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.

P1/2 | "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."

P1/2 | "Preliminary data indicate that the combination of TST001 6mg/kg Q3W plus nivolumab and CAPOX for the 1st 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. Clinical trial information: NCT04495296."

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.