Abstract 5692
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)Table:
1198P
Phase | Patients | Design | Doses | Objective | Status |
---|---|---|---|---|---|
1a | |||||
Dose Escalation | Advanced solid tumors | Accelerated Titration; 3 + 3 escalation | 0.01-0.3 mg/kg; 1-20 mg/kg | Safety, tolerability & PK | Complete; recommended dose (RD) identified |
Dose Exploration | B7-H4 + solid tumors | Pre- and on-treatment biopsies (Bx) | 3 mg/kg; 10 mg/kg | Safety, tolerability, PK & PD | Ongoing |
1a Combo Safety Lead-In | B7-H4+ ovarian cancer | 3 + 3 De-escalation | FPA150 at RD & 200 mg pembrolizumab (pembro) | Safety, tolerability, PK & RD FPA150 | Ongoing |
1b | |||||
3 Mono cohorts | B7-H4+ breast, ovarian & endometrial | Dose Expansion (Bx) | 20 mg/kg | Safety, tolerability, PD & efficacy | Ongoing |
1C1 Combo | B7-H4+ ovarian cancer | Dose Expansion (Bx) | 200 mg pembro & RD FPA150 | Safety, tolerability, PD & efficacy | Not 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 ≥0.3 mg/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 20 mg/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.
Editorial acknowledgement
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.
Resources from the same session
1707 - Clinical utility of precision immunoprofiling and monitoring of the tumor microenvironment using flow cytometry and CyTOF in patients with advanced NSCLC treated with atezolizumab: results from a phase II study for biomarker analysis (EPOC1702)
Presenter: Keisuke Kirita
Session: Poster Display session 3
Resources:
Abstract
3594 - Tumor mutation burden (TMB), PD-L1, IFN-γ signaling identify subgroups of patients (pts) who benefit from durvalumab (D, anti-PDL1) or D and tremelimumab (T, anti-CTLA4) treatment in urothelial bladder cancer (UC)
Presenter: Christophe Massard
Session: Poster Display session 3
Resources:
Abstract
744 - The decrease of TMB, TNB and HLA expression are the Mechanism of Drug Resistance of NSCLC to immunosuppressive PD-1/PD-l1.
Presenter: Sheng Yu
Session: Poster Display session 3
Resources:
Abstract
2350 - Eosinophilia during treatment of immune checkpoint inhibitors (ICIs) predicts succeeding onset of immune-related adverse events (irAEs)
Presenter: Rika Kizawa
Session: Poster Display session 3
Resources:
Abstract
5930 - A transcriptomic immunologic signature predicts favorable outcome in neoadjuvant chemotherapy treated triple negative breast tumors.
Presenter: Javier Pérez-peña
Session: Poster Display session 3
Resources:
Abstract
6127 - Alterations of TMB and TCR repertoires during Chemotherapy in East Asian lung cancer patients without TKI-related driver gene mutations
Presenter: Lele Song
Session: Poster Display session 3
Resources:
Abstract
1310 - Association of SCFA in gut microbiome and clinical response in solid cancer patients treated with andi-PD-1 antibody.
Presenter: Motoo Nomura
Session: Poster Display session 3
Resources:
Abstract
2286 - Extracellular matrix and tissue derived metabolites in a liquid biopsy identifies endotypes of metastatic melanoma patients with differential response to immune checkpoint inhibitor treatment
Presenter: Nicholas Willumsen
Session: Poster Display session 3
Resources:
Abstract
4107 - Pathologic scoring of pre-treatment H&E biopsies predicts overall survival in patients with metastatic clear cell renal cell carcinoma receiving nivolumab monotherapy
Presenter: Julie Stein
Session: Poster Display session 3
Resources:
Abstract
1291 - PD-L1 expression in uncommon EGFR-mutant non-small cell lung cancer and its response to immunotherapy
Presenter: Yun Fan
Session: Poster Display session 3
Resources:
Abstract