Clinical trial NCT05693090: Tipifarnib and Osimertinib in EGFR-mutated Non-Small Cell Lung Cancer
Official title: Phase 1 Study of Tipifarnib and Osimertinib in EGFR-mutated Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: NSCLC
Keywords: EGFR
Tipifarnib
Osimertinib
NSCLC locally advanced
NSCLC metastatic
Lead sponsor: Kura Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1a/b, multicenter, open-label, dose escalation (1a) and dose expansion (1b) study. The purpose of this study is to measure safety, tolerability, and preliminary efficacy with the combination of tipifarnib with osimertinib in patients with advanced/metastatic EGFR-mutated non-small cell lung cancer.


Eligibility criteria: Inclusion Criteria:

* 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.
* The tumor harbors an Ex19del or Ex21-L858R substitution (based on tumor tissue or plasma \[ctDNA\] assessment).
* Treatment-naïve for locally advanced/metastatic EGFR-mutated NSCLC and osimertinib treatment-naïve for NSCLC.
* 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.
* Measurable disease by RECIST v1.1 that meets the criteria for selection as a target lesion according to RECIST v1.1.
* Adequate organ function, as evidenced by the laboratory results.
* Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

* Treatment with any of the following:

  1. Major surgery
  2. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
  3. Medications or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4 or uridine 5'-diphospho (UDP)-glucuronosyltransferase (UGT), or inhibitors of breast cancer resistance protein (BCRP).
  4. Investigational therapy within 2 weeks of Cycle 1 Day 1
  5. Concurrent and/or other active malignancy that has required systemic treatment within 2 years of first dose of study drug (excluding non-melanoma skin cancer, adjuvant hormonal therapy for breast cancer and hormonal treatment for castration-sensitive prostate cancer)
* Spinal cord compression or symptomatic and unstable brain metastases requiring steroids over the last 4 weeks prior.
* Evidence of severe or uncontrolled systemic diseases.
* Refractory nausea and vomiting, chronic gastrointestinal (GI) diseases, inability to swallow the formulated product, or previous significant bowel resection.
* Clinically significant cardiovascular symptoms or disease.
* Received treatment for unstable angina within prior year, myocardial infarction within the prior 6 months, cerebro-vascular attack within the prior year, history of New York Heart Association grade III or greater congestive heart failure, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
* Past medical history of Interstitial Lung Disease (ILD), drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
* Other protocol-defined exclusion criteria may apply.

Primary outcomes:
measure: For Dose Escalation determine a safe and tolerable Phase 2 dose of tipifarnib when used in combination with osimertinib
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: For Dose Escalation characterize the safety of the combination DLTs will be listed for patients who complete the evaluation period for DLT
timeFrame: DLTs will be evaluated at the end of cycle 1 (28 days), but also through study completion, an average of 1.5 years
measure: For Dose Expansion characterize the safety profile of tipifarnib in combination with osimertinib as per NCI CTCAE v5.0 using descriptive statistics of adverse events
timeFrame: Through study completion, an average of 2 years
measure: For Dose Expansion characterize the safety profile of tipifarnib in combination with osimertinib as per NCI CTCAE v5.0 using the percentage of patients who discontinue the combination for related adverse events
timeFrame: First 6 cycles of treatment (28 day treatment cycle)
Secondary outcomes:
measure: To evaluate the efficacy of tipifarnib in combination with osimertinib
timeFrame: Assessed every 8 weeks for the first year and every 12 weeks thereafter up to end of study at approximately 2 years
measure: To evaluate the efficacy of tipifarnib in combination with osimertinib
timeFrame: Assessed every 8 weeks for the first year and every 12 weeks thereafter up to end of study at approximately 2 years
measure: To evaluate the efficacy of tipifarnib in combination with osimertinib
timeFrame: Assessed every 8 weeks for the first year and every 12 weeks thereafter up to end of study at approximately 2 years
measure: To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination
timeFrame: Cycles 1-6 (28 day treatment cycle)
measure: To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination
timeFrame: Cycles 1-6 (28 day treatment cycle)
measure: To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination
timeFrame: Cycles 1-6 (28 day treatment cycle)
measure: To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination
timeFrame: Cycles 1-6 (28 day treatment cycle)
measure: To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination
timeFrame: Cycles 1-6 (28 day treatment cycle)
measure: To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination
timeFrame: Cycles 1-6 (28 day treatment cycle)
measure: To evaluate circulating tumor DNA (ctDNA) as an indicator or response in both ctDNA positive and negative patients by changes in genetic alterations
timeFrame: Monthly for duration of trial participation (an average of 2 years)
measure: To evaluate circulating tumor DNA (ctDNA) clearance rates for patients positive at baseline
timeFrame: Monthly for duration of trial participation (an average of 2 years)
measure: To evaluate circulating tumor DNA (ctDNA) time to detection changes associated with disease progression
timeFrame: Monthly for duration of trial participation (an average of 2 years)
Other outcomes:
Locations:
city: Santa Rosa
country: United States
facility: Providence Medical Group
state: California
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
Study officials:
References: