P1, N=18, Recruiting, Imbioray (Hangzhou) Biomedicine Co., Ltd. | Not yet recruiting --> Recruiting

P1/2, N=56, Recruiting, Aptevo Therapeutics

These results provide the strong rationale for further clinical evaluation ofCBA-1535 in 5T4 positive tumors. CBA-1535 is now under the phase 1 trial in Japan (jRCT2031210708), with 2 parts, the monotherapy and the combination with Pembrolizumab.

Lastly, in dissociated patient-derived tumor samples, DuoBody-CD3x5T4 activated tumor-infiltrating lymphocytes and induced tumor-cell cytotoxicity, even when most tumor-infiltrating lymphocytes expressed PD-1. These data provide an in-depth view on the mechanism of action of a CD3 bsAb in preclinical models of solid cancer.

P1, N=56, Recruiting, Shanghai East Hospital | Trial completion date: Aug 2022 --> May 2023 | Trial primary completion date: Aug 2022 --> Apr 2023

P1, N=56, Recruiting, Shanghai East Hospital | N=136 --> 56

P1b, N=50, Recruiting, NeoTX Therapeutics Ltd. | Trial completion date: Jul 2022 --> Mar 2023 | Trial primary completion date: Apr 2022 --> Dec 2022

P1, N=40, Recruiting, Wuxi People's Hospital

P1b, N=50, Recruiting, NeoTX Therapeutics Ltd. | Trial completion date: Feb 2022 --> Jul 2022 | Trial primary completion date: Nov 2021 --> Apr 2022

P2a, N=35, Recruiting, NeoTX Therapeutics Ltd. | Not yet recruiting --> Recruiting

In head-to-head studies, superior activity of ASN004 was demonstrated against trastuzumab-DM1, in a low-5T4/high-HER2 expressing gastric tumor model, and 10-fold greater potency was found for ASN004 against the 5T4-targeted ADC PF-06263507 in a lung tumor model. In marmoset monkeys, ASN004 was well tolerated at doses up to 1.5 mg/kg Q3W iv, and showed dose-dependent exposure, linear pharmacokinetics, and markedly low exposure of free payload drug. Taken together, these findings identify ASN004 as a promising new ADC therapeutic for clinical evaluation in a broad range of solid tumor types.

P2a, N=35, Not yet recruiting, NeoTX Therapeutics Ltd.

Tumour antigen-specific T17 responses play a beneficial role in preventing post-operative colorectal tumour recurrence.

An excellent safety profile and T-cell responses elicited in the circulation and also detected in the prostate gland support the evaluation of the ChAdOx1-MVA 5T4 vaccine in efficacy trials. It remains to be seen if this vaccination strategy generates immune responses of sufficient magnitude to mediate clinical efficacy and whether it can be effective in late-stage PCa settings, as a monotherapy in advanced disease or as part of multi-modality PCa therapy. To address these questions, the phase I/II trial, ADVANCE, is currently recruiting patients with intermediate-risk PCa, and patients with advanced metastatic castration-resistant PCa, to receive this vaccine in combination with nivolumab.

The results support further investigation of mRNA-based immunotherapy in NSCLC including combinations with immune checkpoint inhibitors.

HDIL2/XRT combined treatment is well tolerated and fairly active in the MM and RCC settings.Legal entity responsible for the study: The authors. Funding: Italian Ministry of Health as part of the “Ricerca Finalizzata 2009 - Direzione Generale della Ricerca Scientifica e Tecnologica” Call for Project Proposals. Clinical trial identification: EudraCT: 2012-001786-32.