A Phase 1, Open-label, Multicenter, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-tumor Activity of VVD-130037, a Kelch-like ECH Associated Protein 1 (KEAP1) Activator, in Participants With 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, and in combination with docetaxel, paclitaxel, or pembrolizumab.
Arms & interventions
- DrugVVD-130037
Oral tablets
- DrugDocetaxel
IV infusion
- DrugPaclitaxel
IV infusion
- DrugPembrolizumab
IV infusion
Outcome measures
Primary
Part 1 (Dose Escalation): Incidence and Severity of Dose-limiting Toxicities (DLTs) During DLT Observation Period
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.
Time frame: 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]
Part 2 (Dose Expansion): Number of Participants With AEs, Serious Adverse Events (SAEs), and Clinical Laboratory Abnormalities
Time frame: Up to approximately 4 years
Secondary
Part 1 (Dose Escalation): Number of Participants With AEs, SAEs, and Clinical Laboratory Abnormalities
Time frame: 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
Time frame: Up to approximately 4 years
Part 2 (Dose Expansion): Overall Response Rate (ORR)
Time frame: Up to approximately 4 years
Part 2 (Dose Expansion): Duration of Response (DOR)
Time frame: Up to approximately 4 years
Part 2 (Dose Expansion): Progression-free Survival (PFS)
Time frame: Up to approximately 4 years
Part 2 (Dose Expansion): Disease Control Rate (DCR)
Time frame: Up to approximately 4 years
Parts 1 and 2 (Dose Escalation and Expansion): Area Under the Plasma Concentration-time Curve (AUC) of VVD-130037
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Parts 1 and 2: Up to approximately 4 years
Eligibility criteria
Study locations (8)
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
Florida Cancer Specialists
Sarasota, Florida, 34232
Moffitt Cancer Center
Tampa, Florida, 33612
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
MDACC
Houston, Texas, 77030
NEXT Dallas
Irving, Texas, 75039
NEXT Virginia
Fairfax, Virginia, 22031
References
- Roy N, Wyseure T, Lo IC, Lu J, Eissler CL, Bernard SM, Bok I, Snead AN, Parker A, Lo UG, Green JC, Inloes J, Jacinto SR, Kuenzi B, Pariollaud M, Negri K, Le K, Horning BD, Ibrahim N, Grabow S, Panda H, Bhatt DP, Wilkerson EM, Saeidi S, Zolkind P, Rush Z, Williams HN, Walton E, Pastuszka MK, Sigler JJ, Tran E, Hee K, McLaughlin J, Ambrus-Aikelin G, Pollock J, Abraham RT, Kinsella TM, Simon GM, Major MB, Weinstein DS, Patricelli MP. A Covalent Allosteric Molecular Glue Suppresses NRF2-Dependent Cancer Growth. Cancer Discov. 2026 May 1;16(5):953-975. doi: 10.1158/2159-8290.CD-25-1187.(PubMed)