Neoadjuvant Regorafenib in Combination with Nivolumab and Short-course Radiotherapy in Stage II-III Rectal Cancer

"Nivolumab will be given at a dose of 240 mg during the pre-operative phase only as indicated below:~* On day 1 and 15, during the Induction treatment~* On day 29, 43 and 57, during the Consolidation treatment"

"Regorafenib will be administered orally once a day at a dose of 60 mg/day (2 tablets of 40 mg), during the pre-operative phase only as indicated below:~* From day 1 to 14, during the Induction treatment~* From day 29 to 49, during the Consolidation treatment"

All study subjects will receive 5 daily fractions of radiotherapy. Each fraction will consist of 5 Gy for a total dose of 25 Gy. Radiotherapy is to start on day 22 and to finish on day 26.

Subject will undergo surgical resection of the primary tumour in the rectum between day 74 and 87. Surgery must be performed according to the principles of total mesorectal excision as described by Heald et al. The type of surgical approach (low anterior resection or abdominoperineal resection, etc.) will be left to the discretion of the treating surgeon.

"Subjects who achieve cCR after pre-operative treatment can, after discussion with the local investigator, decline surgery and opt for a non-operative management. cCR will need to be confirmed between day 67 and 74 by the following procedures per local practise:~* Digital rectal examination~* Rectal endoscopy~* Rectal MRI Subjects who achieve near cCR at the first assessment time point after pre-operative treatment, can be re-assessed 6 to 8 weeks later with the same procedures. If cCR is diagnosed, they can opt for watch \& wait, otherwise they would need to undergo surgical resection.~Subjects who opt for a non-operative management will be followed for tumour recurrence and survival for 5 years after end of treatment visit. Follow-up for these subjects will be more intensive than that for subjects undergoing surgery"