tifcemalimab (TAB004)

P1, N=12, Not yet recruiting, Sichuan University

P2, N=31, Not yet recruiting, RenJi Hospital

P2, N=80, Recruiting, Fudan University

P2, N=100, Not yet recruiting, Shanghai Pulmonary Hospital, Shanghai, China

P2, N=20, Not yet recruiting, Henan Provincial People's Hospital

P1, N=71, Completed, Shanghai Junshi Bioscience Co., Ltd. | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Mar 2024 | Trial primary completion date: Sep 2024 --> Mar 2024

P1/2, N=117, Not yet recruiting, Fudan University

P3, N=756, Recruiting, Shanghai Junshi Bioscience Co., Ltd. | Not yet recruiting --> Recruiting

P3, N=185, Recruiting, Shanghai Junshi Bioscience Co., Ltd. | Not yet recruiting --> Recruiting

P3, N=185, Not yet recruiting, Shanghai Junshi Bioscience Co., Ltd.

Tifcemalimab alone or in combination with toripalimab were well tolerated in all doses evaluated. The combination regimen showed favorable safety and durable efficacy in lymphoma patients with heavily pretreatment, providing evidence for future investigation.

P3, N=756, Not yet recruiting, Shanghai Junshi Bioscience Co., Ltd.

P1, N=71, Active, not recruiting, Shanghai Junshi Bioscience Co., Ltd. | N=170 --> 71

This prompted rapid development and clinical testing of the anti-BTLA blocking antibody Tifcemalimab/icatolimab as the first BTLA-targeted therapy in various ongoing phase I clinical trials with encouraging results on preliminary efficacy and safety profile as monotherapy and combined with other anti-PD-1/PD-L1 therapies. Nevertheless, it is anticipated that the intricate signaling network constituted by BTLA/HVEM/CD160/LIGHT involved in immune response regulation, tumor development and tumor microenvironment could limit therapeutic success. Therefore, in-depth functional characterization in different cancer settings is highly recommended for adequate design and implementation of BTLA-targeted therapies to guarantee the best clinical outcomes to benefit cancer patients.

P2, N=124, Not yet recruiting, Shanghai Pulmonary Hospital, Shanghai, China

We have designed, synthesized and characterized a target-specific, stimuli-responsive MSN platform for the controlled delivery of cisplatin (cisPt) and gemcitabine (Gem) (TAB004-Gem-cisPt-MSNs) with an optimal drug ratio. Moreover, the same MSN platform has been used in a sequential treatment where MSNs containing a Sonic Hedgehog (SHh) inhibitor, cyclopamine (CyP), and the Gem-cisPt-MSNs as the main delivery system led to reduction in the tumor stroma along with an improvement in the treatment of PDAC. Taken together, our findings support the potential of drug delivery using MSN nanoparticles for stroma modulation and to prevent pancreatic cancer progression.

Tifcemalimab alone or in combination with toripalimab were well tolerated in all doses evaluated. The combination showed encouraging preliminary clinical efficacy in patients with R/R HL refractory to anti-PD-1/L1 and/or anti-CD30.

TAB004 treatment slowed the growth of PDA xenograft compared to IgG control and enhanced survival of mice when combined with 5-FU. Since TAB004 significantly reduced colony forming potential and triggered anoikis in the PDA cells, we suggest that it could be used as a potential prophylactic agent to curb tumor relapse after surgery, prevent metastasis and help increase the efficacy of chemotherapeutic agents.

Icatolimab alone or in combination with toripalimab were well tolerated in all doses evaluated and showed preliminary clinical efficacy in patients with R/R lymphoma.

The response was still ongoing over 12 months in the melanoma patient who had progressed upon prior nivolumab and BRAF/MEK inhibitors treatments. Icatolimab monotherapy were well tolerated in all doses evaluated and showed preliminary clinical efficacy as a monotherapy. Icatolimab in combination with toripalimab (anti-PD-1) for the treatment of patients with advanced solid tumors is currently ongoing.

Nevertheless, clinically used combination regimens such as FOLFIRINOX and gemcitabine (Gem)/nab-paclitaxel still face major challenges due to lack of the safe and ratiometric delivery of multiple drugs...The platform is also rendered with additional tumor-specificity via a novel tumor-associated mucin1 (tMUC1)-specific antibody, TAB004. Overall, the platform suppresses tumor growth and eliminates the off-target toxicities of a highly toxic chemotherapy combination.

P1, N=499, Recruiting, Shanghai Junshi Bioscience Co., Ltd. | N=144 --> 499 | Trial completion date: Jan 2023 --> Mar 2026 | Trial primary completion date: Jan 2023 --> Mar 2026

Monoclonal antibody, TAB004, specifically recognizes the aberrantly glycosylated tumor form of MUC1 (tMUC1) in all subtypes of breast cancer including 95% of triple-negative breast cancer (TNBC) while sparing recognition of normal tissue MUC1...A single dose of MUC28z CAR T cells significantly reduced TNBC tumor growth in a xenograft model. Thus, MUC28z CAR T cells have high therapeutic potential against tMUC1-positive TNBC tumors with minimal damage to normal breast epithelial cells.

The human dosimetry results were comparable to other clinically used agents. The results obtained with hTAB004 suggest that the In/Ac-DOTA-hTAB004 combination has significant potential as a theranostic strategy in TNBC and merits further development toward clinical translation.