GI Upper
2026-05-31
RASolute 302
ForPreviously treated metastatic pancreatic cancer (RAS-mut or WT)
HR 0.40
95% CI 0.30-0.53, P<0.001; mOS 13.2 vs 6.7 mo (overall pop)
TL;DRmOS 13.2 vs 6.7mo, HR 0.40 (0.30-0.53), P<0.001 for daraxonrasib vs investigator's-choice chemo in previously treated metastatic pancreatic cancer.
In previously treated metastatic pancreatic cancer with a RAS mutation, daraxonrasib's OS benefit supports it as a systemic option over chemotherapy; the signal does not extend to treatment-naive or localized disease.
| Population · Arm | Median OS | HR (death) | 12-mo OS |
|---|---|---|---|
| G12 · Daraxonrasib | 13.2 mo (10.0-NR) | 0.40 (0.30-0.54) | 53.3% |
| G12 · Chemo | 6.6 mo (5.4-8.2) | — | 8.7% |
| Overall · Daraxonrasib | 13.2 mo (10.0-NR) | 0.40 (0.30-0.53) | 53.2% |
| Overall · Chemo | 6.7 mo (5.8-8.0) | — | 17.3% |
7 details 1 trial watching
Phase 3 RCT, daraxonrasib vs investigator's-choice chemotherapy in previously treated metastatic pancreatic cancer. Two prespecified populations: RAS G12-mutant and overall (G12/G13/Q61 or no RAS mutation identified).
Previously treated metastatic pancreatic cancer. RAS G12 arm n=228 vs 231; overall n=248 vs 252. Overall population also includes tumors with no identified RAS mutation.
Daraxonrasib, an oral RAS(ON) multi-selective inhibitor targeting active GTP-bound RAS, vs investigator's choice cytotoxic chemotherapy.
Primary OS met: median 13.2 vs 6.7 mo, HR 0.40 (0.30-0.53), P<0.001 (overall); HR 0.40 (0.30-0.54) in RAS G12. 12-mo OS 53% vs 17% (overall). Deaths 32% vs 55-56%.
Chemo control (6.6-6.7 mo) matches the historic 2L metastatic PDAC benchmark; no prior targeted agent has shown an OS signal of this magnitude in this setting.
Data limited to a single ASCO LBA OS figure; full safety and PFS not yet reported. Open-label; daraxonrasib median OS upper CI not reached (10.0-NR), so tail durability is immature.
Randomized phase 3, OS primary hit HR 0.40 in 2L metastatic PDAC where no targeted SOC exists; hard endpoint, unprecedented magnitude. Full LBA data pending.
- Sequencing and combination with 1L chemotherapy recruiting Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma Phase 3n=900 · primary completion 2028-06 · 1L daraxonrasib + gem/nab-paclitaxel combination
- Efficacy across RAS-WT vs RAS-mutant subsets
- Full safety and toxicity profile
📚 Sources · 🐦 1 tweet
#ASCO26
— Nicholas Hornstein (@GIMedOnc) May 31, 2026
This one is special.
This is the hottest paper of 2026 and potentially in the history of pancreatic cancer.
Let’s dive in.
RASolute 302: Daraxonrasib vs investigator’s choice chemotherapy in previously treated metastatic pancreatic cancer
Abstract LBA5 (soon!)… pic.twitter.com/Lq7PEjOWAo
2026-05-30 ASCO Annual Meeting 2026
Neo-CRAG
ForHigh-risk locally advanced gastric/EGJ (cT3N2-3 to cT4), fit for D2 resection
mDFS 52.7 vs 24.4 mo
HR 0.750 (95% CI 0.607-0.928), P=0.008
TL;DRAdding neoadjuvant chemoRT (45Gy/25fx) to periop XELOX improved mDFS 52.7 vs 24.4mo (HR 0.75) and mOS 67.5 vs 37.6mo in high-risk LAGC.
The RT read is clean attribution: both arms share the XELOX backbone and the CRT arm got dose-reduced chemo during RT, yet locoregional recurrence halved (9.4% vs 18.3%) with more ypN0 and downstaging. On 45Gy/25fx, this revives neoadjuvant chemoRT for high-risk D2-resected gastric/EGJ, on a non-FLOT backbone.
| Endpoint | CRT | CT | HR (95% CI), P |
|---|---|---|---|
| Median DFS | 52.7 mo | 24.4 mo | 0.750 (0.607-0.928), P=0.008 |
| 3-yr DFS | 55.6% | 42.4% | — |
| Median OS | 67.5 mo | 37.6 mo | 0.781 (0.628-0.970), P=0.025 |
| 5-yr OS | 50.1% | 44.2% | — |
7 details 2 trials watching
Phase 3 open-label RCT, 1:1, N=620 (310/arm), 13 Chinese referral centers, enrolled 2013-2022. Primary: disease-free survival; secondary OS, pCR, R0, safety.
High-risk locally advanced gastric/EGJ adenocarcinoma: cT3N2-3M0, cT4aN+M0, or cT4bNanyM0; 36.3% EGJ (Siewert II/III). All planned standardized D2 gastrectomy.
Both arms: 3 cycles preoperative + 3 cycles adjuvant XELOX (oxaliplatin 130, capecitabine 1000 BID D1-14, Q3W) around D2 gastrectomy.
CRT arm only: concurrent 45 Gy/25 fx begun after chemo cycle 1, with dose-reduced XELOX (oxaliplatin 100, capecitabine 825) during RT. RT is the sole added variable between arms.
Primary DFS met and secondary OS positive, both favoring CRT; pathologic downstaging, ypN0, and locoregional control also improved (see figure and table).
Contrasts with CRITICS and TOPGEAR, where adding radiotherapy to a chemo backbone did not improve survival. A positive DFS/OS here reopens neoadjuvant chemoRT in high-risk, D2-resected LAGC.
Open-label; non-FLOT XELOX backbone limits transfer to current perioperative standard. Single-country (China) with high D2-resection quality; DFS (not OS) was the primary endpoint.
Randomised phase 3, primary DFS and OS both hit, but positive chemoRT diverges from negative CRITICS/TOPGEAR; non-FLOT XELOX backbone limits transfer to current SOC.
In high-risk cT3N2-3/cT4 gastric or EGJ adenocarcinoma planned for D2 gastrectomy on a XELOX backbone, these data support a DFS/OS and locoregional-control benefit from adding neoadjuvant chemoRT; the signal does not extend to FLOT-backbone or metastatic patients.
- Incremental benefit of RT on a FLOT chemo backbone n=776 · primary completion 2023-06 · candidate match
- Generalizability beyond high-quality-D2 Asian centers
- Whether EGJ and distal gastric benefit equally n=4 · primary completion 2024-03 · candidate match
📚 Sources · 🐦 1 tweet
Neo-CRAG: Ph3 RCT (n=620, gastric/GEJ) - adding neoadj chemoRT to peri-op XELOX improved OS (68 v 38 mo).
— Dr. Nina Niu Sanford (@NiuSanford) May 30, 2026
Limitation=non-FLOT, BUT still relevant IMO b/c:
1) DFS/OS benefit substantial.
2) Improvements in pCR, downstg, LRR supports plausible RT effect on OS. #ASCO26 @OncoAlert pic.twitter.com/eeM0Z8p20M