A Phase 1/2 clinical trial (NCT04857372) has commenced, with the first patient dosed to evaluate the safety, tolerability, and preliminary efficacy of a TEAD (transcriptional enhanced associate domain) inhibitor in patients with advanced solid tumors. The trial, conducted at UChicago Medicine and other sites, focuses on patients with limited treatment options, offering a potential new avenue for those with few alternatives.
The trial is enrolling patients aged 18 and older with histologically or cytologically confirmed diagnoses of advanced (unresectable or metastatic) mesothelioma or other solid tumors. Specific inclusion criteria target patients with loss-of-function NF2/LATS1/LATS2 genetic alterations or functional YAP/TAZ fusions, as well as those with malignant epithelioid hemangioendothelioma (EHE). All participants must have failed available standard therapies or be ineligible for such treatments.
The study design incorporates both dose escalation and dose expansion phases. The dose escalation phase will help determine the maximum tolerated dose and recommended Phase 2 dose of the TEAD inhibitor. The dose expansion phase will enroll patients into distinct treatment groups based on tumor type and genetic alterations:
- Group 1: Advanced mesothelioma patients who have failed standard therapies.
- Group 2: Solid tumor patients with NF2 truncating mutations or deletions.
- Group 3: Solid tumor patients with functional YAP/TAZ fusions, including EHE patients.
- Group 4: Advanced non-pleural mesothelioma patients who have failed standard therapies.
Key inclusion criteria also mandate the presence of at least one measurable lesion according to mRECIST v1.1 (for mesothelioma), RECIST v1.1 (for other solid tumors), or RANO (for primary brain tumors) criteria. Patients must also be willing to undergo tumor biopsies at screening/baseline and during therapy.
Exclusion criteria encompass a range of factors, including recent anticancer therapies (within 4 weeks for chemotherapy, biological therapy, or small molecule therapeutics; 6 weeks for cytotoxic agents with delayed toxicities; and 4 weeks for immuno-oncologic therapy), prior treatment with a TEAD inhibitor, and certain pre-existing medical conditions. These include insufficient renal, cardiac, or bone marrow function, as well as active COVID-19 infection and pregnancy. Patients with a history of drug-induced interstitial lung disease are also excluded in Japan.
The trial aims to address a significant unmet need in patients with advanced solid tumors who have exhausted standard treatment options. By targeting the TEAD pathway, which plays a crucial role in tumor growth and metastasis, this study could offer a novel therapeutic approach for these challenging cancers.
