ESMO 2026 Lung Cancer: 10 Abstracts to Watch

The thoracic oncology programme at ESMO Congress 2026 brings together several late-breaking studies that address some of the most important unresolved questions in lung cancer: how to improve maintenance therapy in extensive-stage small-cell lung cancer, whether antibody-drug conjugates can displace chemotherapy in metastatic NSCLC, how best to manage MET-mediated resistance to osimertinib, and whether newer targeted therapies can improve outcomes after established KRAS G12C and EGFR-directed treatment.

The selection below is based on the official ESMO 2026 final programme. Where only the presentation title and study design are publicly available, no efficacy result is inferred before official presentation.

DeLLphi-305: Bringing Tarlatamab Into First-Line Maintenance for ES-SCLC

LBA3 — DeLLphi-305 will report the primary phase III analysis of tarlatamab plus durvalumab versus durvalumab alone as first-line maintenance therapy following induction durvalumab, platinum, and etoposide in extensive-stage small-cell lung cancer. Jacob Sands is listed as first author (Sands et al., 2026). 

The study addresses a logical next step in SCLC treatment development. Immunotherapy plus platinum–etoposide has established maintenance PD-L1 inhibition as part of first-line treatment, but most patients eventually progress. Tarlatamab introduces a fundamentally different immune strategy through DLL3-directed T-cell engagement.

DeLLphi-305 therefore asks whether adding this mechanism before overt relapse, while disease remains controlled after induction, can extend benefit beyond checkpoint inhibition alone. If positive, the implications could extend beyond one drug. The study would support moving T-cell–redirecting therapy earlier in SCLC rather than reserving it entirely for recurrent disease.

OptiTROP-Lung06: Can a TROP2 ADC Replace Chemotherapy in PD-L1-Negative First-Line NSCLC?

LBA66 – OptiTROP-Lung06 is a randomized phase III comparison of sacituzumab tirumotecan plus pembrolizumab versus chemotherapy plus pembrolizumab as first-line treatment for PD-L1-negative advanced nonsquamous NSCLC. Caicun Zhou is listed as first author (Zhou et al., 2026).

This is one of the most conceptually important ADC studies in the programme. Rather than introducing an ADC after multiple prior therapies, OptiTROP-Lung06 tests whether sac-TMT can replace the chemotherapy component of first-line chemoimmunotherapy in a population in which pembrolizumab monotherapy would generally not be sufficient.

The relevant question is therefore not simply whether sac-TMT has activity. It is whether an ADC-based cytotoxic strategy can provide a more effective therapeutic partner for immunotherapy than conventional platinum-based chemotherapy. The trial sits at the intersection of two rapidly expanding treatment classes-checkpoint inhibitors and ADCs, and could help determine whether ADCs begin moving systematically into the first-line NSCLC setting.

OptiTROP-Lung04: Final Overall Survival After EGFR-TKI Progression

LBA67 – OptiTROP-Lung04 will report the final overall survival analysis of sacituzumab tirumotecan versus platinum-based chemotherapy in EGFR-mutated NSCLC after progression on an EGFR tyrosine kinase inhibitor. Li Zhang is listed as first author (Zhang et al., 2026). final_programme_esmo2026

This setting remains particularly important because progression after targeted EGFR therapy is biologically heterogeneous. Some tumors develop actionable resistance mechanisms, but many patients ultimately require broader systemic treatment. Platinum-pemetrexed has historically served as a major benchmark after EGFR-directed therapy, creating a high bar for ADC development.

A final OS analysis is therefore especially meaningful. As more post-EGFR options emerge, progression-free survival alone becomes insufficient to define the optimal sequence. The long-term question is whether introducing an ADC at this point in the disease course improves survival relative to conventional chemotherapy.

Sigvotatug Vedotin: A New ADC Versus Docetaxel

LBA68 will present a phase III comparison of sigvotatug vedotin versus docetaxel in previously treated nonsquamous NSCLC, with Solange Peters listed as first author (Peters et al., 2026). Docetaxel remains a familiar comparator in later-line NSCLC trials, but the number of ADCs challenging that standard continues to increase.

The importance of this study will depend not only on efficacy but on the balance between disease control and toxicity. ADCs are often described as targeted delivery systems, yet payload-related adverse events remain central to their therapeutic index. If sigvotatug vedotin demonstrates a meaningful advantage, it would further support the transition of later-line nonsquamous NSCLC away from conventional single-agent chemotherapy toward biomarker-informed or antigen-directed treatments.

KRASCENDO 1: Divarasib Goes Head-to-Head With Established KRAS G12C Inhibitors

LBA5 – KRASCENDO 1 may provide one of the clearest direct tests yet within the KRAS G12C inhibitor class. The study compares divarasib with sotorasib or adagrasib in previously treated locally advanced or metastatic KRAS G12C-mutated NSCLC. Ferdinandos Skoulidis is listed as first author (Skoulidis et al., 2026).

This design is particularly important because the comparator is not chemotherapy, it is another targeted therapy directed against the same oncogenic alteration.

As targeted treatment classes mature, therapeutic development increasingly moves from demonstrating that a target is druggable toward determining which drug within the class offers the strongest combination of efficacy, durability, CNS activity, safety, and convenience. KRASCENDO 1 therefore has the potential to influence how clinicians differentiate among KRAS G12C inhibitors rather than simply whether they use one.

SAFFRON: Targeting MET-Mediated Resistance After Osimertinib

LBA6 – SAFFRON will report phase III primary results comparing osimertinib plus savolitinib with platinum-pemetrexed in EGFR-mutated advanced NSCLC with MET overexpression and/or amplification after progression on osimertinib. Shun Lu is listed as first author (Lu et al., 2026). This trial represents a precision-resistance strategy.

MET activation is one of the best-characterized bypass mechanisms of resistance to EGFR inhibition. Rather than abandoning EGFR targeting after osimertinib progression, SAFFRON tests whether continued EGFR blockade combined with MET inhibition can outperform a transition to conventional platinum chemotherapy.

The study therefore asks a broader precision-oncology question: when resistance is molecularly defined, should treatment continue to target the original driver while simultaneously suppressing the acquired resistance pathway? A positive result would strengthen the case for obtaining molecular information again at progression rather than treating post-osimertinib disease as a single homogeneous category.

SANOVO: Can MET Resistance Be Targeted Before It Emerges?

LBA69 – SANOVO moves the EGFR/MET strategy even earlier.

The phase III study evaluates savolitinib or placebo combined with osimertinib in treatment-naïve advanced EGFR-mutated NSCLC with MET overexpression, with Yi-Long Wu listed as first author (Wu et al., 2026).

Conceptually, SANOVO and SAFFRON examine two ends of the same biological question. SAFFRON targets MET after resistance has emerged. SANOVO asks whether sufficiently high baseline MET expression identifies a population in which dual EGFR/MET inhibition should be used from the beginning.

This distinction matters. Precision oncology has traditionally reacted to resistance after it appears. SANOVO represents a more anticipatory model in which baseline tumor biology may justify suppressing a likely resistance pathway before clinical progression.

PANKU-Lung01: Bispecific ADC Therapy After Third-Generation EGFR TKI

LBA71 – PANKU-Lung01 is a randomized phase III study of izalontamab brengitecan in EGFR-mutant nonsquamous NSCLC after progression on a third-generation EGFR TKI. Li Zhang is listed as first author (Zhang et al., 2026).

Izalontamab brengitecan is particularly interesting because its development reflects another evolution within the ADC field: the use of bispecific targeting rather than a single surface antigen. Post-EGFR progression is increasingly becoming one of the most competitive areas of lung cancer drug development, with chemotherapy, bispecific antibodies, targeted combinations, and multiple ADC platforms competing for therapeutic position.

PANKU-Lung01 will therefore contribute to a larger question: can a broadly active ADC overcome the biological heterogeneity that develops after prolonged EGFR-directed therapy?

HERON-Lung01: HER3-Directed ADC Therapy After EGFR-TKI Progression

Immediately following PANKU-Lung01, LBA72 – HERON-Lung01 will present interim phase III analyses of ruzaltatug rezetecan, a HER3-directed ADC, versus platinum-based chemotherapy in EGFR-mutated advanced NSCLC after progression on EGFR-TKI therapy. Yi-Long Wu is listed as first author (Wu et al., 2026).

HER3 has become an attractive ADC target in EGFR-mutated NSCLC because it can remain expressed across heterogeneous resistance states even when the mechanism driving progression is no longer directly targetable with another kinase inhibitor. The comparison against platinum chemotherapy makes the clinical question particularly relevant.

If a HER3-directed ADC can outperform chemotherapy after EGFR-TKI progression, it would support a treatment strategy based less on identifying a single resistance mutation and more on exploiting a surface target retained across multiple resistant clones. The close positioning of SAFFRON, PANKU-Lung01, OptiTROP-Lung04, and HERON-Lung01 within the ESMO programme illustrates just how quickly the post-osimertinib landscape is evolving.

Neotorch: Final Analysis of Perioperative Toripalimab

LBA64 – Neotorch will report the final analysis of phase III perioperative toripalimab plus chemotherapy for resectable stage II or III NSCLC, with Shun Lu listed as first author (Lu et al., 2026). Perioperative immunotherapy is now one of the defining developments in early-stage NSCLC.

The field has moved beyond asking whether checkpoint inhibition can improve pathological response before surgery. Increasingly, the critical questions concern durability, event-free survival, overall survival, and the relative contribution of therapy given before versus after resection.

The final Neotorch analysis should therefore be viewed in the context of a broader shift toward systemic treatment spanning the entire perioperative course. As multiple perioperative immunotherapy regimens become available, mature follow-up will be essential for distinguishing them and for determining which patients require both neoadjuvant and adjuvant treatment.

The ESMO 2026 Lung Programme Is Really About Treatment Sequence

Although these ten studies involve different drugs and disease settings, they converge on one central theme: lung cancer treatment is becoming increasingly sequence-dependent. In SCLC, DeLLphi-305 asks whether a therapy already active later in disease should move into first-line maintenance.

In driver-negative nonsquamous NSCLC, OptiTROP-Lung06 and the sigvotatug vedotin trial test whether ADCs can begin replacing conventional chemotherapy. For KRAS G12C disease, KRASCENDO 1 moves beyond target validation toward direct competition within a targeted-drug class.

And in EGFR-mutated NSCLC, the programme contains an unusually dense concentration of studies addressing the same post-osimertinib problem from different directions: MET-directed combination therapy, TROP2 ADCs, bispecific ADCs, HER3 ADCs, and earlier interception of MET biology. That is likely to make the EGFR-mutated sessions among the most consequential parts of the meeting.

The Bottom Line

The ESMO 2026 lung cancer programme reflects a field transitioning from broad therapeutic categories toward increasingly specific treatment architecture. DeLLphi-305 tests DLL3-directed T-cell engagement in first-line SCLC maintenance.

OptiTROP-Lung06 challenges chemotherapy with a first-line ADC–immunotherapy strategy in PD-L1-negative nonsquamous NSCLC. OptiTROP-Lung04 reaches final OS after EGFR-TKI progression.

Sigvotatug vedotin directly challenges docetaxel. KRASCENDO 1 compares one KRAS G12C inhibitor directly with established agents in the class. SAFFRON and SANOVO test MET-directed strategies after and before resistance to osimertinib.

PANKU-Lung01 and HERON-Lung01 bring two different ADC approaches into post-EGFR disease. And Neotorch provides mature perioperative immunotherapy data in resectable NSCLC.

The common question is no longer simply whether these agents are active. It is where they belong in increasingly crowded treatment pathways, and which biological features should determine when they are used. The numerical answers will come with the presentations. Until then, the official ESMO programme defines the questions, not the outcomes.

References

1. Sands, J., et al. (2026). Tarlatamab plus durvalumab versus durvalumab as first-line maintenance therapy following durvalumab, platinum, and etoposide in extensive-stage small-cell lung cancer: Primary analysis of the phase III DeLLphi-305 trial [Late-breaking abstract LBA3]. ESMO Congress 2026.
2. Zhou, C., et al. (2026). Sacituzumab tirumotecan plus pembrolizumab versus chemotherapy plus pembrolizumab as first-line treatment for PD-L1-negative advanced nonsquamous NSCLC: OptiTROP-Lung06 [Late-breaking abstract LBA66]. ESMO Congress 2026.
3. Zhang, L., et al. (2026). Final overall survival analysis of sacituzumab tirumotecan versus platinum-based chemotherapy in EGFR-mutated NSCLC after progression on EGFR-TKI: OptiTROP-Lung04 [Late-breaking abstract LBA67]. ESMO Congress 2026.
4. Peters, S., et al. (2026). Phase III study of sigvotatug vedotin versus docetaxel in previously treated nonsquamous NSCLC [Late-breaking abstract LBA68]. ESMO Congress 2026.
5. Skoulidis, F., et al. (2026). KRASCENDO 1: Divarasib versus sotorasib or adagrasib in previously treated KRAS G12C-mutated NSCLC [Late-breaking abstract LBA5]. ESMO Congress 2026.
6. Lu, S., et al. (2026). Osimertinib plus savolitinib versus platinum–pemetrexed in EGFR-mutated, MET-overexpressed and/or amplified advanced NSCLC after osimertinib: SAFFRON phase III primary results [Late-breaking abstract LBA6]. ESMO Congress 2026.
7. Wu, Y.-L., et al. (2026). Savolitinib or placebo combined with osimertinib in treatment-naïve advanced NSCLC with EGFR mutation and MET overexpression: SANOVO [Late-breaking abstract LBA69]. ESMO Congress 2026.
8. Zhang, L., et al. (2026). PANKU-Lung01: Izalontamab brengitecan in EGFR-mutant nonsquamous NSCLC after progression on a third-generation EGFR TKI [Late-breaking abstract LBA71]. ESMO Congress 2026.
9. Wu, Y.-L., et al. (2026). Ruzaltatug rezetecan versus platinum-based chemotherapy in EGFR-mutated advanced NSCLC progressing after EGFR-TKI: HERON-Lung01 [Late-breaking abstract LBA72]. ESMO Congress 2026.
10. Lu, S., et al. (2026). Toripalimab plus chemotherapy as perioperative treatment for resectable stage II or III NSCLC: Final analysis of the phase III Neotorch study [Late-breaking abstract LBA64]. ESMO Congress 2026.