NSCLCPhase 2NCT03318939
Phase 2 Study of Poziotinib in Participants With NSCLC Having EGFR or HER2 Exon 20 Insertion Mutation
A Phase 2 study testing Poziotinib in people with NSCLC, run by Spectrum Pharmaceuticals, Inc at 63 sites in 8 countries.
Trial summary
This is a Phase 2, open-label, multi-center study to evaluate the efficacy and the safety/tolerability of poziotinib in seven participant cohorts for up to 603 previously treated and treatment-naïve NSCLC participant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC
- What is being tested?
- Poziotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 648 participants
- Where
- 63 sitesin 8 countries
- Study dates
- 11 Oct 2017to 3 Apr 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Participant must be willing and capable of giving written Informed Consent, adhering to dosing and visit schedules, and meeting all study requirements
- Participant has histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) that is not amenable to treatment with curative intent
- Prior treatment status:
- Cohorts 1 and 2: Participant has had at least one prior systemic treatment for locally advanced or metastatic NSCLC
- Cohorts 3 and 4: Participant is treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with poziotinib as determined by the Investigator. Adjuvant/neo-adjuvant therapies (chemotherapy, radiotherapy, or investigational agents) are permissible as long as they end at least 15 days prior to study entry.
- Cohort 5: Participants who meet the criteria for enrollment in Cohorts 1 to 4, but the enrollment in the respective cohort has been closed
Show all 15Show fewer
- Cohort 6: Participant with EGFR mutation-positive NSCLC who progressed while on treatment with first-line osimertinib
- Cohort 7: Participant has had at least one prior systemic treatment for locally advanced or metastatic NSCLC
- Specific mutations:
- Cohort 1 and 3: Documented EGFR exon 20 insertion mutation
- Cohort 2 and 4: Documented HER2 exon 20 insertion mutation
- Cohort 5: Documented EGFR or HER2 exon 20 insertion mutations
- Cohort 6: Documented acquired EGFR mutation (tested after osimertinib progression)
- Cohort 7: Documented EGFR or HER2 activating mutations
- Participant has adequate organ function at Baseline
Who cannot join
- Participant has had previous treatment with poziotinib or any other EGFR or HER2 exon 20 insertion mutation-selective tyrosine kinase inhibitor (TKI) prior to study participation. The currently approved TKIs (ie, erlotinib, gefitinib, afatinib, osimertinib) are not considered to be exon 20 insertion-selective and are permissible (Cohorts 1 and 2).
- Participant is concurrently receiving chemotherapy, biologics, immunotherapy for cancer treatment; systemic anti-cancer treatment or investigational treatment should not be used within 2 weeks or 5 half lives, whichever is longer; local radiation therapy for bone pain may be allowed
- Participant has had other malignancies within the past 3 years, except for stable non-melanoma skin cancer, fully-treated and stable, early-stage prostate cancer, or carcinoma in situ of the cervix or breast without need of treatment
- Participant is pregnant or breast-feeding
Trial locations and contacts
63 sites in 8 countries.
63 sites in 8 countries
United States43 sites
Oncology Physician's Network Inc./OPN Healthcare
Arcadia, California, 91007
University Cancer & Blood Center, LLC
Athens, Georgia, 30607
Texas Oncology- Austin
Austin, Texas, 78745
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
Rocky Mountain Cancer Center
Boulder, Colorado, 80303
Roswell Park Cancer Institute
Buffalo, New York, 14263
Cleveland Clinic
Cleveland, Ohio, 44195
The Ohio State University
Columbus, Ohio, 43210
Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
Hattiesburg Clinic Hematology/Oncology
Hattiesburg, Mississippi, 39401
MD Anderson Cancer Center
Houston, Texas, 77030
UCSD -Moores Cancer Center
La Jolla, California, 92093
Pacific Shores Medical Group
Long Beach, California, 90813
Los Angeles Hematology Oncology Medical Group
Los Angeles, California, 90017
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Baptist Cancer Center
Memphis, Tennessee, 38120
Minnesota Oncology Hematology, P.A.
Minneapolis, Minnesota, 55404
Yale University, Yale Cancer Center Smilow Cancer Hospital at Yale
New Haven, Connecticut, 06510
NYU Langone Medical Center
New York, New York, 10016
Weill Cornell Medical College
New York, New York, 10065
CTCA - Southeastern Regional Medical Center
Newnan, Georgia, 30265
Florida Hospital
Orlando, Florida, 32804
CTCA - Eastern Regional Medical Center
Philadelphia, Pennsylvania, 19124
Mayo Clinic Hospital
Phoenix, Arizona, 85054
North Shore Hematology Oncology Associates P.C. DBA NY Cancer and Blood Specialists
Port Jefferson Station, New York, 11776
Mayo Clinic
Rochester, Minnesota, 55905
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817
UCSF Helen Diller Comprehensive Cancer Center at Mt Zion
San Francisco, California, 94115
UCLA Hematology/Oncology
Santa Monica, California, 90404
Seattle Cancer Care Alliance
Seattle, Washington, 98109
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
Montefiore Einstein Medical Center for Cancer Care
The Bronx, New York, 10461
North Shore Hematology Oncology Associates DBA New York Cancer and Blood Specialists
The Bronx, New York, 10469
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502
Oklahoma Cancer Specialists and Research Institute, LLC
Tulsa, Oklahoma, 74146
Kaiser Permanente Medical Center
Vallejo, California, 94589
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
The Bond & Steele Clinic, P.A. dba Bond Clinic, P.A.
Winter Haven, Florida, 33881
CTCA - Midwestern Regional Medical Center
Zion, Illinois, 60099
Belgium4 sites
Saint Luc University Hospital
Brussels
University Hospitals Leuven
Leuven
Ambroise Pare University Hospital Center
Mons
General Hospital Delta
Roeselare
Canada4 sites
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
London Regional Cancer Program
London, Ontario, N6A 5W9
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
BC Cancer - Vancouver
Vancouver, British Columbia, V5Z 4E6
Israel4 sites
Soroka Medical Center
Beersheba
Rambam Healthcare Campus
Haifa
Hadassah Medical Center
Jerusalem
Rabin Medical Center
Petah Tikva
Italy3 sites
National Cancer Institute, IRCCS, Department of Medical Oncology
Milan
Santa Maria delle Croci Hospital
Ravenna
National Cancer Institute Regina Elena, IRCCS, Operative Unit of Medical Oncology A 1
Rome
France2 sites
Hopital Larrey, CHU Toulouse, Unité d'Oncologie des Voies Respiratoires
Toulouse
Gustave Roussy Oncology Institute, Department of Medical Oncology
Villejuif
Spain2 sites
University Hospital Germans Trias i Pujol, Department of Medical Oncology
Barcelona
University Hospital 12 de Octubre
Madrid
About this study
Official title: A Phase 2 Study of Poziotinib in Patients With Non-Small Cell Lung Cancer (NSCLC), Locally Advanced or Metastatic, With EGFR or HER2 Exon 20 Insertion Mutation (ZENITH20)
This is a Phase 2, open-label, multi-center study to evaluate the efficacy and the safety/tolerability of poziotinib in seven participant cohorts for up to 603 previously treated and treatment-naïve NSCLC participant. Cohorts 3 and 4 were added with Amendment 1 and three additional cohorts were added with Amendment 2 (Cohorts 5, 6 and 7).
Read the detailed description
The Screening period (Day -30 to Day -1) lasts up to approximately 30 days prior to Cycle 1, Day 1. Participant must meet all Inclusion/Exclusion Criteria to participate in the study. Eligible participants will provide written Informed Consent prior to undergoing any study procedures.
Each treatment cycle is 28 calendar days in duration. There will be seven participant cohorts and eligible participants will be enrolled into each cohort in parallel based on epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) exon 20 mutation status and prior treatment status:
- Cohort 1: Previously treated participant with EGFR exon 20 insertion mutation positive NSCLC (complete)
- Cohort 2: Previously treated participant with HER2 exon 20 insertion mutation positive NSCLC (complete)
- Cohort 3: Treatment naïve participant with EGFR exon 20 insertion mutation positive NSCLC (complete)
- Cohort 4: Treatment naïve participant with HER2 exon 20 insertion mutation positive NSCLC (fully enrolled)
- Cohort 5: Participants who meet the criteria for enrollment in Cohort 1 to 4, but the enrollment in the respective cohort has been closed (closed to enrollment)
- Cohort 6: Participants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib (closed to enrollment)
- Cohort 7: Participants with EGFR or HER2 activating mutations (closed to enrollment)
Toxicity will be assessed based on the grade of the adverse events using CTCAE version 4.03.
On Day 1 of each 28-day cycle, the participant's absolute neutrophil count (ANC) must be ≥1.5×10^9/L and platelet count must be ≥100×10^9/L before administering poziotinib. All participants will be treated until disease progression (except for first progression in Cohort 5), death, intolerable adverse events (AEs), or other protocol-specified reasons for participant withdrawal.
- Conditions
- NSCLC
- Being tested
- Poziotinib
- Keywords
- EGFR, HER2, Exon 20 insertion mutation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PoziotinibDrug
The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Poziotinib 16 mg | Experimental | Participants previously treated for epidermal growth factor receptor (EGFR) exon 20 insertion mutation-positive non-small cell lung cancer (NSCLC) received poziotinib, 16 milligrams (mg), orally, once daily (QD) in each 28-day cycle until disease progression, death, intolerable adverse events (AEs), or for up to a maximum of 35 months, whichever occurs first. Receives: Drug: Poziotinib |
| Cohort 2: Poziotinib 16 mg | Experimental | Participants previously treated for human epidermal growth factor receptor 2 (HER2) exon 20 insertion mutation-positive NSCLC received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 32 months, whichever occurs first. Receives: Drug: Poziotinib |
| Cohort 3: Poziotinib 16 mg | Experimental | Treatment naïve participants with EGFR exon 20 insertion mutation-positive NSCLC received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 24 months, whichever occurs first. Receives: Drug: Poziotinib |
| Cohort 4: Poziotinib 8 mg | Experimental | Treatment naïve participants with HER2 exon 20 insertion mutation-positive NSCLC received poziotinib, 8 mg, orally, twice daily (BID) in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 27 months, whichever occurs first. Receives: Drug: Poziotinib |
| Cohort 4: Poziotinib 16 mg | Experimental | Treatment naïve participants with HER2 exon 20 insertion mutation-positive NSCLC received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 27 months, whichever occurs first. Receives: Drug: Poziotinib |
| Cohort 5: Poziotinib 6 mg | Experimental | Participants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 6 mg, orally, BID in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 23 months, whichever occurs first. Receives: Drug: Poziotinib |
| Cohort 5: Poziotinib 8mg | Experimental | Participants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 8 mg, orally, BID in each 28-day cycle until disease progression (except first progression), death, intolerable AEs, or for up to a maximum of 25 months, whichever occurs first. Receives: Drug: Poziotinib |
| Cohort 5: Poziotinib 10 mg | Experimental | Participants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 10 mg, orally, QD in each 28-day cycle until disease progression (except first progression), death, intolerable AEs, or for up to a maximum of 15 months, whichever occurs first. Receives: Drug: Poziotinib |
| Cohort 5: Poziotinib 12 mg | Experimental | Participants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 12 mg, orally, QD in each 28-day cycle until disease progression (except first progression), death, intolerable AEs, or for up to a maximum of 26 months, whichever occurs first. Receives: Drug: Poziotinib |
| Cohort 5: Poziotinib 16 mg | Experimental | Participants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression (except first progression), death, intolerable AEs, or for up to a maximum of 18 months, whichever occurs first. Receives: Drug: Poziotinib |
| Cohort 6: Poziotinib 8 mg | Experimental | Participants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib received poziotinib, 8 mg, orally, BID in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 29 months, whichever occurs first. Receives: Drug: Poziotinib |
| Cohort 6: Poziotinib 16 mg | Experimental | Participants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 7 months, whichever occurs first. Receives: Drug: Poziotinib |
| Cohort 7: Poziotinib 8 mg | Experimental | Participants with EGFR or HER2 activating mutations received poziotinib, 8 mg, orally, BID in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 20 months, whichever occurs first. Receives: Drug: Poziotinib |
| Cohort 7: Poziotinib 16 mg | Experimental | Participants with EGFR or HER2 activating mutations received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 4 months, whichever occurs first. Receives: Drug: Poziotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
ORR was defined as the percentage of participants whose best overall response (BOR) was confirmed to be complete response (CR) or partial response (PR) from the first dose of poziotinib until the last tumor assessment on study. ORR was assessed by the Independent Radiologic Review Committee according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR was defined as the disappearance of all non-nodal target lesions. Any pathological lymph nodes must have become normal (i.e., decrease in the short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD. Additionally, progression of target lesions must not have been present.
Measured: Up to 3 years
Secondary outcomes (3)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as AEs that occur from the first dose of study treatment until 35 (±5) days after the last dose of study treatment.
Measured: Up to 5 years
Disease Control Rate (DCR)
DCR was defined as percentage of participants with best response of CR, PR, or stable disease (SD) from the first dose of poziotinib to the last tumor assessment on study. CR was defined as the disappearance of all non-nodal target lesion. Any pathological lymph nodes must have become normal (i.e., decrease in the short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD. Additionally, progression of target lesions must not have been present. SD was defined as neither sufficient shrinkage of target lesions to qualify for PR nor sufficient increase to qualify for progressive disease (PD).
Measured: Up to 3 years
Duration of Response (DoR)
DoR was evaluated only for participants who had CR or PR and was defined as the time from the date that response evaluation criteria were first met for CR or PR (whichever status was recorded first) until the first subsequent date that PD or death was documented. CR was defined as the disappearance of all non-nodal target lesion. Any pathological lymph nodes must have become normal (i.e., decrease in the short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD. Additionally, progression of target lesions must not have been present. Disease progression was defined as greater than or equal to (≥) 20% increase in the SOD of target lesions taking as reference the nadir SOD (or the baseline, if the baseline is the nadir value). In addition to the relative increase of 20% in SOD, the SOD must also have demonstrated an absolute increase of ≥ 5 mm.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2017
- Study start11 Oct 2017
- Primary completion3 Apr 2023
- Study completion3 Apr 2023
Why it stopped: Strategic business decision (unrelated to safety)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NSCLCStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Each treatment cycle is 28 calendar days in duration. There will be seven participant cohorts and eligible participants will be enrolled into each cohort in parallel based on EGFR or HER2 exon 20 mutation status and prior treatment status: * Cohort 1: Previously treated participants with EGFR exon 20 insertion mutant positive NSCLC (closed to enrollment) * Cohort 2: Previously treated participants with HER2 exon 20 insertion mutant positive NSCLC (closed to enrollment) * Cohort 3: Treatment naïve participants with EGFR exon 20 insertion mutant positive NSCLC (fully enrolled) * Cohort 4: Treatment naïve participants with HER2 exon 20 insertion mutant positive NSCLC * Cohort 5: Participants who meet the criteria for enrollment in Cohort 1 to 4, but the enrollment in the respective cohort has been closed * Cohort 6: Participants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib * Cohort 7: Participants with EGFR or HER2 activating mutations
- Masking
- None (open label)
- Enrolment
- 648 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spectrum Pharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03318939
- Sponsor's protocol ID
- SPI-POZ-202
- Status last verified
- Jun 2026
- First submitted
- 10 Oct 2017
- Last updated
- 12 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Le X, Cornelissen R, Garassino M, Clarke JM, Tchekmedyian N, Goldman JW, Leu SY, Bhat G, Lebel F, Heymach JV, Socinski MA. Poziotinib in Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial. J Clin Oncol. 2022 Mar 1;40(7):710-718. doi: 10.1200/JCO.21.01323. Epub 2021 Nov 29.
PubMed 34843401
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Poziotinib in Patients With Non-Small Cell Lung Cancer (NSCLC), Locally Advanced or Metastatic, With EGFR or HER2 Exon 20 Insertion Mutation (ZENITH20)
- ClinicalTrials.gov ID
- NCT03318939
- Acronym / sponsor ID
- SPI-POZ-202
- Conditions
- NSCLC
- Keywords
- EGFR, HER2, Exon 20 insertion mutation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Strategic business decision (unrelated to safety)
- Enrolment
- 648 participants (actual)
- Lead sponsor
- Spectrum Pharmaceuticals, IncIndustry (pharma, biotech, devices)
- Study start
- 11 Oct 2017 (actual)
- Primary completion
- 3 Apr 2023 (actual)
- Study completion
- 3 Apr 2023 (actual)
- First posted
- 24 Oct 2017 (actual)
- Results
- Posted 12 Jun 2026
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 2, open-label, multi-center study to evaluate the efficacy and the safety/tolerability of poziotinib in seven participant cohorts for up to 603 previously treated and treatment-naïve NSCLC participant. Cohorts 3 and 4 were added with Amendment 1 and three additional cohorts were added with Amendment 2 (Cohorts 5, 6 and 7).
Detailed description
The Screening period (Day -30 to Day -1) lasts up to approximately 30 days prior to Cycle 1, Day 1. Participant must meet all Inclusion/Exclusion Criteria to participate in the study. Eligible participants will provide written Informed Consent prior to undergoing any study procedures.
Each treatment cycle is 28 calendar days in duration. There will be seven participant cohorts and eligible participants will be enrolled into each cohort in parallel based on epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) exon 20 mutation status and prior treatment status:
- Cohort 1: Previously treated participant with EGFR exon 20 insertion mutation positive NSCLC (complete)
- Cohort 2: Previously treated participant with HER2 exon 20 insertion mutation positive NSCLC (complete)
- Cohort 3: Treatment naïve participant with EGFR exon 20 insertion mutation positive NSCLC (complete)
- Cohort 4: Treatment naïve participant with HER2 exon 20 insertion mutation positive NSCLC (fully enrolled)
- Cohort 5: Participants who meet the criteria for enrollment in Cohort 1 to 4, but the enrollment in the respective cohort has been closed (closed to enrollment)
- Cohort 6: Participants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib (closed to enrollment)
- Cohort 7: Participants with EGFR or HER2 activating mutations (closed to enrollment)
Toxicity will be assessed based on the grade of the adverse events using CTCAE version 4.03.
On Day 1 of each 28-day cycle, the participant's absolute neutrophil count (ANC) must be ≥1.5×10^9/L and platelet count must be ≥100×10^9/L before administering poziotinib. All participants will be treated until disease progression (except for first progression in Cohort 5), death, intolerable adverse events (AEs), or other protocol-specified reasons for participant withdrawal.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 14
- Model description
- Each treatment cycle is 28 calendar days in duration. There will be seven participant cohorts and eligible participants will be enrolled into each cohort in parallel based on EGFR or HER2 exon 20 mutation status and prior treatment status: * Cohort 1: Previously treated participants with EGFR exon 20 insertion mutant positive NSCLC (closed to enrollment) * Cohort 2: Previously treated participants with HER2 exon 20 insertion mutant positive NSCLC (closed to enrollment) * Cohort 3: Treatment naïve participants with EGFR exon 20 insertion mutant positive NSCLC (fully enrolled) * Cohort 4: Treatment naïve participants with HER2 exon 20 insertion mutant positive NSCLC * Cohort 5: Participants who meet the criteria for enrollment in Cohort 1 to 4, but the enrollment in the respective cohort has been closed * Cohort 6: Participants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib * Cohort 7: Participants with EGFR or HER2 activating mutations
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Poziotinib 16 mg | Experimental | Drug: PoziotinibParticipants previously treated for epidermal growth factor receptor (EGFR) exon 20 insertion mutation-positive non-small cell lung cancer (NSCLC) received poziotinib, 16 milligrams (mg), orally, once daily (QD) in each 28-day cycle until disease progression, death, intolerable adverse events (AEs), or for up to a maximum of 35 months, whichever occurs first. |
| Cohort 2: Poziotinib 16 mg | Experimental | Drug: PoziotinibParticipants previously treated for human epidermal growth factor receptor 2 (HER2) exon 20 insertion mutation-positive NSCLC received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 32 months, whichever occurs first. |
| Cohort 3: Poziotinib 16 mg | Experimental | Drug: PoziotinibTreatment naïve participants with EGFR exon 20 insertion mutation-positive NSCLC received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 24 months, whichever occurs first. |
| Cohort 4: Poziotinib 8 mg | Experimental | Drug: PoziotinibTreatment naïve participants with HER2 exon 20 insertion mutation-positive NSCLC received poziotinib, 8 mg, orally, twice daily (BID) in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 27 months, whichever occurs first. |
| Cohort 4: Poziotinib 16 mg | Experimental | Drug: PoziotinibTreatment naïve participants with HER2 exon 20 insertion mutation-positive NSCLC received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 27 months, whichever occurs first. |
| Cohort 5: Poziotinib 6 mg | Experimental | Drug: PoziotinibParticipants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 6 mg, orally, BID in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 23 months, whichever occurs first. |
| Cohort 5: Poziotinib 8mg | Experimental | Drug: PoziotinibParticipants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 8 mg, orally, BID in each 28-day cycle until disease progression (except first progression), death, intolerable AEs, or for up to a maximum of 25 months, whichever occurs first. |
| Cohort 5: Poziotinib 10 mg | Experimental | Drug: PoziotinibParticipants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 10 mg, orally, QD in each 28-day cycle until disease progression (except first progression), death, intolerable AEs, or for up to a maximum of 15 months, whichever occurs first. |
| Cohort 5: Poziotinib 12 mg | Experimental | Drug: PoziotinibParticipants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 12 mg, orally, QD in each 28-day cycle until disease progression (except first progression), death, intolerable AEs, or for up to a maximum of 26 months, whichever occurs first. |
| Cohort 5: Poziotinib 16 mg | Experimental | Drug: PoziotinibParticipants who met the criteria for enrollment in Cohort 1 to Cohort 4, but the enrollment in the respective cohort had been closed were enrolled in this cohort and received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression (except first progression), death, intolerable AEs, or for up to a maximum of 18 months, whichever occurs first. |
| Cohort 6: Poziotinib 8 mg | Experimental | Drug: PoziotinibParticipants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib received poziotinib, 8 mg, orally, BID in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 29 months, whichever occurs first. |
| Cohort 6: Poziotinib 16 mg | Experimental | Drug: PoziotinibParticipants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 7 months, whichever occurs first. |
| Cohort 7: Poziotinib 8 mg | Experimental | Drug: PoziotinibParticipants with EGFR or HER2 activating mutations received poziotinib, 8 mg, orally, BID in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 20 months, whichever occurs first. |
| Cohort 7: Poziotinib 16 mg | Experimental | Drug: PoziotinibParticipants with EGFR or HER2 activating mutations received poziotinib, 16 mg, orally, QD in each 28-day cycle until disease progression, death, intolerable AEs, or for up to a maximum of 4 months, whichever occurs first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Participant must be willing and capable of giving written Informed Consent, adhering to dosing and visit schedules, and meeting all study requirements
- Participant has histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) that is not amenable to treatment with curative intent
- Prior treatment status:
- Specific mutations:
- Participant has adequate organ function at Baseline
Key exclusion criteria (4 listed)
- Participant has had previous treatment with poziotinib or any other EGFR or HER2 exon 20 insertion mutation-selective tyrosine kinase inhibitor (TKI) prior to study participation. The currently approved TKIs (ie, erlotinib, gefitinib, afatinib, osimertinib) are not considered to be exon 20 insertion-selective and are permissible (Cohorts 1 and 2).
- Participant is concurrently receiving chemotherapy, biologics, immunotherapy for cancer treatment; systemic anti-cancer treatment or investigational treatment should not be used within 2 weeks or 5 half lives, whichever is longer; local radiation therapy for bone pain may be allowed
- Participant has had other malignancies within the past 3 years, except for stable non-melanoma skin cancer, fully-treated and stable, early-stage prostate cancer, or carcinoma in situ of the cervix or breast without need of treatment
- Participant is pregnant or breast-feeding
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 |
|---|---|---|
| PoziotinibThe poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration. | Drug | Cohort 1: Poziotinib 16 mg, Cohort 2: Poziotinib 16 mg, Cohort 3: Poziotinib 16 mg, Cohort 4: Poziotinib 16 mg, Cohort 4: Poziotinib 8 mg, Cohort 5: Poziotinib 10 mg, Cohort 5: Poziotinib 12 mg, Cohort 5: Poziotinib 16 mg, Cohort 5: Poziotinib 6 mg, Cohort 5: Poziotinib 8mg, Cohort 6: Poziotinib 16 mg, Cohort 6: Poziotinib 8 mg, Cohort 7: Poziotinib 16 mg, Cohort 7: Poziotinib 8 mg |
Primary outcome
Objective Response Rate (ORR)
Time frame: Up to 3 years
ORR was defined as the percentage of participants whose best overall response (BOR) was confirmed to be complete response (CR) or partial response (PR) from the first dose of poziotinib until the last tumor assessment on study. ORR was assessed by the Independent Radiologic Review Committee according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR was defined as the disappearance of all non-nodal target lesions. Any pathological lymph nodes must have become normal (i.e., decrease in the short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD. Additionally, progression of target lesions must not have been present.
3 secondary outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Up to 5 years
Disease Control Rate (DCR)
Time frame: Up to 3 years
Duration of Response (DoR)
Time frame: Up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34843401Le X, Cornelissen R, Garassino M, Clarke JM, Tchekmedyian N, Goldman JW, Leu SY, Bhat G, Lebel F, Heymach JV, Socinski MA. Poziotinib in Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial. J Clin Oncol. 2022 Mar 1;40(7):710-718. doi: 10.1200/JCO.21.01323. Epub 2021 Nov 29.
- Individual participant dataSharing planned: No
Related trials for NSCLC
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
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.
The record lists no contact. Use the official record to reach the sponsor.
63 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Poziotinib in people with NSCLC, run by Spectrum Pharmaceuticals, Inc at 63 sites in 8 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 15 inclusion and 4 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: stopped early, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 63 sites in United States, Belgium, Canada, Israel, Italy and 3 more countries. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Objective Response Rate (ORR) (time frame: Up to 3 years). 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 NCT03318939, which also lists 1 linked publication.
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 12 Jun 2026.