KEY TAKEAWAYS
- The REGINA phase 2 trial aimed to evaluate the efficacy of neoadjuvant Rego, Nivo, and SCRT in locally advanced rectal cancer.
- The primary endpoint was CR (pCR/cCR).
- The criteria were met, supporting further study of Rego, Nivo, SCRT for advanced RC; Rego dose reduced.
Effective strategies to overcome the immune resistance of pMMR/MSS tumors are currently insufficient. Investigative studies indicate that combining immune checkpoint inhibitors, multi-kinase inhibitors, and radiotherapy may have a synergistic effect.
Francesco Sclafani and the team presented an interim efficacy analysis of a multicenter, single-arm, phase II study that aimed to investigate the use of neoadjuvant Regorafenib (Rego), Nivolumab (Nivo), and short-course radiotherapy (SCRT) in patients (pts) with stage II-III rectal adenocarcinoma.
Researchers conducted a study where the treatment included an induction phase with 2 infusions of Nivo 240 mg IV every 14 days and Rego 80 mg/day orally for 2 weeks. This was followed by SCRT of 25 Gy, and then a consolidation phase with 3 infusions of Nivo 240 mg IV every 14 days and Rego 80 mg/day orally for 3 weeks. Surgery was performed 7-8 weeks after SCRT, with a watch-and-wait (w&w) approach permitted. Adjuvant chemotherapy was optional.
Rectal biopsies and DCE-DWI MRI scans were conducted at baseline, week 2, and post- treatment. Blood and stool samples were also collected. The primary endpoint was complete response (CR), defined as pathological (pCR) or clinical complete response (cCR) at 1 year.
The study utilized a Simon 2-stage design, with the first stage involving 36 patients; if 5 or more achieved CR, a second stage would involve an additional 24 pts. The null hypothesis, based on a true CR rate of 12% from the Stockholm III trial, was tested against a 1-sided alternative and rejected if 12 or more CRs were observed (α=5%, β=20% for a true CR rate of ≥24%).
Results indicated that 36 pts were recruited across 9 Belgian centers. Baseline characteristics were as follows: 50% were male, the median age was 64.5 years, 89% had an ECOG performance status of 0, 22% had tumors in the lower rectum, 83% had pMMR/MSS tumors, 92% were cT3, 72% were cN+, 25% had MRF+, and 17% had latero-pelvic N+. Treatment completion rates were 83% for the induction phase, 97% for SCRT, and 61% for the consolidation phase. Grade 3 or higher adverse events, both overall and treatment-related, occurred in 61% and 56% of pts, respectively.
Surgery was performed in 27 pts, with 1 patient withdrawing before surgery. Of these, 8 pts (30%) achieved a pCR, and 16 pts (59%) had a major pathological response (mPR), defined as Dworak tumor regression grade (TRG) ≥3. An additional 8 pts opted for a w&w approach due to achieving a cCR.
Among 24 pts with resected pMMR/MSS tumors, 6 (25%) had pCR, 2 (8%) had ypTisN0, and 14 (58%) had mPR. Further, 5 more pts chose w&w due to achieving cCR.
The study concluded that the predefined statistical criteria were met, supporting further investigation of the combination of Rego, Nivo, and SCRT as neoadjuvant therapy for locally advanced rectal cancer (RC). In the second stage of the study, the dose of Rego will be reduced to 60 mg/day to improve safety.
The trial was sponsored by Jules Bordet Institute.
Source: https://cslide.ctimeetingtech.com/esmogi24hybrid/attendee/confcal/show/session/28
Clinical Trial: https://www.clinicaltrials.gov/study/NCT04503694
Sclafani F, (2024). “Interim efficacy analysis of REGINA, a phase II trial of neoadjuvant regorafenib (Rego), nivolumab (Nivo), and short-course radiotherapy (SCRT) in stage II-III rectal cancer (RC).” Presented at ESMO-GI 2024, (Abstract LBA2)
