Abstract 2497
Background
Frequent over-expression of FRA in ovarian and non-small-cell lung cancer (NSCLC), and relative lack of expression in normal tissue, make it an attractive therapeutic target. Ovarian cancer is the ninth most common cancer in women and the leading cause of death in gynaecological cancer. Lung cancer remains a leading cause of cancer-related death with NSCLC accounting for 80 % of cases. ADCs are the focus of intense interest as a means to provide selective tumor killing with increased efficacy and less off-target toxicity than standard of care chemotherapies. Clinical evaluation of mirvetuximab soravtansine in solid tumor indications demonstrated that FRA can be successfully targeted by an ADC. However, anti-tumor activity appears to be generally limited to patients whose tumors express high levels of FRA. IKS01 is an ADC comprised of an FRA-targeting antibody conjugated via Iksuda’s PermaLink conjugation technology to Femtogenix’s highly potent FGX2-62 payload. FGX2-62 is a pyrridinobenzodiazepine DNA mono-alkylating agent with pM potency in a range of tumor cell lines. IKS01 has been designed to be sufficiently potent to have target-dependent efficacy even in tumors with low or moderate expression of the target antigen.
Methods
IKS01 was generated with a drug to antibody ratio of 2. Efficacy was evaluated in human cell line derived xenograft models with a range of FRA expression, including the choriocarcinoma Jeg-3 model (high expression), the ovarian adenocarcinoma OV-90 model (low expression) and the lung adenocarcinoma NCI-H2110 model (moderate expression). An FRA-targeting benchmark ADC with a format that has shown clinical efficacy was included for comparison.
Results
IKS01 is highly effective in causing tumor regressions in FRA-expressing tumor models at doses that are well tolerated. IKS01 was significantly more active than benchmark ADC in the high FRA-expressing Jeg-3 model and caused complete or near complete regressions in low/moderate FRA-expressing xenograft models where the benchmark ADC showed limited or no activity.
Conclusions
IKS01 shows marked anti-tumor efficacy in pre-clinical models of ovarian and lung cancer, even in models with low or moderate FRA expression.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Iksuda Therapeutics Ltd.
Funding
Iksuda Therapeutics Ltd.
Disclosure
J. Thirlway: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. A. Lodge: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. A. Pelava: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. D.J. Williamson: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. D. Carta: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. M. Al Nakeeb: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. J. Mysliwy: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd. P.J.M. Jackson: Shareholder/Stockholder/Stock options: Femtogenix Ltd. D.E. Thurston: Shareholder/Stockholder/Stock options: Femtogenix Ltd. R.J. Lutz: Shareholder/Stockholder/Stock options: Iksuda Therapeutics Ltd.
Resources from the same session
4883 - A New Population Model Validated Pharmacokinetic Similarity of HLX01 and Rituximab in B-Cell Lymphoma
Presenter: Yuankai Shi
Session: Poster Display session 1
Resources:
Abstract
4908 - Efficacy of salvage therapy in the treatment of Helicobacter pylori-positive gastric low-grade mucosa-associated lymphoid tissue lymphoma
Presenter: Sung-Nam Lim
Session: Poster Display session 1
Resources:
Abstract
2360 - Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing
Presenter: Seok Jae Huh
Session: Poster Display session 1
Resources:
Abstract
2430 - Clinical features, treatment and outcomes of colon and rectum mucosa-associated lymphoid tissue (MALT) lymphoma: Literature reviews published in English between 1993 and 2017
Presenter: Jeong Yeon Kim
Session: Poster Display session 1
Resources:
Abstract
4654 - Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 52 patients
Presenter: Guldane Cengiz Seval
Session: Poster Display session 1
Resources:
Abstract
1732 - Safety and efficacy of Bendamustine and Rituximab (BR) regimen in Indian Chronic Lymphocytic Leukemia patients
Presenter: Ajay Gogia
Session: Poster Display session 1
Resources:
Abstract
5784 - N-terminal B-type natriuretic peptide (NT-proBNP) as an independed prognostic marker for patients with newly diagnosed multiple myeloma complicated by dialysis-dependent renal failure
Presenter: Sergey Semochkin
Session: Poster Display session 1
Resources:
Abstract
836 - The first-line effect of Bortezomib-based Therapy on Clinical Outcomes for Taiwanese Patients with multiple myeloma
Presenter: Ching-Liang Ho
Session: Poster Display session 1
Resources:
Abstract
2085 - Impact of Donor Lymphocyte Infusion in Relapsing Myeloid Neoplasms Post Allogeneic Hematopoietic Stem Cell Transplantation
Presenter: Hanafy Hafez
Session: Poster Display session 1
Resources:
Abstract
6079 - Invasive fungal diseases in patients with Hodgkin’s lymphoma before and after allogeneic hematopoietic stem cell transplantation
Presenter: Marina Popova
Session: Poster Display session 1
Resources:
Abstract