Subgroup analyses in clinical trials are becoming increasingly important. In cancer research, more and more targeted therapies are explored from which probably only a portion of the whole population will benefit. An adaptive design for subgroup selection, the adaptive signature design, was proposed by Freidlin and Simon (2005). We implemented this design in 2 PIIL Vaccine trials (Dreno et al, 2018). In this presentation I will describe statistical and operational aspects of these adaptive trials. Finally, I will propose an extension of this design where subgroup analysis is not performed when the overall results suggest that it is unlikely to achieve statistical significance in the subgroup (Callegaro, 2017). References Freidlin, B., & Simon, R. (2005). Adaptive signature design: an adaptive clinical trial design for generating and prospectively testing a gene expression signature for sensitive patients. Clinical cancer research, 11(21), 7872-7878. Dreno B et al. "MAGE-A3 immunotherapeutic as adjuvant therapy for patients with resected, MAGE-A3-positive, stage Ill melanoma (DERMA): a double-blind, randomised, placebo controlled, phase 3 trial." The Lancet Oncology (2018). Callegaro, A. (2017). Futility for subgroup analyses in the adaptive signature design. Statistical methods in medical research, 0962280217739659.