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NSCLCPhase 1NCT05693090

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

A Phase 1 study testing Tipifarnib and Osimertinib in people with NSCLC, run by Kura Oncology, Inc. at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
NSCLC
What is being tested?
Tipifarnib and Osimertinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited States
Study dates
1 Feb 2023to 27 Jul 2027
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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)
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  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • The Valley Hospital

    Ridgewood, New Jersey, 07450

  • Providence Medical Group

    Santa Rosa, California, 95403

Other trials in United States

About this study

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

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
Being tested
Tipifarnib, Osimertinib
Keywords
EGFR, Tipifarnib, Osimertinib, NSCLC locally advanced, NSCLC metastatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TipifarnibDrug

    Oral administration

  • OsimertinibDrug

    Oral administration

Study groups in NCT05693090
Study groupRoleWhat they receive
Escalation CohortExperimentalAdult participants with EGFR-mutated Non-Small Cell Lung Cancer
Receives: Drug: Tipifarnib; Drug: Osimertinib
Expansion CohortExperimentalAdult participants with EGFR-mutated Non-Small Cell Lung Cancer
Receives: Drug: Tipifarnib; Drug: Osimertinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  2. 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)

    Measured: DLTs will be evaluated at the end of cycle 1 (28 days), but also through study completion, an average of 1.5 years

  3. 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

    Measured: Through study completion, an average of 2 years

  4. 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

    Measured: First 6 cycles of treatment (28 day treatment cycle)

Secondary outcomes (12)

  1. 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

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

  2. 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

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

  3. 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

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

  4. 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

    Measured: Cycles 1-6 (28 day treatment cycle)

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

    Maximum plasma concentration

    Measured: Cycles 1-6 (28 day treatment cycle)

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

    Time to maximum observed concentration

    Measured: Cycles 1-6 (28 day treatment cycle)

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

    Terminal elimination rate constant

    Measured: Cycles 1-6 (28 day treatment cycle)

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

    Terminal half-life

    Measured: Cycles 1-6 (28 day treatment cycle)

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

    Apparent clearance and apparent volume of distribution

    Measured: Cycles 1-6 (28 day treatment cycle)

  10. 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

    Measured: Monthly for duration of trial participation (an average of 2 years)

  11. To evaluate circulating tumor DNA (ctDNA) clearance rates for patients positive at baseline

    Clearance rates for patients who are ctDNA positive at baseline

    Measured: Monthly for duration of trial participation (an average of 2 years)

  12. To evaluate circulating tumor DNA (ctDNA) time to detection changes associated with disease progression

    Time to detection of ctDNA changes associated with disease progression

    Measured: Monthly for duration of trial participation (an average of 2 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2023
  2. Study start1 Feb 2023 (estimated)
  3. Primary completion27 Jul 2027 (estimated)
  4. Study completion27 Jul 2027 (estimated)

Why it stopped: This study was withdrawn due to a strategic business decision; no patients were enrolled.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05693090
Sponsor's protocol ID
KO-TIP-015
Status last verified
Mar 2023
First submitted
12 Dec 2022
Last updated
6 Mar 2023
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tipifarnib and Osimertinib in people with NSCLC, run by Kura Oncology, Inc. at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 6 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

For Dose Escalation determine a safe and tolerable Phase 2 dose of tipifarnib when used in combination with osimertinib (time frame: At the end of Cycle 1 (each cycle is 28 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05693090.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2023.

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