Clinical trial NCT06188208: A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-130850 in Participants With Advanced Solid and Hematologic Tumors
Official title: A Phase 1, Open-Label, 2-Part, Multicenter, First-in-Human Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of the STAT3 Inhibitor VVD-130850 as Single Agent and in Combination With Checkpoint Inhibition in Participants With Advanced Solid and Hematologic Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Advanced Hematologic Tumors
Keywords: VVD-130850
Phase I
First in Human
Cancer
small molecule
STAT3
NSCLC
STK11
LKB1
immunosuppression
Checkpoint inhibitor
PD-1
Lead sponsor: Vividion Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2024-01-03
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: A FIH study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VVD-130850, as single agent and in combination with checkpoint inhibition, in participants with advanced solid and hematologic tumors.


Eligibility criteria: Key Inclusion Criteria:

1. Histologically or cytologically confirmed metastatic or unresectable solid tumor or advanced non-Hodgkin's lymphoma (NHL).
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
3. Adequate organ and bone marrow function as defined in the protocol.
4. For Combination Therapy Expansion:

   * Serine/threonine kinase 11/ liver kinase B1 (STK11/LKB1) mutated non-small cell lung cancer (NSCLC) as assessed by historical (local) test.
   * Must be refractory to or have progressed on or after a platinum-based doublet regimen and an immune checkpoint inhibitor (CPI). These therapies could have been given in the same line of therapy or different lines of therapy.
5. Measurable disease by RECIST version 1.1 as assessed by the Investigator.

Key Exclusion Criteria:

1. Have a diagnosis of immunodeficiency or are receiving systematic steroid therapy or any other form of immunosuppressive therapy.
2. Prior allogeneic transplantation.
3. History of cardiac diseases as defined in detail in the protocol.
4. Clinically significant infection or any eye infection.
5. Active central nervous system (CNS) malignancies (previously treated CNS malignancies are not exclusionary).
6. Combination Therapy Expansion:

   * Known hypersensitivity or contraindication to pembrolizumab or any of its components.
   * Any prior toxicity (Grade 3 or 4) related to immunotherapy leading to treatment discontinuation with the exception of the history of immunotherapy-related endocrinopathy controlled with ongoing medical management (e.g., hypothyroidism, adrenal insufficiency, diabetes).

Primary outcomes:
measure: Dose Escalation: Incidence and Severity of Dose-limiting Toxicities (DLTs) During DLT Observation Period
timeFrame: From Day 1 to Day 21 of Cycle 1 [cycle length=21 days]
measure: Dose Expansion: Number of Participants with AEs and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 4 years
measure: Dose Expansion: Number of Participants with Clinically Significant Changes in Vital Signs
timeFrame: Up to approximately 4 years
measure: Dose Expansion: Number of Participants with Clinically Significant Changes in Laboratory Evaluations
timeFrame: Up to approximately 4 years
Secondary outcomes:
measure: Dose Escalation: QT/Corrected QT (QTc) Interval and Other Electrocardiogram (ECG) Parameters
timeFrame: Up to approximately 4 years
measure: Dose Escalation: Recommended Dose for Expansion (RDE) of VVD-130850 as a Single Agent and in Combination with Pembrolizumab
timeFrame: Up to approximately 4 years
measure: Dose Expansion: Overall Response Rate (ORR)
timeFrame: Up to approximately 4 years
measure: Dose Expansion: Duration of Response (DoR)
timeFrame: Up to approximately 4 years
measure: Dose Expansion: Progression-free Survival (PFS)
timeFrame: Up to approximately 4 years
measure: Dose Expansion: Disease Control Rate (DCR)
timeFrame: Up to approximately 4 years
measure: Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve (AUC) of VVD-130850
timeFrame: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)
measure: Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of VVD-130850
timeFrame: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)
measure: Dose Escalation and Expansion: Apparent Terminal Half-life (t1/2) of VVD-130850
timeFrame: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: California Research Institute
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Austin
country: United States
facility: NEXT Austin
state: Texas
city: Houston
country: United States
facility: MDACC
state: Texas
city: Irving
country: United States
facility: NEXT Dallas
state: Texas
city: San Antonio
country: United States
facility: NEXT San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Huntsman Cancer Institute
state: Utah
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Blacktown
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: Orange
country: Australia
facility: Orange Health Service
state: New South Wales
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Cancer Research South Australia
city: South Brisbane
country: Australia
facility: ICON Cancer Research
city: Barcelona
country: Spain
facility: START Barcelona Hospital HM Nou Delfos
city: Barcelona
country: Spain
facility: Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: NEXT Madrid
city: Madrid
country: Spain
facility: START Madrid CIOCC
city: Madrid
country: Spain
facility: Start Madrid-FJD, Hospital Fundacion Jimenez Diaz
Study officials:
References: