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Found 1 Presentation For Request "1345P"
1345P - Preliminary safety and activity of CLN-081 in NSCLC with EGFR exon 20 insertion mutations (Ins20)
- Zofia Piotrowska (Boston, United States of America)
Abstract
Background
EGFR ins20-mutant NSCLC has been historically difficult to target. While several agents targeting ins20 are in development, reports suggest that wild type (WT) EGFR-related adverse events (AEs) are common and may limit long-term efficacy (Heymach, WCLC 2018, Neal WCLC 2018). CLN-081 (TAS6417) is a novel EGFR TKI with broad activity against clinically relevant EGFR mutations, including ins20(Mol Cancer Ther 2018; 17:1648). CLN-081’s activity against WT EGFR is greatly attenuated relative to ins20, positioning it as an ideal therapeutic candidate. We present the interim results of this multicenter, phase 1/2a trial evaluating CLN-081 in advanced, EGFR ins20-mutant NSCLC.
Methods
Phase 1 dose escalation in this adaptive trial began with an accelerated titration (AT) design, but can convert to a rolling six (R6) design based upon pre-specified safety criteria or at biologically active doses. Cohort expansion in phase 1 can occur at any dose where responses are seen. Transition from phase 1 to 2a is based upon a Simon-Two Stage design. All pts must have received platinum-based chemotherapy. Pts treated with prior ins20-specific TKIs are allowed in AT cohorts only. CLN-081 is dosed twice daily (BID) in 21-day cycles.
Results
As of 14 May 2020, 9 pts [median age- 64 (57-83), median lines of prior therapy- 3 (2-8)] have received CLN-081 at 30 mg (7), 45 mg (1), and 65 mg (1) BID; 5 pts were evaluable for response (RECIST 1.1). The most common AEs were constipation (8%), diarrhea (8%), dizziness (8%), fatigue (8%), and chest pain (8%). No DLTs, grade (gr) 3 diarrhea, or gr 3 rash were reported. There were no clinically significant, CLN-081-related gr ≥ 2 AEs. Among the 5 evaluable pts, 2 pts treated at 30 mg had partial responses (PR) and 3 pts (30, 45, and 65 mg) had stable disease (SD). Both pts with PR (1 confirmed, 1 pending confirmation) previously received poziotinib and TAK-788. Of the 3 pts with SD, 2 received poziotinib or TAK-788 and 1 was EGFR ins20 TKI naïve. Two pts (1 PR, 1 SD) had a history of brain mets. All evaluable pts remain on treatment, having received a median of 3 cycles (2-7).
Conclusions
CLN-081 demonstrates preliminary anti-tumor activity in pts refractory and naïve to other EGFR ins20 inhibitors at the lowest doses tested, with a manageable safety profile.
Clinical trial identification
NCT04036682.
Legal entity responsible for the study
Cullinan Pearl, Inc.
Funding
Cullinan Pearl, Inc.
Disclosure
Z. Piotrowska: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Spectrum; Advisory/Consultancy: Ariad/Takeda; Advisory/Consultancy: Novartis; Advisory/Consultancy: Novartis; Advisory/Consultancy: ImmunoGen; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Genentech; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: InCyte; Advisory/Consultancy: Medtronic; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Spectrum; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Cullinan Pearl, Inc.; Travel/Accommodation/Expenses: AstraZeneca. D. Nguyen: Full/Part-time employment: Pacific Shores Medical Group. N. Tchekmedyian: Advisory/Consultancy: Precision Medicine Advisory Panel; Advisory/Consultancy: Foundation Medicine Virtual Molecular Tumor Board; Advisory/Consultancy: IntrinsiQ Specialty Solutions; Full/Part-time employment: Pacific Shores Medical Group. M.S. Clancy, D. Witter, A. Page, L. Zawel: Full/Part-time employment: Cullinan Pearl, Inc.; Shareholder/Stockholder/Stock options: Cullinan Pearl, Inc. H.A. Yu: Travel/Accommodation/Expenses: Eli Lilly; Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Cullinan Pearl, Inc.; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Pfizer; Advisory/Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.