A Clinical Trial to Evaluate the Safety, Tolerability and Clinical Efficacy of M3T01 Monotherapy and in Combination With Pembrolizumab and Other Systemic Therapies

NCT06719362 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 2024000813
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1 first-in-human, open-label, dose-escalation (3 + 3), dose-expansion clinical trial to evaluate the safety, tolerability and preliminary clinical efficacy of M3T01 (fully human IgG4/kappa monoclonal antibody targeting FasL) in subjects with metastatic or unresectable solid tumors.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Treatment-emergent adverse events

  Safety parameters including clinical assessments, vital signs, laboratory testing, and electrocardiograms (ECG) will be used to assess treatment-emergent adverse events (TEAE). Adverse events will be graded using the NCI-CTCAE v5.0. Investigators will determine relatedness of all treatment emergent adverse events (TEAE) to the investigational agent(s).

  4 years

• Dose-limiting toxicities

  The DLT evaluation period will be defined as the first 21 days after infusion of M3T01 as monotherapy or in combination with other systemic therapies (including pembrolizumab, temozolomide, and FOLFOX). Site investigators will grade toxicities using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  21 days after C1D1

• Serious adverse events

  Clinical assessments, vital signs, laboratory testing, and electrocardiograms (ECG) will be used to assess serious adverse events (SAE) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  4 years

• Immune-related adverse events

  Clinical assessments, vital signs, laboratory testing, and electrocardiograms (ECG) will be used to assess immune-related adverse events (irAE) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  4 years

Secondary Outcomes (3)

• PK Profile of M3T01

  4 years

• Immunogenicity of M3T01

  4 years

• Antitumor Activity of M3T01

  4 years

Study Arms (11)

Part 1A: DL 1

EXPERIMENTAL

M3T01 100 mg as monotherapy.

Drug: M3T01

Part 1A: DL 2

EXPERIMENTAL

M3T01 200 mg as monotherapy.

Drug: M3T01

Part 1A: DL 3

EXPERIMENTAL

M3T01 400 mg as monotherapy.

Drug: M3T01

Part 1A: DL 4

EXPERIMENTAL

M3T01 600 mg as monotherapy.

Drug: M3T01

Part 1A: DL 5

EXPERIMENTAL

M3T01 800 mg as monotherapy.

Drug: M3T01

Part 1B: DL 6

EXPERIMENTAL

M3T01 400 mg in combination with pembrolizumab 200 mg.

Drug: M3T01; Drug: Pembrolizumab

Part 1B: DL 7

EXPERIMENTAL

M3T01 600 mg in combination with pembrolizumab 200 mg.

Drug: M3T01; Drug: Pembrolizumab

Part 1B: DL 8

EXPERIMENTAL

M3T01 800 mg in combination with pembrolizumab 200 mg.

Drug: M3T01; Drug: Pembrolizumab

Part 2A: Newly diagnosed glioblastoma with unmethylated MGMT promoter

EXPERIMENTAL

Subjects will be treated with standard of care chemoradiation therapy consisting of TMZ 75 mg/m2 daily with concurrent radiation therapy (60 Gy administered over 6 weeks). Following chemoradiation therapy, subjects will have a 4-week break from TMZ before starting standard adjuvant TMZ 150-200 mg/m2 days 1-5 of 28-day cycles for 6 cycles. Subjects will be treated with M3T01 at the RP2D through an IV infusion every 3 weeks that will begin concurrently with chemoradiation therapy.

Drug: M3T01; Radiation: Chemoradiation

Part 2B: First-line tx for unresectable/metastatic HER2- esophageal, GEJ, or gastric adenocarcinoma.

EXPERIMENTAL

Subjects with unresectable or metastatic HER2 negative esophageal, gastroesophageal (GEJ), or gastric adenocarcinoma without prior systemic therapy in the metastatic setting will be treated with M3T01 at the RPD2 in combination with standard of care pembrolizumab plus FOLFOX chemotherapy.

Drug: M3T01; Drug: Pembrolizumab; Drug: FOLFOX regimen

Part 2C: Second-line treatment for recurrent/metastatic HNSCC

EXPERIMENTAL

Subjects with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who have developed disease progression after first-line systemic therapy with an anti-PD-1-based regimen in the recurrent or metastatic setting will be treated with M3T01 at the RP2D in combination with pembrolizumab 200 mg IV every 3 weeks for up to 2 years.

Drug: M3T01; Drug: Pembrolizumab

Interventions

M3T01 DRUG

Subjects will be treated with M3T01 through an IV infusion over 1 hour given every 3 weeks.

Part 1A: DL 1; Part 1A: DL 2; Part 1A: DL 3; Part 1A: DL 4; Part 1A: DL 5; Part 1B: DL 6; Part 1B: DL 7; Part 1B: DL 8; Part 2A: Newly diagnosed glioblastoma with unmethylated MGMT promoter; Part 2B: First-line tx for unresectable/metastatic HER2- esophageal, GEJ, or gastric adenocarcinoma.; Part 2C: Second-line treatment for recurrent/metastatic HNSCC

Pembrolizumab DRUG

Pembrolizumab will be given as standard of care to Cohort DL 5+ under Part 1 of the study. Subjects will receive 200 mg IV once every 3 weeks.

Also known as: KEYTRUDA

Part 1B: DL 6; Part 1B: DL 7; Part 1B: DL 8; Part 2B: First-line tx for unresectable/metastatic HER2- esophageal, GEJ, or gastric adenocarcinoma.; Part 2C: Second-line treatment for recurrent/metastatic HNSCC

Chemoradiation RADIATION

Subjects will be treated with standard of care chemoradiation therapy consisting of TMZ 75 mg/m2 daily with concurrent radiation therapy (60 Gy administered over 6 weeks). Following chemoradiation therapy, subjects will have a 4-week break from TMZ before starting standard adjuvant TMZ 150-200 mg/m2 days 1-5 of 28-day cycles for 6 cycles. Subjects will be treated with M3T01 at the RP2D through an IV infusion every 3 weeks that will begin concurrently with chemoradiation therapy.

Part 2A: Newly diagnosed glioblastoma with unmethylated MGMT promoter

FOLFOX regimen DRUG

FOLFOX will be given as standard of care on 14 day cycles. Subjects will receive oxaliplatin 85 mg/m2 IV on Day 1, leucovorin 400 mg/m2 IV on Day 1, fluorouracil 400 mg/m2 IV push on Day 1, and fluorouracil 1,200 mg/m2 IV continuous infusion on Days 1-2 every 14 days for up to 9 cycles.

Also known as: Oxaliplatin, Leucovorin, Fluorouracil

Part 2B: First-line tx for unresectable/metastatic HER2- esophageal, GEJ, or gastric adenocarcinoma.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Life expectancy ≥ 12 weeks.
• Provision of written informed consent (see Section 16.1 and Appendix 18.5.5) for participation in the clinical trial.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1 for subjects with solid tumors other than glioblastoma.
• Karnofsky Performance Status of ≥ 70% for subjects with glioblastoma.
• Tumor tissue from a surgical or core needle biopsy must be provided to the sponsor (fine needle aspirate or cytology specimens are not acceptable). Archival formalin fixed paraffin embedded (FFPE) tissue is acceptable. If archival tumor tissue is not available, a fresh tumor biopsy must be performed.
• Subjects must have a tumor accessible for biopsy while on treatment. If the subject does not have a tumor that is safely accessible for biopsy, the subject may still participate in the clinical trial following authorization from the sponsor. NOTE: Subjects with glioblastoma are not required to have tumor accessible for biopsy and will not undergo a protocol specified biopsy on study.
• Eligible tumor types in Part 1 Dose Escalation will include subjects with histologically or cytologically confirmed metastatic or unresectable solid tumors who have developed disease progression following standard systemic therapy in the unresectable or metastatic setting. Subjects with cancers that harbor a molecularly defined oncogenic target for which an FDA approved therapy is available (including but not limited to EGFR, ROS1, ALK, BRAF, RET, NTRK, KRAS G12C, etc.) should have received this therapy.
• Measurable disease
• Subjects with solid tumors other than glioblastoma must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Subjects with glioblastoma: Part 1: must have measurable disease per Response Assessment in Neuro-Oncology (RANO 2.0); Part 2: measurable disease at baseline is not required as these subjects will have undergone maximal safe resection prior to enrollment.
• Adequate organ function as defined by the following:
• Absolute neutrophil count (ANC) ≥ 1.2 x 109/L.
• Hemoglobin ≥ 9.0 g/dL (without a blood transfusion 2 weeks prior to the hemoglobin measurement).
• Platelet count ≥ 100 x 109/L (without a platelet transfusion 2 weeks prior to the platelet measurement).

You may not qualify if:

• Treatment with anticancer therapy within 14 days or 5 half-lives (whichever is shorter) of cycle 1 day 1. Palliative radiation therapy to a non-CNS metastasis is permitted if completed at least 14 days prior to cycle 1 day 1.
• History of other active malignancy that required treatment within 2 years of enrollment. Exceptions include the following:
• Early-stage/localized tumors that have received definitive/curative treatment and have low risk of recurrence (including but not limited to cutaneous squamous cell or basal cell carcinoma, in situ cervical or bladder cancer, and early-stage prostate cancer).
• Early-stage prostate cancer in which observation without treatment is recommended.
• Clinically significant cardiovascular conditions as defined by the following:
• New York Heart Association (NYHA) congestive heart failure class ≥ II.
• Left ventricular ejection fraction ≤ 50%.
• Clinically significant cardiac arrhythmia requiring treatment within 3 months of enrollment. Subjects with cardiac arrhythmias on stable management for over 3 months prior to enrollment are permitted.
• Prolonged QTcF interval \> 480 ms.
• Myocardial infarction, stroke, or pulmonary embolism within 3 months of enrollment.
• CNS metastases or leptomeningeal carcinomatosis (applicable to subjects with solid tumors other than glioblastoma). Subjects with brain metastases are eligible for participation if one of the following criteria are met:
• CNS metastases have been treated with surgical resection or radiation therapy and have remained stable for at least 4 weeks (repeat imaging required at least 4 weeks following resection or last radiation therapy) prior to cycle 1 day 1.
• The subject is neurologically asymptomatic and there are ≤ 4 CNS metastases no larger than 1 cm.
• Treatment with immunosuppressive medications.
• History of severe pulmonary disease defined as either of the following:

Sponsors & Collaborators

• Providence Health & Services: lead

Study Sites (1)

Providence Portland Cancer Institute - Franz Clinic

Portland, Oregon, 97213, United States

RECRUITING

MeSH Terms

Interventions

pembrolizumab; Chemoradiotherapy; Folfox protocol; Oxaliplatin; Leucovorin; Fluorouracil

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Rom Leidner, MD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tara Foote, RN

CONTACT

503-215-1979; canrsrchstudies@providence.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2024
• First Posted: December 5, 2024
• Study Start: June 17, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2030
• Last Updated: July 10, 2025

Record last verified: 2025-07

Locations

US (1)