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
3252 - Genes involved in DNA replication, chromatin remodeling and cell cycle as potential biomarkers for therapy outcome to immune therapy in patients with metastatic cutaneous malignant melanoma
Presenter: Fernanda Costa Svedman
Session: Poster Display session 3
Resources:
Abstract
5545 - Phase Ib/II Study (SENSITIZE) assessing safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical outcome of domatinostat in combination with pembrolizumab in patients with advanced melanoma refractory/non-responding to prior checkpoint inhibitor therapy
Presenter: Jessica Hassel
Session: Poster Display session 3
Resources:
Abstract
5213 - Genomic landscape of primary malignant melanoma of esophagus
Presenter: Jie Dai
Session: Poster Display session 3
Resources:
Abstract
2716 - A phase III, randomised, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation in patients with high-risk cutaneous squamous cell carcinoma (CSCC)
Presenter: Danny Rischin
Session: Poster Display session 3
Resources:
Abstract
3550 - ILLUMINATE 301: A randomized phase 3 study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy
Presenter: Marcus Butler
Session: Poster Display session 3
Resources:
Abstract
1645 - PRIME002 - Early phase II study of Azacitidine and Carboplatin priming for Avelumab in patients with advanced melanoma who are resistant to immunotherapy
Presenter: Andre Van Der Westhuizen
Session: Poster Display session 3
Resources:
Abstract
4440 - Pembrolizumab (pembro) Plus Lenvatinib (len) for First-Line Treatment of patients (pts) With Advanced Melanoma: Phase 3 LEAP-003 Study
Presenter: Alexander Eggermont
Session: Poster Display session 3
Resources:
Abstract
3454 - Proof of concept study with the histone deacetylase inhibitor vorinostat in patients with resistant BRAFV600 mutated advanced melanoma
Presenter: Sanne Huijberts
Session: Poster Display session 3
Resources:
Abstract
1832 - A phase Ia/Ib clinical study to evaluate the safety, pharmacokinetics (PK) and preliminary anti-tumor activity of FCN-159 in patients with advanced melanoma harboring NRAS-aberrant (Ia) and NRAS-mutation (Ib).
Presenter: Lu Si
Session: Poster Display session 3
Resources:
Abstract
3996 - A Phase I Clinical Trial Investigating the Therapeutic Cancer Vaccine UV1 in Combination with Pembrolizumab as First-Line Treatment of Patients with Malignant Melanoma
Presenter: Sanjiv Agarwala
Session: Poster Display session 3
Resources:
Abstract