Top KOLs Discussing OptiTROP-Lung04
OptiTROP-Lung04 Key Slides & Visuals
ESMO 2026 slides: final overall survival (LBA67)
| Sac-TMT (n=188) | Chemotherapy (n=188) | HR (95% CI) | |
|---|---|---|---|
| OS events, n (%) | 114 (60.6) | 137 (72.9) | — |
| Median OS, months (95% CI) | 25.9 (22.2–27.5) | 17.4 (15.7–20.3) | 0.69 (0.54–0.89), nominal one-sided P = 0.0021 |
| 24-month OS rate, % (95% CI) | 54.1 (46.6–60.9) | 37.2 (30.3–44.2) | — |
| 30-month OS rate, % (95% CI) | 40.5 (33.4–47.5) | 28.4 (22.0–35.2) | — |
| Therapy, n (%) | Sac-TMT (n=173) | Chemotherapy (n=186) |
|---|---|---|
| At least one subsequent treatment | 132 (76.3) | 160 (86.0) |
| Chemotherapy | 85 (49.1) | 101 (54.3) |
| Pemetrexed-based chemotherapy | 78 (45.1) | 25 (13.4) |
| EGFR tyrosine kinase inhibitor | 75 (43.4) | 77 (41.4) |
| Anti-angiogenic agent | 61 (35.3) | 90 (48.4) |
| Immunotherapy (incl. PD-(L)1/VEGF bispecific) | 41 (23.7) | 48 (25.8) |
| Antibody-drug conjugate | 6 (3.5) | 42 (22.6) |
| TROP2 ADC | 3 (1.7) | 16 (8.6) |
| HER3 ADC | 0 | 15 (8.1) |
| EGFR ADC | 0 | 4 (2.2) |
| EGFR/HER3 ADC | 1 (0.6) | 1 (0.5) |
Slides from the same presentation were also posted by @TommyJohn00, @Tony_Calles, @Alfdoc2.
| Sac-TMT (n=188) | Chemotherapy (n=188) | HR (95% CI) | |
|---|---|---|---|
| OS events, n (%) | 114 (60.6) | 119 (63.3) | — |
| Median OS, months (95% CI) | 25.9 (22.2–27.5) | 16.6 (15.1–19.1) | 0.57 (0.42–0.75) |
| 24-month OS rate, % (95% CI) | 54.1 (46.6–60.9) | 32.1 (24.6–39.8) | — |
Slides from the same presentation were also posted by @AdamJanuszewski, @oncologician.
| Subgroup | Events/patients, sac-TMT | Events/patients, chemotherapy | HR (95% CI) |
|---|---|---|---|
| All patients | 114/188 | 137/188 | 0.69 (0.54–0.89) |
| Male | 44/66 | 64/83 | 0.75 (0.51–1.11) |
| Female | 70/122 | 73/105 | 0.66 (0.48–0.92) |
| Age <65 | 75/130 | 97/137 | 0.66 (0.49–0.89) |
| Age ≥65 | 39/58 | 40/51 | 0.70 (0.45–1.10) |
| Ever smoker | 29/43 | 42/53 | 0.73 (0.45–1.17) |
| Never smoker | 85/145 | 95/135 | 0.68 (0.50–0.91) |
| ECOG 0 | 19/35 | 27/43 | 0.73 (0.41–1.32) |
| ECOG 1 | 95/153 | 110/145 | 0.66 (0.50–0.87) |
| 3rd-generation EGFR-TKI in 1st line | 69/118 | 88/117 | 0.64 (0.46–0.87) |
| 3rd-generation EGFR-TKI in 2nd line | 40/60 | 41/60 | 0.81 (0.53–1.26) |
| Brain metastases | 23/33 | 28/36 | 0.76 (0.43–1.32) |
| No brain metastases | 91/155 | 109/152 | 0.66 (0.50–0.88) |
| Liver metastases | 15/25 | 28/33 | 0.52 (0.28–0.99) |
| No liver metastases | 99/163 | 109/155 | 0.72 (0.55–0.95) |
| EGFR L858R | 58/84 | 53/71 | 0.83 (0.57–1.20) |
| EGFR exon 19 deletion | 56/106 | 85/118 | 0.55 (0.39–0.78) |
| T790M negative | 30/48 | 29/40 | 0.76 (0.45–1.26) |
| T790M positive | 20/29 | 24/36 | 0.82 (0.45–1.48) |
| T790M unknown | 64/111 | 84/112 | 0.62 (0.45–0.86) |
| <3 metastatic sites | 30/60 | 38/62 | 0.78 (0.48–1.26) |
| ≥3 metastatic sites | 84/128 | 99/126 | 0.62 (0.46–0.82) |
Slides from the same presentation were also posted by @oncologician.
ESMO 2025 slides: primary PFS and interim OS (LBA5)
Slides from the same presentation were also posted by @HHorinouchi, @DrRiyazShah, @DrYujiUehara, @drtahuahua.
| Sac-TMT (n=188) | Chemotherapy (n=188) | HR (95% CI) | |
|---|---|---|---|
| PFS events, n (%) | 144 (76.6) | 159 (84.6) | — |
| Median PFS, months (95% CI) | 8.3 (6.7–9.9) | 4.3 (4.2–5.5) | 0.49 (0.39–0.62), P < 0.0001 |
| 12-month PFS rate, % (95% CI) | 32.3 (25.5–39.2) | 7.9 (4.4–12.8) | — |
| Prespecified PFS interim analysis (data cutoff Jul 11, 2024) | — | — | 0.47 (0.35–0.62), P < 0.0001 |
| Sac-TMT (n=188) | Chemotherapy (n=188) | |
|---|---|---|
| ORR, % (95% CI) | 60.6 (53.3–67.7) | 43.1 (35.9–50.5) |
| ORR difference, % (95% CI) | 17.0 (7.0–27.1) | |
| DCR, % (95% CI) | 87.2 (81.6–91.6) | 80.3 (73.9–85.7) |
| Median DOR, months (95% CI) | 8.3 (6.2–10.0) | 4.2 (3.0–4.4) |
| 12-month DOR rate, % (95% CI) | 36.3 (27.3–45.3) | 8.1 (3.3–15.8) |
| Sac-TMT (n=188) | Chemotherapy (n=188) | HR (95% CI) | |
|---|---|---|---|
| OS events, n (%) | 67 (35.6) | 101 (53.7) | — |
| Median OS, months (95% CI) | Not reached (21.5–NE) | 17.4 (15.7–20.4) | 0.60 (0.44–0.82), two-sided P = 0.001 (boundary 0.0124) |
| 18-month OS rate, % (95% CI) | 65.8 (58.3–72.3) | 48.0 (40.2–55.4) | — |
| OS censored at start of a subsequent ADC (supplemental) | — | — | 0.56 (0.41–0.77) |
Slides from the same presentation were also posted by @Erman_Akkus, @MarioBalsaMD, @Tony_Calles, @diegoadiazg, @UOzkerim, @MathewGWilson.
| Sac-TMT (n=188) | Chemotherapy (n=188) | HR (95% CI) | |
|---|---|---|---|
| PFS events, n (%) | 143 (76.1) | 160 (85.1) | — |
| Median PFS, months (95% CI) | 8.4 (7.1–9.7) | 4.8 (4.2–5.5) | 0.51 (0.41–0.65), P < 0.0001 |
| 12-month PFS rate, % (95% CI) | 34.7 (27.7–41.7) | 10.7 (6.5–16.0) | — |
KOL-Made Infographics
Summary graphics designed or shared by physicians (not conference slides). Values are as the authors drew them. Click to enlarge.
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@ozdogan_mdWhat physicians are debating about OptiTROP-Lung04
Is a “nominal” P value at the final analysis a problem?
Dr. Antonio Calles 🫁🚭 called the OS benefit real “although nominal p value”. The formal test of OS, the key secondary endpoint in a hierarchy after PFS, was passed at the prespecified interim analysis: HR 0.60 (95% CI 0.44–0.82), two-sided P = 0.001 against an O’Brien-Fleming boundary of 0.0124 (data cutoff July 6, 2025; ESMO 2025 slide; NEJM). The ESMO 2025 abstract printed the same result as one-sided P = 0.0006. The final analysis (about 250 deaths planned; 251 observed) updates the estimate with longer follow-up and reports its P value as nominal: HR 0.69 (0.54–0.89), nominal one-sided P = 0.0021. The hazard ratio moved toward 1 as follow-up grew, while the confidence interval still excludes 1.
LBA67 presentation slides (Wenfeng Fang, ESMO 2026) · ESMO 2025 LBA5 slides (Li Zhang) and Kelun-Biotech release, Oct 20, 2025 · NEJM 2026;394:13-26 (online Oct 19, 2025; doi 10.1056/NEJMoa2512071)Did crossover to later ADCs, or fewer later treatments, shape the survival curves?
Prof Tom John flagged “less subsequent therapies” in the sac-TMT arm, and Aakash Desai highlighted that 22.6% of the chemotherapy arm later received an ADC. Per the LBA67 slide, 76.3% vs 86.0% of patients who stopped study treatment received at least one later therapy; 3.5% vs 22.6% (42/186) received an ADC, mostly TROP2 (8.6%) or HER3 (8.1%) ADCs; and 45.1% vs 13.4% received pemetrexed-based chemotherapy. Adjusting for later ADC use with the prespecified RPSFT model gave HR 0.57 (0.42–0.75), median 25.9 vs 16.6 months. RPSFT rests on modelling assumptions; the unadjusted ITT result (HR 0.69) is the primary OS analysis, and Kelun-Biotech describes the adjusted analysis as supplemental support.
LBA67 presentation slides (Wenfeng Fang, ESMO 2026) · ESMO 2026 abstract LBA67 (programme; click Abstract under LBA67) · Kelun-Biotech release, Oct 25, 2026Will a China-only trial translate to global practice?
Dr Adam Januszewski wrote that “global data will be important”; Dr. Estela Rodriguez noted that “global validation and treatment-sequencing questions remain”; gilberto lopes called the China-only populations the major limitation; and in 2025 Dr Mathew Wilson asked whether worldwide confirmatory trials should be required at all. All registered OptiTROP-Lung04 sites are in China, and Kelun-Biotech sponsored the trial. Global phase 3 trials of sac-TMT monotherapy in EGFR-mutant NSCLC (NCT06305754, NCT06074588) were listed as ongoing on the ESMO 2025 conclusions slide; MSD holds sac-TMT rights outside Greater China.
ClinicalTrials.gov NCT05870319 · ESMO 2025 LBA5 slides (Li Zhang) and Kelun-Biotech release, Oct 20, 2025Toxicity and dose: 5 mg/kg here, 4 mg/kg in OptiTROP-Lung06
Prof Tom John noted “more tox in Sac arm”, and Dr Riyaz Shah reported that the investigators described the stomatitis as manageable. According to Prof Tom John, the invited discussant, Melissa L. Johnson, MD, explained the differences in toxicity between the sac-TMT trials as likely dose related; her slide set OptiTROP-Lung04 (5 mg/kg; grade ≥3 treatment-related AEs 58.5% vs 53.8%) beside OptiTROP-Lung06 (4 mg/kg with pembrolizumab), and her conclusions slide warned that ADC toxicity “shouldn’t be underestimated” and that dose attenuation will be part of ADC adoption. At the final analysis, stomatitis occurred in 62.2% of sac-TMT patients (grade 3 in 4.8%), grade ≥3 neutrophil count decreased in 40.4% vs 33.0%, and grade ≥3 platelet count decreased in 2.1% vs 16.5%; ILD/pneumonitis occurred in one sac-TMT patient (0.5%) and two chemotherapy patients (1.1%), all grade 1–2.
LBA67 presentation slides (Wenfeng Fang, ESMO 2026) · Invited discussant slides (Melissa L. Johnson, ESMO 2026) · Kelun-Biotech release, Oct 25, 2026ADC or chemotherapy first after an EGFR TKI, and how does sac-TMT sit beside Datroway, amivantamab and ivonescimab?
Aakash Desai asked: “ADC or chemo first after EGFR-TKI?” Dr. Estela Rodriguez noted that sac-TMT “competes w Dato-DXd”, and Prof Tom John pointed out that neither arm included osimertinib. In 2025, Tejas Patil framed the readout against the recent Dato-DXd approval and earlier ADC results in this setting. In the US, datopotamab deruxtecan (DATROWAY) has accelerated approval only after prior EGFR-directed therapy and platinum-based chemotherapy, based on response data; OptiTROP-Lung04 tested sac-TMT in place of platinum chemotherapy. Amivantamab (RYBREVANT) with carboplatin and pemetrexed is FDA-approved after progression on an EGFR TKI (MARIPOSA-2), and the ivonescimab-plus-chemotherapy trial HARMONi-A was also run in China; neither regimen was a comparator here, so there is no head-to-head evidence. In the exploratory LBA67 subgroups, the OS hazard ratio was 0.64 after first-line third-generation EGFR-TKI and 0.81 after second-line (overlapping confidence intervals); Stephen V Liu, MD noted the first-line point estimate on the day.
DATROWAY US label (openFDA) · LBA67 presentation slides (Wenfeng Fang, ESMO 2026) · Invited discussant slides (Melissa L. Johnson, ESMO 2026)What about brain metastases?
In 2025 Oriol Mirallas MD summarized the discussion as “no clear benefit” in brain metastases, and Stephen V Liu, MD said he was awaiting more detail on CNS efficacy. The ESMO 2025 discussant, Antonio Passaro, MD, PhD, showed a PFS HR of 0.73 (0.43–1.21) with brain metastases vs 0.43 (0.33–0.56) without, noted that untreated brain metastases were excluded and that brain imaging was not mandated in patients without brain metastases, and suggested “potential overestimation of brain control”. At the 2026 final analysis, the OS HR in the 33 vs 36 patients with brain metastases was 0.76 (0.43–1.32), an exploratory subgroup with a wide confidence interval.
ESMO 2025 LBA5 slides (Li Zhang) and Kelun-Biotech release, Oct 20, 2025 · LBA67 presentation slides (Wenfeng Fang, ESMO 2026)OptiTROP-Lung04 conversations on X
Context: 21.5 months is the lower bound of the 95% CI; median OS was not reached at the interim analysis (ESMO 2025 LBA5).
Physician reactions to OptiTROP-Lung04
ESMO 2026 (final OS)
OptiTROP-Lung04 final OS #ESMO26: sac-TMT vs platinum-pem post EGFR-TKI, EGFRm NSCLC ➡️ mOS 25.9 vs 17.4 mo, HR 0.69 ➡️ 2-yr OS 54.1 vs 37.2% ➡️ 22.6% of chemo arm later got an ADC; RPSFT HR 0.57 ADC or chemo first after EGFR-TKI? @LungCancerRx @OncoAlert @oncodaily https://t.co/GcerKcg8wW
🚨 #ESMO26 | Top Lung Abstracts 🫁 OptiTROP-Lung04 (Phase III- China only trial) Significant mOS 8.5 mo advantage for sac-TMT, a TROP2 ADC, after EGFR-TKI progression in EGFR-mutant NSCLC🫁 vs chemo! 📊 Median OS: 25.9 vs 17.4 months 🔥 HR 0.69 — 31% lower risk of death ⚠️ AEs- cytopenias, stomatitis, opthal, ILD 👉🏽Competes w Dato-DXd already approved in this EGFR+ population based on Tropion-Lung05, Lung01 👉🏽Global validation and treatment-sequencing questions remain. @EGFRResisters #LCSM #LungCancer #ESMO26
Context: in the US, datopotamab deruxtecan (DATROWAY) has accelerated approval for EGFR-mutated NSCLC after prior EGFR-directed therapy and platinum-based chemotherapy (FDA label).
Now an OS win for sac-TMT in EGFR-mutant NSCLC! OptiTROP-Lung04 final OS (LBA67): sac-TMT vs platinum/pemetrexed after progression on an EGFR TKI. mOS 25.9 vs 17.4 mo, HR 0.69. The benefit held after adjusting for later ADC use in the chemo arm. No new safety signals. Pairs with Lung06 below, in PD-L1-negative disease without a driver. https://t.co/d87ursywVT #LCSM #ESMO26 @OncoAlert @Alfdoc2
An 8.5-month OS gain after EGFR-TKI failure! At #ESMO26, Prof. Wenfeng Fang presented final Phase III #OptiTROPLung04 results in EGFR-mutant NSCLC. Sac-TMT vs chemotherapy: OS: 25.9 vs 17.4 months HR 0.69 A potential practice-changing ADC milestone. @OncoDaily @OncoAlert @myesmo #ESMO26
Melissa Johson doing an excellent job discuuing those lung studies and ADC #ESMO2026 https://t.co/3Piy2Re2GH
#ESMO26 Dr. @MLJohnsonMD2 discusses ADCs in NSCLC. Notes that not all are home runs, predicting efficacy is challenging, not chemotherapy but has chemotherapy-toxicity. Much work needed to predict response, widen therapeutic window. https://t.co/HsX3HqEWwG
Johnson: explains the differences in toxicity in the SacTMT trials as likely dose related. Asks if there is a synergy with SacTMT and Pembro? #LCSM #ESMO26 https://t.co/VB568NRg3K
Final OS analysis of sacituzumab tirumotecan (sac-TMT) versus platinum-based chemotherapy in EGFR-mutated non-small cell lung cancer (NSCLC) after progression on EGFR-TKI: Phase III OptiTROP-Lung04 study #ESMO2026 Wen Feng Fang (CN) https://t.co/09KlBZfAxI
🫁 #ESMO2026 OptiTROP-Lung04: Final OS analysis of sac-TMT vs chemotherapy in EGFRm NSCLC after EGFR-TKI progression. 🇨🇳 Chinese-only phase III (n=376) 📈 OS: 25.9 vs 17.4m (HR 0.69) Impressive OS benefit. Global data will be important 2nd line EGFR setting v. complex https://t.co/eDX7HtQF9n
Fang: SacTMT in EGFR OptiTroplung04. Note no Osi in either arm. OS primary endpoint. Impressive benefit, but there are some nuances. Less subsequent therapies, more tox in Sac arm. But 7month benefit hard to ignore these results #LCSM #ESMO26 https://t.co/G2ddmz7h8b
Context: PFS by BICR was the primary endpoint and OS the key secondary endpoint (LBA67 study design slide); the median OS difference was 8.5 months (25.9 vs 17.4).
💥 Sac-TMT hits OS benefit in previously TKI-treated EGFR mutant lung cancer compared to standard carbo-pem chemotherapy (although nominal p value) Another option in a rapid evolving scenario. #ESMO26 #LCSM https://t.co/GhOHXVjCS8
OptiTROP-Lung04; sacTMT v chemoIO in mEGFR post 3rd gen TKI; OS HR 0.69- 9m longer mOS; they say the stomatitis is manageable #ESMO26 @BTOGORG https://t.co/7MiXdNztKk
Context: the control arm was pemetrexed plus carboplatin or cisplatin, without immunotherapy (LBA67 study design slide).
🆙#ESMO26 Proffered Paper I: #LCSM Mets 🔥OptiTROP-Lung04: Final OS Analysis of Sacituzumab Tirumotecan (Sac-TMT) Versus Platinum-Based Chemotherapy in EGFR-Mutated Non-Small Cell Lung Cancer (NSCLC) After Progression on EGFR-TKI: Phase III Study 🎙️Dr. Wenfeng Fang 🔢LBA67 🎯Sustained OS Benefit at 32.3-Mo Follow-Up 🎯Median OS 25.9 vs 17.4mo (HR 0.69; n=376) 🎯24-Mo OS 54.1% vs 37.2% ☑️NCT05870319 🔗 https://t.co/uGHKJfjhvW @OncoAlert @Larvol @myESMO @IASLC @EGFRResisters
#ESMO26 Dr. Wenfeng Fang presents update on OptiTROP-Lung04: sac-TMT (TROP2 ADC) vs platinum + pemetrexed in EGFR mutant NSCLC post TKI therapy. OS favors sac-TMT: 25.9m vs 17.4m, HR 0.69 (even better if 1L was 3G TKI). #ESMOAmbassadors https://t.co/5kuwemKsBj
Impressive FINAL OS results from OptiTROP-Lung04 at #ESMO26! Prof. Fang presents the phase III trial of sacituzumab tirumotecan (Sac-TMT) vs chemotherapy in pts with EGFR-mutated NSCLC after EGFR-TKI progression. 🚀 Median OS: 25.9 vs 17.4 months! ➡️ An impressive 8.5-month difference ➡️ HR 0.69 (95% CI 0.54–0.89) ➡️ 31% reduction in the risk of death 25.9 months median OS is truly remarkable! #ESMOAmbassadors #ESMO26 #LungCancer #NSCLC #EGFR #ADC
ESMO 2025 (primary PFS and interim OS)
OptiTROP-Lung04 results @NEJM after presentation from Li Zhang at #ESMO25. TROP2 ADC sac-TMT improves PFS and OS compared to standard platinum based chemotherapy in EGFR mutant NSCLC post TKI. A high bar has been set. #ESMOAmbassadors https://t.co/lKMMpVpmHS
Sac-TMT ushers in the ADC era for EGFR-mutant lung cancer. In the phase 3 OptiTROP-Lung04 trial, TROP2-targeting ADC monotherapy doubled PFS and cut mortality risk by 40% #ESMO25 #NSCLC #EGFR #TROP2 #ADC #Oncology #LungCancer #PrecisionMedicine #ImmunoOncology #ClinicalTrials #CancerResearch @myESMO @OncLive @CParkMD @tugbawitter @Dr_ElvinaA @atakansare2016 @drmukremin @dr_yakupergun @OncoAlert @alimurattat @DrYukselUrun
#HARMONi-6 & #OptiTROP-Lung04 both large phase3 RCT in a china🇨🇳 only population. Both given Presidentials #ESMO25 Question raised re confirmatory trials in worldwide setting. Is this necessary in 2025? Why don’t we raise this question to EU/US trials?🇪🇺🇺🇸 #oncology #LCSM
🫁 Sacituzumab-tmt: A new SoC for EGFR-TKI–resistant NSCLC? #OptiTROP-Lung04 The first TROP2 ADC to show significant PFS and OS benefits vs platinum chemo, with fewer serious AEs (7.4% vs 17%) and no ILD. Could this redefine post-TKI therapy sequencing? Will this become a global standard too? #CánCare #NSCLC #lcsm #TROP2 #ADC #EGFR #ESMO25
🆙 #ESMO25 🇩🇪 🔥#LCSM Presidential ☑️OptiTROP-Lung04: Sacituzumab tirumotecan (sac-TMT) vs Chemo after EGFR-TKIs ☑️ PFS HR 0.49 (95%CI 0.39-0.62), OS HR 0.60 (95%CI 0.44-0.82) 🎙️ Dr. Li Zhang @OncoAlert @myESMO @Larvol @EGFRResisters https://t.co/foR2iQEIcY https://t.co/hIluZwRTBU
OptiTROP-Lung04 🇨🇳 In EGFRm NSCLC post-EGFR-TKI, sacituzumab tirumotecan↑ PFS (8.3 vs 4.3 mo; HR 0.49) and OS (NR vs 17.4 mo; HR 0.60) vs CTx Potential SoC in EGFR-TKI–resistant NSCLC 🌟 @OncoAlert @myESMO #ESMO25 https://t.co/FVqMHbEmtz
Huge win from OptiTROP-Lung04 study #ESMO25! For pts with EGFRm NSCLC post-TKI progression, Sac-TMT vs. Chemo: 🔹 Primary EP (mPFS): 8.3 vs 4.3 mos (HR 0.49) 🔹mOS: Not Reached vs 17.4 mos (HR 0.60) 🔹 ORR: 60.6% vs 43.1% Sac-TMT significantly improves all key endpoints. #LCSM https://t.co/XsVKjJV3nO
#PresidentialSymposium Encouraging results from the Optitrop-Lung04! #Sac-TMT delivers meaningful PFS and OS improvement over docetaxel in the post-#EGFR and post-platinum setting. While ADCs like Sac-TMT expand our therapeutic toolbox, biomarker-guided strategies—such as #MET-directed combinations or 4th-generation EGFR inhibitors for C797S—remain crucial to tailor therapy and maximize benefit. #esmo25 @Larvol @ozdogan_md @OncoAlert @oncolife @ONCOLife_HP
Context: OptiTROP-Lung04 compared sac-TMT with pemetrexed plus platinum chemotherapy, not docetaxel, in patients whose disease progressed after EGFR-TKI therapy (NEJM, published online 2025). The docetaxel comparison was the phase 2 OptiTROP-Lung03.
#ESMO25 💥 PRESIDENTIAL Session II 📌Opti-TROP-04: Sac-TMT 2l #EGFR #NSCLC 🗣️ Great discussion by @APassaroMD 📌 TROP2/EGFR crosstalk 📌 Increased #TROP2 after #TKI EGFR ✅ Clear positive study in OS PFS and ORR ❌ No clear benefit 🧠 mets @OncoAlert @myESMO @ASCO @_SEOM https://t.co/Ok1PGwxsls
💎 #ESMO25 Presidential Session #LungCancer – Phase III OptiTROP-Lung04: Sacituzumab-TMT vs ChT in EGFRm NSCLC after TKI progression 🎯 mPFS 8.3 vs 4.3 mo | HR 0.49 (95% CI 0.39–0.62, p<0.0001) ✨ OS NR vs 17.4 mo | HR 0.60 (95% CI 0.44–0.82, p=0.001) 💥 ORR 60.6% vs 43.1% | Δ +17% Sac-TMT proves that after resistance hits, precision still strikes back 🥊 @OncoAlert #OncoAlertAF @OncoReporte @myESMO @_SEOM @gecp_org @LungCancerRx @Lung_Cancers
OptiTROP-Lung04 study: Presidential 2 presentation. Phase 3 trial of Sacituzumab tirumotecan (sac-TMT) vs platinum-based chemotherapy in EGFR-mutant NSCLC following progression on EGFR-TKIs. 🟢 4 months PFS gain (8.3 vs 4.3; HR 0.49) 🟢 OS HR 0.6 (17 vs not reached) 🟢 ORR delta 17% (60% vs 43%) 🟢 Mostly chemo tox (more stomatitis, low ocular tox) #ESMO25 #LCSM Simultaneously @NEJM publications @myESMO
🚀 Big news from #ESMO25! In EGFRm NSCLC with TKI resistance, OptiTROP-Lung04 showed that Sacituzumab-TMT significantly outperformed chemo: 🧬 mPFS 8.3 vs 4.3 mo (HR 0.49) 💥 OS HR 0.60 (P = 0.001) 🩸 ORR 60.6% vs 43.1% A promising new treatment option after EGFR-TKI failure. #LungCancer #NSCLC @OncoAlert @myESMO @MedwatchKate @Lung_Cancers @LungSummit @OncoReporte
#OptiTROP-Lung04 🫁Sac-TMT (Trop2 ADC) vs Pt doublet in EGFR mutant #NSCLC 2nd line after targeted therapy mPFS 8.3 vs 4.3months mOS Not Reached vs 17.4months No ILD/pneumonitis. G3 Tox similar in both arms Exciting option, in a challenging setting #ESMO25 @OncoAlert #LCSM https://t.co/3yEhkdmBS1
🔥🚨@OncoAlert Hot Off The Press. Just published @NEJM in conjunction with presentation @myESMO #ESMO25 Results of: 🎯#OptiTROP-Lung04 phase 3 trial of: ⭐️#Sacituzumab tirumotecan (#TROP2 #ADC) VS #Chemotherapy in advanced #EGFR mutant non-small cell #LungCancer after progression on #TKI ✅Statistically Significant Improvement in: ⬆️ #OverallSurvival (#OS) & ⬆️#ProgressionFreeSurvival (#PFS) 👇🏻 https://t.co/h6947b8bjL
👑OptiTROP-Lung04 Presidential 2 #ESMO25 @myESMO ➡️Sacituzumab-trimutecan vs. ChT in EGFR mutant NSCLC progressed after TKI ✅PFS and OS benefit PFS: HR 0.49 (0.39 - 0.62) OS: HR 0.60 (0.44- 0.82) #cancer #oncology #MedX @OncoAlert @OncoReporte https://t.co/4fBeLp7sYW
Sac-TMT; OptiTROP-lung04; sacTMT VS chemo post EGFR TKI ; hierarchical testing; n376; PFS HR 0.49; OS HR 0.60; #ESMO25 https://t.co/Ph69huxDQB
#ESMO25 OptiTROP-Lung04 Sac-tirumotecan vs platinum chemo in EGFR-TKI–resistant NSCLC ✅️mPFS 8.3 vs 4.3 mo (HR 0.49) ✅️mOS NR vs 17.4 mo (HR 0.60) ✅️ORR 61% vs 43% 💬The OS gain post–EGFR-TKI is striking — ADCs are clearly claiming ground across tumor types https://t.co/Lh3HhMTIDt
⭐️LBA6 - OptiTROP-Lung04: With recent Dato-Dxd approval, we will see data on sacituzumab vs doublet chemo in #EGFR #lungcancer. Recall that patritumab (HER3 ADC) failed to meet primary endpoint earlier this year and Dato-Dxd was based on pooled analysis. Could this be the one to buck the trend?
Posted on October 16, 2025, before the ESMO 2025 presentation.
OptiTROP-Lung04 Trial Design
OptiTROP-Lung04 asked whether sacituzumab tirumotecan, a TROP2-directed antibody-drug conjugate with a belotecan-derivative topoisomerase I inhibitor payload (drug-to-antibody ratio 7.4), improves outcomes over platinum doublet chemotherapy once EGFR-mutant NSCLC has progressed on an EGFR TKI. The trial is sponsored and funded by Sichuan Kelun-Biotech (Chengdu, China). The primary analysis was presented by Li Zhang, MD, at the ESMO 2025 Presidential Symposium (LBA5) and published in NEJM; the final OS analysis was presented by Wenfeng Fang, MD, at ESMO 2026 (LBA67, Proffered paper 1: NSCLC, metastatic, October 25, 2026), with Melissa L. Johnson, MD, as invited discussant.
Study Design
Randomized 1:1, open-label, multicenter phase 3 in China (NCT05870319; SKB264-III-09); 188 vs 188 patients. Stratified by prior EGFR-TKI therapy (3rd-generation TKI in first line vs second line vs none) and brain metastases (yes vs no).
Population
Locally advanced (IIIB/IIIC) or metastatic nonsquamous NSCLC with EGFR-sensitizing mutations, progressed after a 3rd-generation EGFR-TKI, or after a 1st/2nd-generation TKI with negative T790M; ECOG PS 0–1; untreated brain metastases excluded. Median age 60 vs 59; prior 3rd-generation TKI in 94.7% (ESMO 2025 abstract); exon 19 deletion 56.4% vs 62.8%.
Interventions
Sac-TMT 5 mg/kg IV every 2 weeks vs pemetrexed 500 mg/m² + carboplatin AUC 5 or cisplatin 75 mg/m² every 3 weeks for up to 4 cycles, then pemetrexed maintenance. Treatment until progression or unacceptable toxicity.
Endpoints
Primary: PFS by BICR (RECIST 1.1). Key secondary: OS, tested hierarchically after PFS. Other secondary: investigator-assessed PFS, ORR, DCR, DOR, safety, quality of life.
Presenters & Discussants
ESMO 2026: Wenfeng Fang, MD (Sun Yat-sen University Cancer Center); discussant Melissa L. Johnson, MD (SCRI). ESMO 2025: Li Zhang, MD (national lead PI); discussant Antonio Passaro, MD, PhD.
Data Cuts
PFS interim: Jul 11, 2024. Final PFS and interim OS: Jul 6, 2025 (median follow-up 18.9 months). Final OS: Aug 6, 2026 (median follow-up 32.3 months; about 250 OS events planned).
OptiTROP-Lung04 in the News
OptiTROP-Lung04 Questions
What is the OptiTROP-Lung04 trial?
OptiTROP-Lung04 (NCT05870319) is a randomized, open-label phase 3 trial run in China by Sichuan Kelun-Biotech. It compared sacituzumab tirumotecan (sac-TMT), a TROP2-directed antibody-drug conjugate, given alone at 5 mg/kg every 2 weeks, with pemetrexed plus carboplatin or cisplatin in 376 patients with EGFR-mutant nonsquamous NSCLC whose disease progressed on EGFR-TKI therapy. The primary endpoint was PFS by blinded independent central review; OS was the key secondary endpoint.
What did the final overall survival analysis show at ESMO 2026?
At the prespecified final OS analysis (LBA67; data cutoff August 6, 2026; median follow-up 32.3 months), median OS was 25.9 months with sac-TMT vs 17.4 months with chemotherapy: HR 0.69 (95% CI 0.54–0.89), nominal one-sided P = 0.0021. The 24-month OS rate was 54.1% vs 37.2%, and the 30-month rate 40.5% vs 28.4%.
What were the earlier results published in NEJM?
At the final PFS analysis and prespecified interim OS analysis (data cutoff July 6, 2025; median follow-up 18.9 months), median PFS by BICR was 8.3 vs 4.3 months (HR 0.49, 95% CI 0.39–0.62), and OS was significantly longer with sac-TMT (HR 0.60, 95% CI 0.44–0.82; two-sided P = 0.001), with 18-month OS of 65.8% vs 48.0%. These results were presented at ESMO 2025 (LBA5) and published in NEJM.
Why is the final P value called nominal?
OS was tested formally, after PFS, at the prespecified interim analysis, where it crossed the efficacy boundary (two-sided P = 0.001 vs a boundary of 0.0124). The final analysis updates that result with longer follow-up, so its P value (one-sided 0.0021) is reported as nominal.
Did later ADC treatment in the chemotherapy arm affect the result?
In the chemotherapy arm, 42 of 186 patients who stopped study treatment (22.6%) later received an ADC, vs 6 of 173 (3.5%) in the sac-TMT arm. After adjustment with the prespecified RPSFT model, median OS was 25.9 vs 16.6 months (HR 0.57, 95% CI 0.42–0.75). The unadjusted HR 0.69 remains the primary OS result.
Is sacituzumab tirumotecan FDA approved?
No. Sacituzumab tirumotecan is not approved by the FDA or the European Medicines Agency for any indication. In China, the NMPA approved it for EGFR-mutant nonsquamous NSCLC after EGFR-TKI therapy based on OptiTROP-Lung04, and for three other indications. MSD (Merck) holds sac-TMT rights outside Greater China. It is a different drug from sacituzumab govitecan (TRODELVY) and from datopotamab deruxtecan (DATROWAY).
Was the trial conducted only in China?
Yes. All ClinicalTrials.gov sites are in China. Several physicians named the China-only population as the main question for global use (see Debates). Global phase 3 trials of sac-TMT in EGFR-mutant NSCLC are ongoing.