Study of MT-6402 in Subjects With Advanced Solid Cancer That Expresses PD-L1

NCT04795713 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: MT-6402-001
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 16

Brief Summary

This will be a Phase 1 Open-label, dose escalation and expansion study of MT-6402 (an Engineered Toxin Body (ETB)) in subjects with advanced solid cancer that expresses PD-L1

Conditions

Advanced Solid Tumor; Non-small Cell Lung Cancer; Squamous Cell Carcinoma of Head and Neck

Keywords

PD-L1 Positive; Relapsed or Refractory; Prior PD-1 or PD-L1 treatment

Outcome Measures

Primary Outcomes (4)

• Evaluate the safety of MT-6402 in subjects with advanced cancer (solid tumors) and to estimate the maximum tolerated dose (MTD)

  Safety as measured by number of subjects with incidence of adverse events using CTCAE v4.0

  28 days (Part 1)

• Evaluate the tolerability of MT-6402 in subjects with advanced cancer (solid tumors) and to estimate the maximum tolerated dose (MTD)

  Tolerability as measured by incidence of adverse events using CTCAE v5.0 and incidence of laboratory abnormalities

  28 days (Part 1)

• Confirm the recommended Phase 2 dose (RP2D)

  Incidence of Adverse Events (AEs)

  28 days (Part 2)

• Evaluate efficacy of MT-6402 in subjects with advanced cancer by objective response rate (ORR) with RECIST 1.1

  ORR using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

  up to 2 years (Part 2)

Secondary Outcomes (11)

• Characterize the PK profile of MT-6402 in subjects with advanced cancer

  up to 2 years (Parts 1 and 2)

• Characterize the PK profile of MT-6402 in subjects with advanced cancer

  up to 2 years (Parts 1 and 2)

• Characterize the PK profile of MT-6402 in subjects with advanced cancer

  up to 2 years (Parts 1 and 2)

• Characterize the PK profile of MT-6402 in subjects with advanced cancer

  up to 2 years (Parts 1 and 2)

• Characterize the PK profile of MT-6402 in subjects with advanced cancer

  up to 2 years (Parts 1 and 2)

Other Outcomes (10)

• Evaluate the immunogenicity of MT-6402 in subjects with advanced cancer

  28 days (Parts 1 and 2)

• Explore immune response to MT-6402 treatment

  28 days (Parts 1 and 2)

• Characterize the PD profile of MT-6402 in subjects with advanced cancer

  Up to 2 years (Parts 1 and 2)

Study Arms (4)

PD-L1 Positive NSCLC

EXPERIMENTAL

Subjects with PD-L1 Positive Lung Carcinoma (NSCLC) who received prior PD-1/PD-L1 treatment

Drug: MT-6402

PD-L1 Positive SCCHN

EXPERIMENTAL

Subjects with PD-L1 Positive Squamous Cell Carcinoma of the head and neck (SCCHN), refractory to or ineligible for platinum-based therapy, who received prior PD-1/PD-L1 treatment

Drug: MT-6402

Other relapsed/refractory PD-L1 positive solid tumors

EXPERIMENTAL

Subjects with any other relapsed or refractory PD-L1 positive solid tumor who received PD-1/PD-L1 treatment.

Drug: MT-6402

PD-L1 positive advanced cancer

EXPERIMENTAL

Subjects with PD-L1 positive advanced cancer (solid tumors)

Drug: MT-6402

Interventions

MT-6402 DRUG

Experimental Treatment

Other relapsed/refractory PD-L1 positive solid tumors; PD-L1 Positive NSCLC; PD-L1 Positive SCCHN; PD-L1 positive advanced cancer

Eligibility Criteria

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

You may qualify if:

• Part A
• Subject must be at least 18 years old and must have histologically confirmed, unresectable, locally advanced, or metastatic PD-L1-expressing solid cancer not amenable to standard treatment, or for whom standard treatment is not available, or in the Investigator's opinion the standard treatment would not be in the subject's best interest. Any level of PD-L1 expression assessed by using any Food and Drug Administration (FDA) approved PD-L1 immunohistochemistry (IHC) assay is accepted. In addition, another PD-L1 assay may be considered acceptable if approved by the Medical Monitor. The assessment should have been performed on the most recent available tissue from a site of metastatic disease (if possible).
• Subject must have evaluable or measurable disease.
• Part B
• Requirements for separate cohorts enrolled in Part B are as follows:
• Cohort 1: Histologically confirmed recurrent or metastatic NSCLC not amenable to standard treatment, or standard treatment is not available, or in the Investigator's opinion the standard treatment would not be in the subject's best interest. NOTE: subjects with driver mutations are only eligible if they have received all appropriate targeted therapies.
• Cohort 2: Histologically confirmed recurrent, resistant, or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) not amenable to standard treatment, or standard treatment is not available, or in the Investigator's opinion the standard treatment would not be in the subject's best interest. Subjects who refuse radical resection are eligible. NOTE: nasopharyngeal cancer, squamous cell carcinoma of any other primary anatomic location in the head and neck, subjects with SCCHN of unknown primary, and subjects with skin squamous cell carcinoma (SCC) of the head and neck are not eligible for this arm. The tumor must be platinum resistant or the subject ineligible for platinum therapy due to hypersensitivity or concerns with ototoxicity.
• Cohort 3: Subjects with any other relapsed or refractory PD-L1 positive solid tumor not amenable to standard treatment, or standard treatment is not available, or in the Investigator's opinion the standard treatment would not be in the subject's best interest, who received PD-1/PD-L1 treatment. Subjects with PD-L1 positive solid tumor types, for which PD-1/PD-L1 treatment is not approved, could be enrolled at the Investigator's discretion and after discussion with the Medical Monitor.
• Positive PD-L1 expression as assessed by an FDA approved PD-L1 IHC assay is required. The assessment should have been performed on the most recently available tissue and form a site of metastatic disease (if possible). Subjects without PD-L1 measured by an FDA-approved diagnostic must have PD-L1 expression confirmed by an FDA-approved diagnostic on either archived tissue or a fresh biopsy. Subjects for whom PD-L1 expression has not been determined and do not have archived tissue will require a fresh biopsy for PD-L1 determination by an FDA-approved diagnostic.
• Subjects must be willing to have a total of 2 on trial biopsies: one at baseline and the other within the last 2 weeks of Cycle 2. Subjects who required a fresh biopsy at screening may utilize the screening biopsy tissue in lieu of the baseline biopsy.
• Subject must have at least 1 measurable tumor lesion according to RECIST 1.1.
• Parts A and B
• Subject must have Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
• Prior treatment must include a CPI (i.e., PD-1 inhibitors, PD-L1 inhibitors with or without CTLA-4 inhibitors) if there is an approved CPI for the specific cancer type. Subjects may also have received CPIs in an investigational setting. Subjects who have not received a CPI and where there is no approved CPI for the specific cancer type could be enrolled at the Investigator's discretion and after discussion with the Medical Monitor.
• Subject must have adequate bone marrow function (NOTE: administration of blood products and growth factors is not allowed within 2 weeks prior to screening laboratory tests):

You may not qualify if:

• Part A
• Subjects without available tissue from a site of metastatic disease or easily biopsied lesion (biopsy sites of non significant risk, in the opinion of the Investigator) or unwilling to consent to biopsy.
• Part B
• Subjects without easily biopsied lesions (biopsy sites of non significant risk, in the opinion of the Investigator) or unwilling to consent to baseline and end of Cycle 2 biopsy. Patients for whom a biopsy is not feasible must be discussed with the Medical Monitor.
• Subjects unwilling to have baseline and on-study core biopsy (last 2 weeks of Cycle 2) performed.
• Parts A and B
• History or current evidence of another neoplastic disease, except cervical carcinoma in situ, superficial noninvasive bladder tumors, curatively treated Stage I to II non melanoma skin cancer or any previous cancer curatively treated \> 2 years before the start of treatment.
• Active autoimmune disease currently under treatment or required systemic treatment within 2 years (replacement therapy, e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency is allowed). Subjects who have not required systemic treatment of an auto-immune disease for at least 2 years may be enrolled if permission is provided after discussion with the Medical Monitor.
• Ongoing \> Grade 1 immune related toxicity caused by prior CPI therapy (i.e., PD-1 inhibitors, PD-L1 inhibitors, or CTLA-4 inhibitors). Subjects with stable endocrinological AEs, e.g., hypothyroidism, adrenal insufficiency, hypopituitarism, or diabetes mellitus, must have been on a stable dose of supplemental therapy for at least 2 weeks before screening to be eligible for this study. History of repeat Grade 2 pneumonitis or carditis on previous CPI and/or Grade 3 immune related adverse event on previous CPI treatment.
• Evidence of active noninfectious ≥ Grade 2 pneumonitis or current evidence of ≥ Grade 3 other underlying pulmonary disease.
• Received any of the following PD-L1 inhibitors within the following time periods prior to the first dose of MT-6402: atezolizumab - 12 months; durvalumab - 7 months; avelumab - 2 months.
• Any concurrent cancer treatment, apart from local treatment of non-target lesions for palliative intent (e.g., local surgery or radiotherapy).
• Prior radiation therapy within 4 weeks before the start of study treatment. NOTE: A lesion in a previously irradiated area can only be considered target lesion if there has been radiographical disease progression since the end of radiation therapy.
• Subjects who have had allogeneic tissue or solid organ transplantation.
• Current evidence of new or growing central nervous system (CNS) metastases during screening. Subjects with known asymptomatic CNS metastases will be eligible if they meet all the following criteria:

Sponsors & Collaborators

• Molecular Templates, Inc.: lead

Study Sites (16)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

USC Medical Center

Los Angeles, California, 90033, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Comprehensive Care and Research Center - Atlanta

Newnan, Georgia, 30265, United States

Location

Comprehensive Care and Research Center - Chicago

Chicago, Illinois, 60099, United States

Location

University of Louisville Health - Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Washington University School of Medicine - St. Louis

St Louis, Missouri, 63110, United States

Location

Dartmouth Hitchcock

Lebanon, New Hampshire, 03766, United States

Location

Carolina BioOncology

Huntersville, North Carolina, 28078, United States

Location

Pennsylvania Cancer Specialists and Research Institute

Gettysburg, Pennsylvania, 17325, United States

Location

Prisma Health

Greenville, South Carolina, 29605, United States

Location

Sanford Cancer Center

Sioux Falls, South Dakota, 57104, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

Oncology Consultants

Houston, Texas, 77024, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Recurrence

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: March 12, 2021
• Study Start: May 27, 2021
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: November 4, 2024

Record last verified: 2024-10

Locations

US (16)