Abstract
Mobocertinib efficacy in patients with NSCLC and EGFR exon 20 insertion mutations (ex20ins) identified by next-generation sequencing (NGS) of circulating tumor DNA (ctDNA).
Author
Joel W. Neal
Stanford University Medical Center, Stanford, CA
info_outline
Joel W. Neal, Ying Li, Ziji Yu, Robert J. Fram, Christopher Danes, Sylvie Vincent, Zofia Piotrowska
Full text
Authors
Joel W. Neal
Stanford University Medical Center, Stanford, CA
info_outline
Joel W. Neal, Ying Li, Ziji Yu, Robert J. Fram, Christopher Danes, Sylvie Vincent, Zofia Piotrowska
Organizations
Stanford University Medical Center, Stanford, CA, Takeda Development Center Americas, Inc., Lexington, MA, Takeda Pharmaceuticals USA, Inc., Lexington, MA, Massachusetts General Hospital, Boston, MA
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
Takeda Development Center Americas, Inc., Lexington, MA, USA
Background:
EGFR
ex20ins are distinct targetable driver mutations present in ~2% of all NSCLC. While most EGFR TKIs have limited effectiveness, mobocertinib is the first oral therapy approved for this unmet need.
EGFR
ex20ins are heterogeneous ( > 60 variants), and PCR testing detects a limited number of variants, leading to undetected disease in ~50% of cases, whereas NGS can identify all such mutations. Testing plasma ctDNA is a noninvasive approach for detection of genomic variants, such as
EGFR
ex20ins.
Methods:
In the mobocertinib phase 1/2 study (NCT02716116), patients were enrolled based on
EGFR
ex20ins detected by various local tissue or liquid clinical trial assays (CTAs). Baseline plasma samples were collected and processed to extract cell-free DNA and were evaluated for
EGFR
ex20ins status using FoundationOne Liquid CDX (F1LCDX), an NGS-based plasma ctDNA test. Concordance between F1LCDX and the CTAs was demonstrated by testing patient samples from the phase 1/2 trial and paired tissue and plasma samples from commercially acquired and stage-matched patients with NSCLC (N = 305). Efficacy analyses by assay method were performed in
EGFR
ex20ins–positive platinum-pretreated patients (PPP; n = 114 [FDA approved population]; data cutoff: 1 Nov 2021) in the phase 1/2 trial.
Results:
Concordance between F1LCDX and CTAs was demonstrated with samples from the CTA-positive (n = 159) and CTA-negative populations (n = 87) tested by F1LCDX where tissue and plasma were assessable; the point estimate of positive percentage agreement (95% CI) was 68.6% (61.0–75.3), and the point estimate of negative percentage agreement was 100% (95.8–100). F1LCDX detected 34 individual
EGFR
ex20ins variant types. In the response evaluable population, patients who tested
EGFR
ex20ins positive by F1LCDX (n = 55) demonstrated confirmed ORR (34.5%) and disease control rate (74.5%), which was comparable to those observed among all PPP in the phase 1/2 trial (confirmed ORR: 28%; confirmed disease control rate: 78%).
Conclusions:
Mobocertinib has shown efficacy in PPP with
EGFR
ex20ins NSCLC. F1LCDX effectively identified patients with
EGFR
ex20ins who may benefit from mobocertinib, providing an additional noninvasive diagnostic option to guide treatment. Clinical trial information: NCT02716116.
Clinical status
Clinical
1 clinical trial
4 organizations
1 drug
1 target
Clinical trial
A Phase 1/2 Study of the Safety, Pharmacokinetics, and Anti-Tumor Activity of the Oral EGFR/HER2 Inhibitor TAK-788 (AP32788) in Non-Small Cell Lung CancerStatus: Active (not recruiting), Estimated PCD: 2025-03-28
Organization
Stanford University Medical Center, Stanford, CAOrganization
Takeda Pharmaceuticals USA, Inc.Organization
Massachusetts General HospitalDrug
MobocertinibTarget
EGFR ex20ins