A Study of Poziotinib in Patients With Epidermal Growth Factor Receptor (EGFR) or Human Epidermal Growth Factor Receptor 2 (HER2) Activating Mutations in Advanced Malignancies

NCT04172597 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: SPI-POZ-203
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2, open-label, multicenter study whose principal objectives are to evaluate the efficacy and safety/tolerability of poziotinib in five cohorts of 30 previously-treated patients each.

Conditions

Breast Cancer; Colorectal Cancer; Solid Tumor; Glioblastome Multiforme

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR was defined as the percentage of participants with confirmed complete response (CR) and partial response (PR) as assessed by the investigator using local radiology evaluation according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR is defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes must have a reduction in the short axis to \<10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.

  Up to 168 days

Secondary Outcomes (3)

• Duration of Response (DoR)

  Up to 168 days

• Disease Control Rate (DCR)

  Up to 168 days

• Percentage of Participants With AE

  Up to 30 days after last dose of study drug (Up to 199 days)

Study Arms (5)

Cohort 1

EXPERIMENTAL

Patients with HER2-positive or HER2-negative BC with a HER2 activating mutation will receive poziotinib 8 milligrams (mg), orally, twice daily (BID) starting on Day 1 of each 28 day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Loperamide may be prescribed for the treatment of diarrhea as needed.

Drug: Poziotinib Hydrochloride; Drug: Loperamide

Cohort 2

EXPERIMENTAL

Patients with CRC with a HER2 activating mutation will receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28 day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Loperamide may be prescribed for the treatment of diarrhea as needed.

Drug: Poziotinib Hydrochloride; Drug: Loperamide

Cohort 3

EXPERIMENTAL

Patients with CRC with a HER2 activating mutation will receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28 day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Loperamide may be prescribed for the treatment of diarrhea as needed.

Drug: Poziotinib Hydrochloride; Drug: Loperamide

Cohort 4

EXPERIMENTAL

Patients with CRC with a HER2 activating mutation will receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28 day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Loperamide may be prescribed for the treatment of diarrhea as needed.

Drug: Poziotinib Hydrochloride; Drug: Loperamide

Cohort 5

EXPERIMENTAL

Patients with CRC with a HER2 activating mutation will receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28 day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Loperamide may be prescribed for the treatment of diarrhea as needed.

Drug: Poziotinib Hydrochloride; Drug: Loperamide

Interventions

Poziotinib Hydrochloride DRUG

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

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Loperamide DRUG

Loperamide as prescribed by the physician.

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

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

You may qualify if:

• Patients must be at least 18 years old.
• Patients must have histologic or cytologic evidence of a malignant solid cancer that is either advanced or metastatic there must be no available therapy known to confer a reasonable likelihood of clinical benefit.
• Patients with BC must have a HER2 activating mutation determined by next-generation sequencing (NGS) performed on either tumor or plasma samples and:
• Immunohistochemistry (IHC) HER2-positive BC that has progressed on trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1) in the metastatic setting, unless there is recurrent disease within 12 months of adjuvant or neoadjuvant treatment.
• IHC HER2-negative, estrogen receptor/progesterone receptor (ER/PR)-positive BC that has progressed on or after appropriate first-line endocrine therapy in the metastatic setting.
• IHC HER2-negative, ER/PR-negative BC that has progressed after first-line treatment (any standard chemotherapy-based regimen) in the metastatic setting.
• Patients with microsatellite instability-high (MSI-H) CRC must have had appropriate checkpoint inhibitor-based therapy.
• Patient's tumor must be positive for an EGFR or HER2 mutation based on DNA testing of either tumor tissue or plasma samples. Patients with documented EGFR or HER2 mutations may be identified by local testing from participating sites using next generation sequencing tests. Patient has a solid tumor with at least one of the listed 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, D769X, V773M, V777X, 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, E709X, E709\_T710del insD, L718X, G719X, I740\_K745dupIPVAIK, I740\_K745dup, V742I, L747X, E746\_A750del, A750P, S768I, S768I/V769L, S768I/V774M, L833V, V769M, V774M, R831C, R831H, L858R, L861Q, A864V.
• Patients must have measurable disease.
• Patients with central nervous system (CNS) metastases must have stable CNS disease and no evidence of growth on imaging for at least 4 weeks following radiation or other locoregional ablative therapy. CNS symptoms must be stable with no requirement for anti-seizure medications and/or \> 2 mg/day dexamethasone equivalent, except for patients with GBM (Cohort 4), in whom anti-seizure medications and/or up to 4 mg/day dexamethasone equivalent is allowed.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ -1.
• Patients must have adequate hematopoietic, renal, and liver functions.

You may not qualify if:

• Patient has an EGFR T790 mutation.
• Patients with GBM enrolled in Cohort 4 has been treated with an inhibitor of vascular endothelial growth factor (VEGF) inhibitor therapy (e.g., bevacizumab).
• Patient requires treatment with a medication that is a strong inhibitor or inducer of CYP3A4 or CYP2D6 or has been treated with such medications within 15 days of poziotinib treatment.
• Patient has ≥ Grade 2 skin disorders (rash), mucositis, or stomatitis within 15 days of poziotinib treatment.
• Patient has a gastrointenstinal disorder or malabsorption that precludes oral drug treatment.
• Patient has active liver or biliary tract disease (except for Gilbert's syndrome, asymptomatic biliary stones, liver metastasis, or stable chronic liver diseases).
• Patient has a history of drug-induced pancreatitis.
• Patient has a history of interstitial lung disease or pneumonitis.
• Patient has a history of congestive heart failure Class III/IV according to the New York Heart Association Functional Classification or a serious cardiac arrhythmia requiring treatment.
• Patient has a high risk of cardiac disease as determined by the Investigator. If patient is deemed to have a high cardiac risk, enrollment may be considered if an echocardiogram (ECHO) or multi-gated acquisition (MUGA) during Screening demonstrates a cardiac ejection fraction \>= 50%.
• Patient has a QTc interval \> 470 ms.
• Patient has a history of another malignancy within the 1 year prior to poziotinib treatment. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including transitional cell carcinoma, cervical intraepithelial neoplasia, and melanoma in situ), organ-confined prostate cancer with no evidence of progressive disease.

Sponsors & Collaborators

• Spectrum Pharmaceuticals, Inc: lead

Study Sites (1)

Pacific Shores Medical Group

Long Beach, California, 90813, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Colorectal Neoplasms

Interventions

Loperamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Howard Franklin, MD
• Organization: Assertio Holdings

Hfranklin@assertiotx.com

224 419 7106

Study Officials

• Jaba Kokhreidze, MD

  Spectrum Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• 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. This is a basket study with five distinct cohorts. Eligible patients will be enrolled into the five cohorts concurrently based on tumor type and mutational status.

Study Record Dates

• First Submitted: November 19, 2019
• First Posted: November 21, 2019
• Study Start: December 23, 2019
• Primary Completion: March 29, 2022
• Study Completion: March 29, 2022
• Last Updated: March 13, 2024
• Results First Posted: March 13, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)