WCLC 2026: Live KOL Reaction
Physician posts about this trial captured live during the IASLC 2026 World Conference on Lung Cancer (Seoul, September 12–15). Quotes are verbatim; each card links to the original post. Last updated 2026-09-15.
T-DXd trying to catch up in the frontline setting with zongertinib and sevabertinib Results from #DESTINYLung04…. #WCLC26 https://t.co/wb9BkFV7dg
🆙#WCLC26 #LCSM Plenary Session 🔥DESTINY-Lung04: First-Line Trastuzumab Deruxtecan (T-DXd) in Patients With Metastatic HER2-Mutant NSCLC: Primary Results 🎙️ @JuliaRotow 🎯PFS HR 0.63 (95%CI 0.50-0.79) 🎯OS HR 1.15 (95%CI 0.88-0.92) 🔢PL03.08 ☑️NCT05048797 🔗 https://t.co/gAahGHJGeA @OncoAlert @Larvol @IASLC
Dr. @JuliaRotow at #WCLC26 with primary results from DESTINY-Lung04: first-line trastuzumab deruxtecan vs platinum + pemetrexed + pembro in advanced HER2 mutant NSCLC. Primary endpoint of PFS favors T-DXd at 14.3 vs 8.3m, HR 0.63 and RR 70% vs 44.5%, DOR 13.7 vs 9.7m, PFS2 22.7 vs 17.3m.
#WCLC26 In DESTINY-Lung04, no OS signal yet. Toxicities led to discontinuation in 16% of both arms. Biggest concern here is the ILD at 20.8% - while most were grade 1/2 and resolved, these are still high rates. This will impact delivery and possibly subsequent therapies... https://t.co/ZUQSd7yaFX
#WCLC26 | DESTINY-Lung04 🧬 Ph3: 1L T-DXd vs pembrolizumab + chemo in advanced HER2m NSCLC (n=454; ~94% HER2 exon20) 📉 PFS: 14.3 vs 8.3 mo; HR 0.63 (95% CI 0.50–0.79; p<0.0001) → ~6-month improvement 🎯 ORR: 70.0% vs 44.5% ⏳ DoR: 13.4 vs 9.7 mo 🧠 Benefit maintained in patients with brain mets: PFS HR 0.62 📊 Interim OS showed no benefit: • 29.3 vs 33.1 mo • HR 1.15 (95% CI 0.88–1.52) ⚠️ Interpretation complicated by subsequent therapy imbalance: HER2-directed therapy 48.0% vs 23.3% in the control vs T-DXd arms 🫁 Adjudicated drug-related ILD/pneumonitis: 20.8% • G≥3: 4.4% • G5: 1.8%
DESTINY-Lung04 at #WCLC26 In 1L HER2-mutant advanced NSCLC, T-DXd significantly improved PFS vs pembrolizumab + chemotherapy: mPFS 14.3 vs 8.3 months (HR 0.63; P<0.0001) ORR: 70.0% vs 44.5% However, no OS benefit was observed at this analysis (29.3 vs 33.1 months; HR 1.15). The first Phase 3 trial showing benefit of a HER2-directed therapy vs SOC in this setting. @OncoAlert @GlopesMd @ManuelDomine @StephenVLiu @weoncologists @OpenMedKate
Dr @JuliaRotow with terrific presentation of DESTINY-Lung04 #WCLC26. ORR 70% vs 44.5%, improved PFS. ‼️No significant OS benefit ; notably, 48% of chemo arm did receive subsequent HER2 directed treatment 🚨ILD any grade 20.8% (78.7% G 1/2) ⭐️Zongertinib my choice for 1L treatment in HER2 TKD alterations
🫁 DESTINY-Lung04: T-DXd in HER2-mutant NSCLC. @JuliaRotow First-line T-DXd significantly improved PFS vs pembro + chemo: 14.3 vs 8.3 months HR 0.63 (95% CI, 0.50-0.79; P<0.0001) ORR was 70.0% vs 44.5%, with median DoR of 13.4 vs 9.7 mo. OS did not favor T-DXd (HR 1.15), with subsequent therapy imbalances limiting interpretation. ILD/pneumonitis occurred in 20.8% with T-DXd, predominantly grade 1/2. #CánCare #oncology #thoraciconcology #lungcancer #NSCLC #HER2 #ADC #WCLC26 @IASLC
DESTINY-Lung04. T-DXd vs pembrolizumab + chemo as 1L therapy in HER2-mutant (exon 19/20) NSCLC by @JuliaRotow #WCLC26 Take: Primary endpoint met PFS 14.3mo (T-DXd) vs 8.3mo. ORR 70% vs 44.5%; DOR 13.4 vs 9.7mo; median treatment duration 12mo vs 7mo. OS at 46.9% maturity numerically favors the control arm: 29.3mo (T-DXd) vs 33.1mo (pembro+chemo), HR 1.15 (0.88–1.52). no OS benefit, with many confounding postreatment. Great to see the comparator here is genuine current SOC not a weaker historical control, which makes the PFS win more meaningful but also makes the OS numbers harder to wave away. Again going back to the ORR/PFS/OS dilemma. #NSCLC #LCSM
DESTINY-Lung04; front line, no protocol mandated x over; n454; 23% have brain mets; mPFS 8.3 v 14.3m HR 0.63; ORR 70%; mDOR 13.4m; no OS benefit! 48% of control arm got subsequent her2 directed therapy: 21% any grade ILD; @Bayer and @Boehringer can give a sigh of relief #WCLC26 https://t.co/LFPLj0hlsF
#WCLC26 Presidential Symposium: DESTINY-Lung04 1L T-DXd vs pembrolizumab + platinum/pemetrexed in metastatic HER2-mutant NSCLC: • PFS 14.3 vs 8.3 mo • HR 0.63 (95% CI 0.50–0.79), P<0.0001 • ORR 70.0% vs 44.5% • DoR 13.4 vs 9.7 mo https://t.co/f2lIDEBgH7
DESTINY-Lung04 🫁 Can T-DXd move up front in HER2-mutant advanced NSCLC? T-DXd vs pembrolizumab + platinum/pemetrexed: → PFS: 14.3 vs 8.3 months → HR 0.63 → ORR: 70% vs 44.5% → DoR: 13.4 vs 9.7 months A compelling improvement in disease control. But the trade-off matters: ILD 20.8%, including 1.8% Grade 5 ILD with T-DXd. OS remains difficult to interpret at this analysis, particularly in the context of imbalanced subsequent therapies. Take-home: T-DXd emerges as an important new first-line option for advanced HER2-mutant NSCLC — with vigilant ILD recognition and monitoring essential. 📚 Reference: DESTINY-Lung04, Phase III study; WCLC 2026. #MVOnco #DESTINYLung04 #TDXd #HER2 #HER2Mutant #NSCLC #LungCancer #ThoracicOncology #WCLC2026 #Oncology
🆙#WCLC26 #LCSM Plenary Session 🔥DESTINY-Lung04: First-Line Trastuzumab Deruxtecan (T-DXd) in Patients With Metastatic HER2-Mutant NSCLC: Primary Results 🎙️ @JuliaRotow 🔢PL03.08 🎯T-DXd Showed Statistically Significant and Clinically Meaningful PFS Improvement vs SOC (Chemo+Pembrolizumab) as First-Line Therapy ☑️NCT05048797 🔗 https://t.co/gAahGHJGeA @OncoAlert @Larvol @IASLC
FDA grants accelerated approval to sevabertinib as first-line HER2 mutant (TKD) NSCLC. Based on SOHO-01 with RR 75% and 38% of those lasting ≥ 12m. Joins zongertinib here, with trastuzumab deruxtecan presumably joining soon based on DESTINY Lung-04. https://t.co/W90xpc8g55
The TKI-vs-ADC Debate: Where Does 1L T-DXd Fit?
Dr. Antonio Calles’ critical read of the readout — the most-viewed physician post on DESTINY-Lung04 of the day — drew a sequencing debate: oral HER2 TKIs first, T-DXd saved for second line? Verbatim, in conversation order. (His “truck test” meme follow-up is below.)
😳 Disappointing results of T-DXd in large randomized phase III Destiny-Lung04 first line in HER2mut NSCLC vs SoC chemo-pembro. Although control arm outperformed, the lack of translation into OS benefit and the concerning safety issues of this agent warrants a lot of discussion, specially in the upcoming data from selective HER2 TKIs, with are associated with better tolerance and safety profile. #WCLC26 @iasclc #lcsm
@Tony_Calles Keep calm and order Zong or Seva ..
@Tony_Calles @NReguart Absolutely! Hard to argue against the safety and convenience of TKIs. If data about T-DXd after HER2 TKI shows a compelling signal, it would further support saving this ADC for 2nd line.
The “Truck Test” — the OS debate, meme edition
Dr. Antonio Calles followed his critical read of the DESTINY-Lung04 survival curves by quote-tweeting himself to call for “the truck test” — and Drs. Balazs Halmos and Paolo Tarantino answered in GIFs. Embedded natively below so the GIFs play; every post is verbatim.
DESTINY-Lung04: impressive PFS with first-line T-DXd, but the OS curve tells a very different story. T-DXd vs pembrolizumab + platinum/pemetrexed: • mPFS: 14.3 vs 8.3 months • HR 0.63 | P<0.0001 • 37% lower risk of progression/death But OS did not favor T-DXd: • mOS: 29.3 vs 33.1 months • HR 1.15 (95% CI 0.88–1.52) • OS remains immature Clinical verdict: A clear first-line PFS win in HER2-mutant NSCLC, but the survival story remains unresolved. #WCLC26 #LungCancer @IASLC @OncoAlert
DESTINY-Lung04 1L Trastuzumab Deruxtecan v PPC, HER2mut NSCLC ✅🔼mPFS 14.3 v 8.3, HR 0.63 ✅🔼ORR 70 v 44% ❌No diff OS ❗️Pneumonitis 20%, 4% Gr3+ 🤔 New 1L option, joining Zongertinib ORR + PFS similar to TKIs OS likely reflects subsequent Rx Watch 🫁! ❓sequencing #WCLC26 https://t.co/MBUSCb0CWL
DESTINY-Lung04 at #WCLC26 In 1L HER2-mutant advanced NSCLC, T-DXd significantly improved PFS vs pembrolizumab + chemotherapy: mPFS 14.3 vs 8.3 months (HR 0.63; P<0.0001) ORR: 70.0% vs 44.5% However, no OS benefit was observed at this analysis (29.3 vs 33.1 months; HR 1.15). The first Phase 3 trial showing benefit of a HER2-directed therapy vs SOC in this setting.
#WCLC26 Presidential Symposium Day 2 🔥#DESTINY-Lung04: First-line trastuzumab deruxtecan (TDxd) vs chemo IO in #HER2-mutant metastatic NSCLC. 🎙️@JuliaRotow ▶️ Median PFS: 14.3 vs 8.3 mo ▶️ HR 0.63; P<0.0001 ▶️ ORR: 70.0% vs 44.5% ▶️ DOR: 13.7 vs 9.7 mo ⬆️ crossover ⚠️Grade ≥3 TRAEs similar 🫁Adjudicated drug-related ILD: 20.8% 👉🏽👉🏽TDxd is more active than chemoIO, competes w oral drugs in market w less chemo side effects 👉🏽👉🏽some caution about ILD but overall we have used this drug safely in 2nd line. @Exon20Group #lcsm @IASLC
My thoughts on DESTINY-Lung04 and 1L HER2 options (from my LinkedIn, sorry so tiny!) #WCLC26 https://t.co/0t5BjaFSg9
An important result from WCLC 2026 that could change clinical practice! Presented at the @IASLC #WCLC26 Presidential Symposium, the Phase III DESTINY-Lung04 trial may bring HER2-targeted therapy into the first-line setting for advanced HER2-mutant NSCLC. In patients with previously untreated, advanced non-squamous NSCLC harboring HER2 (ERBB2) exon 19/20 mutations: T-DXd (Enhertu) vs pembrolizumab + platinum/pemetrexed 🔹 Median PFS: 14.3 vs 8.3 months 🔹 HR 0.63 → 37% reduction in the risk of progression or death 🔹 ORR: 70% vs 44.5% 🔹 Median DoR: 13.4 vs 9.7 months OS data are still immature, with no survival benefit demonstrated at this time. HER2 mutation is becoming an important determinant not only for later-line therapy, but also for first-line treatment selection in NSCLC. These results once again highlight the importance of comprehensive molecular profiling/NGS at diagnosis. @IASLC @oncodaily @OncodailyLung @myESMO @OncBrothers @RManochakian @Latinamd @HosseinBorghaei #WCLC26 #PrecisionOncology #NGS
DESTINY-Lung04: impressive PFS with first-line T-DXd, but the OS curve tells a very different story. T-DXd vs pembrolizumab + platinum/pemetrexed: • mPFS: 14.3 vs 8.3 months • HR 0.63 | P<0.0001 • 37% lower risk of progression/death But OS did not favor T-DXd: • mOS: 29.3 vs 33.1 months • HR 1.15 (95% CI 0.88–1.52) • OS remains immature Clinical verdict: A clear first-line PFS win in HER2-mutant NSCLC, but the survival story remains unresolved. #WCLC26 #LungCancer @IASLC @OncoAlert
#WCLC26 Presidential Symposium Day 2 🔥#DESTINY-Lung04: First-line trastuzumab deruxtecan (TDxd) vs chemo IO in #HER2-mutant metastatic NSCLC. 🎙️@JuliaRotow ▶️ Median PFS: 14.3 vs 8.3 mo ▶️ HR 0.63; P<0.0001 ▶️ ORR: 70.0% vs 44.5% ▶️ DOR: 13.7 vs 9.7 mo ⚠️Grade ≥3 TRAEs similar 🫁Adjudicated drug-related ILD: 20.8% 👉🏽👉🏽TDxd is more active than chemoIO, competes w oral drugs in market w less chemo side effects 👉🏽👉🏽some caution about ILD but overall we have used this drug safely in 2nd line. @Exon20Group #lcsm @IASLC
Top KOLs Discussing DESTINY-Lung04
DESTINY-Lung04 Key Slides & Visuals
DESTINY-Lung04 Top Tweets
𝕏HER2-mutant NSCLC landscape at #TTLC2026 by Dr. Christina Paik👇 In previously treated pts, three FDA approved drugs: T-DXd, Zongertinib, Sevabertinib. 1L phase 3 trials ongoing: DESTINY-Lung04, Beamion LUNG-2 m, SOHO-02. https://t.co/f9meok1tFL
𝕏JUST IN (again, today!) and also from @AstraZeneca: DESTINY-Lung04 Phase III trial showed T-DXd (trastuzumab deruxtecan) PFS > chemo+pembro in FIRST-LINE metastatic HER2-mutant lung cancer (2-4% of all NSCLC) https://t.co/C86sHsx0jN @OncoAlert @OpenMedicineHQ https://t.co/j8VOYZjWAR
𝕏HER2-mutant NSCLC is rapidly becoming a truly targetable disease DESTINY-Lung04 trial to show that upfront HER2-directed T-DXd improves PFS over pembro +chemo The key question now is sequencing: ADC first, or the emerging HER2-selective TKIs? OS and full data will matter. https://t.co/DrR4ebk274
𝕏Enhertu demonstrated statistically significant and clinically meaningful improvement in progression-free survival as 1st-line treatment of patients with HER2-mutant advanced non-small cell lung cancer in DESTINY-Lung04 Phase III trial. https://t.co/AaHX1LPrla
𝕏“The DESTINY-Lung04 data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.” “The trial will continue as planned to evaluate secondary endpoints including overall survival.” https://t.co/2pOoc4jXxd
𝕏Three first-line trials, DESTINY-LUNG04, BEAMION-LUNG02 & SOHO-02, are redefining the HER2-mutant NSCLC landscape. At ILCS 2025, @stephanieplsaw asked how we’ll decide the “winner” if all three outperform Keynote-189: PFS, OS, CNS efficacy, toxicity, or timing of approval? Watch her full talk: https://t.co/qBfsppMWQK Results from BEAMION-LUNG01 (LBA74) & SOHO-01 (LBA75) will offer more insights at #ESMO25. Don’t miss it – add this and other key abstracts to your calendar 👇 https://t.co/50RRVPuS18
𝕏@TumorBoardTues @riess_md @IntegrityCE @DrSanjayPopat @stephanieplsaw @StephenVLiu @LeXiuning @NarjustFlorezMD @SukiPaddaMD @JoelNealMD @Latinamd @jillfeldman4 @Exon20Group @drgandara @LeciaSequist @marinagarassino @peters_solange 21/25 #TumorBoardTuesday 👏Lots of progress for HER2 ex20ins 🫁. More to come! 1️⃣ 1L Anti-HER2 🔹 Ph 3 Beamion LUNG-2: Zongertinib (NCT06151574) 🔹 Ph 3 SOHO-02: Sevabertinib (NCT06452277) 🔹 Ph 3 DESTINY-Lung04: T-DXd (NCT05048797) ➡️ Control=plat/pemetrexed/pembro in all
𝕏🔥DESTINY-Lung04: "Statistically significant and clinically meaningful improvement in PFS" 🆙 @AstraZeneca @DaiichiSankyo 👥Patients: HER2 exon19/20-mutant, unresectable/locally advanced or metastatic non-squamous NSCLC, 1st-line 3⃣Phase III ⚖️Trastuzumab deruxtecan ⚖️Platinum-pemetrexed doublet + pembrolizumab 🔢NCT05048797 #LCSM @OncoAlert @Larvol 🔗 https://t.co/jWxU9lCT3T
𝕏Re- Destiny-Lung04, Phase III of T-DXd vs Chemo in HER2-mutated NSCLC . Big news, although these results anticipated. Will it translate into improved overall survival? https://t.co/28MVd2vhae
𝕏🔔 Destiny-lung04 press release: First proof of evidence that HER2-directed therapies are improving outcomes vs SoC in 1L HER2-mutant NSCLC . Ongoing studies are exploring TDXd in 1L using HER2 IHC and PDL1<50% as biomarkers ( Destiny Lung-06) #some #LCSM https://t.co/08I8k0yno0
About the DESTINY-Lung04 Trial
HER2 (ERBB2) mutations drive roughly 2–4% of nonsquamous NSCLC, disproportionately in younger patients and never-smokers, and until recently had no targeted first-line option: standard care has been PD-(L)1 immunotherapy with or without platinum chemotherapy. Enhertu — a HER2-directed antibody-drug conjugate — changed the treated-disease landscape via DESTINY-Lung02, which earned FDA accelerated approval in previously treated HER2-mutant NSCLC. DESTINY-Lung04 asks the next question: should it move to first line?
On August 17, 2026 — the same morning AstraZeneca announced SAFFRON’s positive readout — Daiichi Sankyo and AstraZeneca reported that T-DXd significantly improved PFS over platinum–pemetrexed plus pembrolizumab. Physicians on this page called it the first proof that HER2-directed therapy beats standard of care up front, while noting what remains open: overall survival is still maturing, and the oral HER2 TKIs zongertinib (Beamion LUNG-2) and sevabertinib (SOHO-02, confirmatory) are running Phase 3 trials against the same control — and sevabertinib (Hyrnuo) already holds FDA accelerated approval for first-line HER2 TKD-mutant NSCLC (September 9, 2026, per SOHO-01) — a sequencing debate the IASLC comparison slide on this page lays out.
Trial Methodology & Results
Study Design
Global, randomized (1:1), open-label Phase 3; actual enrollment 454 (ClinicalTrials.gov; ~264 originally planned). Randomization stratified by smoking history and presence/history of brain metastasis.
Population
Treatment-naive (advanced setting), unresectable locally advanced or metastatic non-squamous NSCLC with HER2 exon 19 or 20 mutation; no other targetable oncogenic alterations.
Interventions
Arm 1: T-DXd (trastuzumab deruxtecan) 5.4 mg/kg. Arm 2: standard of care — platinum (cisplatin or carboplatin) + pemetrexed + pembrolizumab.
Endpoints
Primary: PFS by BICR. Secondary: OS, investigator PFS, ORR, DoR (BICR and investigator), PK, patient-reported tolerability, immunogenicity, safety.
Biomarker
HER2 (ERBB2) exon 19 or 20 activating mutation.
Sponsor
AstraZeneca (ClinicalTrials.gov sponsor) with Daiichi Sankyo as collaborator; Enhertu was discovered by Daiichi Sankyo and is jointly developed and commercialized by both companies.
Efficacy — topline only
T-DXd delivered a statistically significant and clinically meaningful improvement in PFS (primary endpoint, BICR) versus platinum–pemetrexed plus pembrolizumab: median 14.3 vs 8.3 months, HR 0.63 (95% CI 0.50–0.79; P<0.0001). ORR was 70.0% vs 44.5% (odds ratio 2.93), median DoR 13.4 vs 9.7 months, and investigator-assessed PFS2 22.7 vs 17.3 months (HR 0.80, 95% CI 0.62–1.02). At the first OS interim analysis there was no OS benefit (median 29.3 vs 33.1 months; HR 1.15, 95% CI 0.88–1.52; 46.9% maturity); formal OS hypothesis testing is reserved for the second interim and final analyses. (WCLC 2026 presidential session PL03.08, Rotow et al; DCO June 9, 2026)
First HER2-directed medicine to beat global 1L standard of care in Phase 3Daiichi Sankyo topline PR, Aug 17, 2026 · WCLC 2026 primary-results slides (via Dr. Stephen V. Liu)
Safety
Per the WCLC 2026 presentation (investigator-assessed; DCO June 9, 2026): drug-related AEs of any grade occurred in 90.3% with T-DXd (n=226) vs 89.5% with pembrolizumab + chemotherapy (n=220); grade ≥3 in 34.1% vs 33.6%; and drug-related AEs led to discontinuation in 15.9% of both arms. Adjudicated drug-related ILD/pneumonitis — the risk physicians flagged most — occurred in 20.8% of T-DXd patients vs 2.3% (grade ≥3 4.4%, including four grade 5 events); most cases were grade 1/2 (78.7%) and resolved. Median treatment duration was 12.3 vs 7.1 months. (WCLC 2026 presidential session PL03.08, Rotow et al)
Daiichi Sankyo PR, Aug 17, 2026 · WCLC 2026 safety slides (via Dr. Stephen V. Liu, OCR above)Clinical Implications
⚠ First-line T-DXd in HER2m NSCLC is investigational pending full data and regulatory review. ✅ Enhertu remains FDA-approved (accelerated) in previously treated HER2-mutant disease. If the PFS benefit holds up with OS and tolerability, the 1L treatment paradigm for HER2-mutant NSCLC would shift from chemo-immunotherapy to targeted therapy — with sequencing against the oral HER2 TKIs (zongertinib approved Feb 2026 in later lines; Beamion LUNG-2 and SOHO-02 pending) as the next debate.
Source: FDA approval notificationsDESTINY-Lung04 in the News
DESTINY-Lung04 FAQ
What is the DESTINY-Lung04 trial?
DESTINY-Lung04 (NCT05048797) is a global, randomized (1:1), open-label Phase 3 trial testing Enhertu (trastuzumab deruxtecan, T-DXd) as FIRST-LINE treatment versus the global standard of care - platinum (cisplatin or carboplatin) plus pemetrexed plus pembrolizumab - in patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring a HER2 exon 19 or 20 mutation. It is the first head-to-head trial of a HER2-directed therapy against standard of care in this first-line setting. ClinicalTrials.gov lists actual enrollment of 454 patients.
What did the DESTINY-Lung04 results show at WCLC 2026?
Primary results were presented by Dr. Julia Rotow (Dana-Farber Cancer Institute) at the WCLC 2026 presidential session in Seoul on September 14, 2026 (data cutoff June 9, 2026). First-line T-DXd improved median PFS to 14.3 months versus 8.3 months with pembrolizumab plus platinum-pemetrexed (HR 0.63, 95% CI 0.50-0.79; P<0.0001), with ORR 70.0% versus 44.5% and median duration of response 13.4 versus 9.7 months. At the first interim analysis there was no overall survival benefit (median OS 29.3 vs 33.1 months; HR 1.15, 95% CI 0.88-1.52; 46.9% maturity), with interpretation complicated by subsequent HER2-directed therapy in 48.0% of the control arm versus 23.3% of the T-DXd arm. Drug-related adverse events led to discontinuation in 15.9% of both arms, and adjudicated drug-related ILD/pneumonitis occurred in 20.8% of T-DXd patients (grade 5: 1.8%).
Is Enhertu approved for HER2-mutant lung cancer?
Yes - for previously treated disease: Enhertu holds FDA accelerated approval for adults with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations after a prior systemic therapy (based on DESTINY-Lung02 and/or DESTINY-Lung05), and a separate accelerated approval for previously treated HER2-positive (IHC 3+) solid tumors with no satisfactory alternative treatment options. The FIRST-LINE use studied in DESTINY-Lung04 is investigational.
Who is eligible in DESTINY-Lung04?
Adults with treatment-naive (in the advanced setting), unresectable, locally advanced or metastatic non-squamous NSCLC with a HER2 exon 19 or 20 mutation and no other targetable oncogenic alterations.
Why does DESTINY-Lung04 matter?
HER2-mutant NSCLC often affects younger patients and historically lacked a targeted first-line option - standard first-line care has been immunotherapy with or without chemotherapy. DESTINY-Lung04 is the first Phase 3 trial to show a PFS benefit for a HER2-directed medicine over that global standard in first line, and it lands in an increasingly competitive space alongside the oral HER2 TKIs zongertinib (Beamion LUNG-2, Phase 3 against the same control) and sevabertinib, which received FDA accelerated approval for first-line HER2 TKD-mutant NSCLC on September 9, 2026 (SOHO-01), with SOHO-02 as its confirmatory Phase 3.