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EGFR Exon 20 MutationPhase 2NCT03066206

Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC

A Phase 2 study testing Poziotinib in people with EGFR Exon 20 Mutation and ERBB2 Gene Mutation, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial studies how well poziotinib works in treating patients with non-small lung cancer with an EGFR or HER2 exon 20 mutation that is stage IV or has come back (recurrent). Poziotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Poziotinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
93 participants
Where
1 siteUnited States
Study dates
17 Mar 2017to 16 Feb 2026
Phase
Phase 2
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

  • Histologically or cytologically confirmed stage IV or recurrent solid tumor not amenable to curative intent therapy
  • Cohort 1 specific inclusion criteria: NSCLC with documented EGFR exon 20 mutation by one of the following Clinical Laboratory Improvement Act (CLIA) certified tests: OncoMine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay or by a Food and Drug Administration (FDA) approved device using cobas EGFR mutation test version (v)2 or therascreen EGFR RGQ PCt kit; Mutations include D770_N771insSVD, D770_N771insNPG, V769_D770insASV, H773_V774insNPH, or any other exon 20 in-frame insertion or point mutation excluding T790M
  • Cohort 2 specific inclusion criteria: NSCLC with documented HER2 exon 20 mutation by a CLIA certified tests: Oncomine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay; eligible mutations include A775_G776insYVMA, G776_V777insVC, or P780_Y781insGSP, or any other in-frame exon 20 insertion mutation or point mutation including, but not limited to, L755S, G776V, and V777L
  • Cohort 3 specific inclusion criteria: NSCLC with documented EGFR exon 20 mutation (excluding T790M) by one of the following CLIA certified tests: OncoMine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay or by an FDA approved device using cobas EGFR mutation test v2 or therascreen EGFR RGQ PCt kit; mutations include D770_N771insSVD, D770_N771insNPG, V769_D770insASV, H773_V774insNPH, or any other exon 20 in-frame insertion or point mutation excluding T790M
  • Cohort 4 specific inclusion criteria: solid tumor (excluding NSCLC) harboring EGFR or HER2 exon 20 mutations documented by one of the following CLIA certified tests: Oncomine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay
  • Cohort 5 specific inclusion criteria: solid tumor harboring HER2 exon 19 mutation documented by one of the following CLIA certified tests: Oncomine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay
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  • Patients must have exhausted all FDA-approved standard of care options for locally advanced or metastatic disease, or are ineligible for FDA-approved standard of care options, or refusing to receive FDA-approved standard of care options. Previously untreated patients are allowed only in cohort 1 and 3 and are eligible only if EGFR Exon 20 mutation is confirmed using an FDA approved device/test such as cobas EGFR Mutation Test v2, therascreen EGFR RGQ PCR Kit or other FDA tests prior to study enrollment
  • Patient has adequate tumor tissue obtained from a biopsy or surgical procedure to enable molecular profiling for retrospective central laboratory confirmation of the mutation. If tissue is not available, the patient must have biopsy accessible disease and must be willing to undergo a biopsy prior to the study
  • Measurable disease by RECIST 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Ability to take pills by mouth
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9.0 g/dL
  • Total bilirubin =< 2 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 institutional upper limit of normal of =< 5 x ULN if liver metastases are present
  • Alkaline phosphatase =< 2.5 institutional upper limit of normal of =< 5 x ULN if liver metastases are present
  • Creatinine clearance >= 50 mL/min/1.73 m^2 by Cockcroft-Gault equation
  • Brain metastases are allowed, as long as they are stable and do not require treatment with anticonvulsants or escalating doses of steroids
  • Females of childbearing potential must have a negative serum or urine pregnancy test and must agree to use adequate contraception for the duration of the study and six months after; adequate contraception methods include: birth control pills (e.g. combined oral contraceptive pill), barrier protection (e.g. condom plus spermicide, cervical/vault cap or intrauterine device), and abstinence; females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause); women will be considered post-menopausal if they have been amenorrheic for the past 12 months without an alternative medical cause
  • The following age-specific requirements must also apply:
  • Women < 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments; the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must also be in the post-menopausal range (as per the institution)
  • Women >= 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of all exogenous hormonal treatments, or have had radiation-induced oophorectomy with the last menses > 1 year ago, or have had chemotherapy-induced menopause with > 1 year interval since last menses, or have had surgical sterilization by either bilateral oophorectomy or hysterectomy
  • Non-sterilized males who are sexually active with a female partner of childbearing potential must use adequate contraception for the duration of the study and 90 days after the last dose of study medication; adequate contraception methods include: birth control pills (e.g. combined oral contraceptive pill), barrier protection (e.g. condom plus spermicide, cervical/vault cap or intrauterine device), and abstinence
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • EGFR T790M mutation or any other acquired EGFR exon 20 mutation; patients with coexisting primary EGFR exon 20 and T790M mutations are eligible
  • Have received or are receiving an investigational medicinal product (IMP) or other systemic anticancer treatment within 2 weeks prior to the first dose of study treatment
  • Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
  • Have known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, has been treated with surgery and/or radiation, and has been stable without requiring escalating corticosteroids nor anti-convulsant medications for at least 4 weeks prior to the first dose of study medication
  • Known hypersensitivity to poziotinib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to poziotinib
  • Cardiac conditions as follows:
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  • Patient has a history of congestive heart failure (CHF) class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment
  • Patient has a cardiac ejection fraction < 50% by either echocardiogram or multi-gated acquisition (MUGA) scan
  • Have any unresolved chronic toxicity with Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade >= 2, from previous anticancer therapy, except for alopecia
  • Patient is unable to take drugs orally due to disorders or diseases that may affect gastrointestinal function, such as inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis) or malabsorption syndrome, or procedures that may affect gastrointestinal function, such as gastrectomy, enterectomy, or colectomy
  • Have any condition or illness that, in the opinion of the investigator, might compromise patient safety or interfere with the evaluation of the safety of the drug
  • Pregnant or breastfeeding women
  • History of another primary malignancy within 2 years prior to starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ
  • Recent major surgery within 4 weeks prior to starting study treatment, with the exception of surgical placement for vascular access
  • Male or female patients of reproductive potential who are not employing an adequate method of birth control; adequate contraception methods include: birth control pills (e.g. combined oral contraceptive pill), barrier protection (e.g. condom plus spermicide cervical/vault cap or intrauterine device), and abstinence
  • Uncontrolled intercurrent illness including, but not limited to, uncompensated respiratory, cardiac, hepatic, or renal disease, active infection (including hepatitis B, hepatitis C, human immunodeficiency virus [HIV], and active clinical tuberculosis), or renal transplant; ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirements
  • Active bleeding disorders.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase II Study of Poziotinib in EGFR or HER2 Mutant Advanced Solid Tumors

This phase II trial studies how well poziotinib works in treating patients with non-small lung cancer with an EGFR or HER2 exon 20 mutation that is stage IV or has come back (recurrent). Poziotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth..

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the objective response rate (ORR) to poziotinib according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in non-small cell lung cancer (NSCLC) with EGFR exon 20 mutations.

II. Assess the objective response rate (ORR) to poziotinib according to RECIST 1.1 criteria in NSCLC with HER2 (ErBB2) exon 20 mutations.

III. Assess the objective response rate (ORR) to poziotinib according to RECIST 1.1 criteria in advanced solid tumors with EGFR exon 20 or HER2 exon 20 mutations.

IV. Assess the objective response rate (ORR) to poziotinib according to RECIST 1.1 criteria in advanced solid tumors with HER2 exon 19 mutations ORR will be calculated as the percent of patients whose best confirmed response is complete response (CR, defined as disappearance of all target lesions) or partial response (PR, defined as at least a 30% decrease in the sum of longest diameter [LD] of target lesions, taking as reference the baseline sum LD).

SECONDARY OBJECTIVES:

  1. Disease control rate (complete response + partial response + stable response) of poziotinb in cohort 1 and 2, analyzed independently.

II. Progression free survival of poziotinb in cohort 1 and 2, analyzed independently.

III. Overall survival of poziotinb in cohort 1 and 2, analyzed independently. IV. Duration of response of poziotinb in cohort 1 and 2, analyzed independently.

  1. Safety and toxicity.

EXPLORATORY OBJECTIVES:

  1. To assess molecular markers associated with resistance and response to poziotinib, including secondary mutations.

OUTLINE:

Patients receive poziotinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.

Being tested
Poziotinib
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.

  • PoziotinibDrug

    Also called HM781-36B, NOV120101

    Given PO

Study groups in NCT03066206
Study groupRoleWhat they receive
Treatment (poziotinib)ExperimentalPatients receive poziotinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Poziotinib

What is being measured

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

  1. Objective response rate a in patients with estimated glomerular filtration rate (EGFR) exon 20 mutant non-small Cell Lung Cancer (NSCLC) (Cohort 1)

    According to Response Evaluation Criteria in Solid Tumors 1.1 criteria.

    Measured: Up to 4 years

  2. Objective response rate a in patients with human epidermal growth factor receptor 2 (HER2) exon 20 mutant non-small Cell Lung Cancer (NSCLC) (Cohort 2)

    According to Response Evaluation Criteria in Solid Tumors 1.1 criteria.

    Measured: Up to 4 years

Secondary outcomes (5)

  1. Disease control rate (complete response + partial response + stable disease) of poziotinb in cohort 1 and 2, analyzed independently

    Will be estimated along with 95% confidence intervals.

    Measured: Up to 4 years

  2. Progression free survival of poziotinb in cohort 1 and 2, analyzed independently

    Will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on progression free survival.

    Measured: Up to 4 years

  3. Overall survival of poziotinb in cohort 1 and 2, analyzed independently

    Will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on overall survival.

    Measured: Up to 4 years

  4. Duration of response of poziotinb in cohort 1 and 2, analyzed independently

    Duration of response will be measured.

    Measured: Up to 4 years

  5. Incidence of adverse events

    Assessed by Common Terminology Criteria for Adverse Events version 4.03. Toxicity data will be summarized by frequency tables.

    Measured: Up to 4 years

Timeline

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

  1. First posted28 Feb 2017
  2. Study start17 Mar 2017
  3. Primary completion16 Feb 2026
  4. Study completion16 Feb 2026

Why it stopped: \<75% participation

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
93 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03066206
Sponsor's protocol ID
2016-0783
Other IDs
NCI-2017-00831, 2016-0783
Status last verified
Feb 2026
First submitted
23 Feb 2017
Last updated
20 Feb 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Miyamura BV, Mambetsariev I, Fricke J, Arias-Romero J, Cadman K, Shrestha S, Pisick E, Nguyen D, Malhotra J, Reyes A, Salgia R. Current paradigm of EGFRins20 in non-small cell lung cancer: A long way forward. Med. 2025 Sep 12;6(9):100803. doi: 10.1016/j.medj.2025.100803. Epub 2025 Aug 8.

    PubMed 40782807

  • Elamin YY, Robichaux JP, Carter BW, Altan M, Tran H, Gibbons DL, Heeke S, Fossella FV, Lam VK, Le X, Negrao MV, Nilsson MB, Patel A, Vijayan RSK, Cross JB, Zhang J, Byers LA, Lu C, Cascone T, Feng L, Luthra R, San Lucas FA, Mantha G, Routbort M, Blumenschein G Jr, Tsao AS, Heymach JV. Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity. Cancer Cell. 2022 Jul 11;40(7):754-767.e6. doi: 10.1016/j.ccell.2022.06.006.

    PubMed 35820397

  • Elamin YY, Robichaux JP, Carter BW, Altan M, Gibbons DL, Fossella FV, Lam VK, Patel AB, Negrao MV, Le X, Mott FE, Zhang J, Feng L, Blumenschein G Jr, Tsao AS, Heymach JV. Poziotinib for Patients With HER2 Exon 20 Mutant Non-Small-Cell Lung Cancer: Results From a Phase II Trial. J Clin Oncol. 2022 Mar 1;40(7):702-709. doi: 10.1200/JCO.21.01113. Epub 2021 Sep 22.

    PubMed 34550757

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Poziotinib in people with EGFR Exon 20 Mutation and ERBB2 Gene Mutation, run by M.D. Anderson Cancer Center at 1 site 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 26 inclusion and 17 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 20 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 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?

The study was stopped early (reason given: \<75% participation). Results are not available in the source record.

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 a in patients with estimated glomerular filtration rate (EGFR) exon 20 mutant non-small Cell Lung Cancer (NSCLC) (Cohort 1) (time frame: Up to 4 years). The study lists 2 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 NCT03066206, which also lists 3 linked publications.

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 20 Feb 2026.

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