Adcendo inks MSD supply deal to run ADC-Keytruda combination study

Copenhagen-based Adcendo plans to start a Phase Ib trial of the combination in the second half of the year. Participants will receive ADCE-T02, Adcendo’s tissue factor (TF)-directed ADC, with the anti-PD-1 checkpoint inhibitor Keytruda. Adcendo, which will sponsor the trial, began a Phase I monotherapy trial of ADCE-T02 in 2024. 

The planned trial reflects evidence of the potentially synergistic effects of giving ADCs with checkpoint inhibitors. ADCs destroy tumors through the targeted delivery of cytotoxic payloads, releasing cancer cell antigens that prime and activate immune cells. The effect, which is called immunogenic cell death (ICD), could enhance the efficacy of drugs such as Keytruda that orchestrate immune attacks against tumors. 

Researchers have identified multiple promising pairings of ADCs and checkpoint inhibitors, including the combination of Astellas’ and Pfizer’s Padcev and Keytruda. The European Medicines Agency approved the combination for first-line treatment of advanced urothelial cancer in 2024. 

Seagen, now part of Pfizer, tested a TF-directed ADC with Keytruda in a Phase I/II trial. While researchers reported “encouraging” data in 2023, Pfizer recently terminated the study based on “strategic decisions.” Genmab sells the ADC, Tivdak, in Europe.

Like Adcendo, Sutro Biopharma is developing a TF-directed ADC that could compete with Tivdak. Sutro started a Phase I trial last year. The study includes a cohort of metastatic cancer patients who will receive the ADC with Keytruda. 

Adcendo’s ADCE-T02 and Sutro’s STRO-004 use different payloads than Tivdak. Pfizer’s and Genmab’s ADC delivers the tubulin inhibitor monomethyl auristatin E (MMAE), whereas ADCE-T02 and STRO-004 use the topoisomerase-1 inhibitor exatecan. In a preclinical study, Seagen found MMAE had a stronger effect than exatecan on immune response genes related to ICD. 

Testing tolerability

Adcendo has identified safety and tolerability as an area ADCE-T02 may be able to improve on Tivdak, which is associated with adverse events including ocular toxicities, peripheral neuropathy and bleeding. Some of the side effects may reflect Tivdak’s inhibition of coagulation Factor X activation. By designing an ADC without those effects, Adcendo may achieve improved tolerability and a wider therapeutic window.

The planned Phase Ib will generate evidence of the safety and tolerability of ADCE-T02 when given with Keytruda. Adcendo plans to test escalating doses of ADCE-T02 in combination with the standard dose of MSD’s drug.