The first naked anti-TROP2 antibody progresses to a Phase 1/2a clinical trial

On 24 October 2024, Cancer Research UK ("CRUK") and KisoJi Biotechnology Inc. ("KBI") announced that they have entered into an agreement to advance KBI's lead antibody, KJ-103, into a first-in-human Phase 1/2a clinical trial at CRUK's Centre for Drug Development. 

KJ-103 and TROP2

As explored in depth in Bristows' recent Science Series sessions (which included talks on: (i) Antibody Drug Conjugates ("ADCs") and radiopharmaceuticals; and (ii) oncolytic viruses and cancer vaccines), ADCs are a revolutionary targeted therapy that harness the specificity of antibodies to deliver drugs directly to target cells. However, there are several challenges associated with the development and use of ADCs including, amongst other things, unavoidable toxic off-target effects and tumour cells developing resistance to the ADC. 

Unlike ADCs, KJ-103 (a single domain 'naked' anti-TROP2 antibody that was humanised by LifeArc in partnership with KBI) does not need a cytotoxic payload and instead acts by recruiting immune cells to kill target cancer cells. KJ-103 specifically binds to TROP2 (trophoblast cell surface antigen-2), a membrane glycoprotein that is widely expressed on a range of different tumour types including colorectal, head and neck, ovarian, breast and lung cancers. KJ-103 binds to TROP2 in a different location from where current TROP2 ADCs bind and crucially, in several preclinical solid tumour models, KJ-103 has been shown to have high levels of potency and specificity without the toxicity or resistance seen with ADCs. 

Next steps

While KJ-103 may offer a potential alternative treatment for people living with TROP2-expressing cancers, particularly in cases where TROP2 ADCs have been ineffective or unsuitable due to their toxicity profiles, it is important to note that this is still early stage research and there is still a lot of work to do and hurdles to overcome before any treatment would become generally available to people living with such cancers. The Phase 1/2a clinical trial will focus on testing the safety, side effects and best dose of the treatment, with the outcome of such trial determining whether the treatment can then be progressed to a larger Phase 3 clinical trial which is the key hurdle for determining whether a new treatment can be approved for use. 

Nevertheless, KJ-103 is yet another example of the continuing advancements in innovative therapeutic approaches and modalities for cancer treatment. As the first naked antibody to target TROP2 cancers, we will be monitoring the progress of the KJ-103 clinical trial closely and look forward to reporting on any further developments