In this randomized open-label trial, 47 patients with metastatic urothelial cancer who had progressed on platinum chemotherapy received either atezolizumab alone (n=21) or atezolizumab plus CYT107 (n=19) given weekly for four doses. The primary endpoint was objective response rate (ORR). Patients were predominantly male (81%), with a median age of 64. Disease sites included lymph nodes (70%), lung (36%), liver (23%), and bone (15%). The combination therapy arm demonstrated an ORR of 26.3% versus 23.8% with atezolizumab alone (p=0.428). While the primary endpoint was not met, the complete response rate was higher with combination therapy (10.5% vs 4.8%). Three patients on combination therapy had responses exceeding 21 months versus one patient on atezolizumab monotherapy. Treatment-related adverse events were comparable between arms, with lower grade 3-4 events in the combination arm (21% vs 37%). Correlative studies showed significant CD4+ and CD8+ T cell expansion in combination therapy responders, particularly memory stem cells, along with elevated baseline CCL4 and decreased VEGF-A levels.
Notably, the study was closed after 40 of the planned 48 patients due to changing standard of care and withdrawal of atezolizumab's approval. The lowest active dose of CYT107 was used and only given for one cycle, which may have limited efficacy. The biomarker analysis generates hypotheses suggesting that CYT107 enhances anti-tumor immunity by preferentially expanding memory stem cells, which can mediate durable immune responses.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
References:
- Sweis RF, Chatta GS, Jain RK, et al. A phase II open label, randomized clinical trial of atezolizumab with or without human recombinant IL-7 (CYT107) in advanced urothelial cancer. Clinical Cancer Research. 2024.