Fig. 2

Cohort design of the safety stop-and-go lead-in phase (HYPO-group). The safety lead-in phase follows a 6 + 6 design in order to carefully evaluate the toxicity of the treatment in the HYPO-group with respect of the occurrence of a grade 3/4 pneumonitis (“event”) within 8 weeks after the end of TRT. Two events in the first six patients, two events in the first 12, or two events in the first 18 patients will result in termination of the HYPO-group (“Stop”). If no event is observed within the first two safety cohorts, i.e. the first 12 patients, the HYPO-arm will be opened for full enrollment with close toxicity assessment with respect to pneumonitis grade 3/4, and terminated as soon as two events are reported within the subsequent six patients (“Go*”). Full enrollment in the HYPO-arm will only take place if the criteria for the non-toxicity scenario are met, i.e. ≤ 1 event in n = 18 patients (“Go”)