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

Stopped early · Phase 1

Conditions studied: Advanced Solid Tumor, Non-small Cell Lung Cancer, Squamous Cell Carcinoma of Head and Neck

In brief

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

Key facts

Study ID

NCT04795713

Run by

Molecular Templates, Inc.

People needed

64

Starts

2021-05-27

Expected to finish

2024-10-31

Last updated by the study team

2024-11-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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):
• absolute neutrophil count (ANC) ≥ 1,500/μL
• platelet count ≥ 100,000/μL
• hemoglobin ≥ 8.0 g/dL
• Subject must have adequate renal function, based on estimated creatinine clearance (eCrCl) ≥ 50 mL/min, calculated by the Cockcroft-Gault equation.
• NOTE: At the Investigator's discretion, the eCrCl result < 50 mL/min may be verified by measured creatinine clearance (mCrCl) based on the 24-hour urine collection. Subjects with mCrCl ≥ 50 mL/min will be eligible irrespective of the eCrCl result calculated by the Cockcroft-Gault equation.
• Subject must have adequate hepatic function, as determined by:
• total bilirubin (or direct bilirubin for subjects with Gilbert's disease) < 1.5 × upper limit of normal (ULN)
• aspartate aminotransferase (AST) ≤ 3 × ULN (or ≤ 5 × ULN if liver metastasis)
• alanine aminotransferase (ALT) ≤ 3 × ULN (or ≤ 5 × ULN if liver metastasis)
• Subject must have adequate serum albumin (albumin ≥ 2.5 g/dL)

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.
• Received approved or investigational treatment for the disease under study (except PD L1 inhibitors where exclusion criterion 6 applies) within 4 weeks before the start of treatment. For small molecules (MW < 0.9 kDa), the washout is 5 half-lives, but at least 2 weeks.
• 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:
• Evidence of leptomeningeal metastasis.
• Have stable CNS disease on the computed tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before screening compared with prior neuro imaging.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the start of study treatment.
• History or current evidence of significant cardiovascular disease before the start of treatment, including but not limited to the following conditions:
• Angina pectoris requiring anti-anginal medication, (chest pain: Common Terminology Criteria for Adverse Events [CTCAE] Grade ≥ 2)
• Clinically significant valvular disease.
• Myocardial infarction within 12 months prior to the start of treatment.
• Arterial thrombosis or pulmonary embolism within 3 months before the start of treatment.
• History of Grade ≥ 2 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria Class ≥ II.

Where it is running

• City of Hope Medical Center — Duarte, California, United States
• USC Medical Center — Los Angeles, California, United States
• Cedars Sinai Medical Center — Los Angeles, California, United States
• Comprehensive Care and Research Center - Atlanta — Newnan, Georgia, United States
• Comprehensive Care and Research Center - Chicago — Chicago, Illinois, United States
• University of Louisville Health - Brown Cancer Center — Louisville, Kentucky, United States
• Washington University School of Medicine - St. Louis — St Louis, Missouri, United States
• Dartmouth Hitchcock — Lebanon, New Hampshire, United States
• Carolina BioOncology — Huntersville, North Carolina, United States
• Pennsylvania Cancer Specialists and Research Institute — Gettysburg, Pennsylvania, United States
• Prisma Health — Greenville, South Carolina, United States
• Sanford Cancer Center — Sioux Falls, South Dakota, United States
• Tennessee Oncology, PLLC — Nashville, Tennessee, United States
• Mary Crowley Cancer Research — Dallas, Texas, United States
• Oncology Consultants — Houston, Texas, United States
• South Texas Accelerated Research Therapeutics, LLC — San Antonio, Texas, United States

Full record on ClinicalTrials.gov

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