osemitamab (TST001)

P1/2, N=320, Recruiting, Suzhou Transcenta Therapeutics Co., Ltd. | Trial completion date: Nov 2024 --> May 2025 | Trial primary completion date: Aug 2024 --> Feb 2025

P1/2, N=150, Active, not recruiting, Suzhou Transcenta Therapeutics Co., Ltd. | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2024 --> Nov 2024

The human/humanized anti‑CLDN18.2 mAb osemitamab, and ADCs AZD0901, IBI343 and LM‑302, with single‑agent ORRs of 28‑60%, have been tested in phase III clinical trials. In addition, bsAbs, CAR T cells and their derivatives targeting CLDN4, 6 or 18.2 are in phase I and/or II clinical trials. AZD0901, IBI343, zolbetuximab and the anti‑CLDN1 mAb ALE.C04 have been granted fast track designation or priority review designation by the US Food and Drug Administration.

Updated data indicate that the combination of TST001 plus nivolumab and CAPOX as the 1L treatment for patients with G/GEJ cancer is safe and well tolerated with very encouraging anti-tumor activities, especially for patients with high/medium CLDN18.2 expression when cross comparing to historical data.

Preliminary data indicate that the combination of TST001 6mg/kg Q3W plus nivolumab and CAPOX for the 1 st line treatment of patients with G/GEJ cancer is safe and well tolerated with encouraging preliminary anti-tumor activities. Updated clinical data, including PFS and DoR will be reported at the time of the conference.

P1/2, N=320, Recruiting, Suzhou Transcenta Therapeutics Co., Ltd. | Trial completion date: Apr 2024 --> Nov 2024 | Trial primary completion date: Dec 2023 --> Aug 2024

"Transcenta Holding Limited...and Agilent Technologies, announce a collaboration to develop a Claudin18.2 (CLDN18.2) companion diagnostic to support TranStar301 global Phase III pivotal trial of Osemitamab (TST001) in combination with Nivolumab and chemotherapy as first-line treatment in patients with CLDN18.2 expressing locally advanced or metastatic gastric or gastroesophageal (G/GEJ) adenocarcinoma."

In preclinical studies, [Lu]Lu-TST001 demonstrated significant antitumor efficacy with acceptable toxicity. It exhibits strong potential for clinical translation, providing a new promising treatment option for CLDN18.2-overexpressing tumors, including GC.

P3, N=950, Not yet recruiting, Suzhou Transcenta Therapeutics Co., Ltd.

P2, N=8, Completed, Shanghai Zhongshan Hospital | Recruiting --> Completed | N=40 --> 8 | Trial completion date: Jul 2024 --> May 2023

Anti-tumor activity data from 58 patients with 1L G/GEJ adenocarcinoma treated with osemitamab and capecitabine and oxaliplatin (CAPOX) showed patients with average concentration in 56 days above 24 μg/mL tended to have a better ORR. Grade 2+ nausea/vomiting are found to be associated with osemitamab exposure; however, simulations demonstrated the proportion of patients that developed Grade 2+ nausea or vomiting by 6 months were just slightly higher (< 10% in difference) following 6 mg/kg Q3W than 3 mg/kg Q3W. Conclusions Osemitamab at 6mg/kg Q3W or 4mg/kg Q2W are predicted to have favorable PK/PD/safety profiles and might be associated with better ORR in combination with SOC compared to the lower doses.

Encouraging anti-tumor activities have been observed regardless of the CLDN18.2 expression levels, including expression as low as ≥10% tumor cells staining ≥1+, <40% tumor cells staining <2+ or 3+. Overall survival data will be presented.

A dosimetry estimation study showed that the effective dose of &lsqb;Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq, which is within the range of acceptable doses for nuclear medicine research. Taken together, these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.

Funding: Suzhou Transcenta Therapeutics Co., Ltd.Background: Claudin18.2 antibody plus chemotherapy is a clinically validated approach for patients with high CLDN18.2 expressing tumors, which has been proven by zolbetuximab. Osemitamab plus CAPOX as first-line treatment for patients with G/GEJ cancer demonstrated good safety and tolerability. Encouraging anti-tumor activities have been observed regardless of the CLDN18.2 expression levels above 10%, 1+ per central LDT assay.

P1/2, N=320, Recruiting, Suzhou Transcenta Therapeutics Co., Ltd. | Phase classification: P1 --> P1/2 | N=210 --> 320 | Trial completion date: Jan 2023 --> Apr 2024 | Trial primary completion date: Aug 2022 --> Dec 2023

Combinations with nivolumab are being explored in the US study too (NCT04396821). Clinical trial information: NCT04495296.

P1/2; N=45; Not yet recruiting; Sponsor:Henan Cancer Hospital

P1/2, N=124, Recruiting, Suzhou Transcenta Therapeutics Co., Ltd. | Phase classification: P1 --> P1/2

Conclusions TST001 in combination with CAPOX in first-line G/GEJ cancer patients is safe and encouraging anti-tumor activities have been observed. Additional data from the dose expansion cohort will be updated at the meeting.

P2, N=40, Recruiting, Shanghai Zhongshan Hospital | Not yet recruiting --> Recruiting

TST001 in combination with CAPOX in first line gastric cancer patients is safe and encouraging anti-tumor activities have been observed. Additional data from the 6 mg/kg dose expansion cohort will be updated at the meeting.

P2, N=40, Not yet recruiting, Shanghai Zhongshan Hospital

P1, N=210, Recruiting, Mabspace Biosciences (Suzhou) Co., Ltd. | Not yet recruiting --> Recruiting

P1, N=210, Not yet recruiting, Mabspace Biosciences (Suzhou) Co., Ltd.