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
2600 - Atezolizumab (atezo) vs chemotherapy (chemo) in patients (pts) with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): a long-term overall survival (OS) and safety update from the Phase III IMvigor211 study
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3598 - Three-Year Follow-Up From the Phase 3 KEYNOTE-045 Trial: Pembrolizumab (Pembro) Versus Investigator’s Choice (Paclitaxel, Docetaxel, or Vinflunine) in Recurrent, Advanced Urothelial Cancer (UC)
Presenter: Andrea Necchi
Session: Poster Display session 3
Resources:
Abstract
2382 - First Report of Efficacy and Safety From a Phase 2 Trial of Tislelizumab, an Anti-PD-1 Antibody, for the Treatment of PD-L1+ Locally Advanced or Metastatic Urothelial Carcinoma (UC) in Asian Patients
Presenter: Dingwei Ye
Session: Poster Display session 3
Resources:
Abstract
2388 - Quality of Life of Metastatic Urothelial Cancer (mUC) Patients Treated with Enfortumab Vedotin (EV) Following Platinum-Containing Chemotherapy and a Checkpoint Inhibitor (CPI): Data from EV-201 Cohort 1
Presenter: Bradley McGregor
Session: Poster Display session 3
Resources:
Abstract
3748 - Safety and efficacy of atezolizumab (atezo) in patients (pts) with autoimmune disease (AID): subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
1126 - Validation of the VIO prognostic index in patients with metastatic urothelial carcinoma treated with immune-checkpoint inhibitors
Presenter: Rafael Morales Barrera
Session: Poster Display session 3
Resources:
Abstract
3693 - Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer
Presenter: Justin Matulay
Session: Poster Display session 3
Resources:
Abstract
4840 - Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
1221 - Clinical outcomes by sex with atezolizumab (atezo) monotherapy in patients (pts) with locally advanced/metastatic urothelial carcinoma (mUC)
Presenter: Jean Hoffman-censits
Session: Poster Display session 3
Resources:
Abstract
1715 - National Small Cell Bladder Cancer Audit: Results from 26 UK institutions
Presenter: Caroline Chau
Session: Poster Display session 3
Resources:
Abstract