Phase 1
MIRACLE-2
ForMSS unresectable metastatic rectal cancer, synchronous mets, first-line
TL;DR68% ORR, median OS 23.2mo, 18% NED in MSS unresectable metastatic rectal ca (N=50).
vs leading data
- MSS mCRC historically IO-refractory; RT + chemo used here as immune sensitizers to overcome PD-1 resistance
| Endpoint | Result (N=50) | 95% CI |
|---|---|---|
| ETS rate (1° EP) | 76.0% | 62.4-86.8% |
| ORR | 68.0% | 53.6-80.0% |
| DCR | 88.0% | 76.0-95.2% |
| Median OS | 23.2 mo | 15.1-31.3 |
| Median PFS | 9.3 mo | 7.1-11.5 |
8 details
Methods
- 🔍 Phase I prospective single-arm; N=50; MSS RC primary ≤10cm from anal verge, synchronous unresectable mets; RAS/BRAF-mut 56%
- 🔍 HFRT to primary + HFRT/SBRT to mets → systemic; resectable disease → primary resection + metastasectomy/ablation; primary cCR → watch-and-wait eligible
- 💊 Systemic regimen by RAS/BRAF status
- Mutant: FOLFOX + bevacizumab + tislelizumab
- Wild-type: FOLFIRI + cetuximab + tislelizumab
- Reassessment q8wk; tislelizumab 200mg Q2W
Results
- 📊 18% (9/50) reached NED
- 📊 1-yr OS 93.3%; 1-yr PFS 33.4%
- 📊 Median DOR 8.0mo (95% CI 5.2-10.8) among 34 responders; 1-yr DOR rate 20%
Critique
- ⚠️ Grade 3/4 TRAEs: substantial hematologic burden
- lymphopenia 36.7%
- neutropenia 26.5%
- leukopenia 20.4%
- no grade 5 events
- ⚠️ Phase I single-arm, N=50, med f/u 19.9mo; no randomised comparator; NED durability and generalizability unproven
Open questions
- Predictive biomarkers for RT + IO response in MSS mCRC
- Durability of NED beyond 2 years
- Whether benefit extends to MSS colon (non-rectal) primaries
📚 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