Puma Biotechnology Inc · NASDAQ:PBYI
Puma Biotechnology — WCLC 2020
12 slides from Puma Biotechnology's conference presentation, 2020
Slide 1: Neratinib in pretreated EGFR exon 18-mutant NSCLC: initial findings from the SUMMIT basket trial
Neratinib in pretreated EGFR exon 18-mutant non-small cell lung cancer (NSCLC): initial findings from the SUMMIT basket trial Valentina Boni,1 Christophe Dooms,2 Barbara Haley,3 Santiago Viteri,4 Amit Mahipal,5 J. Marie Suga,6 Lisa D. Eli,7 Alshad S. Lalani,7 Richard Bryce,7 Feng Xu,7 Naisargee Shah
Slide 2: Conflict of interest disclosures: Valentina Boni
Conflict of interest disclosures: Valentina Boni Financial interests Employment: START Madrid-CIOCC, Hm Hospitales Sanchinarro Consulting or Advisory Role: Puma Biotechnology; Ideaya Biosciences; Loxo Therapeutics, CytomX Therapeutics; Guidepoint; Oncoart Institutional financial support for clinical
Slide 3: EGFR exon 18 mutations represent 5% of all EGFR mutations detected in lung cancer
EGFR exon 18 mutations represent 5% of all EGFR mutations detected in lung cancer EGFR mutations associated with drug resistance EGFR mutations associated with drug sensitivity EGFR Exon EGFR exon 18 mutations Sharma SV, et al. Nature Rev Cancer 2007;7:169–81
Slide 4: EGFR exon 18 mutations are highly sensitive to neratinib in vitro
EGFR exon 18 mutations are highly sensitive to neratinib in vitro Neratinib: oral, irreversible, tyrosine kinase inhibitor of EGFR (ERBB1), HER2 (ERBB2), & HER4 (ERBB4)* Comparative TKI effects in EGFR exon 18 Western blot analyses of transfected HEK293 cells # (G719A) mutation-positive Ba/F3 cells#
Slide 5: EGFR exon 18 mutations are highly sensitive to neratinib: a POC trial
EGFR exon 18 mutations are highly sensitive to neratinib: a POC trial Prior phase 2 trial of neratinib in EGFR TKI-refractory NSCLC 4/167 (2%) pts had EGFR exon 18 mutations (G719X) – 1 patient did not have measurable disease by central review All patients with G719 mutations (n=4) had clinical bene
Slide 6: SUMMIT study design for EGFR exon 18-mutant lung cancer cohort
SUMMIT study design for EGFR exon 18-mutant lung cancer cohort Open-label, single-arm cohort Study endpoints and trial design features Primary endpoint Neratinib monotherapy • Objective response rate at first post-baseline tumor (240 mg, oral daily) assessment (Week 8) (ORRWk8) Secondary endpoints M
Slide 7: EGFR exon 18-mutant lung cancer cohort: baseline characteristics
EGFR exon 18-mutant lung cancer cohort: baseline characteristics Patient characteristics Safety/efficacy evaluable patients (n=11) Median age, years (range) 67 (56–83) <65 years, n (%) 4 (36) ≥65 years, n (%) 7 (64) Gender, n (%) Female 5 (45) Male 6 (55) ECOG performance status, n (%) 5 (45) 0 6 (5
Slide 8: EGFR exon 18-mutant lung cancer cohort: Efficacy summary
EGFR exon 18-mutant lung cancer cohort: Efficacy summary Efficacy evaluable patients TKI pre-treated subgroup Parameter (n=11) (n=10) Objective response (confirmed),a n 4 4 CR 0 0 PR 4 4 ORR,a† % (95% CI) 36 (11–69) 40 (12–74) Best overall response, n 6 6 CR 0 0 PR 6 6 Best overall response rate, %
Slide 9: Treatment duration, best response and best change in tumor size
EGFR exon 18-mutant lung cancer cohort: Treatment duration, best response and best change in tumor size 100 Mutation category G719A u G719X G719X + E709X G719X G719X + S768I G719C; S768I; T790M G719C; E709K u 50 E709_T710delinsD; EGFRamp Best change from baseline (%) G719X u G719X; S768I G719C; S768
Slide 10: Most common treatment-emergent adverse events >10%
EGFR exon 18-mutant lung cancer cohort: Most common treatment-emergent adverse events >10% Safety evaluable patients (n=11) Key safety findings TEAE, n (%) Any grade Grade ≥3 Well tolerated with mandatory loperamide prophylaxis (first 2 cycles) Diarrhea 5 (45.5) 0 4 patients (36%) reported grade 1 a
Slide 11: Case study
Case study Female, 61 years, former smoker Dec 2016: stage IV lung adenocarcinoma with lung, lymph nodes, bone and brain metastasis and EGFR (G719X) mutation Dec 2016: SBRT on brain; 1st-line erlotinib achieving SD as best response and clinical benefit Nov 2018: asymptomatic brain/lung progression;
Slide 12: Summary/conclusions
Summary/conclusions Single-arm phase 2 trial showing early clinical efficacy of single-agent neratinib in TKI-refractory EGFR exon 18-mutant NSCLC – Confirmed ORR: 40% & Stable disease (≥ 16 weeks): 40% – CBR: 80% – DOR: 7.5 months – Median PFS: 9.1 months Well-tolerated with no evidence of grade 3