Abstract Disclosures. 2/2. First Author: Jose Baselga, MD, PhD, FASCO

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1 Phase III study of taselisib (GDC-0032) + fulvestrant (FULV) v FULV in patients (pts) with estrogen receptor (ER)- positive, PIK3CA-mutant (MUT), locally advanced or metastatic breast cancer (MBC): Primary analysis from SANDPIPER. Presented Sunday, June 3, 2018 Authors: Jose Baselga, Susan Faye Dent, Javier Cortés, Young-Hyuck Im, Véronique Diéras, Nadia Harbeck, Ian E. Krop, Sunil Verma, Timothy R. Wilson, Huan Jin, Lijia Wang, Frauke Schimmoller, Jerry Y. Hsu, Jing He, Michelino DeLaurentiis, Pamela Drullinsky, William Jacot; Memorial Sloan Kettering Cancer Center, New York, NY; The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada; Vall d Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Ramón y Cajal University Hospital, Madrid, Spain; Samsung Medical Center, Seoul, Korea, Republic of (South); Institut Curie, Paris, and Centre Eugène Marquis, Rennes, France; Brustzentrum der Universität München (LMU), Munich, Germany; Dana-Farber Cancer Institute, Boston, MA; Tom Baker Cancer Centre, Department of Oncology, University of Calgary, Calgary, AB, Canada; Genentech Inc., South San Francisco, CA; Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; Institut du Cancer de Montpellier, Montpellier, France View Less Abstract Disclosures Background: Taselisib, a potent, selective PI3K inhibitor, has enhanced activity in PIK3CA-MUT BC cell lines and conrmed partial responses in PIK3CA-MUT BC as a single-agent or with FULV. We assessed taselisib + FULV in pts with ER-positive, HER2-negative, PIK3CA-MUT locally advanced or MBC. Methods: SANDPIPER (NCT ) is a double-blind, placebo (PBO)-controlled, randomized, phase III study. Postmenopausal pts with disease recurrence or progression during or after an aromatase inhibitor were randomized 2:1 to receive taselisib (4 mg oral, qd) or PBO + FULV (500 mg). Stratication factors were: visceral disease, endocrine sensitivity, and geographic region. Pts with PIK3CA-MUT tumors, assessed by central cobas PIK3CA Mutation Test, were randomized separately from non-mut tumors. The primary endpoint was investigator-assessed progression-free survival (INV-PFS) in pts with PIK3CAMUT tumors. Secondary endpoints included objective response rate (ORR), overall survival (OS), clinical benet rate (CBR), duration of objective response (DoR), PFS by blinded independent central review (BICR-PFS), and safety. Results: 516 pts were randomized in the PIK3CA-MUT intention-to-treat (ITT) population. Ecacy is shown in the Table. Taselisib + FULV signicantly improved INV-PFS (hazard ratio [HR] 0.70) as conrmed by BICRPFS (HR 0.66). OS is immature. The most common grade 3 adverse events (AEs; preferred terms) in the taselisib + FULV arm in safety-evaluable pts who received 1 dose of treatment were diarrhea (12%), hyperglycemia (10%), colitis (3%), and stomatitis (2%). AEs led to more taselisib discontinuations (17% v 2%) and dose reductions (37% v 2%), v PBO. Conclusions: Taselisib + FULV signicantly improved INV-PFS, v PBO + FULV, in pts with ER-positive, HER2-negative, PIK3CA-MUT locally advanced or MBC. The safety prole is largely consistent with previous studies. Clinical trial information: NCT ITT PBO + FULV Taselisib + FULV Median INV-PFS, mo N= N= HR 0.70 (p=.0037) Baseline measurable disease n=134 n=264 ORR, % p=.0002 CBR, % DoR, mo n= n= Meeting Library Phase III study of taselisib (GDC-0032) + fulvestrant (FULV) <em>v</em> FULV in patients (pts) with estrogen rec 2/2 First Author: Jose Baselga, MD, PhD, FASCO Meeting: 2018 ASCO Annual Meeting Session Type: Oral Abstract Session

2 Session Title: Breast Cancer Metastatic Abstract #: LBA1006 Clinical Trial Registry Number: NCT Citation: J Clin Oncol 36, 2018 (suppl; abstr LBA1006)

3 AZD5363 plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (PAKT): A randomised, double-blind, placebo-controlled, phase II trial. Presented Sunday, June 3, 2018 Authors: Peter Schmid, Jacinta Abraham, Stephen Chan, Duncan Wheatley, Murray Brunt, Gia Nemsadze, Richard Baird, Yeon Hee Park, Peter Hall, Timothy Perren, Robert C. Stein, Mangel László, Jean-Marc Ferrero, Melissa Phillips, John Conibear, Shah-Jalal Sarker, Aaron Prendergast, Hayley Cartwright, Kelly Mousa, Nicholas C. Turner; Queen Mary University of London, London, United Kingdom; Velindre NHS Trust, Cardiff, United Kingdom; Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom; Royal Cornwall Hospitals NHS Trust, Truro, United Kingdom; University Hospitals of North Midlands NHS Trust, Stafford, United Kingdom; Institute of Clinical Oncology, Tbilisi, Georgia; Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; Samsung Medical Center, Seoul, Korea, Republic of (South); NHS Lothian, Edinburgh, United Kingdom; Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom; University College London Hospitals NHS Foundation Trust, London, United Kingdom; Medical University of Pécs, Institute of Oncology, Pecs, Hungary; Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France; Barts Health NHS Trust, London, United Kingdom; St Bartholomew's Hospital, London, United Kingdom; Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Royal Marsden NHS Foundation Trust, London, United KingdomView Less Background: The PI3K/AKT signalling pathway is frequently activated in triple-negative breast cancer (TNBC). AZD5363 is a highly-selective, oral, small molecule AKT inhibitor. The PAKT trial investigated the addition of AZD5363 to paclitaxel as 1 st -line therapy for TNBC. Methods: This investigator-led, double-blind, placebo-controlled, randomised phase II trial, recruited women with previously untreated, metastatic TNBC at 42 sites in 6 countries. Patients were randomly assigned (1:1) to paclitaxel 90mg/m 2 (days 1, 8, & 15) with either AZD5363 (400mg BD) or placebo (days 2-5, 9-12, 16-19) every 28 days until disease progression or unacceptable toxicity. The primary endpoint was progression free survival (PFS). Secondary endpoints included overall survival (OS), PFS in the subgroup with PIK3CA/AKT1/PTENalterations, response, and safety. Results: Between 05/2014 and 06/2017, 140 patients were randomised to paclitaxel + AZD5363 (n = 70) or paclitaxel + placebo (n = 70). Median duration of follow-up was 18.2 months (95% CI, 13.6 to 24.0). In the ITT analysis, median PFS was 5.9 months (m) for AZD5363 compared to 4.2m for placebo (hazard ratio [HR], 0.75; 95% CI, 0.52 to 1.08; one-sided p = 0.06; two-sided p = 0.11 [predefined significance level of 0.10, one-sided]). Median OS was 19.1m for AZD5363 compared to 12.6m for placebo (HR, 0.64; 95% CI, 0.40 to 1.01; one-sided p = 0.02; two-sided p = 0.04). Results for the subgroup with PIK3CA/AKT1/PTEN-altered tumours will be presented. Most common grade 3 or worse adverse events were diarrhoea (12% [8/68] of AZD5363-treated patients vs 1% [1/70] of placebo-treated patients), infection (4% vs 1%), neutropenia (3% vs 3%), rash (4% vs 0) and fatigue (4% vs 0). Conclusions: The trial met its primary endpoint. Addition of AZD5363 to 1st-line paclitaxel therapy for TNBC resulted in significantly longer PFS and OS. AZD5363 warrants further investigation for the treatment of TNBC. Clinical trial information: NCT First Author: Peter Schmid, MD, PhD, FCRP Meeting: 2018 ASCO Annual Meeting Session Type: Oral Abstract Session

4 Session Title: Breast Cancer Metastatic Abstract #: 1007 Clinical Trial Registry Number: NCT Citation: J Clin Oncol 36, 2018 (suppl; abstr 1007)

5 Overall survival (OS) update of the double-blind placebo (PBO)-controlled randomized phase 2 LOTUS trial of firstline ipatasertib (IPAT) + paclitaxel (PAC) for locally advanced/metastatic triple-negative breast cancer (mtnbc). Presented Sunday, June 3, 2018 Authors: Rebecca Dent, Seock-Ah Im, Marc Espie, Sibel Blau, Antoinette R. Tan, Steven J. Isakoff, Mafalda Oliveira, Cristina Saura, Matthew Wongchenko, Amy V. Kapp, Wai Y. Chan, Stina M. Singel, Daniel J. Maslyar, Jose Baselga, Sung- Bae Kim; National Cancer Center, Singapore; Seoul National University Hospital, and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea, Republic of (South); Hospital Saint Louis, Breast Disease Center, Paris, France; Northwest Medical Specialties, Puyallup, WA; Levine Cancer Institute, Charlotte, NC; Massachusetts General Hospital, Boston, MA; Vall d Hebron University Hospital, Vall d Hebron Institute of Oncology (VHIO), Barcelona, Spain; Genentech, Inc., South San Francisco, CA; Memorial Sloan Kettering Cancer Center, New York, NY; Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of (South)View Less Background: In LOTUS (NCT ), adding the oral AKT inhibitor IPAT to first-line PAC for mtnbc improved progressionfree survival (PFS; primary endpoint) [Kim, Lancet Oncol 2017]. The stratified PFS hazard ratio (HR) in the intentto-treat (ITT) population (n = 124) was 0.60 (95% CI ; p = 0.037; median PFS 6.2 vs 4.9 months with IPAT vs PBO, respectively). In prespecified analyses of patients (pts) with PIK3CA/AKT1/PTEN-altered tumors, the unstratified PFS HR was 0.44 (95% CI ; median 9.0 vs 4.9 months). We now report updated OS results in the ITT population after OS events in ~50% of pts. OS results in the PIK3CA/AKT1/PTEN-altered subgroup are immature. Methods: Eligible pts had measurable inoperable mtnbc previously untreated with systemic therapy. Pts were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval (6 12 months vs > 12 months vs not applicable) and tumor IHC PTEN status, and randomized 1:1 to PAC 80 mg/m 2 (d1, 8, & 15) with either IPAT 400 mg or PBO (d1 21) q28d until progression or unacceptable toxicity. OS was a prespecified secondary endpoint. Results: The table shows results after 23 months follow-up (data cutoff 26 July, 2017). No new safety signals were seen. Conclusions: The previously observed PFS improvement with IPAT was followed by a trend toward improved OS (~5-month difference in the medians) at the updated OS analysis. Post-progression therapy was similar. These findings support further evaluation of first-line IPAT + PAC for mtnbc in the ongoing IPATunity130 (NCT ) randomized phase 3 trial. Final OS results from LOTUS are expected in Clinical trial information: NCT Parameter IPAT + PAC (n = 62) OS events, n (%) 33 (53) Median OS, months (95% CI) 23.1 ( ) OS hazard ratio (95% CI) Stratified: 0.62 ( ) Unstratified: 0.77 ( ) 1-year OS rate, % (95% CI) 83 (73 93)

6 Parameter IPAT + PAC (n = 62) Post-progression systemic anti-cancer therapy, n (%) 47 (76) Immunotherapy 7 (11) Adverse event leading to treatment discontinuation, n (%) a IPAT/PBO 4 (7) PAC 7 (11) a n = 61 in IPAT + PAC arm First Author: Rebecca Alexandra Dent, MD Meeting: 2018 ASCO Annual Meeting Session Type: Oral Abstract Session Session Title: Breast Cancer Metastatic Abstract #: 1008 Clinical Trial Registry Number: NCT Citation: J Clin Oncol 36, 2018 (suppl; abstr 1008)