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

NCT04172597

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Diffuse Midline Glioma, H3 K27M-Mutant
  • Gastric Carcinoma
  • Glioblastoma
  • Malignant Solid Tumor
  • WHO Grade III Glioma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 2 Study of Poziotinib in Patients With EGFR or HER2 Activating Mutations in Advanced Malignancies
  • Official Title: A Phase 2 Study of Poziotinib in Patients With EGFR or HER2 Activating Mutations in Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: SPI-POZ-203
  • NCT ID: NCT04172597

Conditions

  • Breast Cancer
  • Colorectal Cancer
  • Solid Tumor
  • High Grade Glioma

Interventions

DrugSynonymsArms
Poziotinib HydrochlorideCohort 1

Purpose

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.

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
    

Trial Arms

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

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:24 months
Safety Issue:
Description:Proportion of patients whose best overall response is confirmed CR or PR

Secondary Outcome Measures

Measure:Duration of Response (DoR)
Time Frame:24 months
Safety Issue:
Description:Time from the first CR or PR until progressive disease or death
Measure:Disease Control Rate (DCR)
Time Frame:24 months
Safety Issue:
Description:Proportion of patients whose best overall response is CR, PR, or SD

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Spectrum Pharmaceuticals, Inc

Trial Keywords

  • EGFR activating mutations
  • HER2 activating mutations
  • HER2-positive breast cancer
  • HER2-negative breast cancer

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