Celltrion

AimsTo demonstrate pharmacokinetic equivalence of CT-P39 administered via auto-injector (CT-P39 AI) and European Union-approved reference omalizumab via pre-filled syringe (EU-OMA PFS) in healthy Japanese adults.Participants & MethodsThis open-label, Phase 1 study randomized participants (1:1) to a single 150 mg/mL dose of CT-P39 AI or EU-OMA PFS. The primary endpoint was pharmacokinetic equivalence per area under the concentration-time curve from time zero to infinity (AUC0-inf) and maximum serum concentration (Cmax). Equivalence was concluded if the 90% confidence intervals (CIs) for the ratios of geometric least-squares means (gLSMs) were contained within the predefined 80-125% equivalence margin. Secondary endpoints comprised additional pharmacokinetics, pharmacodynamics, safety, and immunogenicity.ResultsOverall, 65 and 64 individuals were randomized to CT-P39 AI and EU-OMA PFS, respectively. Pharmacokinetic equivalence between CT-P39 AI and EU-OMA PFS was demonstrated for both AUC0-inf (ratio of gLSMs [90% CI] 101.66 [95.31-108.45]) and Cmax (93.91 [87.20-101.14]). Thirty-nine (60.0%; CT-P39 AI) and 32 (50.8%; EU-OMA PFS) participants experienced treatment-emergent adverse events (TEAEs) with no serious TEAEs. Secondary endpoints were comparable between groups.ConclusionsCT-P39 AI was pharmacokinetically equivalent to EU-OMA PFS following a single dose in healthy Japanese individuals; pharmacodynamics, safety, and immunogenicity were comparable.

The primary objective of the MEGA-J study (UMIN-CTR number UMIN000057308) was to assess the safety of CT-P13, an infliximab biosimilar, in Japanese patients with Crohn's disease (CD), ulcerative colitis (UC), and/or rheumatoid arthritis (RA) after switching from reference infliximab. Data were collected over 5 years, following initiation of CT-P13 treatment within routine clinical practice. Interim findings are reported (cut-off: last patient's Year 2 visit). The primary endpoint was the incidence of uncommon adverse drug reactions (ADRs), including tuberculosis and serious infections. Overall, 220 patients were enrolled (123 CD; 74 UC; 23 RA). Forty-eight (39.0%), 37 (50.0%), and 3 (13.0%) patients reported ≥1 uncommon ADR in the CD, UC, and RA groups, respectively. The majority (94.3%) were unrelated to CT-P13. No cases of tuberculosis and one unrelated case of serious infection was reported. Nineteen (8.6%) patients discontinued treatment for reasons related to CT-P13. Overall, CT-P13 was well tolerated, demonstrating the safety of long-term treatment in real-world practice.

Many ADC drugs in clinical trials are showing poor performance without providing sufficient dose due to dose-limiting toxicity, which is rooted from on-target toxicity related to payload itself. There are many efforts to increase the therapeutic index (TI) of ADC, but research on discovering novel payloads based on unique anticancer mechanisms of action is relatively limited. We have developed unique ADC platform technology by adopting multi-drug payloads concept, where we aim to achieve three different goals, (1) increasing MTD and lowering MED (2) showing cytotoxic activity in antigen low-expressed cell lines (3) overcoming resistance cell lines with better cytotoxic effects. This study began with the search for a drug combination that could maintain or increase efficacy of MMAE even with lower dose of MMAE. Drugs with various mechanisms of action were tested to select a combination that showed a high synergy effect with MMAE, and a cell cycle regulating drug was found to offer the most synergistic combination efficacy with MMAE. By conjugating a dual-payload with two-different mechanisms of action to HER2 antibody(trastuzumab), the resulting ADC(CTPH-02) was confirmed to show synergistic effect in terms of cytotoxicity. Very excitingly, CTPH-02 shows significantly high synergistic efficacy in the case of cell lines with low HER2 antigen expression. These findings based on the right combination of two-different payloads open a new paradigm for ADC drug design strategies in cancer therapy in order to provide treatment options to wider range of cancer patients such as low TPS % with low IHC score. Chang-Sun Lee, Myeong Joo Kim, Da hyun Kim, Soyeon Lim, Jiwoo Lee, Eunseok Choi, Wonbin Ha, Han ah Kim, Jaebeom Park, Seung Chan Kim. Discovery of the synergistic dual-payload antibody-drug conjugate (CTPH-02) by combination of MMAE and novel payloads [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6755.