Phase 1
MIRACLE-2
For1L unresectable MSS rectal cancer, synchronous liver/lung mets
TL;DR68% ORR, mOS 23.2mo, 18% NED with RT-primed chemo + tislelizumab in MSS unresectable met rectal ca.
The RT-relevant read is technique: HFRT to the primary plus HFRT/SBRT to mets, delivered first to prime immunity, but no dose or fractionation in source, so it doesn't transfer to practice yet. 18% (9/50) converted to NED via resection or watch-and-wait. Near-universal lymphopenia (95.9% all-grade, 36.7% G3/4) undercuts a strategy premised on RT-driven T-cell activation.
| Metric | n (%) | 95% CI |
|---|---|---|
| CR | 1 (2.0%) | |
| PR | 33 (66.0%) | |
| SD | 10 (20.0%) | |
| PD | 6 (12.0%) | |
| ORR | 34 (68.0%) | 53.6-80.0% |
| DCR | 44 (88.0%) | 76.0-95.2% |
| ETS | 38 (76.0%) | 62.4-86.8% |
9 details 2 trials watching
Prospective single-arm phase I, N=50, Fudan University Shanghai Cancer Center. Data cutoff Dec 31 2025; median follow-up 19.9 mo (95% CI 16.4-23.4).
MSS rectal cancer, primary ≤10cm from anal verge, synchronous unresectable mets. 76% male, median age 57; 52% liver, 8% lung, 40% both; RAS/BRAF-mut 56%.
RT delivered first as an immune primer: HFRT to the primary, HFRT or SBRT to metastases. Dose, fractionation, and target volumes not reported in source.
Post-RT, biomarker-gated: FOLFOX-bevacizumab-tislelizumab (RAS/BRAF-mut) or FOLFIRI-cetuximab-tislelizumab (WT); tislelizumab 200mg Q2W. Resection/metastasectomy if converted, watch-and-wait if primary cCR.
Primary: ETS rate (≥20% target shrinkage at 8wk). Secondary: DCR, DOR, OS, PFS, safety.
ETS 76.0%, ORR 68.0%, DCR 88.0%; 18% (9/50) reached NED. Median OS 23.2mo, PFS 9.3mo, DOR 8.0mo (endpoints in table).
| Endpoint | Median | 95% CI | 1-yr rate |
|---|---|---|---|
| OS | 23.2 mo | 15.1-31.3 | 93.3% |
| PFS | 9.3 mo | 7.1-11.5 | 33.4% |
| DOR (n=34) | 8.0 mo | 5.2-10.8 | 20% |
Single-arm phase I, N=50, no comparator to isolate RT's contribution. Surrogate primary (ETS at 8wk), short median DOR (8mo), and near-universal lymphopenia (95.9%).
Single-arm phase I, N=50; surrogate primary (ETS at 8wk); no comparator to isolate RT's contribution to the immune-priming effect.
- RT's added benefit over chemo plus PD1 alone in MSS mCRC
- Optimal RT dose and fractionation for immune priming in MSS mCRC recruiting Regorafenib Alone or in Combination With Hypofractionated/Low-dose Radiotherapy Plus Toripalimab for Metastatic Colorectal Cancer Phase 2n=108 · primary completion 2025-04 · randomized hypofrac+LDRT + toripalimab, MSS mCRCrecruiting Standard Systemic Therapy Combined With High/Low-dose Radiotherapy Plus Toripalimab for Metastatic Colorectal Cancer Phase 2n=96 · primary completion 2026-12 · high + low-dose RT + toripalimab in MSS mCRC
- Predictive biomarker for MSS response to trimodal therapy
📚 Sources · 🐦 1 tweet
MIRACLE-2: RT to primary/mets -> chemo + tislelizumab in MSS unresectable met rectal ca (N=50): 68% ORR & median OS 23 mo.
— Dr. Nina Niu Sanford (@NiuSanford) May 31, 2026
Early, single-arm data, but ~1 in 5 pts reached NED.
Suggests RT + systemic + PD1 blockade could overcome immune resistance in MSS mCRC. #ASCO26 @OncoAlert pic.twitter.com/sjnUW8x7f3