A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-159642 in Participants With Advanced Solid Tumors

NCT06804824 | Recruiting Phase 1 FDA Drug

• 1 other identifier: VVD-159642-01
• Study Type: interventional
• Target: 220
• Locations: 2 countries
• Sites: 9

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.

Conditions

Advanced Solid Tumors

Keywords

RAS; PI3K; KRAS; MEK; Phase I; solid tumors; KRAS G12C; HER2

Outcome Measures

Primary Outcomes (4)

• Part 1: Incidence and Severity of Dose-limiting Toxicities (DLTs)

  From Day 1 to Day 21 of Cycle 1 [cycle length=21 days]

• Part 2: Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to approximately 29 months

• Part 2: Incidence and Severity of Clinically Significant Changes in Vital Signs

  Up to approximately 29 months

• Part 2: Incidence and Severity of Clinically Significant Changes in Laboratory Evaluations

  Up to approximately 29 months

Secondary Outcomes (9)

• Part 1: Recommended Dose for Expansion (RDE) of VVD-159642 as a Single Agent

  Up to approximately 29 months

• Part 2: Recommended Phase 2 Dose (RP2D) of VVD-159642 as a Single Agent and in Combination with Sotorasib and Trametinib

  Up to approximately 29 months

• Part 2: Overall Response Rate (ORR)

  Up to approximately 29 months

• Part 2: Duration of Response (DoR)

  Up to approximately 29 months

• Part 2: Progression-free Survival (PFS)

  Up to approximately 29 months

Study Arms (4)

Part 1: Dose Escalation: VVD-159642 Single Agent

EXPERIMENTAL

Participants will receive ascending doses of VVD-159642, orally, daily in 21-day treatment cycles during Part 1.

Drug: VVD-159642

Part 2: Dose Expansion (Cohort A): VVD-159642 Single Agent

EXPERIMENTAL

Participants will receive VVD-159642 at the recommended dose for expansion (RDE), orally, daily in 21-day treatment cycles during Part 2.

Drug: VVD-159642

Part 2: Dose Expansion (Cohort B): VVD-159642 + Sotorasib

EXPERIMENTAL

Participants will receive VVD-159642 at RDE orally, daily in combination with sotorasib, in 21-day treatment cycles after a safety run-in.

Drug: VVD-159642; Drug: Sotorasib

Part 2: Dose Expansion (Cohort C): VVD-159642 + Trametinib

EXPERIMENTAL

Participants will receive VVD-159642 at RDE orally, daily in combination with trametinib, in 21-day treatment cycles after a safety run-in.

Drug: VVD-159642; Drug: Trametinib

Interventions

VVD-159642 DRUG

Oral capsules

Part 1: Dose Escalation: VVD-159642 Single Agent; Part 2: Dose Expansion (Cohort A): VVD-159642 Single Agent; Part 2: Dose Expansion (Cohort B): VVD-159642 + Sotorasib; Part 2: Dose Expansion (Cohort C): VVD-159642 + Trametinib

Sotorasib DRUG

Oral tablets

Part 2: Dose Expansion (Cohort B): VVD-159642 + Sotorasib

Trametinib DRUG

Oral tablets

Part 2: Dose Expansion (Cohort C): VVD-159642 + Trametinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Vividion Therapeutics, Inc.: lead

Study Sites (9)

START Mid West

Grand Rapids, Michigan, 49546, United States

RECRUITING

NEXT Austin

Austin, Texas, 78758, United States

RECRUITING

NEXT Dallas

Irving, Texas, 75039, United States

RECRUITING

START San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

NEXT San Antonio

San Antonio, Texas, 78299, United States

RECRUITING

START Mountain

Ogden, Utah, 84401, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Clinical Research South Australia (CRSA)

Adelaide, South Australia, 5000, Australia

RECRUITING

Linear Clinical

Nedlands, Western Australia, 6009, Australia

RECRUITING

MeSH Terms

Interventions

sotorasib; trametinib

Central Study Contacts

Vividion Clinical Trial Call Center

CONTACT

858-345-9752; clinicaltrials@vividion.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2025
• First Posted: February 3, 2025
• Study Start: February 25, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); AU (2)