Increases of CD45+ and CD8+ T-cell infiltrates, as well as CD8+ T-cell activation, observed in xenograft tumor tissues were time and JNJ-79032421 dose dependent. Overall, these data suggest that JNJ-79032421 may offer meaningful clinical activity by avoiding binding to sMSLN.

P1, N=37, Completed, Amgen | Active, not recruiting --> Completed

Therapeutically, it caused dose-dependent tumor regression (TGI: 58% at 50 kBq; 92% at 150 kBq) and prolonged survival (>60 days vs. 0-1% in controls, p < 0.001). &lsqb;225Ac]Ac-Macropa-PEG6-Amatuximab is stable, selective, and therapeutically effective, demonstrating Macropa-based 225Ac chelation as a stable platform for targeted α-therapy of PDAC.

Quantitative ex vivo fluorescence analysis of excised xenografts demonstrated that combining ch10D7ICG and amatuximabICG enhances tumor-associated fluorescence by 2.8- to 12.5-fold compared with either agent alone. The results support the potential of dual-targeted, antibody-based fluorescence imaging for enhanced intraoperative visualization and excision of PDAC, including for tumors with heterogeneous expression of either or both of the targeted receptors CDCP1 and MSLN.

P1, N=37, Active, not recruiting, Amgen | N=220 --> 37 | Trial completion date: Feb 2028 --> Apr 2026 | Trial primary completion date: Jun 2027 --> Apr 2026 | Recruiting --> Active, not recruiting

P1/2, N=262, Recruiting, Sichuan Huiyu Pharmaceutical Co., Ltd | Not yet recruiting --> Recruiting

MSLN-TTC showed good tolerability, but the maximum tolerated dose could not be determined due to discontinuations after antidrug antibody formation. Stable disease was observed in 12 out of 36 patients.

Model was developed based on digitized individual level CK, categorical antitumor activity and percentage tumor antigen expression dataset from following phase-1 dose-escalation studies: (A) anti-mesothelin CAR-T in multiple cancer indications (n = 15, cohorts w/ and w/o LDC), (B) gavocabtagene autoleucel (n = 7, w/ and w/o LDC) in multiple indications, (C) anti-glypican 3 CAR-T in advanced hepatocellular carcinoma (n = 13, dose-range 0.7-5.18 billion) and (D) anti-PSMA/TGFβ CAR-T in prostate cancer (n = 10, w/ and w/o LDC)...Using model simulation, CAR-T cell expansion was found to be dependent on initial tumor burden and antigen positive tumor fraction. The developed PBPK-PD model could be leveraged as an effective tool in future to provide mechanistic understanding on CK-PD behavior of cell therapies targeting solid tumors.

P1, N=32, Terminated, Zymeworks BC Inc. | N=160 --> 32 | Trial completion date: Dec 2027 --> Oct 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Nov 2027 --> Sep 2025; Sponsor decision

P1, N=160, Active, not recruiting, Zymeworks BC Inc. | Recruiting --> Active, not recruiting

P1/2, N=57, Active, not recruiting, TCR2 Therapeutics | N=36 --> 57 | Trial primary completion date: Nov 2028 --> Nov 2024

P1/2, N=262, Not yet recruiting, Sichuan Huiyu Pharmaceutical Co., Ltd