HER2-Expressing Solid Tumors
Conditions
Keywords
Anti-HER2 chimeric antigen receptor, Chimeric Antigen Receptor (CAR), mRNA, Lipid nanoparticle (LNP), Urothelial carcinoma, Endometrial carcinoma, Ovarian epithelial carcinoma, Breast carcinoma (all subtypes), Gastric adenocarcinoma, Esophageal adenocarcinoma, Non-small cell lung cancer, Colorectal carcinoma, Biliary cancer (including Gallbladder carcinoma and extrahepatic cholangiocarcinoma)
Brief summary
This clinical trial is designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of MT-304 in adults with advanced HER2-expressing solid tumors. The main questions it aims to answer are: * What is the safety profile of MT-304 when administered alone or with nivolumab? * What is the recommended Phase 2 dose (RP2D) of MT-304? Participants will: * Receive MT-304 alone (every 14 days) or with nivolumab (every 28 days). * Attend regular clinic visits for assessments and monitoring. * Continue treatment until disease progression, unacceptable toxicity, or study discontinuation.
Detailed description
This multicenter, open-label, Phase 1 trial is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of MT-304 in adults aged 18 and older with advanced HER2-expressing solid tumors. The study consists of two treatment modules: * Module 1 (Monotherapy): Participants receive MT-304 every 14 days for 28-day cycles, with dosing adjustments based on clinical benefit and safety evaluations. * Module 2 (Combination Therapy): Participants receive MT-304 in combination with nivolumab, administered every 14 days and 28 days, respectively, also allowing for dosing adjustments. The Bayesian Optimal Interval (BOIN) design will guide dose escalation, overseen by a Safety Review Committee to establish the recommended Phase 2 dose (RP2D). Regular assessments, including vital signs and laboratory tests, will monitor safety and efficacy throughout the trial, with follow-up visits for up to 2 years post-treatment.
Interventions
DRUGMT-304
Safety, tolerability, and pharmacokinetics will be evaluated.
DRUGMT-304 + Nivolumab
Combination therapy begins after monotherapy dose clearance by the Safety Review Committee.
Sponsors
Myeloid Therapeutics
CREATE Medicines
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged 18 years or above * Histologically confirmed diagnosis of metastatic or advanced epithelial cancer expressing HER2 (Note: Participants with other tumor types expressing HER2 may be considered pending discussion with the Medical Monitor). * Measurable lesion per RECIST 1.1 criteria. * Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0 or 1. * Adequate Organ function
Exclusion criteria
* Known active CNS metastasis and/or carcinomatous meningitis. * Any acute illness including fever. * History of symptomatic congestive heart failure * History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. * Uncontrolled pleural effusion, pericardial effusion, or ascites * Active autoimmune disease not related to prior therapy for primary malignancy that has required systemic therapy in the last 1 year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Type, incidence and severity of Adverse Events | Up to 90 days from the last dose of Investigational Medicinal Product (IMP) | Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v5. |
| Number of Participants With Change From Baseline in Vital Signs (Composite Safety Outcome) | Up to 30 days from the last dose of IMP | Body temperature, body weight, pulse rate, and blood pressure (systolic and diastolic) assessed collectively; participants with clinically significant changes in any vital sign parameter will be summarized as a composite safety outcome. |
| Number of Participants With Abnormal Clinical Laboratory Parameters (Composite Safety Outcome) | Up to 30 days from the last dose of IMP | Hematology, clinical chemistry, coagulation, virology testing, and urinalysis assessed collectively; participants with abnormalities in any laboratory parameter will be summarized as a composite safety outcome. |
| Number of Participants With Change From Baseline in ECG Parameters (Composite Safety Outcome) | Screening through Day 28, with assessments performed on Screening, Day 1 (pre-dose), and Day 28. | PR interval, QRS duration, QT interval, corrected QT interval (QTc), and heart rate assessed collectively from 12-lead ECG recordings; participants with clinically significant changes in any ECG parameter will be summarized as a composite safety outcome. |
| Maximum Tolerated Dose (MTD) | 28 days from the last dose of IMP | The MTD in Module 1 (monotherapy) will be determined based on dose-limiting toxicities (DLTs). |
| Optimal Biological Dose (OBD) | 28 days from the last dose of IMP | The OBD in Module 2 (combination) will be identified based on dose-limiting toxicities (DLTs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) | From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days). | PK Parameter: Maximum plasma concentration (Cmax) |
| To assess adverse events of special interest (AESI) by measuring infusion reaction | Upto 90 days from the last dose of IMP | — |
| To assess adverse events of special interest (AESI) by measuring cytokine release syndrome (CRS) | Upto 90 days from the last dose of IMP | — |
| To assess adverse events of special interest (AESI) by measuring immune effector cell-associated neurotoxicity syndrome (ICANS) | Upto 90 days from the last dose of IMP | — |
| To assess adverse events of special interest (AESI) by measuring hypersensitivity reaction | Upto 90 days from the last dose of IMP | — |
| To assess the incidence of second primary malignancies reported as adverse events of special interest (AESI) occurring during the study treatment period and long-term follow-up. | From first dose of Investigational Medicinal Product (IMP) through end of study and follow-up (up to 2 years) | — |
Countries
Australia
Contacts
CONTACTProject Manager
CONTACTClinical Department
STUDY_DIRECTORMatthew Maurer, MD
Myeloid Therapeutics
Outcome results
None listed