HER2-positive Solid Cancers Clinical Trial
— MT-5111Official 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
| Verified date | June 2023 |
| Source | Molecular Templates, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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
| Status | Terminated |
| Enrollment | 50 |
| Est. completion date | April 27, 2023 |
| Est. primary completion date | February 1, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Cancer Research South Australia | Adelaide | South Australia |
| Australia | Southern Highlands Cancer Centre | Bowral | New South Wales |
| Australia | St. Vincent's Hospital Melbourne | Fitzroy | Melbourne, VIC |
| Australia | Macquarie University Hospital (Clinical Trials Unit) | Macquarie | New South Wales |
| Australia | Sunshine Hospital - Western Health | Saint Albans | Victoria |
| Australia | Goulburn Valley Health | Shepparton | Victoria |
| New Zealand | New Zealand Clinical Research (Christchurch) | Christchurch | |
| United States | University of Michigan | Ann Arbor | Michigan |
| United States | Novant Health Cancer Institute | Charlotte | North Carolina |
| United States | Northwestern University | Chicago | Illinois |
| United States | University of Chicago Medical Center | Chicago | Illinois |
| United States | Sylvester Comprehensive Cancer Center (University of Miami) | Coral Gables | Florida |
| United States | Mary Crowley Cancer Research | Dallas | Texas |
| United States | Sarah Cannon Research Institute | Denver | Colorado |
| United States | St. Joseph Heritage Healthcare | Fullerton | California |
| United States | Prisma Health | Greenville | South Carolina |
| United States | South Broward Hospital District d/b/a Memorial Healthcare System | Hollywood | Florida |
| United States | Mayo Clinic (Florida) | Jacksonville | Florida |
| United States | Cancer and Blood Specialty Clinic | Los Alamitos | California |
| United States | Sarah Cannon Research Institute | Nashville | Tennessee |
| United States | Orlando Health | Orlando | Florida |
| United States | South Broward Hospital District d/b/a Memorial Healthcare System | Pembroke Pines | Florida |
| United States | Mayo Clinic (Arizona) | Phoenix | Arizona |
| United States | BRCR Medical Center | Plantation | Florida |
| United States | Mayo Clinic (Minnesota) | Rochester | Minnesota |
| United States | Washington University | Saint Louis | Missouri |
| United States | The University of Texas Health Science Center | San Antonio | Texas |
| United States | Cedars-Sinai Medical Center | Santa Monica | California |
| United States | UCLA Hematology & Oncology | Santa Monica | California |
| United States | Novant Health Forsyth Medical Center | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| Molecular Templates, Inc. |
United States, Australia, New Zealand,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | To correlate the pharmacodynamic markers of cancer under study (for breast cancer subjects using historic data, if available) | The expression of HER2, Estrogen Receptor (ER), Progesterone Receptor (PgR) and Ki67 (exploratory) on the tumor cell analyzed by immunohistochemistry | Screening (baseline) | |
| Other | To correlate the pharmacodynamic markers of cancer under study relationship for MT-5111 using the PK, pharmacodynamics, safety, and tumor response variables. | Serum-HER2 (s-HER2) | Screening (baseline), every 6 weeks (± 1 week) and within 7 days of the EoT Visit. | |
| Other | If warranted by the study results, to evaluate the exposure-response relationship for MT-5111 | Analyze data collected for all primary, secondary and exploratory endpoints using the PK, pharmacodynamics, safety, and tumor response variables | Screening (baseline), every 6 weeks (± 1 week) and within 7 days of the EoT Visit. | |
| Other | To evaluate overall Survival | 30 days after last dose, and every 3 months for up to 24 months | ||
| Primary | To evaluate safety and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) | 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 | 21 day cycle | |
| Primary | To evaluate tolerability and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) | Evaluation of tolerability of MT-5111 as measured by number of subjects with dose limiting toxicities (DLTs) | 21 day cycle | |
| Secondary | PK as measured by concentrations of free MT-5111 (Maximum Plasma Concentration [Cmax]) | Evaluation of the pharmacokinetic profile of MT-5111 | Day 1, Day 8, and Day 15 in Each 21-Day cycle | |
| Secondary | PK as measured by concentrations of free MT-5111 (Time to reach maximum concentration after drug administration [Tmax]) | Evaluation of the pharmacokinetic profile of MT-5111 | Day 1, Day 8, and Day 15 in Each 21-Day cycle | |
| Secondary | PK as measured by concentrations of free MT-5111 (Area Under the Curve [AUC]) | Evaluation of the pharmacokinetic profile of MT-5111 | Day 1, Day 8, and Day 15 in Each 21-Day cycle | |
| Secondary | To evaluate the tumor response to MT-5111 | Objective response rate (ORR) defined as the proportion of subjects with either a complete response or a partial response as determined by investigator assessment | Screening, approximately every 6 weeks, at End of Treatment and 30 days after the last dose | |
| Secondary | To evaluate the immunogenicity of MT-5111 | Immunogenicity as measured by MT-5111 (anti-drug antibody [ADA] titer) | Screening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visit | |
| Secondary | To evaluate the immunogenicity of MT-5111 | Immunogenicity as measured by MT-5111 (neutralizing antibody [NAb]) | Screening (baseline), Day 1 of each 21 day cycle, at the End of Treatment and the Follow-up Visit |