Top 10 to Watch
Targeted Therapy & Early-Stage Strategy
1) LBA4 — HARMONi-6
Phase III study of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small cell lung cancer (HARMONi-6).
What it’s about: Tests a bispecific antibody against a PD-1 inhibitor, both with chemo.
Why it matters: First head-to-head bispecific vs PD-1 in frontline Sq-NSCLC; potential to redefine the immunotherapy backbone.
2) LBA5 — OptiTROP-LUNG04
Sacituzumab tirumotecan vs platinum-based chemotherapy in EGFR mutated non-small cell lung cancer following progression on EGFR-TKIs: results from the randomized, multi-center phase III OptiTROP-Lung04 study.
What it’s about: Evaluates ADC–chemotherapy combination after EGFR-TKI failure.
Why it matters: Addresses the post-TKI gap; could introduce ADC combinations as second-line standard.
3) LBA69 — SKYSCRAPER-03
SKYSCRAPER-03: Phase III, open-label, randomised study of atezolizumab ± tiragolumab vs durvalumab in locally advanced, unresectable, stage III non-small cell lung cancer after platinum-based concurrent chemoradiation.
What it’s about: Head-to-head comparison of dual I/O (PD-L1 + TIGIT) versus the standard durvalumab consolidation in unresectable stage III NSCLC after cCRT.
Why it matters: A practice-defining trial; if positive, could unseat durvalumab monotherapy as the standard post-CRT consolidation and redefine maintenance I/O strategies in locally advanced disease.
Peri-Operative and Adjuvant Immunotherapy
4) LBA67 — KEYNOTE-671 (5-year follow-up)
Perioperative pembrolizumab in early-stage non-small cell lung cancer: 5-year follow-up from KEYNOTE-671.
What it’s about: Final OS and durability data.
Why it matters: Confirms long-term survival benefit and safety of peri-operative I/O in early-stage NSCLC.
5) LBA68 — Adjuvant durvalumab after CR in early-stage NSCLC
CCTG BR.31: Adjuvant durvalumab in resected non-small cell lung cancer : Final overall survival and minimal residual disease analyses.
What it’s about: Evaluates adjuvant-only I/O benefit.
Why it matters: Completes the peri-operative landscape; clarifies if adjuvant durva adds benefit beyond neoadjuvant approaches.
6) LBA66 — ELEVATE
Ensartinib as adjuvant therapy in patients with stage IB–IIIB ALK positive non-small cell lung cancer after complete tumor resection: The phase III randomized ELEVATE trial.
What it’s about: Explores ALK TKI use post-surgery.
Why it matters: First adjuvant ALK trial; could replicate ADAURA’s impact for ALK-driven disease.
Targeted Therapy Evolution
7) LBA77 — FLAURA-2
FLAURA2: Exploratory overall survival analysis in patients with poorer prognostic factors treated with osimertinib ± platinum-pemetrexed chemotherapy as first-line treatment for EGFR-mutated advanced NSCLC.
What it’s about: Definitive OS update for the frontline EGFR TKI + chemo trial.
Why it matters: If OS benefit confirmed, chemo-TKI combo may replace TKI monotherapy as standard first line.
8) LBA73 — ALEX (final analysis)
Final overall survival and safety analysis of the phase III ALEX study of alectinib vs crizotinib in patients with previously untreated, advanced ALK-positive non-small cell lung cancer.
What it’s about: Provides the longest survival dataset in ALK disease.
Why it matters: Confirms sustained survival advantage and long-term tolerability; a benchmark for next-gen ALK inhibitors.
9) LBA72 — NORTHSTAR
NorthStar: A phase II randomized study of osimertinib (OSI) with or without local consolidative therapy (LCT) for metastatic EGFR-mutant non-small cell lung cancer (NSCLC).
What it’s about: Assesses whether local therapy extends control in oligometastatic EGFR+ disease.
Why it matters: Could refine treatment of oligoprogressive EGFR patients by combining precision local and systemic strategies.
HER2 Frontiers
10) LBA74 — BEAMION-LUNG 1 and LBA75 — SOHO-01
Zongertinib as first-line treatment in patients with advanced HER2-mutant NSCLC: Beamion LUNG 1.
Sevabertinib in advanced HER2-mutant non-small cell lung cancer: Results from the SOHO-01 study.
What it’s about: Two parallel HER2-targeted TKIs in first-line and post-ADC settings.
Why it matters: Marks HER2 therapy’s shift from ADC-based regimens to oral precision agents; data may define future sequencing.
Looking Ahead
From ADC–chemotherapy combinations to adjuvant ALK inhibition, ESMO 2025 highlights the convergence of targeted and immunotherapy strategies across NSCLC subtypes.
The full OncoBrief ESMO 2025 Summary, including late-breaking and practice-defining trials, will be published after the conference.
Full session details and times are available in the ESMO 2025 program.
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