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Background FPA150 is a fully human antibody against B7-H4 (a transmembrane protein of the B7 family) blocking negative regulatory function in T cells. FPA150 additionally exhibits enhanced antibody-dependent cell-mediated cytotoxicity and in vivo synergizes with anti-PD1 agents. We initiated a phase Ia/Ib evaluation of safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and activity in monotherapy (mono) and with anti-PD1 (combo). A current update of this ongoing trial is provided. Methods Trial design (see table).Table1198PTablePhasePatientsDesignDosesObjectiveStatus1aDose EscalationAdvanced solid tumorsAccelerated Titration; 3+3 escalation0.01-0.3mg/kg; 1-20mg/kgSafety, tolerability & PKComplete; recommended dose (RD) identifiedDose ExplorationB7-H4 + solid tumorsPre- and on-treatment biopsies (Bx)3mg/kg; 10mg/kgSafety, tolerability, PK & PDOngoing1a Combo Safety Lead-InB7-H4+ ovarian cancer3+3 De-escalationFPA150 at RD & 200mg pembrolizumab (pembro)Safety, tolerability, PK & RD FPA150Ongoing1b3 Mono cohortsB7-H4+ breast, ovarian & endometrialDose Expansion (Bx)20mg/kgSafety, tolerability, PD & efficacyOngoing1C1 ComboB7-H4+ ovarian cancerDose Expansion (Bx)200mg pembro & RD FPA150Safety, tolerability, PD & efficacyNot yet started Results At 3/15/2019 data snapshot, 29 pts with solid tumors (12 ovarian, 7 GI, 3 GYN, 3 head/neck, 2 GU, and 2 other) received FPA150 in dose escalation (n=21) and dose exploration (n=8). FPA150 demonstrated ∼ dose-proportional exposure at doses ≥0.3mg/kg and half-life of 1-2 weeks. To date, no dose-limiting toxicities, treatment-related serious adverse events or treatment-related adverse events (TRAEs) leading to drug discontinuation have been identified (1 Grade 3 TRAE of decreased lymphocyte count); others were Grade 1-2, with most common being diarrhea (16.7%), and fatigue (13.8%). Enrollment to phase Ib mono and phase Ia combo is ongoing. Expanded safety, PD and activity from phase Ib mono and phase Ia combo will be presented. Conclusions FPA150 RD for phase Ib mono identified as 20mg/kg (Sachdev, ASCO 2019). Mono appears well tolerated during dose escalation/exploration allowing evaluation in combination therapy. Sachdev, J et al. Phase Ia/1b study of first-in-class B7-H4 antibody, FPA150, as monotherapy in patients with advanced solid tumors. Proc Am. Soc. Clin. Oncol 2019. Clinical trial identification NCT03514121. Legal entity responsible for the study Five Prime Therapeutics, Inc. Funding Five Prime Therapeutics, Inc. Disclosure Z.A. Wainberg: Advisory / Consultancy: Bristol Meier Squibb; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: Merck; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Bayer. J.C. Sachdev: Honoraria (self): Celgene; Honoraria (self): Novartis; Honoraria (self): Puma Technology; Honoraria (self): Tempus; Honoraria (self): Ipsen; Advisory / Consultancy: Celgene; Research grant / Funding (institution): Celgene; Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy: Five Prime Therapeutics. T. Bauer: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses, institution: Ignyta; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Guardant Health; Advisory / Consultancy, Research grant / Funding (institution): Loxo; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Self and institution: Pfizer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Moderna Therapeutics; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Medpacto; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): MabVax; Research grant / Funding (institution): Stemline Therapeutics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Glaxo Smith Kline; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Immunogen; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Merimack; Research grant / Funding (institution): Immunogen. S. Pant: Advisory / Consultancy: Mirati Therapeutics; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Red hill Biopharma Ltd; Advisory / Consultancy: Xencor; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: Novartis; Advisory / Consultancy: Rgenix; Advisory / Consultancy: Sanofi-Aventis; Advisory / Consultancy: Arqule; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Onco Response; Advisory / Consultancy: Sanofi US Services Inc; Advisory / Consultancy: GlaxoSmith Kline; Speaker Bureau / Expert testimony: Tyme, Inc; Speaker Bureau / Expert testimony: 4-D Pharma. S. Chawla: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Threshold Pharmaceuticals; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: CytRx; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Ignyta; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Immune Design; Honoraria (self), Speaker Bureau / Expert testimony: TRACON Pharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Karyopharm Therapeutics; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sarcoma Alliance for REsearch Through Collaboration; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen. N. Marina: Full / Part-time employment: Five Prime Therapeutics. H. Xiang: Full / Part-time employment: Five Prime Therapeutics. W. Deng: Full / Part-time employment: Five Prime Therapeutics. M. Schmidt: Full / Part-time employment: Five Prime Therapeutics. A. Patnaik: Advisory / Consultancy: Bayer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Genentech; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Bristo-Myers Squibb; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Plexxikon; Research grant / Funding (institution): Corvus Pharmaceuticals; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Forty-seven; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): Infinity Pharmaceuticals; Research grant / Funding (institution): Proximagen; Research grant / Funding (institution): Pieris; Research grant / Funding (institution): Surface Oncology; Research grant / Funding (institution): Livson; Research grant / Funding (institution): Vigeo Therapeutics; Research grant / Funding (institution): Astella Pharma. P. LoRusso: Advisory / Consultancy: AbbVie; Advisory / Consultancy: Agios; Advisory / Consultancy: Alexion; Advisory / Consultancy: Ariad; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: GenMab; Advisory / Consultancy: Glenmark; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Menarini; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche-Genentech; Advisory / Consultancy: Genentech; Advisory / Consultancy: CytomX; Advisory / Consultancy: Omniox; Advisory / Consultancy: Ignyta; Advisory / Consultancy: Takeda; Advisory / Consultancy: SOTIO; Advisory / Consultancy: Cybrexa; Advisory / Consultancy: Agenus; Advisory / Consultancy: Tyme.