ESMO 2026 Insight | Part 1

Introducing our Four-part Series

This October, Lumanity’s oncology experts joined the crowds in Madrid for Europe’s largest cancer conference. ESMO has also become a go-to venue for the first look at data out of China. Roughly one-third of the studies presented were China-based, which makes the congress an important “first read” for many new modalities. Across tumor types, we heard the central question shift from “does it work?” to “where does it belong, for whom, and can patients get it?” Potent new agents are moving into earlier lines of therapy. That makes patient selection, sequencing, evidence quality, pricing and access as important as efficacy. It also raises a further question: will early data from China-based trials hold up in global populations and different health systems?

Our experts joined the attendees to hear the data and the conversations around it. In this series, we share what we heard in the sessions and in the corridors, and what to expect over the next 12–18 months.

What’s coming next:

• Part 2 / Wednesday: Raising the bar, raising the stakes. Next-generation therapies in lung, pancreatic and ovarian cancer, and the pressure to show a clear difference from competitors.
• Part 3 / Thursday: Refining and redefining standard of care. Bladder cancer, glioblastoma, lymphoma and myeloma, and how to find the right treatment intensity for each patient.
• Part 4 / Friday: Looking forward to new paradigms. New immunotherapy modalities, radiopharmaceuticals and delivery, and new models of evidence generation

The Breakthroughs Continue in Pancreatic and Gastric Cancers: What ESMO 2026 Means for Their Future

Jakub Kaczor, MSc, PhD, Vice President, Strategy Consulting

Across ESMO’s pancreatic and gastro-esophageal sessions, the debate has moved past whether new agents work. The question now is whether their evidence will hold up with guideline committees, HTA bodies and payers.

Pancreatic cancer: from “does it work” to “who gets it, and at what price“

Eligibility is up for debate. Additional analyses of daraxonrasib, the first approved pan-RAS inhibitor, reopened the question of who should receive it. Progression assessments differed between central review and investigators, and censoring was uneven between arms in an open-label trial. Together, these suggest the signal behind limiting European guideline recommendations to RAS G12-mutant disease may be an artefact. Overall survival benefit held across subgroups. Daraxonrasib significantly improved OS vs SOC chemo in patients with previously treated mPDAC overall (with or without an identified tumor RAS mut; mOS 13.2 vs 6.7 mo; HR, 0.40) and in patients with RAS G12 mut mPDAC (OS HR, 0.40; PFS HR, 0.45).

Narrow labels and guideline restrictions are now a commercial risk as well as a clinical one. Sponsors should ask early whether the data support a broad population. They should also be ready to challenge restrictive recommendations with the evidence-quality argument rather than accept them.

The next wave will add biomarkers. Early combination work pairs the PRMT5 inhibitor vopimetostat with daraxonrasib or the G12D-specific zoldonrasib in MTAP-deleted, RAS-mutant disease. Results are early, from a small, single-arm, sponsor-funded dose-escalation study. The commercial implications are worth noting:

• Narrower populations. A second biomarker, MTAP deletion, sits on top of RAS status. That means an extra testing step and a smaller addressable population.
• Harder evidence design. Choosing comparators and endpoints is difficult when the backbone drug, daraxonrasib, is itself still being assessed.
• Higher access stakes. Combinations built on premium-priced backbones will face affordability scrutiny from the outset.

Price will shape access. With a US list price of around $477,000 a year, daraxonrasib is already a test case for turning breakthrough value into broad access. EU reimbursement is decided country by country, and the Joint Clinical Assessment is ahead. Pricing strategy will therefore decide how many patients actually benefit.

Gastric and GEJ cancers: Different modality, same dilemma

The same pattern appears in gastric and gastro-esophageal junction (GEJ) cancer, with two claudin 18.2 (CLDN18.2)-directed antibody–drug conjugates (ADCs):

• Arcotatug tavatecan is a novel CLDN18.2-targetedADC that showed overall survival improvement over chemo (with 34.8% of events, median OS was 9.9 months vs 7.4 months). However, it raised questions about an Asia-only population, pending quality-of-life data, and CLDN18.2 expression falling below eligibility thresholds after prior claudin-targeted therapy.
• Sonesitatug vedotin results from a global phase 3 eases the transferability concern. It showed an overall survival benefit across CLDN18.2 expression subgroups vs investigator’s choice of therapy in both 3L+ (median 10.0 vs 5.0 mo, HR 0.47) and in 2L+ (median 10.6 vs 6.4 mo, HR 0.58). Progression-free survival in the intent-to-treat population did not meet the threshold for statistical significance.

Endpoints, comparators and sequencing will each shape how these claudin-directed agents are judged. A strong survival result alongside a missed co-primary progression endpoint gives HTA bodies room to challenge the evidence. The control arm is a mix of standard options, so payers may also probe how much of the gain reflects a weak comparator. As more claudin-directed agents arrive, biomarker re-testing between lines becomes a planning issue rather than an afterthought.

As transformative mechanisms reach some of oncology’s hardest-to-treat tumours, efficacy alone will no longer decide uptake. Established players and newcomers alike will need to:

• Stress-test endpoint choices
• Plan bridging data beyond the regions where pivotal trials ran
• Build biomarker re-testing into sequencing strategies
• Set pricing strategy early

Takeaways

The new questions in GI oncology aren’t about whether the drugs work. They’re about whether the evidence holds up, whether the biomarker still applies, whether the data travel beyond the trial’s region, and whether the price lets patients get the drug. Developers who plan for all four from phase 2 will set the terms; the rest will spend launch defending them. accuracy, share of voice, and sentiment in AI generated outputs are all within reach.

For years, progress in head and neck cancer has been slow, particularly once disease returns or spreads. At ESMO 2026, presentations spanning immunotherapy, antibody-drug conjugates (ADCs), surgery and quality of life pointed to a welcome change. But more options will bring a new challenge: deciding which treatment belongs where.

Earlier treatment brings different questions

In locally advanced HNSCC, where cure is often the aim, the debate is as much about how much treatment patients need. Following KEYNOTE-689, research including OPTIMAL and circulating tumour DNA analyses from KEYNOTE-412 is exploring treatment intensity and ways to identify patients at greater risk.

In selected early-stage disease, the phase 3 ‘Best-of’ trial found similar mean swallowing scores after surgery and radiotherapy at 12 months (83 versus 86), while the phase 2 QoLATI study also highlighted quality of life and patient preferences.

For companies, the lesson is not always to add treatment, but to prove when its benefit is worth the burden.

A more crowded first-line R/M market

For recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab-based regimens remain central to first-line treatment. Several studies offered a glimpse of a more competitive future.

In the phase 2 study HexAgon-HN, ordastobart plus pembrolizumab achieved a 48.3% response rate versus 26.5% with pembrolizumab alone in patients with high PD-L1 expression (CPS ≥20).

In a separate Chinese phase 2 study, the ADC iza-bren plus pembrolizumab produced a 47.4% confirmed response rate at the selected dose in 38 first-line patients.

Meanwhile, OrigAMI-4 investigated amivantamab, an EGFR/MET-targeting bispecific antibody, alongside pembrolizumab and up to six cycles of chemotherapy. Among 22 evaluable patients excluding HPV-associated oropharyngeal cancer, 77% achieved a confirmed response.

Importantly across all these studies a promising response rate may get a drug noticed, but it will not, on its own, secure a place in treatment. Developers need to show which patients benefit most and what their regimen offers beyond existing options.

Previously treated patients added another dimension

In heavily pretreated recurrent or metastatic nasopharyngeal cancer, phase 3 TAISHAN-301 reported a 50.8% confirmed response rate with the B7-H3-targeting ADC tambotatug pelitecan versus 25.8% with chemotherapy.

With survival data immature, the findings raise questions about treatment sequencing and how these therapies will fit into different regional treatment pathways.

Takeaways

ESMO 2026 offered welcome momentum in head and neck cancers, a space which has had limited innovation for a decade, but greater choice will bring tougher decisions for clinicians, patients and payers. The real risk is developing against today’s standard of care when the clinical landscape may look very different at launch. Companies need to anticipate future competitors; define the patients they can genuinely help and generate evidence that changes clinical decisions.