Tipifarnib and Osimertinib in EGFR-mutated Non-Small Cell Lung Cancer

NSCLC Clinical Trial

Official title:

Phase 1 Study of Tipifarnib and Osimertinib in EGFR-mutated Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05693090
• Other study ID #: KO-TIP-015
• Status: Withdrawn
• Phase: Phase 1
• Start date: February 1, 2023
• Est. completion date: July 27, 2027

Study information

• Verified date: March 2023
• Source: Kura Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 27, 2027
• Est. primary completion date: July 27, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• NSCLC

Intervention

Drug:
• Tipifarnib
Oral administration
• Osimertinib
Oral administration

Locations

Country	Name	City	State
United States	The Valley Hospital	Ridgewood	New Jersey
United States	Providence Medical Group	Santa Rosa	California

Sponsors (1)

Lead Sponsor	Collaborator
Kura Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	For Dose Escalation determine a safe and tolerable Phase 2 dose of tipifarnib when used in combination with osimertinib	Occurrence of DLTs during first treatment cycle	At the end of Cycle 1 (each cycle is 28 days)
Primary	For Dose Escalation characterize the safety of the combination DLTs will be listed for patients who complete the evaluation period for DLT	Descriptive statistics of adverse events per NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0)	DLTs will be evaluated at the end of cycle 1 (28 days), but also through study completion, an average of 1.5 years
Primary	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	Descriptive statistics of adverse events per the NCI CTCAE v5.0	Through study completion, an average of 2 years
Primary	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	Percentage of patients who discontinue the combination for tipifarnib and/or osimertinib related adverse events prior to completing 6 cycles of treatment	First 6 cycles of treatment (28 day treatment cycle)
Secondary	To evaluate the efficacy of tipifarnib in combination with osimertinib	Objective Response Rate (ORR), measures evaluated according to RECIST v.1.1 assessed by investigator	Assessed every 8 weeks for the first year and every 12 weeks thereafter up to end of study at approximately 2 years
Secondary	To evaluate the efficacy of tipifarnib in combination with osimertinib	Duration of Response (DOR) assessed from (CR) or (PR) until (PD), initiation of new anticancer treatment or study withdrawal	Assessed every 8 weeks for the first year and every 12 weeks thereafter up to end of study at approximately 2 years
Secondary	To evaluate the efficacy of tipifarnib in combination with osimertinib	Progression-free survival (PFS) measures evaluated according to RECIST v.1.1 assessed by investigator	Assessed every 8 weeks for the first year and every 12 weeks thereafter up to end of study at approximately 2 years
Secondary	To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination	Area under the concentration-time curve (AUC) from time 0 to time of last concentration measured and from time 0 extrapolated to infinity	Cycles 1-6 (28 day treatment cycle)
Secondary	To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination	Maximum plasma concentration	Cycles 1-6 (28 day treatment cycle)
Secondary	To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination	Time to maximum observed concentration	Cycles 1-6 (28 day treatment cycle)
Secondary	To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination	Terminal elimination rate constant	Cycles 1-6 (28 day treatment cycle)
Secondary	To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination	Terminal half-life	Cycles 1-6 (28 day treatment cycle)
Secondary	To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination	Apparent clearance and apparent volume of distribution	Cycles 1-6 (28 day treatment cycle)
Secondary	To evaluate circulating tumor DNA (ctDNA) as an indicator or response in both ctDNA positive and negative patients by changes in genetic alterations	Determine prevalence of tumor-derived genetic alterations of ctDNA collected at baseline, on-treatment and at disease progression	Monthly for duration of trial participation (an average of 2 years)
Secondary	To evaluate circulating tumor DNA (ctDNA) clearance rates for patients positive at baseline	Clearance rates for patients who are ctDNA positive at baseline	Monthly for duration of trial participation (an average of 2 years)
Secondary	To evaluate circulating tumor DNA (ctDNA) time to detection changes associated with disease progression	Time to detection of ctDNA changes associated with disease progression	Monthly for duration of trial participation (an average of 2 years)