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

Vividion Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: Sotorasib; Drug: VVD-159642; Drug: Trametinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06804824

VVD-159642-01

Details and patient eligibility

About

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.

Enrollment: 220 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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220 participants in 4 patient groups

Part 1: Dose Escalation: VVD-159642 Single Agent

Experimental group

Description:

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

Treatment:

Drug: VVD-159642

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

Experimental group

Description:

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

Treatment:

Drug: VVD-159642

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

Experimental group

Description:

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

Treatment:

Drug: VVD-159642

Drug: Sotorasib

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

Experimental group

Description:

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

Treatment:

Drug: Trametinib

Drug: VVD-159642