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BEAMION Lung-1 Trial Overview

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About the Beamion LUNG-1 Trial

The Beamion LUNG-1 trial is a Phase Ib dose expansion study evaluating the efficacy and safety of a targeted therapy in patients with non-small cell lung cancer (NSCLC) harboring HER2 tyrosine kinase domain (TKD) mutations. Eligible participants were previously treated patients with confirmed HER2 TKD-mutated NSCLC. The primary endpoint was the confirmed objective response rate (ORR) as assessed by central independent review, with secondary endpoints including progression-free survival (PFS) and duration of response (DoR). The trial demonstrated promising results, with ORRs of 72.4% and 78.2% at the 120 mg and 240 mg dose levels, respectively. The safety profile was manageable, with most adverse events being mild to moderate in severity, and diarrhea and rash reported as the most common. Importantly, the investigational therapy also showed efficacy in patients with central nervous system (CNS) metastases. These findings were presented by Dr. Biagio Ricciuti at the 2024 World Conference on Lung Cancer (#WCLC24). Additional insights were shared via social media by Dr. Ricciuti, Dr. Balazs Halmos, and the LUNGevity Foundation.

Table of Contents

Major Presentations and Milestones

Beamion Lung-1 Trial design, results, and conclusions

Beamion-Lung-1 Sentiments and Criticisms

Beamion Lung-1 Temporal Sentiment Arc

 

Major Presentations and Milestones 

Primary Speakers Driving the Story

• Stephen V. Liu, MD (WCLC 2024 live thread; presidential plenary coverage): "Dr. Gerrina Ruiter presents an update on the Beamion LUNG-1 study: zongertinib in #HER2 mutant NSCLC at the #WCLC24 Presidential Plenary. Here, Phase Ib cohort 1: previously treated NSCLC with a #HER2 TKD mutation that set the dose of 120mg by mouth daily." https://x.com/StephenVLiu/status/1833173135539200247

• https://x.com/StephenVLiu/status/1833173146096271639

• https://x.com/StephenVLiu/status/1833173164752515364

• Sanjay Popat, MD (WCLC 2024 presenter; early interpretation): "Zongertinib BEAMION-Lung01 pretreated HER2 TKD M+. 120Mg dose chosen. 65% YVMA. 1% g3 diarrhea. Low G3+ TRAEs. ORR 72.4%. Intracranial ORR 33% (RANO). Another highly active HER2 TKI. Looking forward to future development #WCLC24" https://x.com/DrSanjayPopat/status/1833170854756434431

• Hidehito Horinouchi, MD, PhD (WCLC 2024 presidential plenary highlight): "🔥#WCLC24 Presidential 2 🎙️Dr. Gerrina Ruiter 🎯Primary Phase Ib Analysis of Beamion LUNG-1: Zongertinib (BI 1810631) in Patients with HER2 Mutation-Positive NSCLC #LCSM @IASLC @OncoAlert" https://x.com/HHorinouchi/status/1833170888294068254

• NEJM (AACR 2025 publication signal): "Presented at #AACR25: Among patients with tumors harboring tyrosine kinase domain mutations who received zongertinib (a selective inhibitor of the HER2 tyrosine kinase), 71% had a response, and median progression-free survival was 12.4 months. Full study results:" https://x.com/NEJM/status/1916841088897409037

KOL Reactions to the Presentation

• Devika Das, MD: "SOHO1 and BEAMION Lung01… Decent ORR, CNS response +, heavily pretreated pop… Looking forward to subsequent trials. Important to send molecular profile!" https://x.com/DevikaDasMD/status/1833171932281295134

• Dr. Riyaz Shah: "…Significant GI and skin tox for EGFR sparing; ORR 67%; icORR 33% feels a bit low;" https://x.com/DrRiyazShah/status/1833170519241486718

• Jacob Plieth (biotech journalist): "…ORRs of 60-70% with zongertinib & BAY2927088, but watch the tox!" https://x.com/JacobPlieth/status/1833168147911774395

• Kelsey Pan, MD, MPH: "…promising new oral therapies, BAY2927088 and Zongertinib, emerging in the HER2 mutated NSCLC space with intracranial data…" https://x.com/KelseyPanMD/status/1833209118221643803

• Chul Kim, MD, MPH: "ORR: 72.4% with 120 mg and 78.2% with 240 mg (DoR and PFS immature)… Encouraging intracranial response…" https://x.com/chulkimMD/status/1833170753912803542

Trial Design, Results, and Conclusions Subsection A: Core Design/Results (as amplified by KOLs)

• Primary endpoints and efficacy framing:

  • Stephen V. Liu emphasized Phase Ib cohort 1 in previously treated HER2 TKD-mutant NSCLC, noting the recommended 120 mg daily dose and early efficacy: "RR of 66.7%, after randomization implemented, RR 72.4% at 120mg (vs 78.2% at 240mg). DCR rate 95-100%. DOR and PFS pending (2/3 of pts still on therapy)." Links: https://x.com/StephenVLiu/status/1833173135539200247

• • NEJM formalized key outcomes in TKD-mutant tumors: "71% had a response, and median progression-free survival was 12.4 months." Link: https://x.com/NEJM/status/1916841088897409037

• Safety and tolerability signals (GI/skin, LFTs):

  • Stephen V. Liu detailed AE rates at WCLC24: "Diarrhea in 43% but only 1% grade 3 at the 120mg dose. Rash in 24%, ALT elevation in 19% (8% G3), AST 21% (5% G3)." Link: https://x.com/StephenVLiu/status/1833173146096271639

• Subgroup and molecular context:

  • YVMA was the most common TKD mutation and featured high activity (multiple KOLs referenced YVMA):
    • "Most common mutation is the YVMA…" (Stephen V. Liu, WCLC24) https://x.com/StephenVLiu/status/1833173146096271639
    • "…outstanding RR (up to 90% for key YVMA subset)…" (Balazs Halmos) 

      2 great presentations on novel ErbB2 TKIs- BAY2927088/zongertinib
      ☑️outstanding RR (up to 90% for key YVMA subset)
      ☑️fair tolerance
      ☑️signal of CNS activity
      Main problem we might face…embarrassment of riches- btw tdxd and these 2 exciting agents- which Her-bal therapy to choose? pic.twitter.com/RArcJQewV5

      — Balazs Halmos (@BalazsHalmosMD) September 9, 2024

KOL deep-dives on design/results with links and framing:

• Stephen V. Liu, MD (WCLC24 and ESMO25 threads): dose, cohorts, TKD focus, evolving efficacy/AE profile, and CNS signal.

  • WCLC24 thread: https://x.com/StephenVLiu/status/1833173135539200247 https://x.com/StephenVLiu/status/1833173146096271639 https://x.com/StephenVLiu/status/1833173164752515364
  • ESMO25 first-line thread (cohort 2, treatment-naive TKD): "Included 74 pts… RR 77%, DCR 96% (!), time to response 1.4m… median DOR/PFS not reached, 6m DOR 80%, 6m PFS 79%." https://x.com/StephenVLiu/status/1979819145249304646 https://x.com/StephenVLiu/status/1979819148491596017 https://x.com/StephenVLiu/status/1979819151607955829 https://x.com/StephenVLiu/status/1979819154900500949 https://x.com/StephenVLiu/status/1979819158054568124

• Oncology Brothers (multi-post breakdowns; regulatory/implementation bridge):

  • "Zongertinib (oral TKI) now @US_FDA approved based off #BeamionLung1… 71% ORR… mDoR 14.1m, mPFS 12.4…" (noting ≥Gr3 AEs <20%) https://x.com/OncBrothers/status/1953870964405510192
  • "…approved… we had a chance to 🗣️ Her2 testing, trial, findings, AEs and sequencing…" https://x.com/OncBrothers/status/1959987969714168207
  • ESMO25 highlights including Beamion LUNG-1: https://x.com/OncBrothers/status/1986460456744329373

Subsets and Deeper Reads

• Biagio Ricciuti, MD PhD (dose/subgroup safety and CNS details): "120 mg, ORR 72.4%, ≥G3 AEs 17%; 240 mg, ORR 78.2%, ≥G3 AEs 19%… CNS ORR (RANO-BM) 33% and 40%." https://x.com/BiagioRicciutMD/status/1833297767550357986

• Stephen V. Liu, MD (ESMO25 1L TKD cohort thread with sequential posts; list in order): https://x.com/StephenVLiu/status/1979819145249304646 https://x.com/StephenVLiu/status/1979819148491596017 https://x.com/StephenVLiu/status/1979819151607955829 https://x.com/StephenVLiu/status/1979819154900500949 https://x.com/StephenVLiu/status/1979819158054568124

• Abdulaziz AlJassim (DrZ_84) (ESMO25 updates across agents; 1L zongertinib): "…77% ORR / 96% DCR in 1L (Beamion LUNG-1) with mostly G1-2 AEs… Phase III Beamion LUNG-2 underway vs SoC" https://x.com/DrZ_84/status/1979475127902642582

Translational/Biomarker Takeaways

• TKD mutation and YVMA subset:
  • "Most common mutation is the YVMA…" (Stephen V. Liu) https://x.com/StephenVLiu/status/1833173146096271639
  • "…up to 90% for key YVMA subset…" (Balazs Halmos) https://x.com/BalazsHalmosMD/status/1833172404719452483
• CNS efficacy and intracranial activity:
  • "…intracranial RR of 41% in Cohort 1… await data from ongoing cohort 4…" https://x.com/StephenVLiu/status/1979819154900500949
  • Multiple KOLs citing intracranial response (e.g., Popat: "Intracranial ORR 33% (RANO)"; Chul Kim: "Encouraging intracranial response"). https://x.com/DrSanjayPopat/status/1833170854756434431 https://x.com/chulkimMD/status/1833170753912803542

Subsection D: Practical/Implementation Questions

• Practice positioning and competition (TKIs vs ADC):
  • Antonio Calles, MD: "…two new ‘osimertinibs’ for HER2 mutations… hit the 70% response rate threshold… Competitive indication with Trastu-DXd." https://x.com/Tony_Calles/status/1833177671909384440
• Ethical control design and crossover:
  • Crispin Hiley, MD, PhD: "Is it ethical to NOT have crossover in the control arm for such highly active drugs targeting HER2 mutations. I think not…" https://x.com/crispinhiley/status/1979202459873505666
• Sequencing and real-world implementation:
  • Oncology Brothers (podcast/video on testing, AEs, sequencing): https://x.com/OncBrothers/status/1959987969714168207
• Publication-driven pragmatism:
  • Rami Manouchakian, MD ("Hot Off The Press" NEJM thread): https://x.com/RManochakian/status/1916870845030453616
  • Dipesh Uprety, MD: "…ORR 71%… mDoR 14.1 mo & mPFS 12.4 mo" https://x.com/DipeshUpretyMD/status/1916868688591946050

Trial Sentiments - Standard of Care and Critical Appraisals

Strongly Supportive/SOC-Leaning Voices

• Stephen V. Liu, MD (practice-changing tone; threads across WCLC24 and ESMO25): https://x.com/StephenVLiu/status/1979819158054568124

• Sanjay Popat, MD (high activity, intracranial responses; forward-looking): https://x.com/DrSanjayPopat/status/1833170854756434431

• Kelsey Pan, MD, MPH (enthusiasm for oral TKIs with CNS data): https://x.com/KelseyPanMD/status/1833209118221643803

• Oncology Brothers (approval-focused summaries; implementation lens): https://x.com/OncBrothers/status/1953870964405510192

• NEJM (publication signal consolidating evidence): https://x.com/NEJM/status/1916841088897409037

Critical/Contrarian Perspectives

• Jacob Plieth: "…ORRs of 60-70%… but watch the tox!" https://x.com/JacobPlieth/status/1833168147911774395

• Dr. Riyaz Shah: "…Significant GI and skin tox for EGFR sparing… icORR 33% feels a bit low;" https://x.com/DrRiyazShah/status/1833170519241486718

• Crispin Hiley, MD, PhD: "Is it ethical to NOT have crossover in the control arm for such highly active drugs targeting HER2 mutations. I think not." https://x.com/crispinhiley/status/1979202459873505666

Temporal Sentiment Arc

2024 (WCLC 2024 primary Phase Ib readout; cautious enthusiasm)

• Primary URLs: https://x.com/StephenVLiu/status/1833173135539200247 https://x.com/StephenVLiu/status/1833173164752515364 https://x.com/DrSanjayPopat/status/1833170854756434431 https://x.com/chulkimMD/status/1833170753912803542 https://x.com/JacobPlieth/status/1833168147911774395 
• Tone summary: Initial WCLC24 reactions highlighted strong response rates at 120/240 mg (ORR 72.4–78.2%) with manageable AEs and encouraging intracranial activity. KOLs debated tolerability (“watch the tox”) and the clinical meaning of icORR ~33–41% while acknowledging promising systemic activity. The field framed zongertinib as an emerging HER2 TKI with a rapidly evolving evidence base.

2025 (AACR 2025 publication; consolidation and precision)

• Primary URLs: https://x.com/NEJM/status/1916841088897409037 https://x.com/RManochakian/status/1916870845030453616 https://x.com/DipeshUpretyMD/status/1916868688591946050 https://x.com/HHorinouchi/status/1915397817897828432 
• Tone summary: With NEJM/AACR25, the community aligned around key metrics in TKD-mutant tumors (ORR 71%, median PFS 12.4 months; mDOR ~14.1 months cited by KOLs). Discussion shifted to durability, consistency across subgroups, and safety profiles in the context of clinical adoption. Pragmatic voices began emphasizing trial design rigor and real-world applicability.

2025 (ESMO 2025 first-line cohort; deepening dataset and CNS focus)

• Primary URLs: https://x.com/StephenVLiu/status/1979819145249304646 https://x.com/StephenVLiu/status/1979819148491596017 https://x.com/StephenVLiu/status/1979819154900500949 https://x.com/DrZ_84/status/1979475127902642582 https://x.com/crispinhiley/status/1979202459873505666 
• Tone summary: First-line cohort data (RR 77%, DCR 96%, 6m DOR 80%, 6m PFS 79%) bolstered enthusiasm and emphasized CNS efficacy signals. Debate intensified around Phase III design ethics (mandatory crossover) and comparative positioning vs SOC and ADCs. The narrative matured toward careful optimism with attention to control design and patient selection.

2025 (Implementation phase: approval, education, and sequencing)

• Primary URLs: https://x.com/OncBrothers/status/1953870964405510192 https://x.com/OncBrothers/status/1959987969714168207 https://x.com/OncBrothers/status/1986460456744329373 https://x.com/Tony_Calles/status/1833177671909384440 
• Tone summary: With approval-focused communications, KOLs pivoted to testing pathways, adverse event management, and sequencing relative to ADCs (e.g., T-DXd). Conversations highlighted "embarrassment of riches" in HER2-mutant NSCLC and the need for rational first-line strategies pending Phase III readouts. Practical implementation content (podcasts, videos) reinforced clinician education.

Final Tone: The community evolved from early WCLC24 optimism about response and CNS signals to publication-driven confidence in core outcomes (ORR _{70%, median PFS} 12 months) and then to nuanced ESMO25 first-line positioning with emphasis on CNS efficacy and trial design ethics. Supportive voices frame zongertinib as potentially practice-changing in HER2 TKD-mutant NSCLC (especially with CNS activity), while critical appraisals continue to focus on toxicity vigilance, intracranial response magnitude, and the necessity of crossover in Phase III to ensure ethical and interpretable results.

Professional resources

BEAMION Lung-1

KOL Sentiment Table