Clinical trial NCT06804824: A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-159642 in Participants With Advanced Solid Tumors
Official title: A Phase 1/1b, Open-Label, Multicenter, First-in-Human Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-Tumor Activity of VVD-159642, a RAS-PI3Kα Inhibitor, as a Single Agent and in Combination in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: RAS
PI3K
KRAS
MEK
Phase I
solid tumors
KRAS G12C
HER2
Lead sponsor: Vividion Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2025-02-03
Enrollment: 220
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 (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of VVD-159642, a rat sarcoma viral oncogene-phosphatidylinositol 3-kinase alpha (RAS-PI3Kα) inhibitor, as a single agent and in combination with either sotorasib or trametinib in participants with advanced solid tumors.


Eligibility criteria: Key Inclusion Criteria:

* For Part 1 Dose Escalation, the prospective participant must have histologically confirmed pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), non-small cell lung cancer (NSCLC), or any solid tumor that harbors a rat sarcoma viral oncogene (RAS) alteration \[Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), Harvey rat sarcoma viral oncogene homolog (HRAS)\] as per local /historical testing; any solid tumor that harbors an epidermal growth factor receptor (EGFR) alteration as per local/historical testing; or human epidermal growth factor receptor 2 (HER2) overexpression (immunohistochemistry \[IHC\] 3+ or IHC 2+/fluorescence in situ hybridization \[FISH\] positive) as per local/historical testing.
* Have histologically or cytologically confirmed metastatic or unresectable solid tumors.
* Measurable disease by RECIST version 1.1 as assessed by the investigator.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
* Adequate bone marrow, kidney, and liver function as defined in the protocol.
* Able to take oral medications.

Key Exclusion Criteria:

* Active central nervous system (CNS) malignancies.
* History of cardiac diseases as defined in detail in the protocol.
* Uncontrolled arterial hypertension despite optimal medical management (per investigator's opinion).
* History of inflammatory bowel disease or any malabsorption syndrome or any conditions that would interfere with enteral absorption and/or may interfere with the conduct of the study.
* Active hepatitis B infection \[positive for hepatitis B surface antigen and Hepatitis B virus deoxyribonucleic acid (DNA)\].
* Active hepatitis C infection (positive anti-hepatitis C virus \[HCV\] antibody and quantitative HCV ribonucleic acid (RNA) results greater than the lower limits of detection of the assay).

Primary outcomes:
measure: Part 1: Incidence and Severity of Dose-limiting Toxicities (DLTs)
timeFrame: From Day 1 to Day 21 of Cycle 1 [cycle length=21 days]
measure: Part 2: Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 29 months
measure: Part 2: Incidence and Severity of Clinically Significant Changes in Vital Signs
timeFrame: Up to approximately 29 months
measure: Part 2: Incidence and Severity of Clinically Significant Changes in Laboratory Evaluations
timeFrame: Up to approximately 29 months
Secondary outcomes:
measure: Part 1: Recommended Dose for Expansion (RDE) of VVD-159642 as a Single Agent
timeFrame: Up to approximately 29 months
measure: Part 2: Recommended Phase 2 Dose (RP2D) of VVD-159642 as a Single Agent and in Combination with Sotorasib and Trametinib
timeFrame: Up to approximately 29 months
measure: Part 2: Overall Response Rate (ORR)
timeFrame: Up to approximately 29 months
measure: Part 2: Duration of Response (DoR)
timeFrame: Up to approximately 29 months
measure: Part 2: Progression-free Survival (PFS)
timeFrame: Up to approximately 29 months
measure: Part 2: Disease Control Rate (DCR)
timeFrame: Up to approximately 29 months
measure: Parts 1 and 2: Area Under the Plasma Concentration-time Curve (AUC) of VVD-159642 as a Single Agent and in Combination With Sotorasib and Trametinib
timeFrame: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)
measure: Parts 1 and 2: Maximum Plasma Concentration (Cmax) of VVD-159642 as a Single Agent and in Combination With Sotorasib and Trametinib
timeFrame: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)
measure: Parts 1 and 2: Half-life (t1/2) of VVD-159642 as a Single Agent and in Combination With Sotorasib and Trametinib
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: Grand Rapids
country: United States
facility: START Mid West
state: Michigan
city: Austin
country: United States
facility: NEXT Austin
state: Texas
city: Irving
country: United States
facility: NEXT Dallas
state: Texas
city: San Antonio
country: United States
facility: START San Antonio
state: Texas
city: San Antonio
country: United States
facility: NEXT San Antonio
state: Texas
city: Ogden
country: United States
facility: START Mountain
state: Utah
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Adelaide
country: Australia
facility: Clinical Research South Australia (CRSA)
state: South Australia
city: Nedlands
country: Australia
facility: Linear Clinical
state: Western Australia
Study officials:
References: