Status:

TERMINATED

Tarlox and Sotorasib in Patients With KRAS G12C Mutations

Lead Sponsor:

Medical University of South Carolina

Collaborating Sponsors:

Rain Oncology Inc

Conditions:

Non-Small Cell Lung Cancer

Eligibility:

All Genders

18+ years

Phase:

PHASE1

PHASE2

Brief Summary

This is a Phase IB dose expansion trial with safety lead-in evaluating the safety, clinical activity/efficacy of the combination of tarloxotinib and sotorasib in patients with KRAS G12C mutation who h...

Detailed Description

KRAS acts as a key protein in transducing signals from cell surface receptors, such as receptor tyrosine kinases (RTKs) into cells to initiate a network of cytoplasmic and nuclear signaling cascades t...

Eligibility Criteria

Inclusion

  • Histologically confirmed diagnosis of squamous or non-squamous NSCLC with KRAS G12C mutation
  • Unresectable or metastatic disease
  • No available treatment with curative intent
  • Must have previously received treatment with at least a platinum-containing chemotherapy regimen
  • Must have previously received at least one month trial of sotorasib or a therapy targeting KRAS G12C mutation with documented progression. If sotorasib dose from prior therapy was reduced for toxicity, patients that meet the above criteria are expected to receive study treatment at the reduced dose.
  • Must have measurable or evaluable disease as defined by RECIST 1.1
  • Age \>18 years
  • Life expectancy of at least 3 months
  • Recovery from adverse effect of prior therapy at the time of enrollment
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Laboratory values within the screening period:
  • Absolute neutrophile count \> 1000/mm3
  • Platelet count \> 100,000 /mm3
  • Hemoglobin \> 8 in the absence of transfusions for at least 2 weeks
  • Total bilirubin \< 1.5 x upper limit of normal (or \< 3 x ULN if associated with liver metastases or Gilbert's disease)
  • Aspartate transaminase (AST) or alanine transaminase (ALT) \< 3 x ULN (or \< 5x ULN if associated with liver metastases
  • Creatinine clearance (CrCl) \> 60 mL/min
  • Women of child-bearing potential agrees to use contraception while participating in the study and for a period of 6 months following termination of study treatment
  • Completed informed consent process
  • Willing to comply with clinical trial instructions and requirements.

Exclusion

  • Active brain metastases. Patients are eligible if brain metastases are asymptomatic measuring no more than 2.0 cm each and confined to the cerebral hemispheres if neurologically stable and must be on a stable or tapering dose of corticosteroids for at least 2 weeks prior to C1D1.
  • History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow pills
  • Congestive heart failure \> NYHA Class 3
  • QTc \> 480 milliseconds or family history of Long QT syndrome
  • Ongoing need for a medication with a known risk of Torsades de Pointes that cannot be switched to alternative treatment prior to study entry.
  • Pregnancy or breast feeding
  • Has known activating oncogene-driver mutations, including but not limited to KRAS, ALK, ROS1, RET, BRAF, NTRK1/2/3, MET, EGFR
  • Previously have received anti-EGFR or anti-HER2 TKIs
  • Previously have received anti-EGFR or anti-HER2 monoclonal antibodies
  • Clinically active or symptomatic interstitial lung disease
  • AST and ALT\>3xULN if no hepatic metastases are present; \>5xULN if hepatic metastases are present; total bilirubin \>1.5xULN; 3xULN with direct bilirubin \>1.5 x ULN in the presence of Gilbert's syndrome
  • Known concurrently malignancy that is expected to require active treatment within 2 years or may interfere with the interpretation of the efficacy and safety outcomes of this study.
  • Infection requiring systemic treatment within 7 days prior to cycle 1 day1.

Key Trial Info

Start Date :

March 7 2022

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

December 31 2023

Estimated Enrollment :

5 Patients enrolled

Trial Details

Trial ID

NCT05313009

Start Date

March 7 2022

End Date

December 31 2023

Last Update

December 16 2025

Active Locations (1)

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Page 1 of 1 (1 locations)

1

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States, 29425