At ASCO26, Ferdinandos Skoulidis presented the interim analysis of the phase 2b TRITON study․ Here are some reactions and key takeaways shared by the oncology community on X․
UT MD Anderson:
“New data from the phase 2b TRITON study suggest that adding tremelimumab to durvalumab + chemotherapy may improve response outcomes in patients with STK11-, KEAP1-, and/or KRAS-mutated metastatic non-squamous NSCLC. Presented by Dr. Ferdinandos Skoulidis at ASCO26, interim results showed higher ORR, longer durability of response and a safety profile consistent with known therapies.”
“TRITON interim analysis
Tremelimumab + durvalumab + chemo vs pembrolizumab + chemo․ 1L NSQ mNSCLC with STK11/KEAP1/KRAS mutations
Abstract 8515։ Phase 2b randomized US study։ T+D+CT n=41 vs P+CT n=43․ IA focused on ORR, DoR, and safety
Response:
- cORR 39.0% vs 34.9%
- uORR 48.8% vs 41.9%
Duration of response: mDoR NR vs 6.4 mo
Numerically higher ORR in key subgroups:
- KRASm: 45.2% vs 31.4%
- KRASm only: 48.0% vs 33.3%
- STK11m ± co-mut: 36.4% vs 25.0%
Safety broadly similar
- Low discontinuation rates
- No new safety signals
Early IA: T+D+CT showed a modest numerical signal in ORR/DoR vs P+CT, with similar safety. Longer follow-up will be important.”
“TRITON study at ASCO26: chemo + durva + treme vs chemo + pembro in non-squamous NSCLC w/ STK11, KEAP1, and/or KRAS mutations.
Higher ORR w/ dual ICI, except KEAP1-mutant outcomes appear similar. Small pt #’s and overlapping co-mutations make these exploratory signals. PFS pending.”
“The TRITON study interim results presented by Ferdinandos Skoulidis, UT MD Anderson, looked at metastatic nonsquamous NSCLC with STK11, KEAP1, and/or KRAS mutations. Pts appeared to benefit from adding tremelimumab to durvalumab plus chemotherapy compared with pembrolizumab plus chemotherapy. These genomic subgroups may benefit from this triplet strategy, though this is an interim analysis and progression-free survival is still blinded.”
“Interim analysis of TRITON suggests potential benefit from adding tremelimumab to durvalumab + chemo in 1L metastatic nsqSCLC harboring STK11, KEAP1 and/or KRAS mutations.
- ORR: 39.0% vs 34.9% with pembro + chemo
- Median DoR not reached vs 6.4 months
- 100% vs 58.3% of responders maintained response at 6 months
- In KRASmut tumors: ORR 48.0% vs 33.3%
Grade 3/4 TRAEs were similar between arms, supporting the feasibility of CTLA-4 intensification in this molecularly defined population.”
“Dr. Ferdinandos Skoulidis presents randomized phase 2b TRITON study at ASCO26: chemo + durvalumab + tremelimumab vs chemo + pembro in non-squamous NSCLC with STK11, KEAP1, and/or KRAS mutations. RR numerically favors dual checkpoint in the challenging STK11 and KRAS subsets. PFS pending.”
“TRITON asks the uncomfortable question in 1L NSCLC:
Can CTLA-4 rescue the “cold” STK11/KEAP1/KRAS-mutant subgroup?
- Phase 2b, n=84
- 1L non-squamous mNSCLC
- STK11 and/or KEAP1 and/or KRAS mutated
T+D+chemo vs pembro+chemo
Key signal:
- ORR: 39.0% vs 34.9%
- Unconfirmed ORR: 48.8% vs 41.9%
- Median DoR: NR vs 6.4 mo
Safety looked broadly similar:
- G3/4 TRAEs: 41.5% vs 41.9%
- Discontinuation: 2.4% vs 4.7%
My take: Not practice-changing yet. But this is exactly the biomarker-defined immunotherapy question we need in NSCLC. PFS/OS will decide whether this is signal or strategy.”
“Rapid Oral
TRITON: Tremelimumab + durvalumab + CT vs pembro + CT in 1L NSQ NSCLC with STK11, KEAP1, and/or KRAS mut
- ORR 39% vs 34.9%
- KRAS: ORR 48% vs 33.3%.”
“TRITON: PhII, Durva + Treme + Chemo vs. Chemo + IO in mNSCLC w/ STK11 +/- KEAP1 mutation:
- ORR: 39% vs. 34.9%
- Who should get intensified dual ICI moving forward?”
“ASCO 2026 | TRITON IA
Tremelimumab + Durvalumab + Chemotherapy vs Pembrolizumab + Chemotherapy
- Confirmed ORR: • 39.0% vs 34.9%
- Unconfirmed ORR: • 48.8% vs 41.9%
- Duration of Response: • Not reached vs 6.4 months
Subgroup signals favored the CTLA-4/PD-L1 combination:
- STK11-mutant: 36.4% vs 25.0%
- KRAS-mutant: 45.2% vs 31.4%
- KRAS-mutant only: 48.0% vs 33.3%
Safety was broadly comparable between arms, with low discontinuation rates and no new safety signals. These are early, small-number data, but they align with prior observations from POSEIDON that adding CTLA-4 blockade may help overcome resistance associated with STK11/KEAP1 biology. Interesting signal. Practice-changing? Not yet.”
Title: Tremelimumab (T) + durvalumab (D) + chemotherapy (CT) vs
pembrolizumab (P) + CT in 1L non-squamous (NSQ) metastatic NSCLC
(mNSCLC) with STK11, KEAP1, and/or KRAS mutations (mut): Interim
analysis (IA) of the phase 2b TRITON study
Authors: Ferdinandos Skoulidis, Hossein Borghaei, Edward B. Garon, Ticiana Leal, Jacob Kaufman, Stephen V. Liu, Eric S. Nadler, Sandip Pravin Patel, Solange Peters, Biagio Ricciuti, Tarek Mekhail, Ajeet Gajra, Eric C. McGary, Vu Phan, James Stevenson, Richard Lynen, Ugochinyere Emeribe, Aida Myftiu, Ashish Gautam, John V. Heymach
Read the Full Abstract.
AcceleRET-Lung: Pralsetinib Improves First-Line PFS In RET Fusion–Positive Advanced NSCLC
