Spectrum Pharmaceuticals : Poziotinib administered twice daily improves safety and tolerability in patients with EGFR or HER2 exon 20 mutations

Poziotinib administered twice daily improves safety and tolerability in patients with EGFR or HER2 exon 20 mutant NSCLC (ZENITH20-5)

X Le1, E Shum2, JM Suga3, JR Brahmer4, C Dooms5, H Mamdani6, H Nechustan7, JW Riess8, A Spira9, JA

Barrett10, LK Dreiling10, G Bhat10, F Lebel10, MA Socinski11

on behalf of ZENITH20 Study Group

1UT MD Anderson Cancer Center, Houston, TX; 2NYU Laura & Isaac Perlmutter Cancer Center, New York, NY; 3Kaiser Permanente Medical Center, Vallejo, CA; 4Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; 5University Hospitals Leuven, Leuven, BE; 6Karmanos Cancer Institute, Detroit, MI; 7Hadassah Medical Center, Jerusalem, IL; 8University of California Davis Comprehensive Cancer Center, Sacramento, CA; 9Virgiania Cancer Specialists, PC, Fairfax, VA; 10Spectrum Pharmaceuticals, Inc, Irvine, CA; 11AdventHealth Hematology and Oncology, Orlando, FL

Poziotinib is an investigational drug not approved by the FDA

2021 AACR Virtual Annual Meeting Plenary Clinical Trial Abstract: #5176	Presenter: Xiuning Le MD PhD

Introduction

• Effective treatment for patients with metastatic non-small cell lung cancer (mNSCLC) harboring EGFR or HER2 exon 20 insertion mutations represents an important unmet medical need.1
• Poziotinib is a potent, irreversible, tyrosine kinase inhibitor (TKI) targeting EGFR and HER2 exon 20 insertion mutations.2-4
• The safety and efficacy of once daily (QD) dosing with poziotinib at 16mg QD has been established previously in a large, multicentric study with blinded central image review.5
• Poziotinib has a short half-life of 7.2 hours allowing for twice daily (BID) dosing in order to reduce Cmax and associated toxicity.
• Preliminary safety with poziotinib administered BID dosing has been recently presented at 2021 ESMO TAT in patients treated for EGFR and HER2 exon 20 NSCLC suggesting improved tolerability.
• Here we present updated safety and preliminary efficacy of BID dosing.

2

Material and Methods

• ZENITH20 (NCT03318939) is a Phase 2, open-label,multi-cohort,multi-center study designed to evaluate the efficacy and the safety/tolerability of poziotinib in previously treated and treatment- naïve patients with NSCLC.
• The ongoing ZENITH20-Cohort 5 enrolls patients with locally advanced or mNSCLC with EGFR or HER2 exon 20 insertion mutations.
• Patients are being randomized to various arms: 10, 12, and 16 mg QD or 6 and 8 mg BID.
• Dose reductions are allowed in the presence of toxicity and patients are treated until death, disease progression or intolerable toxicity.

3

Entry Criteria

Inclusion Criteria

• Histologically or cytologically confirmed NSCLC which is locally advanced or metastatic
• Documented EGFR or HER2 exon 20 insertion mutation by a tissue next generation sequencing test
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Stable CNS metastases are allowed

Exclusion Criteria

• Previously treated with poziotinib or any other EGFR or HER2 exon 20 insertion mutation- selective TKI
• EGFR exon20 point mutation

4

Figure 1. ZENITH20: a Phase 2 multi-cohort international trial

Fully Enrolled

Cohort 1

Previously treated NSCLC with EGFR exon 20 insertions (16mg QD)

Cohort 2

Previously treated NSCLC with HER2 exon 20 insertions (16mg QD)

Cohort 3

First-line NSCLC with

EGFR exon 20

insertions (16mg QD)

Objectives

• Primary
• • Objective Response Rate (ORR)
• Secondary
• • Disease Control Rate (DCR)
  • Duration of Response (DOR)
  • Safety & Tolerability

ORR based on Central independent imaging review

Cohort 5: Randomized to various dose and schedule

• Simon's 2-stage design
• • Stage 1: 19 patients per arm
  • >3 responders

Enrolling

Cohort 4

First-line NSCLC with

HER2 exon 20

insertions

(16mg QD; 8mg BID)

Cohort 5

NSCLC with EGFR or

HER2 exon 20 mut

(6mg, 8mg BID;

10mg, 12mg, 16mg

QD)

Cohort 6

EGFR Osimertinib

Failures

(8mg BID)

Cohort 7

Atypical EGFR or HER2

mutations (8mg BID)