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

• Status: Not yet recruiting
• Trial end date: 2025-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1 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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vitrac Therapeutics, LLC
• Collaborator: Westat

Criteria

Inclusion Criteria:

1. Males and females ≥ 18 years of age

2. Have locally advanced or metastatic histologically or cytologically confirmed NSCLC, KRAS G12C-mutated

3. 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.

4. 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

5. 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

• Naïve to KRAS G12C inhibitor therapy

6. Expansion Phase:

• 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

7. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

8. Have discontinued previous treatments for cancer, except for sotorasib for subjects to receive VIC-1911 plus sotorasib combination treatment, and have resolution, except where otherwise stated in the inclusion criteria, of all clinically significant toxic effects of prior cancer treatment, surgery, or radiotherapy to Grade ≤ 1

9. Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2

10. Life expectancy of ≥ 3 months

11. Subjects with asymptomatic stable, brain metastases following prior local therapy (e.g., stereotactic radiosurgery [SRS], stereotactic body radiation therapy [SBRT], or surgery) are allowed

12. Adequate hematologic without ongoing transfusion support:

• Hemoglobin (Hb) ≥ 8 g/dL

• Absolute neutrophil count (ANC) ≥ 1.0 x 10^9 cells/L

• Platelets ≥ 75 x 10^9 cells/L

13. Adequate renal and hepatic function:

• Creatinine ≤ 1.5 times the upper limit of normal (ULN), or calculated creatinine clearance ≥ 50 mL/minute x 1.73 m2 per the Cockcroft-Gault formula

• Total bilirubin ≤ 1.5 times the ULN, unless due to Gilbert's disease, or < 3 times the ULN for subjects with liver metastases

• ALT/AST ≤ 2 times the ULN, or < 3 times the ULN for subjects with liver metastases

14. Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women of child-bearing potential (WCBP). Sexually active WCBP and male subjects must agree to use adequate methods to avoid pregnancy throughout the study and for 28 days after the completion of study treatment.

Exclusion Criteria:

1. 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

2. History of corneal epithelial cysts or other ocular events leading to blurred vision, or has medically relevant abnormalities identified on screening ophthalmologic examination

3. Symptomatic pneumonitis/interstitial lung disease requiring medical intervention

4. Symptomatic central nervous system metastasis

5. Leptomeningeal carcinomatosis

6. Inability to swallow oral medication

7. Gastrointestinal conditions that could impair absorption or tolerance of study drugs

8. Current hematologic malignancies

9. 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

10. 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

11. Other active infection requiring IV antibiotic usage within the last week prior to study treatment

12. 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.

13. Previous MEK or EGFR inhibitor therapy

14. Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results

15. Receipt of an investigational product on a clinical trial within 5 elimination half-lives or within 28 days, whichever is shorter, prior to C1D1 on this study, or currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study

16. Previously completed or withdrawn from any other study investigating an aurora kinase A inhibitor

17. Known hypersensitivity to VIC-1911 or its components

18. If female, pregnant, breast-feeding, or planning to become pregnant