CRI-CIMT-EATI-AACR INTERNATIONAL CANCER IMMUNOTHERAPY CONFERENCE TRANSLATING SCIENCE INTO SURVIVAL SEPTEMBER 25th to 28th, 2019 - PARIS Abstracts BOOK www.cancerimmunotherapyconference.org SESSION A fined as complete response or partial response or stable disease POSTER SESSION A for at least 8 weeks) of 45% (17/38). ORR was 11% (2/19) in PD-L1 negative and 17% (2/12) in PD-L1 positive pts. Pts with 2 lines or more of prior therapy had an ORR of 20% (5/25), regardless of PD-L1 status. Treatment-related Grade 3/4 AEs occurred in 23% Combination therapies with immune of pts, with dehydration, hypotension, and myalgia as the most checkpoint blockers frequently reported (4.7% each), consistent with previous reports. Conclusion : Clinical activity was observed in mTNBC pts treated A001 / Clinical activity of BEMPEG plus NIVO observed in with BEMPEG plus NIVO, notably in pts with poor prognostic fea- tures or negative predictive clinical factors for CPI benefit, includ- metastatic TNBC : preliminary results from the TNBC co- ing negative PD-L1 status. Additional efficacy analyses, including hort of the Ph1/2 PIVOT-02 study ORR, duration of response, and biomarker analyses, will be pre- sented. These data support future development of this doublet in mTNBC pts who are PD-L1 negative at baseline, in combination Sara Tolaney (Dana-Farber Cancer Institute), Capucine Baldini with chemotherapy. This study (NCT02983045) and registration- (Institut Gustave Roussy), Alexander Spira (Virginia Cancer Spe- al studies in other solid tumor settings are ongoing. cialists), Daniel Cho (New York University Langone Medical Cen- ter - NYU Cancer Institute), Giovanni Grignani (Fondazione del Piemonte per l Oncologia IRCCS Candiolo), Dariusz Sawka (POO Keywords : BEMPEG, NKTR-214, Triple-negative breast cancer, Szpital Specjalistyczny w Brzozowie), Fabricio Racca (Instituto Nivolumab. Oncologico Baselga at Hospital Quiron Salud Barcelona), Philippe Bedard (Princess Margaret Cancer Centre), Annemie Rutten (GZA Ziekenhuizen Campus Sint-Augustinus), EJ Liao (Nektar Thera- Immunotherapies, cell based peutics), Sunny Xie (Nektar Therapeutics), Sue Currie (Nektar Therapeutics), Lin Wei (Nektar Therapeutics), Mary Tagliaferri (Nektar Therapeutics), Stina Singel (Nektar Therapeutics), Debu A002 / Skewed T cell distribution in pancreatic cancer Tripathy (MD Anderson Cancer Center). patients Background : Recent advances in the treatment of metastatic tri- ple-negative breast cancer (mTNBC) include the use of check- Cecile Alanio (Institute for Immunology, Department of Systems point inhibitor (CPI) therapy. CPIs, in combination with chemo- Pharmacology and Translational Therapeutics, University of Penn- therapy, has been shown to prolong survival in mTNBC pts with sylvania, Perelman School of Medicine, Philadelphia, USA), Katelyn PD-L1 positive baseline status. However, CPI monotherapy is less T Byrne (Abramson Cancer Center and Department of Medicine, active, with objective response rates (ORR) ranging from 5% (Ad- University of Pennsylvania, Philadelphia, USA), Mohamed Ab- ams, Dirix) to 10% (Emens). ORR with CPI monotherapy also ap- del-Hakeem (Institute for Immunology, Department of Systems pears to be lower in PD-L1 negative baseline pts, ranging from Pharmacology and Translational Therapeutics, University of Penn- 0% (Emens) to 5% (Adams), as well as in 2L pts, with reported ≥ sylvania, Perelman School of Medicine, Philadelphia, USA), Takuya ORR of 6% (Emens). Another reported negative predictive factor Ohtani (Institute for Immunology, Department of Systems Phar- for CPI benefit in these pts includes prior taxane (Schmid). Thus, macology and Translational Therapeutics, University of Pennsyl- more effective CPI treatment combinations are needed, partic- vania, Perelman School of Medicine, Philadelphia, USA), Meredith ularly in pts with PD-L1 negative tumors. The safety and clinical Stone (Abramson Cancer Center and Department of Medicine, activity of bempegaldesleukin (BEMPEG or NKTR-214), a CD-122 University of Pennsylvania, Philadelphia, USA ; Division of Hema- preferential IL-2 pathway agonist, plus the anti-PD1 CPI, nivolum- tology-Oncology, Department of Medicine, Perelman School of ab (NIVO) was evaluated in PIVOT-02, a multicenter Phase 1/2 Medicine, University of Pennsylvania, Philadelphia, Pennsylvania), study in multiple solid tumor settings and includes a cohort of pts Jean-Christophe Beltra (Institute for Immunology, Department of with mTNBC. PIVOT-02 recently reported promising preliminary Systems Pharmacology and Translational Therapeutics, Univer- clinical activity and safety data for pts with metastatic melano- sity of Pennsylvania, Perelman School of Medicine, Philadelphia, ma and urothelial cancers. This is the first report of BEMPEG plus USA), Josephine Giles (Institute for Immunology, Department of NIVO in mTNBC. Systems Pharmacology and Translational Therapeutics, Univer- sity of Pennsylvania, Perelman School of Medicine, Philadelphia, Methods : 43 pts with mTNBC received BEMPEG (0.006 mg/kg) USA), Austin Huffman (Abramson Cancer Center and Depart- + NIVO (360 mg) q3w. Pts were categorized by line of therapy ment of Medicine, University of Pennsylvania, Philadelphia, USA), (1L, 1L but early relapse [defined as metastatic relapse within 12 Bertram Bengsch (Department of Medicine II, Gastroenterology, months of last chemotherapy in EBC setting], 2L, 3L). In addi- ≥ Hepatology, Endocrinology, and Infectious Diseases, University tion to PD-L1 status, other predictive or prognostic clinical factors Medical Center Freiburg and Signalling Research Centres BIOSS were assessed, including the following five : age, disease-free in- and CIBSS, University of Freiburg, Germany), Sarah Henrickson terval, LDH, number and type of metastatic sites, and prior tax- (Institute for Immunology, Department of Systems Pharmacol- ane. Response was assessed every 3 cycles by RECIST v1.1. Per ogy and Translational Therapeutics, University of Pennsylvania, protocol, ORR was evaluated in the 38 pt efficacy-evaluable pop- Perelman School of Medicine, Philadelphia, USA), Nan-Ping Weng ulation, defined as pts with at least 1 post-baseline tumor assess- (Lymphocyte Differentiation Section, Laboratory of Molecular ment (5 were not evaluable : 3 clinical progressions, 2 deaths due Biology and Immunology, NIA, National Institutes of Health, Bal- to progressive disease after 1 cycle). Baseline immunohistochem- timore, Maryland 21224), Janáe A Ritz-Romeo (Division of Hema- istry (IHC) analysis for PD-L1 was performed using 28-8 pharmDx tology-Oncology, Department of Medicine, Perelman School of (Dako) and defined as PD-L1 negative (<1% tumor cell expression) Medicine, University of Pennsylvania, Philadelphia, Pennsylvania), and PD-L1 positive ( 1% tumor cell expression). Safety and toler- ≥ Mark O’Hara (Division of Hematology-Oncology, Department of ability were assessed by adverse event (AE) analysis reported by Medicine, Perelman School of Medicine, University of Pennsyl- CTCAE v4.03. vania, Philadelphia, Pennsylvania), J Joseph Melenhorst (Center of Cellular Immunotherapies, Abramson Cancer Center and the Results : 42 of the 43 patients reported at least 1 of the 5 poor Department of Pathology and Laboratory Medicine, Perelman prognostic or negative predictive clinical factors for CPI ben- School of Medicine, University of Pennsylvania, Philadelphia, PA efit, with a median of 2. Baseline factors that indicated a poor 19104, USA), Simon Lacey (Center of Cellular Immunotherapies, prognosis population include : young age (21% 40 years old), ≤ Abramson Cancer Center and the Department of Pathology and 51% PD-L1-negative, 65% who had received 2 lines or more treat- Laboratory Medicine, Perelman School of Medicine, University of ment in the metastatic setting, and 40% had elevated LDH. Lung Pennsylvania, Philadelphia, PA 19104, USA), Regina M Young (Cen- and liver were the most common sites of metastasis occurring in ter of Cellular Immunotherapies, Abramson Cancer Center and 46.5% and 23.3% respectively, and 44% of all pts had 3 meta- ≥ the Department of Pathology and Laboratory Medicine, Perelman static organ sites. ORR in the 38 efficacy-evaluable pts was 13% School of Medicine, University of Pennsylvania, Philadelphia, PA (5/38), regardless of PD-L1 status, with a disease control rate (de- 19104, USA), Gregory L Beatty (Abramson Cancer Center and FIFTH CRI-CIMT-EATI-AACR INTERNATIONAL CANCER IMMUNOTHERAPY CONFERENCESEPT. 25 - 28, 2019 - PARIS, FRANCE 2 SESSION A Department of Medicine, University of Pennsylvania, Philadelphia, associated with GBM, are non-ideal targets because they are also USA ; Division of Hematology-Oncology, Department of Medicine, expressed in other normal organs. We show that “prime-and-kill” Perelman School of Medicine, University of Pennsylvania, Phila- dual antigen recognition circuits can overcome this challenge in delphia, Pennsylvania), Robert H Vonderheide (Abramson Cancer vitro and in vivo. Where a synthetic Notch (synNotch) receptor Center and Department of Medicine, University of Pennsylvania, that recognizes a specific but heterogeneous antigen (EGFRvIII) is Philadelphia, USA), Carl H June (Center of Cellular Immunothera- engineered to locally induce expression of a CAR that kills neigh- pies, Abramson Cancer Center and the Department of Pathology boring cells expressing tumor-associated antigens. This type of and Laboratory Medicine, Perelman School of Medicine, Universi- circuit spatially integrates recognition of multiple antigen