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

NCT05693090 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: KO-TIP-015
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

NSCLC

Keywords

EGFR; Tipifarnib; Osimertinib; NSCLC locally advanced; NSCLC metastatic

Outcome Measures

Primary Outcomes (4)

• 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)

• 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

• 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

• 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 Outcomes (12)

• To evaluate the efficacy of tipifarnib in combination with osimertinib

  Assessed every 8 weeks for the first year and every 12 weeks thereafter up to end of study at approximately 2 years

• To evaluate the efficacy of tipifarnib in combination with osimertinib

  Assessed every 8 weeks for the first year and every 12 weeks thereafter up to end of study at approximately 2 years

• To evaluate the efficacy of tipifarnib in combination with osimertinib

  Assessed every 8 weeks for the first year and every 12 weeks thereafter up to end of study at approximately 2 years

• To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination

  Cycles 1-6 (28 day treatment cycle)

• To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination

  Cycles 1-6 (28 day treatment cycle)

Study Arms (2)

Escalation Cohort

EXPERIMENTAL

Adult participants with EGFR-mutated Non-Small Cell Lung Cancer

Drug: Tipifarnib; Drug: Osimertinib

Expansion Cohort

EXPERIMENTAL

Adult participants with EGFR-mutated Non-Small Cell Lung Cancer

Drug: Tipifarnib; Drug: Osimertinib

Interventions

Tipifarnib DRUG

Oral administration

Escalation Cohort; Expansion Cohort

Osimertinib DRUG

Oral administration

Escalation Cohort; Expansion Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Treatment with any of the following:
• Major surgery
• 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
• 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).
• Investigational therapy within 2 weeks of Cycle 1 Day 1
• 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.

Sponsors & Collaborators

• Kura Oncology, Inc.: lead

Study Sites (2)

Providence Medical Group

Santa Rosa, California, 95403, United States

Location

The Valley Hospital

Ridgewood, New Jersey, 07450, United States

Location

MeSH Terms

Interventions

tipifarnib; osimertinib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: January 20, 2023
• Study Start: February 1, 2023
• Primary Completion (Estimated): July 27, 2027
• Study Completion (Estimated): July 27, 2027
• Last Updated: March 6, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)