrations of free MT-5111 (Time to reach maximum concentration after drug administration [Tmax])Day 1, Day 8, and Day 15 in Each 21-Day cycleEvaluation of the pharmacokinetic profile of MT-5111
PK as measured by concentrations of free MT-5111 (Maximum Plasma Concentration [Cmax])Day 1, Day 8, and Day 15 in Each 21-Day cycleEvaluation of the pharmacokinetic profile of MT-5111
PK as measured by concentrations of free MT-5111 (Area Under the Curve [AUC])Day 1, Day 8, and Day 15 in Each 21-Day cycleEvaluation of the pharmacokinetic profile of MT-5111
To evaluate the tumor response to MT-5111Screening, approximately every 6 weeks, at End of Treatment and 30 days after the last doseObjective 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-5111Screening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up VisitImmunogenicity as measured by MT-5111 (anti-drug antibody \[ADA\] titer)

Other

MeasureTime frameDescription
To evaluate overall Survival30 days after last dose, and every 3 months for up to 24 months—
If warranted by the study results, to evaluate the exposure-response relationship for MT-5111Screening (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
To correlate the pharmacodynamic markers of cancer under study (for breast cancer subjects using historic data, if available)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.Screening (baseline), every 6 weeks (± 1 week) and within 7 days of the EoT Visit.Serum-HER2 (s-HER2)

Countries

Australia, New Zealand, United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 19, 2026