Study of MT-302 in Adults With Advanced or Metastatic Epithelial Tumors (MYE Symphony)

• ClinicalTrials.gov Identifier: NCT05969041
• Recruitment Status: Recruiting
• First Posted: August 1, 2023
• Last Update Posted: January 18, 2024
• Sponsor: Myeloid Therapeutics
• Information provided by (Responsible Party): Myeloid Therapeutics

Tracking Information

• First Submitted Date: July 6, 2023
• First Posted Date: August 1, 2023
• Last Update Posted Date: January 18, 2024
• Actual Study Start Date: August 2, 2023
• Estimated Primary Completion Date: August 31, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 28, 2023)

• To evaluate the safety and tolerability of MT-302 through incidence of Adverse Events [ Time Frame: Up to Week 20 ]
  Adverse Events will be graded according to the NCI-CTCAE, version 5.0
• To establish the maximum tolerated dose (MTD) [ Time Frame: Up to Week 20 ]
  based on dose limiting toxicities (DLTs) and the recommended Phase 2 dose (RP2D)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 28, 2023)

• To further characterize the safety of MT-302 through incidence of Adverse Events [ Time Frame: Up to Week 20 ]
  Adverse Events will be graded according to the NCI-CTCAE, version 5.0
• To assess the pharmacokinetics (PK) of MT-302 [ Time Frame: Up to Week 20 ]
  PK parameter: Plasma concentrations
• To assess the pharmacokinetics (PK) of MT-302 [ Time Frame: Up to Week 20 ]
  PK parameter: Area under curve (AUC0-last, AUC 0-∞)
• To assess the pharmacokinetics (PK) of MT-302 [ Time Frame: Up to Week 20 ]
  PK parameter: Time of maximum observed plasma concentration (tmax)
• To assess the pharmacokinetics (PK) of MT-302 [ Time Frame: Up to Week 20 ]
  PK parameter: Apparent terminal Half-life (t1/2)
• To assess the pharmacokinetics (PK) of MT-302 [ Time Frame: Up to Week 20 ]
  PK parameter: Plasma Clearance (CL)
• To assess the pharmacokinetics (PK) of MT-302 [ Time Frame: Up to Week 20 ]
  PK parameter: Volume of Distribution (Vd)
• To assess the pharmacokinetics (PK) of MT-302 [ Time Frame: Up to Week 20 ]
  PK parameter:Mean residence time (MRT)
• To assess the pharmacokinetics (PK) of MT-302 [ Time Frame: Up to Week 20 ]
  PK parameter: terminal rate constant ( λz)
• Determine rate of ICANS [ Time Frame: Up to Week 20 ]
  For grading of potential immune effector cell-associated neurotoxicity syndrome (ICANS), use of the 10-point immune effector cell-associated encephalopathy (ICE) screening tool
• Determine rate of Grade 3-5 CRS [ Time Frame: Up to Week 20 ]
  ASCO CRS Grading

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of MT-302 in Adults With Advanced or Metastatic Epithelial Tumors
• Official Title: MYE Symphony: A Phase 1, Open-Label, First-in-Human, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of MT-302 in Adults With Advanced or Metastatic Epithelial Tumors
• Brief Summary: MYE Symphony is a multicenter, open-label, Phase 1 first-in-human study to assess the safety, tolerability, and define the RP2D of MT-302 in participants with advanced epithelial cancer.

Detailed Description

The study has 4 Cohorts. Each Cohort has 4 Cycles. For Cohorts 1-3, the dosing regimen will be every 14 days for 3 doses, followed by administration once every 28 days for three doses. For Cohort 4, the dosing regimen will be modified. Participants will receive one dose of MT-302 every week for 3 doses, followed by administration once every 28 days for three additional doses.

A Safety Review Committee (SRC) will provide oversight for this study. The primary responsibility of the SRC is to safeguard study participants by reviewing and assessing the clinical safety data being collected during the conduct of the study.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Epithelial Tumors, Malignant

Intervention

Drug: MT-302 (A)

MT-302 is an investigational drug

Study Arms

Experimental: A (MT-302)

Participants will receive MT-302 through intravenous infusion.

Intervention: Drug: MT-302 (A)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 28, 2023): 48
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2028
• Estimated Primary Completion Date: August 31, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Adults age ≥ 18 inclusive at the time the Informed Consent Form (ICF) is signed.

2. Histologically proven, metastatic or advanced epithelial cancer including the following cancer types:

   1. Urothelial
   2. Cervical
   3. Ovarian epithelial
   4. Triple-negative breast
   5. HR+/HER2- breast
   6. Pancreatic ductal adenocarcinoma
   7. Gastric adenocarcinoma
   8. Esophageal carcinoma
   9. Non-small cell lung
   10. Colorectal
3. Progressive disease at baseline, refractory or relapsed to standard of care or who have declined standard therapy.
4. Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria v 1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1.
6. Life expectancy of > 12 weeks.
7. Echocardiogram (ECHO) or multiple gated acquisition scan showing an ejection fraction greater than or equal to 50%.
8. Electrocardiogram (ECG) showing no clinically significant abnormality at Screening or showing an average QTc interval < 450 msec in males and < 470 msec in females (< 480 msec for participants with bundle branch block). Either Fridericia's or Bazett's formula may be used to correct the QT interval.
9. Oxygen saturation of greater than or equal to 90% on room air measured by pulse oximetry.
10. Adequate organ function as defined by laboratory values at Screening.
11. Willing and able to provide written informed consent.
12. Willing to perform and comply with all study procedures including undergoing study-related biopsies and attending clinic visits as scheduled.
13. Men must abstain from sperm donation during study treatment or for 4 months following last dose of study treatment.
14. Men and WOCBP must be willing to practice a highly effective method of contraception.

Exclusion Criteria:

1. Known active CNS metastasis and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression for at least 4 weeks by repeat imaging), clinically stable, and without requirement of steroid treatment for at least 14 days prior to the first dose of study intervention.
2. Pregnant or nursing women.
3. Must be > 28 days beyond major surgery, including hepatectomy or joint replacement.
4. Prior allogeneic bone marrow transplantation or solid organ transplant.
5. Spinal cord compression not definitively treated with surgery and/or radiation.
6. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
7. Any acute illness including fever (> 100.4° F or > 38° C) within 7 days prior to Day 1
8. Active systemic bacterial, fungal, or viral infection within 7 days prior to Day 1. Participant cannot have tested positive for COVID-19 within 7 days prior to Day 1.
9. Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV).

10. Other primary malignancies, except:

    1. Adequately treated basal cell or squamous cell carcinoma
    2. In situ carcinoma of the cervix or bladder, treated curatively and without evidence of recurrence for at least 2 years prior to the study, or
    3. A primary malignancy which has been completely resected and in complete remission for at least 2 years
11. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
12. Prior grade > 3 immune-related AEs such as pneumonitis, colitis, hepatitis, nephritis; prior dermatitis and endocrinopathies are allowed provided corticosteroids are no longer required and endocrine-replacement therapy is stable and discontinued from prior therapy.
13. Active autoimmune disease not related to prior therapy for primary malignancy that has required systemic therapy in the last 1 year.
14. History of symptomatic congestive heart failure (New York Heart Association classes II-IV) or serious active arrhythmias or other clinically significant cardiac disease within 12 months of enrollment.
15. Toxicity from previous anti-cancer therapy defined as toxicities (other than alopecia, or laboratory values listed above) not yet resolved to NCI CTCAE v5.0 Grade ≤ 1 or baseline. Participants with chronic Grade 2 toxicities (eg, peripheral neuropathy, laboratory values) may be eligible per the discretion of the Investigator and Medical Monitor.

16. Has received:

    1. Radiotherapy within 2 weeks of first administration of MT-302
    2. Cytotoxic chemotherapy for treatment of the primary malignancy within 28 days or 5 half-lives, whichever is shorter, of administration of MT-302
    3. Immune therapy for primary malignancy (eg, monoclonal antibody therapy, checkpoint inhibitors) within 28 days or 5 half-lives, whichever is shorter of first administration of MT-302
    4. Targeted therapies for primary malignancy within 28 days or 5 half-lives, whichever is shorter, of first administration of MT-302
    5. Anti-cancer vaccine within 12 weeks of first administration of MT-302
    6. COVID-19 mRNA vaccine within 6 weeks of first administration of MT-302
17. Has received a live vaccine ≤ 6 weeks prior to first administration of MT-302
18. Has received packed red blood cells or platelet transfusion within 2 weeks prior to first administration of MT-302
19. History of an allergic reaction to any of the excipients
20. Enrollment in another interventional clinical trial within 28 days or 5 half-lives of the drug, whichever is shorter, of first administration of MT-302
21. Any other condition that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with the study requirements.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Shinam Garg; +61 2 9171 3260; Shinam.garg@novotech-cro.com

Contact: Clinical Operations; +1 617 465 1022; mt-302clinical@myeloidtx.com

• Listed Location Countries: Australia

Administrative Information

• NCT Number: NCT05969041
• Other Study ID Numbers: MTX-TROP2-302
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Myeloid Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Myeloid Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Matthew Maurer, MD; Myeloid Therapeutics

• PRS Account: Myeloid Therapeutics
• Verification Date: January 2024