Phase 1 Study of Tipifarnib and Osimertinib in EGFR-mutated Non-Small Cell Lung Cancer
The purpose of this study is to measure safety and tolerability and preliminary efficacy with the combination of tipifarnib with osimertinib in patients with advanced/metastatic EGFR-mutated NSCLC.
- Age ≥ 18 years at the time of signing informed consent.
- Histologically or cytologically confirmed stage IIIB (locally advanced) or IV (metastatic) adenocarcinoma of the lung (e.g., this may occur as systemic recurrence after prior surgery for early-stage disease or patients may be newly diagnosed with stage IIIB/IV disease). Patients with mixed histology are eligible if adenocarcinoma is predominant histology.
- The tumor harbors (based on tumor tissue or plasma [ctDNA] assessment) one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, Ex21-L858R substitution) either alone or in combination with other EGFR mutations, as determined by an FDA-approved test by a Clinical Laboratory Improvement Amendments (CLIA)-certified (US sites) or an accredited (outside the US) local laboratory.
- Treatment naïve for locally advanced/metastatic EGFR mutated NSCLC and osimertinib treatment naïve for NSCLC. Patients in both Phase 1a and 1b who are osimertinib naïve for NSCLC must be eligible for treatment with osimertinib as determined by the participating study center.
- ECOG performance score of 0 or 1 with no clinically significant deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks (Appendix 6) (Oken 1982).
- Measurable disease by RECIST v1.1 (Appendix 5) that meets the criteria for selection as a target lesion according to RECIST v1.1. The presence of at least one measurable target lesion per RECIST v1.1 must be confirmed by local radiology prior to patient entry.
- Adequate organ function, as evidenced by the following laboratory results:
- Absolute neutrophil count (ANC) > 1500 cells/mm3
- Platelet count > 75,000 cells/mm3
- Hemoglobin > 8.0 g/dL
- Patients are allowed to receive transfused red blood cell (RBC) to achieve this level.
- Total bilirubin ≤ 1.5 × upper limit of normal (ULN), except in patients with previously documented Gilbert’s syndrome, in which case the direct bilirubin should be less than or equal to the ULN
- AST (serum glutamic oxaloacetic transaminase [SGOT]) and ALT (serum glutamic pyruvic transaminase [SGPT]) ≤ 1.5 × ULN
- Alkaline phosphatase ≤ 2.5 × ULN, Alkaline phosphatase < 5×ULN for patients with hepatic and/or bone metastases
- Acceptable renal function with a calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formulas
- The patient must meet/continue to meet these criteria at the time of first dosing, as confirmed by review of analysis performed within 72 hours of C1D1.
- Capable, according to the Investigator, of complying with the study’s requirements and restrictions.
- Female patients of child-bearing potential and male patients with female partners of child-bearing potential must follow protocol-specified guidance for avoiding pregnancy (Appendix 3) while on treatment and for at least 42 days (for females) and 4 months (for males), respectively after last dose of study drug (tipifarnib and/or osimertinib). Female patients must have a negative serum pregnancy test within 72 hours prior to start of study intervention.
- No breast feeding at any time during the study.