Clinical trial NCT04044170: Poziotinib in Patients With NSCLC Having EGFR or HER2 Exon 20 Insertion Mutation
Official title: A Phase 2 Study of Poziotinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With EGFR or HER2 Exon 20 Mutation in China and Korea
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: NSCLC
Lead sponsor: Hanmi Pharmaceutical Company Limited
Sponsor class: INDUSTRY
First posted: 2019-08-05
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Each treatment cycle is 28 calendar days in duration. There will be two patient cohorts and eligible patients will be enrolled into each cohort in parallel based on EGFR or HER2 exon 20 mutation status:

* Cohort 1 : Previously treated patients with EGFR exon 20 insertion mutation positive NSCLC
* Cohort 2 : Previously treated patients with HER2 exon 20 insertion mutation positive NSCLC
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, open-label, multicenter study to evaluate the efficacy and the safety/tolerability of poziotinib in two patient cohorts for up to 114 previously treated NSCLC patients with any systemic therapy (57 patients with EGFR exon 20 insertion mutations and 57 patients with HER2 exon 20 insertion mutations).

Detailed description: The Screening period (Day -30 to Day -1) lasts up to approximately 30 days prior to Cycle 1, Day 1. Patients must meet all Inclusion/Exclusion Criteria to participate in the study. Eligible patients will provide written Informed Consent prior to any study procedures.

Each treatment cycle is 28 calendar days in duration. There will be two patient cohorts and eligible patients will be enrolled into each cohort in parallel based on EGFR or HER2 exon 20 mutation status:

* Cohort 1 : Previously treated patients with EGFR exon 20 insertion mutation positive NSCLC (N=57)
* Cohort 2 : Previously treated patients with HER2 exon 20 insertion mutation positive NSCLC (N=57) Toxicity will be assessed based on the severity grade of the adverse events using CTCAE version 4.03.

Poziotinib (16 mg) will be taken orally, once daily (QD) with food and a glass of water at approximately the same time each morning.

All patients will be treated until disease progression, death, intolerable adverse events (AEs), or other protocol-specified reasons for patient withdrawal.

Eligibility criteria: Inclusion Criteria:

1. Patient is at least 18 years of age (or country's legal age of majority if the legal age was \> 18 years) at the time of obtaining informed consent.
2. Patient must be willing and capable of giving written Informed Consent, adhering to dosing and visit schedules, and meeting all study requirements
3. Patient has histologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) that is not amenable to treatment with curative intent
4. Patient has had at least one prior systemic treatment for NSCLC, but no more than three prior systemic therapy
5. Patient has adequate tumor tissue obtained from a biopsy or surgical procedure to enable molecular profiling for central laboratory confirmation of the mutation.
6. Patient is positive for EGFR or HER2 exon 20 mutations based on tissue testing:

   * Cohort 1: Documented EGFR exon 20 insertion mutation (including duplication mutations)
   * Cohort 2: Documented HER2 exon 20 insertion mutation (including duplication mutations)
7. Patient has measurable disease, as per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Metastatic lesions in CNS or in brain cannot be used for target lesions.
8. Brain metastases may be allowed if patient's condition is stable.
9. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 and has a life-expectancy of more than 6 months
10. Patient has recovered from prior systemic therapy for metastatic disease to Grade ≤1 for non-hematologic toxicities (except for Grade ≤2 peripheral neuropathy) and has adequate hematologic, hepatic, and renal function at Baseline
11. Patient is willing to practice 2 forms of contraception, one of which must be a barrier method, from study entry until at least 30 days after the last dose of poziotinib
12. Females of childbearing potential must have a negative pregnancy test within 30 days prior to enrollment. Females who are postmenopausal for at least 1 year (defined as more than 12 months since last menses) or who are surgically sterilized do not require this test.

Exclusion Criteria:

1. Patient has EGFR T790M mutation or any other acquired EGFR exon 20 point mutation
2. Patient 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.
3. Patient has had radiotherapy (intention for cure) or surgery (other than surgical placement for vascular access and minimally invasive procedures including some biopsy procedures) within 2 weeks prior to start of study treatment with poziotinib
4. 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
5. Patient has a high risk of cardiac disease, as determined by the Investigator, may undergo either echocardiogram (ECHO) or multi-gated acquisition (MUGA) during Screening and has a cardiac ejection fraction \<50%.
6. Patient 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
7. Patient is confirmed to have clinically significant or recent acute gastrointestinal disease presenting as diarrhea and/or coloenteritis as a main symptom.
8. Patient has an active Grade ≥2 skin disorder, rash, mucositis, or skin infection that needs medication or therapy or existing Grade ≥2 skin toxicity from previous therapies.
9. Presence or history of interstitial lung disease (ILD), drug-induced ILD, or presence of radiation pneumonitis
10. Patient is unable to take drugs orally due to disorders or diseases that may affect gastrointestinal function, such as inflammatory bowel diseases or malabsorption syndrome, or procedures that may affect gastrointestinal function
11. Patient has an active liver disease or biliary tract disease (except for Gilbert's disease, asymptomatic biliary stones, liver metastasis, or stabilized chronic liver diseases)
12. Patient has known hypersensitivity to poziotinib or has a history of allergic reactions attributed to chemically similar compounds or other tyrosine kinase inhibitors (TKIs)
13. Patient has an active uncontrolled infection, underlying medical condition, or other serious illness that would not be appropriate for this study
14. Patient has unstable, uncontrolled, active bleeding disorders that the investigator considers that the patient could be at increased risk or not be suitable for treatment in this study
15. Patient is pregnant or breast-feeding.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: 24 months
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: 24 months
measure: Duration of Response (DoR)
timeFrame: 24 months
measure: Progression-free Survival (PFS)
timeFrame: 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Beijing Chest Hospital
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
city: Chengdu
country: China
facility: Sichuan Cancer Hospital and Institute
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
city: Guangzhou
country: China
facility: Guangdong General Hospital
city: Guangzhou
country: China
facility: Guangdong Panyu Central Hospital
city: Hangzhou
country: China
facility: Shi Run Run Shaw Hospital, Zhejiang University
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shenzhen
country: China
facility: University of Hong Kong-Shenzhen Hospital
city: Wuhan
country: China
facility: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Hanmi Pharmaceuticals
name: Hanmi Pharmaceuticals
role: STUDY_DIRECTOR
References: