Puma Biotechnology Inc · NASDAQ:PBYI
Puma Biotechnology — AACR Annual Meeting 2017
25 slides from Puma Biotechnology's conference presentation, 2017
Slide 1: Neratinib in HER2- or HER3-mutant solid tumors: SUMMIT phase 2 basket study
Oral CT001 Neratinib in HER2- or HER3-mutant solid tumors: SUMMIT, a global, multi-histology, open-label, phase 2 ‘basket’ study David M. Hyman,1 Sarina Piha-Paul,2 Jordi Rodon,3 Cristina Saura,3 Geoffrey I. Shapiro,4 David I. Quinn,5 Victor Moreno, 6 Ingrid Mayer,7 Carlos Arteaga,7 Valentina Boni,8
Slide 2: HER2 (ERBB2) mutations
HER2 (ERBB2) mutations • Subsets of somatic HER2 mutations are seen at relatively low frequencies across multiple tumor types • Activating HER2 mutations result in constitutive kinase signaling, activation of growth promoting/ survival pathways, oncogenic transformation and enhanced tumor growth in
Slide 3: Neratinib in HER2-mutant cancer
Neratinib in HER2-mutant cancer • Neratinib is an oral, irreversible pan-HER tyrosine kinase inhibitor • Neratinib leads to potent inhibition of intracellular signaling, cell proliferation and colony formation of HER2-mutant tumor cell lines in vitro1,2 • HER2-mutant alleles have distinct differenti
Slide 4: SUMMIT 'basket' study design
SUMMIT ‘basket’ study design HER2 or HER3 mutations Endometrial (documented by local testing) Gastroesophageal Primary endpoint • Objective response rate at week 8 (ORR8) Ovarian Secondary endpoints • ORR (confirmed) Colorectal • Clinical benefit rate (CBR) • Progression-free survival (PFS) Bladder/
Slide 5: Enrollment by tumor type
Enrollment by tumor type Neratinib monotherapy (n=141) HER2-mutation positive Lung cancer 26 (18.4) Breast cancer 25 (17.7) Bladder/urinary tract cancer 16 (11.3) Solid tumors (NOS) 15 (10.6) Colorectal cancer 12 (8.5) Biliary tract cancer 9 (6.4) Endometrial cancer 7 (5.0) Cervical cancer 5 (3.5) G
Slide 6: Baseline demographics
Baseline demographics HER2 mutant HER3 mutant Total Patient characteristics (n=124) (n=17) (n=141) Age Median (range), years 61 (30–83) 66 (39–82) 61 (30–83) <65 years, n (%) 81 (64.8) 7 (43.8) 88 (62.4) ≥65 years, n (%) 43 (34.7) 10 (58.8) 53 (37.6) Gender, n (%) Female 79 (63.7) 13 (76.5) 92 (65.2
Slide 7: Distribution of HER2 mutations
Distribution of HER2 mutations 7
Slide 8: Distribution of HER3 mutations
Distribution of HER3 mutations No clinical activity seen in HER3-mutant cohort 8
Slide 9: Patient disposition
Patient disposition HER2 mutant HER3 mutant Total Parameter (n=124) (n=17) (n=141) Patients continuing on treatment, n (%) 10 0 10 Treatment discontinuation, n (%) 114 (91.9) 17 (100.0) 131 (92.9) Death 2 (1.6) 1 (5.9) 3 (2.1) Disease progression 88 (71.0) 16 (94.1) 104 (73.8) Adverse event 5 (4.0)
Slide 10: Efficacy in HER2-mutant patients by tumor type
Efficacy in HER2-mutant patients by tumor type 10
Slide 11: Efficacy in HER2-mutant patients by tumor type
Efficacy in HER2-mutant patients by tumor type 11
Slide 12: Efficacy in HER2-mutant patients by tumor type
Efficacy in HER2-mutant patients by tumor type 12
Slide 13: Efficacy in HER2-mutant patients by tumor type
Efficacy in HER2-mutant patients by tumor type 13
Slide 14: Efficacy in HER2-mutant patients by tumor type
Efficacy in HER2-mutant patients by tumor type 14
Slide 15: Efficacy in HER2-mutant patients by allele
Efficacy in HER2-mutant patients by allele 15
Slide 16: Efficacy in HER2-mutant patients by allele
Efficacy in HER2-mutant patients by allele 16
Slide 17: Efficacy in HER2-mutant patients by allele
Efficacy in HER2-mutant patients by allele 17
Slide 18: Integrated efficacy by tumor type and HER2 mutation
Integrated efficacy by tumor type and HER2 mutation 18
Slide 19: Efficacy summary
Efficacy summary HER2mut HER3mut Breast Bladder Lung Colorectal Biliary tract Cervical NOS (n=25) (n=16) (n=26) (n=12) (n=9) (n=5) (n=17) ORR at week 8, n (%) 8 (32.0) 0 (0.0) 1 (3.8) 0 (0.0) 2 (22.2) 1 (20.0) 0 (0.0) [95% CI] [14.9–53.5] [0.0–20.6] [0.1–19.6] [0.0–26.5] [2.8–60.0] [0.5–71.6] [0.0–2
Slide 20: Incidence of treatment-emergent adverse events (≥10%)
Incidence of treatment-emergent adverse events (≥10%) Neratinib monotherapy (N=141) Adverse event, n (%) Any grade Grade ≥3 Diarrhea 104 (73.8) 31 (22.0) Nausea 61 (43.3) 3 (2.1) Vomiting 58 (41.1) 3 (2.1) Constipation 49 (34.8) 2 (1.4) Fatigue 45 (31.9) 5 (3.5) Decreased appetite 40 (28.4) 1 (0.7)
Slide 21: Characteristics of diarrhea
Characteristics of diarrhea Neratinib monotherapy Adverse event, n (%) (N=141) Incidence of diarrhea, n (%)a Any grade 104 (73.8) Grade 3 31 (22.0) Action taken with neratinib, n (%) Permanent discontinuation 4 (2.8) Dose reduction 2 (1.4) Temporary hold 21 (14.9) Serious diarrhea (hospitalized or i
Slide 22: Agreement between local and central assessment of HER2 mutations
Agreement between local and central assessment of HER2 mutations • >98% concordance was observed between local and central HER2 Enrollment mutation assay assays (n=124) Archival FFPE tumor Local test (MSK-IMPACT1) (n=96) (n=28) Archival FFPE tumor 98% N/A (MSK-IMPACT1) (48/49) Central testing (retro
Slide 23: Plasma ctDNA at progression reveals acquired HER2 T798I gatekeeper mutation
Plasma ctDNA at time of neratinib clinical progression reveals acquired HER2 (T798I) gatekeeper mutation that induces resistance AROMATASE INHIBITORS FULVESTRANT NERATINIB 2010 2011 2012 2013 2014 2015 2016 Chest wall Bone Skin mets recurrence mets SUMMIT Fulvestrant trial added PD ER+ / HER2– diagn
Slide 24: Conclusions
Conclusions • Neratinib activity was influenced by both tumor lineage and mutation type: – Breast cancer: single-agent activity observed. Combination with fulvestrant in ER+ disease underway – Biliary cancer and cervical cancer: preliminary single-agent activity; enrollment ongoing – Lung cancer: re
Slide 25: Acknowledgements
Acknowledgements The authors would like to thank: • All of the patients and their families • SUMMIT study investigators and clinical trial staff 25