Carcinoma, Non-Small-Cell LungPhase 1NCT03446417
A Study of ZN-e4 in Subjects With Epidermal Growth Factor Receptor Mutated Non-Small Cell Lung Cancer
A Phase 1 study testing ZN-e4 in people with Carcinoma, Non-Small-Cell Lung, run by Zeno Pharmaceuticals, Inc. at 7 sites in 2 countries.
Trial summary
This is a Phase 1/2, open-label, multicenter, sequential dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of ZN-e4 administered orally in subjects with advanced non-small cell lung cancer (NSCLC) with activating EGFR mutations who have progressed while on… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- ZN-e4
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 20 Apr 2018to 15 Nov 2022
- 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
- Histologically or cytologically confirmed metastatic or advanced inoperable diagnosis of NSCLC
- Documented radiographic progression on the last treatment administered prior to enrolling in the study.
- Phase 1 only: Confirmation that the tumor harbors an EGFR mutation known to be associated with aberrations that are amenable to EGFRi therapy including but not limited to: G719X, exon 19 deletion, exon 21 L858R, and L861Q. OR - Must have experienced clinical benefit from an EGFRi,
- All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 or baseline before the start of study drug dosing (with the exception of alopecia [any grade permitted] and neurotoxicity [Grade 1 or 2 permitted]).
- Measurable disease meeting the criteria specified by RECIST v1.1
- Phase 2, Cohort 1 only: Subjects must have confirmation of tumor T790M mutation status (confirmed positive) and are osimertinib naïve
- Phase 2, Cohort 2 only: EGFR aberrations that are amenable to EGFRi therapy, including but not limited to: G719X, exon 19 deletion, exon 21 L858R, and L861Q, and be EGFRi naïve
Who cannot join
- Subjects who have received only neoadjuvant or adjuvant therapy for NSCLC.
- Phase 1 only: Treatment with an EGFRi within 7 days or 5 half-lives of the first dose of study treatment, whichever is shorter.
- Phase 1 only: Cytotoxic chemotherapy, investigational agents, or any anticancer therapy for the treatment of advanced NSCLC (other than EGFRi) within 21 days of the first dose of study treatment.
- Prior treatment with immunotherapy within 3 months prior to the first dose of study treatment.
- Radiotherapy within 28 days of first dose of study treatment; subjects given palliative radiotherapy to peripheral sites (e.g., bone metastases) may enter the study before 28 days have elapsed provided the radiated sites do not contain lesions which may be used to evaluate response, and must have recovered from any acute, reversible effects.
- Known or suspected central nervous system (CNS) metastases or leptomeningeal disease (Phase 1 only). Subjects with previously treated brain or CNS metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy, does not have brain metastasis related symptoms, is not requiring systemic steroids for at least 2 weeks prior to study drug administration, and any whole brain radiation therapy was completed at least 4 weeks prior to study drug administration, or any stereotactic radiosurgery (SRS) was completed at least 2 weeks prior to study drug administration.
- Prior allogeneic bone marrow transplantation.
- History of a concurrent or second malignancy except for: adequately treated local basal cell or squamous cell carcinoma of the skin; cervical carcinoma in situ; superficial bladder cancer; breast carcinoma in situ; adequately treated Stage 1 or 2 cancer currently in complete remission; any other cancer that has been in complete remission for ≥5 years.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States5 sites
Site 6
Charlotte, North Carolina, 28204
Site 5
Detroit, Michigan, 48201
Site 2
Duarte, California, 91010
Site 1
East Setauket, New York, 11733
Site 3
Gettysburg, Pennsylvania, 17325
About this study
Official title: A Phase 1/2 Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of ZN-e4 (KP-673) in Patients With Advanced Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor (EGFR) Mutations
This is a Phase 1/2, open-label, multicenter, sequential dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of ZN-e4 administered orally in subjects with advanced non-small cell lung cancer (NSCLC) with activating EGFR mutations who have progressed while on treatment with an EGFR tyrosine kinase inhibitor (TKI) agent (other lines of treatment are allowed, except for other epidermal growth factor receptor inhibitors [EGFRis]) for Phase 1; and for Phase 2, subjects who have T790M+ and are osimertinib naïve (Cohort 1), and also those who have not been treated with an EGFR Inhibitor (EGFRi) (Cohort2).
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- ZN-e4
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZN-e4Drug
Oral dose, tablet, daily dosing
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 | Experimental | Up to 9 sequential dose escalation cohorts to determine maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is identified. Receives: Drug: ZN-e4 |
| Phase 2 | Experimental | MTD/RP2D in subjects:
Cohort 1: with T790M mutation in epidermal growth factor receptor (EGFR) gene, and are osimertinib naïve.
Cohort 2: EGFRm amenable to EGFR inhibitor therapy (eg, exon 19 del, L858R) and who have never been treated with EGFRis. Receives: Drug: ZN-e4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Observed dose limiting toxicities
Measured: 1 Cycle (21 days)
Secondary outcomes (1)
Safety and tolerability as measured by incidence of treatment emergent adverse events
Measured: Through study completion, approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2018
- Study start20 Apr 2018
- Primary completion17 Jan 2022
- Study completion15 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zeno Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Zeno Pharmaceuticals, Study director, Zeno Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03446417
- Sponsor's protocol ID
- ZN-e4-001
- Status last verified
- Jan 2024
- First submitted
- 16 Feb 2018
- Last updated
- 25 Jan 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of ZN-e4 (KP-673) in Patients With Advanced Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor (EGFR) Mutations
- ClinicalTrials.gov ID
- NCT03446417
- Acronym / sponsor ID
- ZN-e4-001
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Zeno Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Apr 2018 (actual)
- Primary completion
- 17 Jan 2022 (actual)
- Study completion
- 15 Nov 2022 (actual)
- First posted
- 26 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1/2, open-label, multicenter, sequential dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of ZN-e4 administered orally in subjects with advanced non-small cell lung cancer (NSCLC) with activating EGFR mutations who have progressed while on treatment with an EGFR tyrosine kinase inhibitor (TKI) agent (other lines of treatment are allowed, except for other epidermal growth factor receptor inhibitors [EGFRis]) for Phase 1; and for Phase 2, subjects who have T790M+ and are osimertinib naïve (Cohort 1), and also those who have not been treated with an EGFR Inhibitor (EGFRi) (Cohort2).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 | Experimental | Drug: ZN-e4Up to 9 sequential dose escalation cohorts to determine maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is identified. |
| Phase 2 | Experimental | Drug: ZN-e4MTD/RP2D in subjects: Cohort 1: with T790M mutation in epidermal growth factor receptor (EGFR) gene, and are osimertinib naïve. Cohort 2: EGFRm amenable to EGFR inhibitor therapy (eg, exon 19 del, L858R) and who have never been treated with EGFRis. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years
- Histologically or cytologically confirmed metastatic or advanced inoperable diagnosis of NSCLC
- Documented radiographic progression on the last treatment administered prior to enrolling in the study.
- Phase 1 only: Confirmation that the tumor harbors an EGFR mutation known to be associated with aberrations that are amenable to EGFRi therapy including but not limited to: G719X, exon 19 deletion, exon 21 L858R, and L861Q. OR - Must have experienced clinical benefit from an EGFRi,
- All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 or baseline before the start of study drug dosing (with the exception of alopecia [any grade permitted] and neurotoxicity [Grade 1 or 2 permitted]).
Key exclusion criteria (8 listed)
- Subjects who have received only neoadjuvant or adjuvant therapy for NSCLC.
- Phase 1 only: Treatment with an EGFRi within 7 days or 5 half-lives of the first dose of study treatment, whichever is shorter.
- Phase 1 only: Cytotoxic chemotherapy, investigational agents, or any anticancer therapy for the treatment of advanced NSCLC (other than EGFRi) within 21 days of the first dose of study treatment.
- Prior treatment with immunotherapy within 3 months prior to the first dose of study treatment.
- Radiotherapy within 28 days of first dose of study treatment; subjects given palliative radiotherapy to peripheral sites (e.g., bone metastases) may enter the study before 28 days have elapsed provided the radiated sites do not contain lesions which may be used to evaluate response, and must have recovered from any acute, reversible effects.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZN-e4Oral dose, tablet, daily dosing | Drug | Phase 1, Phase 2 |
Primary outcome
Observed dose limiting toxicities
Time frame: 1 Cycle (21 days)
1 secondary outcome
Safety and tolerability as measured by incidence of treatment emergent adverse events
Time frame: Through study completion, approximately 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zeno Pharmaceuticals study director
Zeno Pharmaceuticals
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ZN-e4 in people with Carcinoma, Non-Small-Cell Lung, run by Zeno Pharmaceuticals, Inc. at 7 sites in 2 countries.
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 8 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: finished, as of the sponsor's last update on 25 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Bosnia and Herzegovina. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Observed dose limiting toxicities (time frame: 1 Cycle (21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Jan 2024.