Advanced Solid Tumors
Conditions
Keywords
VVD-130037, First-in-Human, KEAP1, NRF2, Cancer, small molecule, squamous cell histology, esophageal adenocarcinoma
Brief summary
A FIH dose escalation and dose expansion study to evaluate VVD-130037 in participants with advanced solid tumors as a single agent, and in combination with docetaxel, paclitaxel, or pembrolizumab.
Interventions
DRUGVVD-130037
Oral tablets
DRUGDocetaxel
IV infusion
DRUGPaclitaxel
IV infusion
DRUGPembrolizumab
IV infusion
Sponsors
Vividion Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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. * Any prior toxicity (Grade 3 or 4) related to immunotherapy leading to treatment discontinuation (Combination Expansion Cohort) * Medical history of (noninfectious) pneumonitis/interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active pneumonitis/ILD (Combination Expansion Cohort)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 (Dose Escalation): Incidence and Severity of Dose-limiting Toxicities (DLTs) During DLT Observation Period | Part 1: Single Agent and Docetaxel/Pembrolizumab Combination Therapy: From Day 1 to Day 21 of Cycle 1 [cycle length=21 days] and Part 1: Paclitaxel Combination Therapy: From Day 1 to Day 28 of Cycle 1 [cycle length=28 days] | Incidence and severity of DLTs will be assessed per DLT criteria set forth in the protocol based on adverse events (AEs) evaluated per National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
| Part 2 (Dose Expansion): Number of Participants With AEs, Serious Adverse Events (SAEs), and Clinical Laboratory Abnormalities | Up to approximately 4 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 (Dose Escalation): Number of Participants With AEs, SAEs, and Clinical Laboratory Abnormalities | Up to approximately 4 years | — |
| Part 2 (Dose Expansion): Recommended Phase 2 Dose (RP2D) of VVD-130037 as a Single Agent and in Combination with Docetaxel, Paclitaxel, or Pembrolizumab | Up to approximately 4 years | The RP2D will be based on safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of VVD-130037 as single agent, and in combination with docetaxel, paclitaxel, or pembrolizumab during Part 2. |
| Part 2 (Dose Expansion): Overall Response Rate (ORR) | Up to approximately 4 years | ORR is defined as the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator assessment. |
| Part 2 (Dose Expansion): Duration of Response (DOR) | Up to approximately 4 years | DOR is defined as the time from initial response of CR or PR to progressive disease or death, whichever comes first per RECIST version 1.1 by investigator assessment. |
| Part 2 (Dose Expansion): Progression-free Survival (PFS) | Up to approximately 4 years | PFS is defined as the time from the date of randomization to the time of confirmed disease progression or death, whichever occurs first per RECIST version 1.1 by investigator assessment. |
| Part 2 (Dose Expansion): Disease Control Rate (DCR) | Up to approximately 4 years | DCR is defined as the percentage of participants achieving CR or PR, or stable disease (SD) per RECIST version 1.1 by investigator assessment. |
| Parts 1 and 2 (Dose Escalation and Expansion): Area Under the Plasma Concentration-time Curve (AUC) of VVD-130037 | Parts 1 and 2: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days for Single Agent and Docetaxel/Pembrolizumab Combination Therapy and cycle length=28 days for Paclitaxel Combination Therapy) | — |
| Parts 1 and 2 (Dose Escalation and Expansion): Maximum Observed Concentration (Cmax) of VVD-130037 | Parts 1 and 2: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days for Single Agent and Docetaxel/Pembrolizumab Combination Therapy and cycle length=28 days for Paclitaxel Combination Therapy) | — |
| Parts 1 and 2 (Dose Escalation and Expansion): Apparent Terminal Half-life (T1/2) of VVD-130037 | Parts 1 and 2: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days for Single Agent and Docetaxel/Pembrolizumab Combination Therapy and cycle length=28 days for Paclitaxel Combination Therapy) | — |
| Parts 1 and 2 (Dose Escalation and Expansion): QT/Corrected QT (QTc) Interval and Other Electrocardiogram (ECG) Parameters | Parts 1 and 2: Up to approximately 4 years | Number of participants with changes in QT/QTc interval and other ECG parameters will be assessed. |
Countries
South Korea, Spain, United States
Contacts
CONTACTVividion Clinical Trial Call Center
Outcome results
None listed