Abstract 1006P
Background
ACE1702 is manufactured with a proprietary low-cost method using oNK immortalized cell source with stable high expression of multiple NK activation receptors, including CD16, conjugated to anti-HER2 IgG via ACC, and low levels of inhibitory receptors. Preclinical in vitro & in vivo studies and initial data from Ph1 study (NCT04319757) of patients [pts] with advanced HER2 tumors will be presented.
Methods
ACE1702 activity was evaluated by in vitro cytotoxicity assay and in vivo xenograft model to enable a multicenter Ph1 study to evaluate safety, PK/PD, and antitumor response and define a recommended Ph2 dose. Up to 36 pts with advanced HER2 IHC ≥ 2+ tumors are to be enrolled to receive low dose lymphodepletion [LD] followed by an assigned level of escalating ACE1702 doses 0.3-15 billion [B] cells/cycle. [Total cycle dose delivered in 3 infusions].
Results
In vitro, ACE1702 lysed 3 cell lines [1+ - 3+ HER2] using low effector:target ratios. In NSG xenografts, ACE1702 suppressed HER2 tumor growth by Day 4 and through the 29-day study using 2 infusions/week x 3 weeks. By MAR2021, 7pts received 0.3-3B cells/cycle and were evaluable for toxicity and response. Common AEs were lymphopenia (n=6), leukopenia (n=4), neutropenia (n=4) [all due to LD] and fatigue (n=4) [1 Gr1 related to drug] and all improved by 30 days post-drug. No dose limiting toxicity [DLT], cytokine release syndrome [CRS], neurotoxicity or graft vs. host disease [GvHD] was observed. Only 1 SAE [pulmonary embolism], unrelated to drug, was reported. At 3B cells/cycle, peak blood concentrations occurred at 4hrs post initial infusion, and detectable up to 48hrs. At 3B cells/cycle, 1 pt with HER2 2+ refractory salivary gland tumor achieved a partial response by RECIST with increased serum IFNγ and IL10, but not IL6.
Conclusions
In pre-clinical studies, ACE1702 exhibited cancer-specific cytotoxicity and superior potency against low HER2 tumors. Preliminary data in pts showed no CRS, GvHD, or DLTs through doses of 3B cells/cycle and antitumor activity in a HER2 < 3+ tumor. Dose escalation continues up to 15B cells/cycle with updated clinical data to be provided.
Clinical trial identification
NCT04319757.
Editorial acknowledgement
Legal entity responsible for the study
Acepodia Inc.
Funding
Acepodia Inc.
Disclosure
S.A. Piha-Paul: Non-Financial Interests, Institutional, Research Grant: AbbVie, Inc.; Non-Financial Interests, Institutional, Research Grant: ABM Therapeutics, Inc.; Non-Financial Interests, Institutional, Research Grant: Acepodia, Inc; Non-Financial Interests, Institutional, Research Grant: Alkermes; Non-Financial Interests, Institutional, Research Grant: Aminex Therapeutics; Non-Financial Interests, Institutional, Research Grant: Amphivena Therapeutics, Inc.; Non-Financial Interests, Institutional, Research Grant: BioMarin Pharmaceutical, Inc; Non-Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Non-Financial Interests, Institutional, Research Grant: Bristol Myers Squib; Non-Financial Interests, Institutional, Research Grant: Cerulean Pharma, Inc.; Non-Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical Co., Ltd; Non-Financial Interests, Institutional, Research Grant: Curis, Inc.; Non-Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Non-Financial Interests, Institutional, Research Grant: Eli Lilly; Non-Financial Interests, Institutional, Research Grant: ENB Therapeutics; Non-Financial Interests, Institutional, Research Grant: Five Prime Therapeutics; Non-Financial Interests, Institutional, Research Grant: F-Star Therapeutics; Non-Financial Interests, Institutional, Research Grant: Gene Quantum; Non-Financial Interests, Institutional, Research Grant: Genmab A/S; Non-Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Non-Financial Interests, Institutional, Research Grant: Helix BioPharma Corp.; Non-Financial Interests, Institutional, Research Grant: Incyte Corp.; Non-Financial Interests, Institutional, Research Grant: Jacobio Pharmaceuticals Co., Ltd.; Non-Financial Interests, Institutional, Research Grant: Medimmune, LLC.; Non-Financial Interests, Institutional, Research Grant: Medivation, Inc.; Non-Financial Interests, Institutional, Research Grant: Merck Sharp and Dohme Corp.; Non-Financial Interests, Institutional, Research Grant: Novartis Pharmaceuticals; Non-Financial Interests, Institutional, Research Grant: Pieris Pharmaceuticals, Inc.; Non-Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Institutional, Research Grant: Principia Biopharma, Inc.; Non-Financial Interests, Institutional, Research Grant: Puma Biotechnology, Inc.; Non-Financial Interests, Institutional, Research Grant: Rapt Therapeutics, Inc.; Non-Financial Interests, Institutional, Research Grant: Seattle Genetics; Non-Financial Interests, Institutional, Research Grant: Silverback Therapeutics; Non-Financial Interests, Institutional, Research Grant: Taiho Oncology; Non-Financial Interests, Institutional, Research Grant: Tesaro, Inc.; Non-Financial Interests, Institutional, Research Grant: TransThera Bio; Non-Financial Interests, Institutional, Research Grant: NCI/NIH; Non-Financial Interests, Institutional, Research Grant: P30CA016672 – Core Grant. D. Mahalingam: Non-Financial Interests, Personal, Speaker’s Bureau: Amgen Inc.; Non-Financial Interests, Personal, Speaker’s Bureau: Eisai Co., Ltd.; Non-Financial Interests, Personal, Speaker’s Bureau: Exelixis, Inc.; Non-Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squib; Non-Financial Interests, Institutional, Research Grant: Acepodia Biotech Inc. H. Li: Financial Interests, Personal, Full or part-time Employment: Acepodia Inc. E. Wu: Financial Interests, Personal, Full or part-time Employment: Acepodia Inc. M. Kurman: Financial Interests, Personal, Full or part-time Employment: Acepodia Inc. S. Lee: Financial Interests, Personal, Full or part-time Employment: Acepodia Inc. Y. Lin: Financial Interests, Personal, Full or part-time Employment: Acepodia Inc. S. Tang: Financial Interests, Personal, Full or part-time Employment: Acepodia Inc. C. Hsiao: Financial Interests, Personal, Full or part-time Employment: Acepodia Inc. J. Pan: Financial Interests, Personal, Full or part-time Employment: Acepodia Inc. S. Chien: Financial Interests, Personal, Full or part-time Employment: Acepodia Inc. All other authors have declared no conflicts of interest.