VIC-1911 Monotherapy in Combination With Sotorasib for the Treatment of KRAS G12C-Mutant Non-Small Cell Lung Cancer

NCT05374538 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: VIC-1911-01
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 5

Brief Summary

This is a Phase 1a/1b study of aurora kinase A inhibitor VIC-1911 administered as monotherapy and in combination with sotorasib for the treatment of locally advanced or metastatic KRAS G12C-mutant non-small cell lung cancer(NSCLC).

Conditions

Non-small Cell Lung Cancer

Keywords

KRAS G12C mutation; AURA kinase; VIC-1911; KRAS G12C; sotorasib

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)

  Safety and tolerability assessed by adverse events(AEs) and serious adverse events (SAEs)

  9 months

Secondary Outcomes (6)

• Objective Response Rate

  Assessed at the end of Cycle 2 and every 2 cycles thereafter up to 8 months. Each cycle is 28 days.

• Duration of Response

  Assessed at the end of Cycle 2 and every 2 cycles thereafter up to 8 months. Each cycle is 28 days.

• Time to Response

  Assessed at the end of Cycle 2 and every 2 cycles thereafter up to 8 months. Each cycle is 28 days.

• Disease Control Rate

  Assessed at the end of Cycle 2 and every 2 cycles thereafter up to 8 months. Each cycle is 28 days.

• Progression-Free Survival

  Assessed from the date of the first dose of study drug to the first evidence of disease progression or death, whichever is earlier, assessed up to 9 months

Other Outcomes (4)

• Mean Plasma Concentrations of VIC-1911 Alone and in Combination With Sotorasib

  Was to be assessed C1D1; C1D15; C2D1; C4D1; C6D1 (each cycle is 28 days). The study terminated early with only 3 subjects analyzed C1D1 and 2 subjects analyzed C1D15.

• Circulating Tumor DNA (ctDNA) in Plasma (Pharmacodynamic Endpoint)

  Cycle 1 Day 1 pre-dose and at progression of disease

• Tumor Biopsies for Biomarker Assessment (Pharmacodynamic Endpoint)

  Pre-study, Cycle 3 Day 1, and at progression of disease

Study Arms (5)

Dose Escalation Phase, Cohort 1a: VIC-1911 monotherapy

EXPERIMENTAL

Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC refractory to or relapsed on prior KRASG12C inhibitor therapy will receive VIC-1911 monotherapy.

Drug: VIC-1911

Dose Escalation Phase, Cohort 1b: VIC-1911 plus sotorasib combination therapy

EXPERIMENTAL

Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC refractory to or relapsed on prior KRASG12C inhibitor therapy or are naive to KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy. Only Dose Level 1 was opened and all 3 subjects received sotorasib 960 mg QD PO, VIC-1911 75 mg BID PO.

Drug: VIC-1911; Drug: sotorasib

Expansion Phase, Cohort 2a: VIC-1911 monotherapy

EXPERIMENTAL

Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC refractory to or relapsed on prior KRASG12C inhibitor therapy will receive VIC-1911 monotherapy.

Drug: VIC-1911

Expansion Phase, Cohort 2b: VIC-1911 plus sotorasib combination therapy

EXPERIMENTAL

Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC refractory to or relapsed on prior KRASG12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy.

Drug: VIC-1911; Drug: sotorasib

Expansion Phase, Cohort 2c: VIC-1911 plus sotorasib combination therapy

EXPERIMENTAL

Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC naive to KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy.

Drug: VIC-1911; Drug: sotorasib

Interventions

VIC-1911 DRUG

VIC-1911 tablets for oral administration

Dose Escalation Phase, Cohort 1a: VIC-1911 monotherapy; Dose Escalation Phase, Cohort 1b: VIC-1911 plus sotorasib combination therapy; Expansion Phase, Cohort 2a: VIC-1911 monotherapy; Expansion Phase, Cohort 2b: VIC-1911 plus sotorasib combination therapy; Expansion Phase, Cohort 2c: VIC-1911 plus sotorasib combination therapy

sotorasib DRUG

Sotorasib tablets for oral administration

Also known as: LUMAKRAS

Dose Escalation Phase, Cohort 1b: VIC-1911 plus sotorasib combination therapy; Expansion Phase, Cohort 2b: VIC-1911 plus sotorasib combination therapy; Expansion Phase, Cohort 2c: VIC-1911 plus sotorasib combination therapy

Eligibility Criteria

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

You may qualify if:

• Males and females ≥ 18 years of age
• Have locally advanced or metastatic histologically or cytologically confirmed NSCLC, KRAS G12C-mutated
• The presence of a KRAS G12C mutation should be established prior to entry as assessed in a CLIA qualified laboratory. Testing may be done on tumor tissue (archival or fresh) or on ctDNA from blood.
• Have received at least 1 prior line of cancer therapy with a PD-1 or PD-L1 inhibitor with or without platinum-based chemotherapy (unless subject is not eligible or refuses chemotherapy or PD-1/PD-L1 therapy and have documented progression on all prior cancer therapies
• Dose Escalation Phase:
• Cohort 1a: (VIC-1911 monotherapy): Locally advanced or metastatic NSCLC refractory to or relapsed on at least 1 prior cancer therapy as noted above, and relapsed/refractory on KRAS G12C inhibitor therapy as the most recent cancer therapy prior to study
• Cohort 1b: (VIC-1911 plus sotorasib): Locally advanced or metastatic NSCLC:
• Refractory to or relapsed on at least 1 prior cancer therapy as noted above, and relapsed/refractory on KRAS G12C inhibitor therapy as the most recent cancer therapy prior to study, or
• Refractory to or relapsed on at least 1 prior cancer therapy as noted above, and Naïve to KRAS G12C inhibitor therapy
• Expansion Phase 1b:
• Cohort 2a: (VIC-1911 monotherapy): Locally advanced or metastatic NSCLC refractory to or relapsed on at least 1 prior cancer therapy as noted above, and relapsed/refractory on KRAS G12C inhibitor therapy as the most recent cancer therapy prior to study
• Cohort 2b: (VIC-1911 plus sotorasib): Locally advanced or metastatic NSCLC refractory to or relapsed on at least 1 prior cancer therapy as noted above, and relapsed/refractory on KRAS G12C inhibitor therapy as the most recent cancer therapy prior to study
• Cohort 2c: (VIC-1911 plus sotorasib): Locally advanced or metastatic NSCLC refractory to or relapsed on at least 1 prior cancer therapy as noted above, and naïve to KRAS G12C inhibitor therapy
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2

You may not qualify if:

• Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV
• QT interval corrected for rate (QTc) \> 480 msec on the ECG obtained at Screening using Fridericia method for QTc calculation
• Medications that are inhibitors or inducers of UDP-glucuronosyltransferases (UGTs) are prohibited in the Dose Escalation Phase
• History of corneal epithelial cysts or other ocular events leading to blurred vision, or has medically relevant abnormalities identified on screening ophthalmologic examination
• Symptomatic pneumonitis/interstitial lung disease requiring medical intervention
• Symptomatic central nervous system metastasis
• Leptomeningeal carcinomatosis
• Inability to swallow oral medication
• Gastrointestinal conditions that could impair absorption or tolerance of study drugs
• Current hematologic malignancies
• Second, active primary solid tumor malignancy that, in the judgement of the Investigator or Sponsor Medical Monitor, may affect the interpretation of results, with the exception of carcinoma in situ of any origin, non-muscle invasive bladder cancer, and Gleason \< 3+3 prostate cancer
• Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment within the last week prior to study treatment
• Other active infection requiring IV antibiotic usage within the last week prior to study treatment
• Unable to tolerate marketed dose of KRAS G12C inhibitor on prior therapy for subjects to be enrolled in combination VIC-1911 plus sotorasib treatment cohorts. Alternatively, these subjects may be able to enroll in the VIC-1911 monotherapy treatment cohort, upon discussion with the Medical Monitor and Study Chair.
• Previous MEK or EGFR inhibitor therapy

Sponsors & Collaborators

• Vitrac Therapeutics, LLC: lead
• Westat: collaborator

Study Sites (5)

University of California Davis

Sacramento, California, 95817, United States

Location

Yale Cancer Center

North Haven, Connecticut, 06473, United States

Location

Emory University Winship Cancer Center

Atlanta, Georgia, 30322, United States

Location

University of Maryland Cancer Center

Baltimore, Maryland, 21201, United States

Location

New York University Langone Health Perlmutter Cancer Cancer

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

sotorasib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

The study was terminated early due to subsequent approval of additional KRAS G12C inhibitor therapies since this study was initiated, providing clinicians with more choices for treatment of subjects with KRAS G12C-mutant NSCLC. Thus, no formal efficacy analyses, and no pharmacodynamic determinations, were performed.

Results Point of Contact

• Title: Linda Paradiso, DVM, Chief Development Officer
• Organization: VITRAC Therapeutics, LLC

linda.paradiso@vitractherapeutics.com

713-898-8965

Study Officials

• Sarah Goldberg, MD, MPH

  Yale Cancer Center, Yale University

  STUDY CHAIR

• Linda J Paradiso, DVM

  Vitrac Therapeutics, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Model Details: Dose Escalation Phase followed by Expansion Phase. A total of 24 subjects are anticipated in Dose Escalation Phase, Cohort 1a. A total of 12 subjects are anticipated in Dose Escalation Phase, Cohort 1b. A total of 29 subjects are anticipated in Expansion Phase, Cohort 2a. A total of 29 subjects are anticipated in Expansion Phase, Cohort 2b. A total of 46 subjects are anticipated in Expansion Phase, Cohort 2c.

Study Record Dates

• First Submitted: May 10, 2022
• First Posted: May 16, 2022
• Study Start: November 9, 2022
• Primary Completion: August 26, 2023
• Study Completion: August 26, 2023
• Last Updated: May 1, 2025
• Results First Posted: May 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)