KRAS / RAS targeting: from platform to Phase 3
The floor also showed dual ON/OFF (VS-7375) and RM-055, built for amplification and daraxonrasib-resistant models.
The floor rewrote the question from “how long can G12C monotherapy last” to “who first makes first-line pancreatic cancer a standard.” daraxonrasib’s Phase 3 is still the only RAS-inhibitor overall-survival win.
GI-102 (Subprotocol C) – daraxonrasib + GnP in 1L mPDAC shows early signal 👇
#AACR26
🧬 Setting
1L metastatic PDAC, RAS-mutant cohort (n=40)
💊 Regimen
Daraxonrasib (RAS(ON) inhibitor) + gemcitabine/nab-paclitaxel
👥 Study population
Median age 69
ECOG 0-1: 100%
Liver mets: 70%
KRAS G12D dominant (50%)
📊 Efficacy
ORR: 58%
DCR: 90%
6-mo PFS: 84%
6-mo OS: 90%
ctDNA clearance: 61%
⚠️ Safety
Grade ≥3 TRAEs: 73%
Serious TRAEs: 28%
No Grade 5 AEs
👉 Rash most common (mostly G1-2)
🔄 Dose modifications
Daraxonrasib: 60%
GnP: 75%
Discontinuation low (5–15%)
🎯 Takeaway
Strong early activity + manageable toxicity
👉 One of the most promising RAS(ON) combos in PDAC so far
⚡ Phase 3 ongoing: RASolute-303 (daraxonrasib ± GnP vs GnP)
📖 Full data presented at AACR 2026 (O’Reilly et al., LB337)
@OncoAlert @myesmo @esmo_open @ASCO @AACR #OncoTwitter #MedTwitter #PancreaticCancer #RAS
Heat 40 · 25 likes · 1 reply · 14 reposts
Nina Dashti-Gibson, Amy L. Olex, Rachel K. Myrick, Alexa M. Barber, David C. Boyd, Emily K. Zboril, Katarzyna M. Tyc, Mikhail G. Dozmorov, Guang-Yu Yang, Nicholas T. Woods, Jose G. Trevino, J Chuck Harrell
Read the abstract →Kayla Tyskiewicz, Markus Hippich, Tristan Cates, Gervaise Henry, Gilad Silberberg, Nicole Spanburg, Madeline Westcott, Daniel Ciznadija, Michael Boice, Paul Heverly, Frank Smith, Marianna Zipeto, Stefano Cairo, Sebastian Brabetz
Read the abstract →Nataliya Tovbis Shifrin, Mariela Moreno Ayala, Cristina Blaj, Kevin Chen, Felix Mbuga, Joaquin Pechuan Jorge, Rashi Raghulan, Rich Liang, Linh Tran, Enrico Payson, Alice Kumamoto, Alexander McNamara, Marie Josette Catherine Menard, Michael Weiss, Lillian Seu, Elsa Quintana
Read the abstract →Ferdinandos Skoulidis, Kathryn C. Arbour, Sanjay Popat, Colin R. Lindsay, Hidehito Hironouchi, Gérard Zalcman, Alessandra Curioni-Fontecedro, Jarushka Naidoo, Adrianus J. de Langen, Lin Tao, Erica Su, Minoti Hiremath, Achim Rittmeyer, Melissa Johnson
Read the abstract →Eileen M. O'Reilly, Brian Wolpin, Shubham Pant, Joel Randolph Hecht, Jennifer Valerin, Dae Won Kim, Nilofer Azad, Kyaw Aung, Lin Tao, Sumit Kar, Hina Patel, Rashmi Vora, Aparna Hegde, Alexander Spira, Alexander Starodub, Benjamin Herzberg, Ignacio Garrido-Laguna
Read the abstract →Brian M. Wolpin, Benjamin L. Musher, Gulam A. Manji, Wungki Park, Alexander Spira, Nilofer Azad, Vaia Florou, Tiago Biachi De Castria, Mark H. O'Hara, Erkut Borazanci, Aparna Parikh, John Strickler, Joel Randolph Hecht, Shubham Pant, Shiraj Sen, E. Gabriela Chiorean, W. Clay Gustafson, Hina Patel, Vidya Seshadri, Yan Zheng, Davendra Sohal
Read the abstract →Source: x.com · x.com