Abstract 6587
Background
CLEVER-1 is a scavenger receptor that is highly expressed on tumor associated macrophages (TAMs) and mediates the clearance of “unwanted” self-components. Pre-clinical studies demonstrate that CLEVER-1 inhibition switches TAMs to a pro-inflammatory phenotype and reactivates CD8+ T-cell responses with a robust anti-tumour activity (Viitala et al. Clin Cancer Res 2019). Targeting CLEVER-1 could overcome the immunosuppressive tumour microenvironment and has led to the development of FP-1305, a humanized anti-CLEVER-1 IgG4-antibody.
Methods
MATINS (Macrophage Antibody To INhibit immune Suppression) trial is a multicenter first-in-human phase I/II study (NCT03733990) to assess the tolerability, safety and preliminary efficacy of FP-1305 in patients (pts) with advanced, IO-refractory melanoma, cholangiocarcinoma, hepatocellular, colorectal, and pancreatic ductal adenocarcinoma (PDAC)
Results
11 pts (median age 57) were enrolled in four cohorts (0.3, 1.0, 3.0 or 10 mg/kg) and received 1-8 cycles (median 3) of FP-1305 every three weeks. FP-1305 has been well tolerated without dose-limiting toxicities. Most frequent treatment-emergent adverse events (AEs; ≥20%) were fatigue and raised ALT and AST levels. Initial FP-1305 dosing led to an increase in blood NK cells (median 154 %), CD8+/CD4+ T cell ratio (median 121 %), B cells (median 143 %) and a decrease in regulatory T cells (median 65 % from baseline). Clinical benefits have been observed in two colorectal cancer pts. One with an ongoing partial response (-52%) and another with disease stabilization along with a decline in Carcinoembryonic antigen (CEA). The updated safety and efficacy results will be reported.
Conclusions
FP-1305 is the first macrophage checkpoint candidate promoting immune switch with promising tolerability and clinical anti-tumor activity. Analysis of circulating immune cells after administration of FP-1305 demonstrates Th1 activation as well as mobilization of NK cells and B cells.
Clinical trial identification
EudraCT: 2018-002732-24 (obtained 09 Jul 2018).
Editorial acknowledgement
Legal entity responsible for the study
Faron Pharmaceuticals Ltd.
Funding
Faron Pharmaceuticals Ltd.
Disclosure
P. Bono: Full / Part-time employment, Employment: Terveystalo; Advisory / Consultancy, Shareholder / Stockholder / Stock options, Stock owenership and Scientific Board member: TILT Biotherapeutics; Spouse / Financial dependant, Family member’s stock ownereship: Faron pharmaceuticals; Advisory / Consultancy: Faron pharmaceuticals; Advisory / Consultancy, Scientific Board member: Oncorena; Advisory / Consultancy: Pfizer; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Orion Pharma; Advisory / Consultancy: Ipsen ; Honoraria (self), Data safety monitoring Board member: Herantis Pharma. M. Hollmen: Advisory / Consultancy, Shareholder / Stockholder / Stock options, patent holder: faron pharmaceuticals. P. Jaakkola: Advisory / Consultancy: Faron Pharmaceuticals. S. Shetty: Advisory / Consultancy: Faron Pharmaceuticals. A. Thibault: Full / Part-time employment: Simbec-Orion. M.J.A. de Jonge: Advisory / Consultancy: Faron Pharmaceuticals. A.R. Minchom: Advisory / Consultancy: Faron Pharmaceuticals. Y.T. Ma: Advisory / Consultancy: Faron Pharmaceuticals. C. Yap: Advisory / Consultancy: Faron Pharmaceuticals. D. Robbrecht: Advisory / Consultancy: Faron Pharmaceuticals. S. Jalkanen: Shareholder / Stockholder / Stock options: Faron Pharmaceuticals. M.K. Karvonen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Faron Pharmaceuticals. J. Mandelin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Faron Pharmaceuticals. J. Koivunen: Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneza; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: KaikuHealth; Research grant / Funding (self): Roche. All other authors have declared no conflicts of interest.
Resources from the same session
5576 - Genomic characteristics and predicted ancestry of NTRK1/2/3 and ROS1 fusion-positive tumors from >165,000 pan-solid tumors
Presenter: Timothy R Wilson
Session: Poster Discussion – Developmental therapeutics
Resources:
Abstract
4536 - Safety and preliminary clinical activity of repotrectinib in patients with advanced ROS1/TRK fusion-positive solid tumors (TRIDENT-1 study)
Presenter: Alexander Drilon
Session: Poster Discussion – Developmental therapeutics
Resources:
Abstract
5684 - Durability of response with larotrectinib in adult and pediatric patients with TRK fusion cancer
Presenter: David Hyman
Session: Poster Discussion – Developmental therapeutics
Resources:
Abstract
2937 - Phase 1 Study of AMG 510, a Novel Molecule Targeting KRAS G12C Mutant Solid Tumors
Presenter: Ramaswamy Govindan
Session: Poster Discussion – Developmental therapeutics
Resources:
Abstract
4748 - Phase 1/2 study of combined BCL-XL and MEK inhibition with navitoclax (N) and trametinib (T) in KRAS or NRAS mutant advanced solid tumors
Presenter: Ryan Corcoran
Session: Poster Discussion – Developmental therapeutics
Resources:
Abstract
4556 - Genomic Profiling of Three Pathways through Molecular Profiling-based Assignment of Cancer Therapy (NCI- MPACT)
Presenter: Alice Chen
Session: Poster Discussion – Developmental therapeutics
Resources:
Abstract
4548 - Precision Medicine: Preliminary Results from the Initiative for Molecular Profiling and Advanced Cancer Therapy 2 (IMPACT 2) Study.
Presenter: Apostolia Maria Tsimberidou
Session: Poster Discussion – Developmental therapeutics
Resources:
Abstract
1915 - A Phase I study of ATR inhibitor, AZD6738, as monotherapy in advanced solid tumours (PATRIOT Part A, B)
Presenter: Magnus Dillon
Session: Poster Discussion – Developmental therapeutics
Resources:
Abstract
4517 - Updated results of the PARP1/2 inhibitor pamiparib in combination with low-dose (ld) temozolomide (TMZ) in patients (pts) with locally advanced or metastatic solid tumors
Presenter: Agostina Stradella
Session: Poster Discussion – Developmental therapeutics
Resources:
Abstract
2588 - Safety, antitumor activity, and pharmacokinetics (PK) of pamiparib (BGB-290), a PARP1/2 inhibitor, in patients (pts) with advanced solid tumors: updated phase 1 dose-escalation/expansion results
Presenter: Mark Voskoboynik
Session: Poster Discussion – Developmental therapeutics
Resources:
Abstract