Poziotinib in Patients With NSCLC Having EGFR or HER2 Exon 20 Insertion Mutation

NCT04044170 | Terminated Phase 2

• 1 other identifier: HM-PHI-202
• Study Type: interventional
• Target: 5
• Locations: 2 countries
• Sites: 26

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).

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  The proportion of subjects who achieve Complete Response (CR) and Partial Response (PR) by the best response from the first dose of poziotinib to the end of study.

  24 months

Secondary Outcomes (3)

• Disease Control Rate (DCR)

  24 months

• Duration of Response (DoR)

  24 months

• Progression-free Survival (PFS)

  24 months

Study Arms (1)

Poziotinib

EXPERIMENTAL

* 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

Drug: Poziotinib

Interventions

Poziotinib DRUG

The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.

Also known as: HM781-36B

Poziotinib

Eligibility Criteria

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

You may qualify if:

• 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.
• Patient must be willing and capable of giving written Informed Consent, adhering to dosing and visit schedules, and meeting all study requirements
• Patient has histologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) that is not amenable to treatment with curative intent
• Patient has had at least one prior systemic treatment for NSCLC, but no more than three prior systemic therapy
• Patient has adequate tumor tissue obtained from a biopsy or surgical procedure to enable molecular profiling for central laboratory confirmation of the mutation.
• 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)
• 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.
• Brain metastases may be allowed if patient's condition is stable.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 and has a life-expectancy of more than 6 months
• 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
• 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
• 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.

You may not qualify if:

• Patient has EGFR T790M mutation or any other acquired EGFR exon 20 point mutation
• 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.
• 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
• 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 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%.
• 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
• Patient is confirmed to have clinically significant or recent acute gastrointestinal disease presenting as diarrhea and/or coloenteritis as a main symptom.
• 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.
• Presence or history of interstitial lung disease (ILD), drug-induced ILD, or presence of radiation pneumonitis
• 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
• 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)
• Patient has known hypersensitivity to poziotinib or has a history of allergic reactions attributed to chemically similar compounds or other tyrosine kinase inhibitors (TKIs)
• Patient has an active uncontrolled infection, underlying medical condition, or other serious illness that would not be appropriate for this study
• 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
• Patient is pregnant or breast-feeding.

Sponsors & Collaborators

• Hanmi Pharmaceutical Company Limited: lead

Study Sites (26)

Beijing Cancer Hospital

Beijing, China

Location

Beijing Chest Hospital

Beijing, China

Location

Beijing Hospital

Beijing, China

Location

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, China

Location

Peking Union Medical College Hospital

Beijing, China

Location

Jilin Cancer Hospital

Changchun, China

Location

The First Hospital of Jilin University

Changchun, China

Location

The Third Xiangya Hospital of Central South University

Changsha, China

Location

Sichuan Cancer Hospital and Institute

Chengdu, China

Location

West China Hospital of Sichuan University

Chengdu, China

Location

Fujian Provincial Cancer Hospital

Fuzhou, China

Location

Guangdong General Hospital

Guangzhou, China

Location

Guangdong Panyu Central Hospital

Guangzhou, China

Location

Shi Run Run Shaw Hospital, Zhejiang University

Hangzhou, China

Location

The First Affiliated Hospital, Zhejiang University

Hangzhou, China

Location

Zhejiang Cancer Hospital

Hangzhou, China

Location

The Second Hospital of Anhui Medical University

Hefei, China

Location

Shanghai Chest Hospital

Shanghai, China

Location

University of Hong Kong-Shenzhen Hospital

Shenzhen, China

Location

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

Location

Chungbuk National University Hospital

Cheongju-si, South Korea

Location

National Cancer Center

Gyeonggi-do, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

MeSH Terms

Interventions

HM781-36B

Study Officials

• Hanmi Pharmaceuticals

  Hanmi Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Model Details: 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

Study Record Dates

• First Submitted: August 1, 2019
• First Posted: August 5, 2019
• Study Start: July 30, 2019
• Primary Completion: April 13, 2020
• Study Completion: April 13, 2020
• Last Updated: November 17, 2020

Record last verified: 2020-11

Locations

KR (5); CN (21)