A Phase 1 and 2 Study of VMD-102 in Hepatocellular Carcinoma and Other Solid Tumors

NCT07636785 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: VMD-01C
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to evaluate the safety and tolerability to determine (i) the recommended Phase 2 dose (RP2D) of VMD-102 (Phase 1), and (ii) preliminary anti-tumor efficacy (Phase 2), in participants with advanced HCC, metastatic uveal melanoma (MUM), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). The pharmacokinetics (PK), preliminary anti-tumor activity, and potential biomarkers of VMD-102 will also be assessed. VMD-102 will be the first selective PKC epsilon (PKCε or PKCe) kinase inhibitor to enter human clinical testing. Preclinical VMD-102 anti-tumor activities in mouse liver/HCC tumor models and preclinical toxicology and pharmacology studies support this study.

Conditions

Metastatic Uveal Melanoma; Renal Cell Carcinoma (RCC); Colorectal Cancer (CRC); Nonsmall Cell Lung Cancer; Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (3)

• Number and severity of treatment-emergent adverse events (TEAE) (Phase 1)

  TEAE

  First cycle (21 days per cycle)

• To determine the recommended Phase 2 dose (RP2D) for VMD-102 (Phase 1)

  RP2D

  First cycle (21 days per cycle)

• Progression-Free Survival (PFS) (Phase 2)

  Defined as the time from enrollment to tumor progression or death from any cause.

  Up to 18 months

Secondary Outcomes (7)

• Area under the plasma concentration versus time curve (AUC) of VMD-102

  On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)

• Peak plasma concentration (Cmax) of VMD-102

  On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)

• Incidence of Dose Limiting Toxicities

  During the Cycle 1 (each cycle is 21 days)

• Objective Response Rate (ORR)

  Up to 18 months

• Disease Control Rate (DCR)

  Up to 18 months

Study Arms (1)

Phase 1 and Phase 2

EXPERIMENTAL

Phase 1: The dose escalation will evaluate escalating dose levels of VMD-102 in approximately 25 participants. This phase will assess the safety, pharmacokinetics and tolerability of VMD-102 during cycle 1 (of 21-day cycle) with participants of advanced HCC, MUM, RCC, NSCLC, and CRC to determine the maximum tolerated dose (MTD) and the RP2D. Retrospective biomarker studies for the preclinical identified biomarkers may be carried out from tumor tissue and blood samples collected from participants. Phase 2: The Phase 2 dose expansion will employ a Bayesian Optimal Phase II (BOP2) design to enroll participants to assess the anti-tumor activity and safety of VMD-102 in Cohort 1 (approximately 43) participants with HCC, and Cohort 2 (approximately 43) participants with MUM, RCC, NSCLC and CRC. A biomarker guided enrollment criterion may be added via amendment. For each of two cohorts, once RP2D is determined, the Phase 2 expansion may be opened in both cohorts parallelly.

Drug: VMD-102

Interventions

VMD-102 DRUG

A small organic molecule oral drug in the tablet form

Also known as: Single agent

Phase 1 and Phase 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytological or radiological diagnosis of advanced (unresectable and/or metastatic) HCC, MUM, RCC, NSCLC and CRC that is not responsive to standard of care (SOC), had progressed following SOC, is intolerant to SOC, or for whom the SOC is not considered appropriate by the investigator.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0, or 1.
• Has at least one measurable target lesion according to RECIST v1.1 \[Response Evaluation Criteria In Solid Tumors\], or mRECIST \[modified RECIST\] for unresectable HCC participants, and either (a). has not been previously treated with local therapy (e.g., radiation therapy, hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy), or (b). if the target lesion was within the field of local therapy, the lesion has shown an increase in size of 25% or greater following local therapy.
• Adequate organ function evidenced by:
• Hematology
• Hemoglobin ≥ 9 g/dL (SI Units: 90 g/L) (post-transfusion if transfusion-dependent)
• Platelet count ≥ 60000/mm3 (60 x109/L) without support(transfusion) within 7 days of testing
• Absolute neutrophil count (ANC) ≥ 1500/mm3 (1.5x109/L) Chemistry
• Total bilirubin (TBIL) ≤ 2.0 x upper limit of normal (ULN). (For participants with Gilbert's syndrome, TBIL ≤3.0 x ULN provided that direct bilirubin DBIL) is \<30% of the TBIL)
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 1 ≤ 5 x U LN (participants with advanced HCC or liver metastases)
• AST and/or ALT 1 ≤ 3 x ULN (participants without known liver disease or liver metastases)
• Calculated creatinine clearance or 24h urine creatinine clearance ≥50 mL/min using Cockroft-Gault formula.
• Serum creatinine ≤ 1.5x ULN
• Coagulation (unless taking an anti-coagulant):
• Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (except for participants receiving therapeutic anticoagulants)

You may not qualify if:

• Received anticancer therapy with radiation, immunotherapy, a biologic, surgery and/or tumor embolization within the past 2 weeks or 5 half-lives (whichever is longer).
• Currently pregnant, nursing, or planning to become pregnant during the course of study.
• The Fridericia Corrected QT (QTcF) interval ≥ 480 msec.
• Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system (Section 14.8); or presence of clinically significant and uncontrolled cardiac disease, as assessed by the investigator. Such as but not limited to: symptomatic congestive heart failure, unstable angina, cardiac arrhythmia.
• Unstable or uncompensated respiratory, hepatic, renal, or cardiac disease that would compromise the participant's safety or interfere with assessment of the drug.
• Psychological, familial, sociological, geographical or other concurrent conditions that would interfere with safety evaluation, limit the participant's ability to follow the procedures in the protocol or otherwise jeopardize compliance with the protocol. Participants with uncontrolled major depression, bipolar disorder, or severe anxiety disorder are excluded.
• Participants have multiple factors that affect their oral medication (such as inability to swallow and intestinal obstruction or resection).
• Participants have long-term unhealed wounds or fractures.
• Participants have uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage.
• Any current medical conditions, including impairment of GI function or GI disease, which would alter the absorption, distribution, metabolism or excretion of VMD-102 including but not limited to:
• Severe uncontrolled nausea or vomiting.
• Severe uncontrolled diarrhea or ongoing active diarrhea requires medications (e.g. bile acid sequestrant, loperamide).
• A history of short bowel syndrome; irritable bowel syndrome with diarrheal signs/symptoms or require medications.
• Clinically diagnosed malabsorption secondary to bowel resection.
• Active Ulcerative colitis or Crohn's disease requiring medication for control.

Sponsors & Collaborators

• VM Discovery, Inc.: lead

Study Sites (1)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Uveal Melanoma; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms

Interventions

Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Clinical Development

  VM Discovery, Inc.

  STUDY CHAIR

Central Study Contacts

Jay Wu, PhD

CONTACT

+1-510-661-6770 ext. 101; OM@VMDiscovery.com

Study Design

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

Study Record Dates

• First Submitted: May 4, 2026
• First Posted: June 9, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): December 1, 2031
• Last Updated: June 9, 2026

Record last verified: 2026-06

Locations

US (1)