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A Study of Poziotinib in Patients With EGFR or HER2 Activating Mutations in Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT04172597
Recruitment Status : Recruiting
First Posted : November 21, 2019
Last Update Posted : November 13, 2020
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc

Brief Summary:
This is a Phase 2, open-label, multicenter study to evaluate the efficacy and the safety/tolerability of poziotinib in five patient cohorts for up to 150 previously treated patients with any systemic therapy (Cohort 1: 30 Patients that have HER2-positive or HER2-negative breast cancer with HER2 activating mutations, Cohort 2: 30 Patients that have colorectal cancer with HER2 activating mutations, Cohort 3: Patients that have solid tumors (except NSCLC, breast cancer, or colorectal cancer) with HER2 activating mutations, Cohort 4: 30 Patients that have high-grade glioma with EGFR activating mutations, and Cohort 5: 30 Patients that have solid tumors (except NSCLC or high-grade glioma) with EGFR activating mutations.

Condition or disease Intervention/treatment Phase
Breast Cancer Colorectal Cancer Solid Tumor High Grade Glioma Drug: Poziotinib Hydrochloride Phase 2

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 undergoing any study procedures.

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

  • Cohort 1: Patients that have HER2-positive or HER2-negative breast cancer with HER2 activating mutations.
  • Cohort 2: Patients that have colorectal cancer with HER2 activating mutations
  • Cohort 3: Patients that have solid tumors (except NSCLC, breast cancer, or colorectal cancer) with HER2 activating mutations
  • Cohort 4: Patients that have high-grade glioma with EGFR activating mutations
  • Cohort 5: Patients that have solid tumors (except NSCLC or high-grade glioma) with EGFR activating mutations

All patients will be treated 28 days per cycle until 24 months of treatment, disease progression, death, intolerable adverse events (AEs), or other protocol-specified reasons for patient withdrawal

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Each treatment cycle is 28 calendar days in duration. This is a basket study with five patient cohorts and eligible patients will be enrolled into each cohort in parallel based on EGFR or HER2 mutation-positive malignant solid tumors status.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Poziotinib in Patients With EGFR or HER2 Activating Mutations in Advanced Malignancies
Actual Study Start Date : December 23, 2019
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Poziotinib
  • Cohort 1: Patients that have HER2-positive or HER2-negative breast cancer with HER2 activating mutations
  • Cohort 2: Patients that have colorectal cancer with HER2 activating mutations
  • Cohort 3: Patients that have solid tumors (except NSCLC, breast cancer, or colorectal cancer) with HER2 activating mutations
  • Cohort 4: Patients that have high-grade glioma with EGFR activating mutations
  • Cohort 5:Patients that have solid tumors (except NSCLC or high-grade glioma) with EGFR activating mutations
Drug: Poziotinib Hydrochloride
The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 24 months ]
    Proportion of patients whose best overall response is confirmed CR or PR


Secondary Outcome Measures :
  1. Duration of Response (DoR) [ Time Frame: 24 months ]
    Time from the first CR or PR until progressive disease or death

  2. Disease Control Rate (DCR) [ Time Frame: 24 months ]
    Proportion of patients whose best overall response is CR, PR, or SD



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Patient is 18 years or older.
  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 a metastatic solid tumor that meets at least one of the following criteria:

    • has progressed on a standard therapy
    • has no available standard therapy
    • In the opinion of the investigator, patient is not a candidate for or would be unlikely to tolerate or receive benefit from standard therapy
  4. Patient is positive for EGFR or HER2 mutations based on DNA genetic testing of either tumor tissue or plasma samples, but tissue is preferred. Patients with documented EGFR or HER2 mutations are identified by local testing from participating sites using next generation sequencing (NGS) test. Patient with a solid tumor with at least one of the listed activating mutations.

    • Cohort 1: Patients that have breast cancer with HER2 activating mutations (N=30)
    • Cohort 2: Patients that have colorectal cancer with HER2 activating mutations (N=30)
    • Cohort 3: Patients that have solid tumors (except NSCLC, breast cancer, or colorectal cancer) with HER2 activating mutations (N=30)
    • Cohort 4: Patients that have high-grade glioma with EGFR activating mutations (N=30)
    • Cohort 5: Patients that have solid tumors (except NSCLC or high-grade glioma) with EGFR activating mutations (N=30)

    Activating Mutations Cohorts 1-3. HER2 Activating Mutations (at least one of the following) Furin-Like/Extracellular. S310F/Y Transmembrane. I655V, V659E, R678Q, V697L Kinase Domain. Exon 20 insertion, T733I, L755X, I767M, D769H/N/Y, V773M, V777L/M, L786V, V842I, T862I, L869R

    Cohorts 4-5. EGFR Activating Mutations (at least one of the following) Extracellular & Transmembrane: EGFRvIII, R108K, R222C, A289T, P596L, G598V Kinase Domain: Exon 20 insertion, E709K, G719X, V742I, E746_A750del, S768I, V769M, V774M, R831C, R831H, L858R, L861Q, A864V

  5. Patient has measurable disease, as per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and/or RANO Criteria for Cohort 4. These target lesion(s) must be radiographically measurable. CNS metastatic lesions cannot be considered target lesions in Cohorts 1-3 and in Cohort 5.
  6. Brain metastases may be allowed if patient's condition is stable. Stable brain metastases are defined as stable symptoms, no requirement for high dose or increasing doses of systemic corticosteroid (except Cohort 4 where anti-seizure medication [Keppra] and dexamethasone up to or equivalent to 4 mg daily), nor progression on imaging studies for at least 4 weeks prior to enrolment.
  7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  8. 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, as defined by:

    • Absolute neutrophil count (ANC) must be ≥1.0×109/L
    • Platelet count ≥ 75 × 109/L
    • Hemoglobin ≥ 9.0 g/dL
    • Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/serum glutamic-pyruvic transaminase (ALT/SGPT) ≤2.5 ×upper limit of normal (ULN); if hepatic metastases are present, ≤5.0×ULN
    • Creatinine clearance ≥ 50 mL/min (calculated according to Cockcroft and Gault formula)

Exclusion Criteria:

  1. Patient has primary tumors in central nervous system (CNS) or in brain, including glioblastoma multiforme (GBM), meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or unstable brain metastasis except if qualified under inclusion criteria for Cohort 4.
  2. Patient with T798M or T798I mutations in HER2, or patients with the T790M mutation in EGFR.
  3. Patients with breast or gastric cancers with HER2 copy number alterations/amplifications/over expressions and no HER2 activating mutations.
  4. Patient has received anticancer chemotherapy, biologics, immunotherapy, targeted therapy (including HER2 targeted therapy), curative-intent radiotherapy, or other investigational treatment within 15 days. Local radiation therapy for bone pain may be allowed. Standard and approved hormonal therapies for hormonal receptor positive tumors are allowed.
  5. Patient has not recovered (i.e, still at > Grade 1) from drug-induced pancreatitis or has a history of drug-induced pancreatitis.
  6. Patient has not recovered (i.e, still at > Grade 1) from interstitial lung disease or has a history of interstitial lung disease or radiation pneumonitis.
  7. 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.
  8. 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%.
  9. Patient has a history of other malignancies within the last 3 years, except for non-melanoma skin cancer, carcinoma in situ of the cervix, or PSA-stable, asymptomatic, early stage of prostate cancer or superficial bladder cancer without active treatment.
  10. Patient is unable to take drugs orally due to disorders or diseases that may affect gastrointestinal function or malabsorption syndrome.
  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 a medical condition that in the opinion of the investigator or medical monitor would put her/him at an unreasonable risk including drug toxicity during the trial.
  13. Patient has had recent major surgery or invasive procedure within 15 days prior to starting study treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04172597


Contacts
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Contact: Lyndah Dreiling, MD 949-788-6700 lyndah.dreiling@sppirx.com
Contact: Cheyney Fermin, MPH SPI-POZ-203Basket@sppirx.com

Locations
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United States, California
Pacific Shores Medical Group Recruiting
Long Beach, California, United States, 90813
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
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Study Director: Lyndah Dreiling, MD Spectrum Pharmaceuticals, Inc
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Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT04172597    
Other Study ID Numbers: SPI-POZ-203
First Posted: November 21, 2019    Key Record Dates
Last Update Posted: November 13, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Spectrum Pharmaceuticals, Inc:
EGFR activating mutations
HER2 activating mutations
HER2-positive breast cancer
HER2-negative breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases