a first-in-human (fih) study to evaluate the safety and tolerability of vvd-130037 in participants with advanced solid tumors

Conditions: Advanced Solid Tumors

Summary: a fih dose escalation and dose expansion study to evaluate vvd-130037 in participants with advanced solid tumors as a single agent, in combination with docetaxel, and in combination with paclitaxel.


Eligibility criteria:
key inclusion criteria for parts 1 and 2: * histologically or cytologically confirmed metastatic or unresectable solid tumor. * measurable disease by response evaluation criteria in solid tumors version 1.1 (recist v1.1) as assessed by the investigator. * have progressed on or after all prior standard-of-care therapies for metastatic disease. * eastern cooperative oncology group (ecog) performance status ≤1. * adequate organ and marrow function as defined in the protocol. additional key inclusion criteria for part 2: * participants with squamous non-small cell lung cancer (sqnsclc) with or without nuclear factor erythroid 2-related factor 2 (nrf2 \[nfe2l2\]) and/or cullin 3 (cul3) mutations. * participants with advanced sqnsclc must be refractory to or have progressed on or after a platinum-based doublet regimen and an immune checkpoint inhibitor. * participants with advanced head and neck squamous cell carcinoma (hnscc) must have received prior treatment with platinum-based chemotherapy, an immune checkpoint inhibitor (for tumors with known programmed death-ligand 1 \[pd-l1\] expression, microsatellite instability-high, or mismatch repair deficiency, and an anti-epidermal growth factor receptor agent) (combination expansion cohort). * participants with advanced esophageal squamous cell carcinoma (escc) must have received prior treatment with platinum-based chemotherapy, an immune checkpoint inhibitor (for tumors with known pd-l1 expression) (combination expansion cohort). * participants with a known driver mutation, including activating epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements, should have progressed after appropriate targeted treatment. * participants with known human epidermal growth factor receptor 2 overexpression should have progressed after appropriate targeted treatment. key exclusion criteria for parts 1 and 2: * participant is known to have a mutation that has no expectation of benefit from vvd-130037. current such mutations include the following: 1. keap1 nonsense mutation (any position) 2. keap1 frameshift mutation (any position) * any unresolved toxicity grade ≥2 per ctcae version 5.0 from previous anticancer treatment. * current or prior treatment with anti-epileptic medications for the treatment or prophylaxis of seizures. * history of seizure or condition that may predispose to seizure. * history or presence of central nervous system (cns) metastases or spinal cord compression. * uncontrolled arterial hypertension despite optimal medical management. * risk factors for abnormal heart rhythm/qt prolongation as defined in the protocol. * history of the following cardiac diseases: i) congestive heart failure (new york heart association \[nyha\] class \>ii), ii) unstable angina, iii) new onset angina within past 6 months, iv) myocardial infarction within the past 6 months, v) clinically significant arrhythmias within past 6 months.

Keywords: vvd-130037 first-in-human keap1 nrf2 cancer small molecule squamous cell histology esophageal adenocarcinoma