---
title: "OptiTROP-Lung05 interim: sacituzumab tirumotecan plus pembrolizumab in PD-L1–positive NSCLC"
id: "nature-reviews-clinical-oncology-0-does-optitrop-lung05-open-a-new-frontier-for-first-line-adc-ici-combinations-in"
canonical_url: "https://medichelpline.com/clinical-feed/nature-reviews-clinical-oncology-0-does-optitrop-lung05-open-a-new-frontier-for-first-line-adc-ici-combinations-in"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "Nature Reviews Clinical Oncology"
source_url: "https://www.nature.com/articles/s41571-026-01183-6"
published_at: "2026-07-20T12:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# OptiTROP-Lung05 interim: sacituzumab tirumotecan plus pembrolizumab in PD-L1–positive NSCLC
## Provenance & Clinical Metadata
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- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** Nature Reviews Clinical Oncology
- **Source URL:** [Original Journal Publication](https://www.nature.com/articles/s41571-026-01183-6)
- **Published At:** 2026-07-20T12:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- Interim results from the randomized, open-label, phase III **OptiTROP-Lung05** trial show that adding the TROP2-targeted antibody–drug conjugate **sacituzumab tirumotecan** to **pembrolizumab** improved **progression-free survival** versus pembrolizumab alone in patients with **PD-L1–positive advanced non‑small‑cell lung cancer**. - The OptiTROP-Lung05 analysis reported in Lancet is an interim evaluation; detailed effects on **overall survival** have not yet been reported in the source article and remain a key unresolved question. - The author highlights several outstanding clinical and implementation issues before this combination could be accepted as a new standard of care, including confirmation of long-term safety, durability of benefit, and global generalizability of the trial findings. - Biomarker refinement is identified as necessary: better selection strategies beyond PD-L1 expression and use of TROP2 quantitation or other predictive markers may be needed to identify patients most likely to benefit. - The commentary situates OptiTROP-Lung05 within a broader context of first-line immunotherapy and chemoimmunotherapy trials (for example, pivotal pembrolizumab studies) and of ADC–ICI combination research in other tumour types, underscoring a growing clinical interest in combining **antibody–drug conjugates** with immune checkpoint inhibitors. - The author notes precedent and related evidence from other studies of ADC–ICI combinations and single-agent pembrolizumab trials cited in the references, but emphasizes that the OptiTROP-Lung05 interim findings require further data and analyses to address safety, survival, biomarkers and applicability across populations. - Specific details such as numerical hazard ratios, absolute PFS estimates, toxicity rates, and overall survival data were not reported in the preview commentary and therefore are not available in the source text. - The author declares competing interests, listing consulting fees and honoraria from multiple industry partners; this disclosure is reported in the article’s ethics declarations.
## Clinical Analysis & Structured Key Points
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Accept all cookies Reject optional cookies Skip to main content Advertisement View all journals Saved research Search Log in Explore content About the journal Publish with us Subscribe Sign up for alerts RSS feed nature nature reviews clinical oncology news & views article News & Views Published: 20 July 2026 Lung cancer Does OptiTROP-Lung05 open a new frontier for first-line ADC–ICI combinations in NSCLC? Myung-Ju Ahn Nature Reviews Clinical Oncology (2026) Cite this article Save article Interim data from the phase III OptiTROP-Lung05 trial demonstrate that adding the TROP2-targeted antibody–drug conjugate sacituzumab tirumotecan to pembrolizumab improves progression-free survival in patients with PD-L1-positive advanced-stage non-small-cell lung cancer. Herein, I present several questions that need to be addressed before this combination can be considered a new standard of care, such as effect on overall survival, long-term safety, global generalizability and biomarker refinement. This is a preview of subscription content, access via your institution Access options Access through your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription $32.99 / 30 days cancel any time Learn more Subscribe to this journal Receive 12 print issues and online access $189.00 per year only $15.75 per issue Learn more Rent or buy this article Prices vary by article type from$1.95 to$39.95 Learn more Prices may be subject to local taxes which are calculated during checkout Additional access options: Log in Learn about institutional subscriptions Read our FAQs Contact customer support References Mok, T. S. K. et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 393, 1819–1830 (2019). Article PubMed Google Scholar Reck, M. et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N. Engl. J. Med. 375, 1823–1833 (2016). Article PubMed Google Scholar Gandhi, L. et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N. Engl. J. Med. 378, 2078–2092 (2018). Article PubMed Google Scholar Paz-Ares, L. et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N. Engl. J. Med. 379, 2040–2051 (2018). Article PubMed Google Scholar Powles, T. et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. N. Engl. J. Med. 390, 875–888 (2024). Article PubMed Google Scholar Tolaney, S. M. et al. Sacituzumab govitecan plus pembrolizumab for advanced triple-negative breast cancer. N. Engl. J. Med. 394, 354–366 (2026). Article PubMed Google Scholar Hong, S. et al. First-line sacituzumab tirumotecan with tagitanlimab in advanced non-small-cell lung cancer: a phase 2 trial. Nat. Med. 31, 3654–3661 (2025). Article PubMed Google Scholar Xiong, A. et al. Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): interim analysis of a randomised, open-label, phase 3 trial. Lancet 407, 2607–2619 (2026). Article PubMed Google Scholar Ahn, M.-J. et al. Datopotamab deruxtecan versus docetaxel for previously treated advanced or metastatic non-small cell lung cancer: the randomized, open-label phase III TROPION-Lung01 study. J. Clin. Oncol. 43, 260–272 (2025). Article PubMed Google Scholar Garassino, M. C. et al. Normalized membrane ratio of TROP2 by quantitative continuous scoring is predictive of clinical outcomes in TROPION-Lung 01. J. Thorac. Oncol. 19, S2–S3 (2024). Article Google Scholar Download references Author information Authors and Affiliations Division of Hematology-Oncology, Department of Internal Medicine, Hanyang University Seoul Hospital, Hanyang University College of Medicine, Seoul, Korea Myung-Ju Ahn Corresponding author Correspondence to Myung-Ju Ahn. Ethics declarations Competing interests M.-J.A. has received consulting fees from Amgen, Arcus, AstraZeneca, BMS, Daiichi-Sankyo, Eli Lilly, Genexin, Merck, MSD, Novartis, Ono, Pfizer, Roche, Takeda, VORONOI and Yuhan; and honoraria from Amgen, AstraZeneca, BMS, Eli Lilly, Merck, MSD, Ono, Roche, Takeda and Yuhan. Rights and permissions Reprints and permissions About this article Cite this article Ahn, MJ. Does OptiTROP-Lung05 open a new frontier for first-line ADC–ICI combinations in NSCLC?. Nat Rev Clin Oncol (2026). https://doi.org/10.1038/s41571-026-01183-6 Download citation Published 20 July 2026 Version of record 20 July 2026 DOI https://doi.org/10.1038/s41571-026-01183-6 Subjects Lung cancer Targeted therapies Access through your institution Buy or subscribe Sections References References Author information Ethics declarations Rights and permissions About this article Advertisement Nature Reviews Clinical Oncology (Nat Rev Clin Oncol) ISSN 1759-4782 (online) ISSN 1759-4774 (print) nature.com footer links About Nature Portfolio About us Press releases Press office Contact us Discover content Journals A-Z Articles by subject protocols.io Nature Index Publishing policies Nature portfolio policies Open access Author & Researcher services Reprints & permissions Research data Language editing Scientific editing Nature Masterclasses Research Solutions Libraries & institutions Librarian service & tools Librarian portal Open research Recommend to library Advertising & partnerships Advertising Partnerships & Services Media kits Branded content Professional development Nature Awards Nature Careers Nature Conferences Regional websites Nature Africa Nature China Nature India Nature Japan Nature Middle East Privacy Policy Use of cookies Your privacy choices/Manage cookies Legal notice Accessibility statement Terms & Conditions Your US state privacy rights © 2026 Springer Nature Limited
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