Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC

NCT03066206 | Terminated Phase 2 FDA Drug

• 2 other identifiers: 2016-0783NCI-2017-00831
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

Brief 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..

Conditions

EGFR Exon 20 Mutation; ERBB2 Gene Mutation; Recurrent Lung Non-Small Cell Carcinoma; Stage IV Non-Small Cell Lung Cancer AJCC v7

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 4 years

• 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.

  Up to 4 years

Secondary Outcomes (5)

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

  Up to 4 years

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

  Up to 4 years

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

  Up to 4 years

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

  Up to 4 years

• Incidence of adverse events

  Up to 4 years

Study Arms (1)

Treatment (poziotinib)

EXPERIMENTAL

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

Drug: Poziotinib

Interventions

Poziotinib DRUG

Given PO

Also known as: HM781-36B, NOV120101

Treatment (poziotinib)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed stage IV or recurrent solid tumor not amenable to curative intent therapy
• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Spectrum Pharmaceuticals, Inc: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• 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.

  PMID: 35820397 DERIVED

• 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.

  PMID: 34550757 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

HM781-36B

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yasir Y Elamin

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2017
• First Posted: February 28, 2017
• Study Start: March 17, 2017
• Primary Completion: February 16, 2026
• Study Completion: February 16, 2026
• Last Updated: February 20, 2026

Record last verified: 2026-02

Locations

US (1)