2021 ASCO Annual Meeting: CNS activity of poziotinib in NSCLC with exon 20 insertion mutations

RD-POZ-0013

CNS ACTIVITY OF POZIOTINIB IN NSCLC WITH EXON 20 INSERTION MUTATIONS

Xiuning Le1, Marina C Garassino2, Robin Cornelissen3, Mark A Socinski4, Nishan Tchekmedyian5, Julian R Molina6, Christina S Baik7, Arsela Prelaj8, Chul Kim9, Sharon Leu10, Lyndah K Dreiling10, Francois Lebel10, Jeffrey M Clarke11

1The University of Texas MD Anderson Cancer Center, Houston, TX; 2University of Chicago Medical Center, Chicago, IL; 3Erasmus Medical Center, Rotterdam, Netherlands; 4AdventHealth Cancer Institute, Orlando, FL; 5Pacific Shores Medical Group, Huntington Beach, CA; 6Mayo Clinic, Rochester, MN; 7Seattle Cancer Care Alliance, Seattle, WA; 8Istituto Nazionale Tumori of Milan, Italy; 9 Georgetown University, Washington DC; 10Spectrum Pharmaceuticals, Irvine, CA; 11Duke University Medical Center, Durham, NC

Poziotinib is an investigational drug not approved by the FDA

Disclosures

Xiuning Le, receives consulting/advisory fees from EMD Serono (Merck KGaA), AstraZeneca, Spectrum Pharmaceuticals, Inc., Eli Lilly, Boehringer Ingelheim, Bristol-Myers Squibb and Celgene, and Research Funding from Eli Lilly, and Boehringer Ingelheim.

3

Introduction

• Metastatic NSCLC harboring EGFR or HER2 exon 20 insertion mutations is a uniformly fatal disease and represents an unmet medical need
• Brain metastasis in NSCLC is frequent, occurs in up to 25% of patients and is associated with short survival (mOS of 2-5 months following WBRT1)
• Poziotinib is a potent, irreversible TKI that targets exon 20 insertion mutations
• Two previous case reports in exon 20 mutated brain metastases suggest poziotinib CNS penetration2, 3
• Here we present poziotinib CNS activity in NSCLC with EGFR or HER2 exon 20 insertion mutations in the ongoing ZENITH20 Study

1Langer CJ, Mehta MP. et al. J Clin Oncol. 2005 2Pandey A et al, Clin Breast Cancer, 2018

3Tchekmedyian N, et al. JTO Clin and Res Reports, 2020

Xiuning Le, MD PhD

The University of Texas MD Anderson Cancer Center

Figure 1. ZENITH20 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)
  • • Based on Central Independent Review
• Secondary
• • Duration of Response (DOR)
  • Safety & Tolerability
• Baseline CNS assessment required only in

symptomatic patients

• Stable CNS metastasis allowed if:

• Asymptomatic, without requirement for high-dose steroids or anti-convulsant therapy
• After recent RT, sequential post-txt MRI ≥ 4 wks showing stable disease
• Intracranial assessment based modified RECIST by central review

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)

Table 1. Demographics and Patient Disposition

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	CNS Subgroup	Non-CNS Subgroup	All Patients
	N=36	N=248	N=284
Median age, yrs (range)	58.5 (30, 75)	61 (25, 86)	60.5 (25, 86)
Gender: female / male	25 / 11	154 / 94	179 / 105
ECOG Status: 0 / 1	13 / 23	108 / 140	12 / 163
n (%)
EGFR	22 (61)	172 (69)	194 (68)
HER2	14 (39)	76 (31)	90 (32)
Length of Follow-up (months)
Median (Min, Max)	5.5 (0.9, 11.1)	9.2 (0.03, 26.0)	9.2 (0.03, 26.0)

Pooled analysis ZENITH20 cohorts 1-3

Xiuning Le, MD PhD

The University of Texas MD Anderson Cancer Center