What the 2026 European Society for Medical Oncology Congress means for biotech investors.
The 2026 European Society for Medical Oncology (ESMO) Congress in Madrid provided important evidence of progress across oncology drug development:
A number of late-stage programs, led by Moderna’s melanoma vaccine, produced data that could support FDA submissions,
Approved drugs showed benefits in combinations and earlier treatment settings, such as Amgen’s tarlatamab in first-line small cell lung cancer, and
Early studies returned positive results, including a remarkable 75% tumor response rate in a Phase 1 trial of J&J’s prostate cancer drug, acquired with biotech Halda Therapeutics, and Tango’s RAS combination in pancreatic cancer.
“I think 10 years from now, all of first-generation naked chemotherapy will be replaced for all of the major tumor types by something better.”
Rod Wong, RTW Investments Founder and CIO, on The RTW Podcast, Ep. 304
Listen to the full conversation
What are the investment implications?
Several new therapeutic approaches demonstrated they can improve patient outcomes. Markets often react to the primary endpoint; we look for benefit that holds up when a drug is used earlier in treatment or alongside other drugs. The next questions are which drugs can produce durable benefits in larger trials, work in additional cancers and earlier lines of therapy, secure regulatory approval, and achieve commercial adoption.
All four therapeutic approaches highlighted in our ESMO 2026 Preview (individualized cancer vaccines, RAS inhibitors, antibody-drug conjugates [ADCs], and T-cell engagers) produced positive clinical data in difficult-to-treat cancers. Several trials demonstrated improvements in overall survival against active treatments.
The meeting was encouraging overall because the progress extended across different mechanisms and tumor types. It was not uniformly positive, as some high-profile studies missed their efficacy goals. Whether each approach can move from a single-target product to a multi-cancer platform will be answered as trials in other cancers read out.
Did Moderna’s Vaccine Confirm a Product or Validate a Platform?
The data confirmed that Moderna’s individualized cancer vaccine could become a product in post-surgery melanoma. In a trial of more than 1,100 melanoma patients who had surgery to remove their tumors, some received Moderna’s vaccine, intismeran autogene, plus Merck’s Keytruda (pembrolizumab), while others received Keytruda alone1. The two companies reported that patients on the combination were 42% less likely to have their cancer return or to die (hazard ratio [HR]=0.58)*, and 82.2% had no recurrence at two years, against 70.0% on Keytruda alone2. The benefit emerged after the first six months, and it is too early to know whether patients are living longer3. A platform needs the same effect in a second tumor type, and three Phase 3 lung cancer trials are next.4
* How Do You Read a Hazard Ratio?
A hazard ratio compares how quickly events, such as cancer returning or death, occur in two groups. A value of 1.0 means no difference, and below 1.0 favors the new treatment.
In INTerpath-001 it was 0.58: at any point in follow-up, patients on the combination had about 58% of the risk of recurrence or death of patients on Keytruda alone, a 42% reduction.
The 95% confidence interval, 0.45 to 0.75, is the range of true effects consistent with the data. It stays below 1.0, so the result is statistically significant.
Check timing too. The ratio was 0.99 in the first six months and 0.42 afterward, so one number can hide when the benefit starts.
Do RAS Combinations Hold Up After RevMed’s Rasonque?
Early evidence says yes, and the sample is still small. At ESMO, Tango Therapeutics reported that its drug, vopimetostat, plus Revolution Medicines’ daraxonrasib (Rasonque™) produced an 82% response rate (18 of 22 patients), with 88% progression free at nine months.5 6
Revolution Medicines showed that Rasonque’s survival benefit held across RAS mutation subtypes, including G12D (HR=0.49), where its response rate had looked weaker than some other mutant types.
Other RAS programs also reported in Madrid. Incyte’s G12D inhibitor in combination with a cocktail of chemotherapy agents produced response rates of 81% to 89% in pancreatic cancer, and a Phase 3 is under way.7 Roche’s divarasib cut the risk of death by 44% against first-generation KRAS G12C inhibitors in lung cancer (median survival 17.7 vs 12.0 months).8 GenFleet’s pan-RAS inhibitor GFH276 had a 41.1% response rate in 61 evaluable pancreatic cancer patients.9
How Much of the Market Can Antibody-Drug Conjugates Win?
Enough to reshape lung cancer, with strong data from China.
In patients with EGFR-mutant lung cancer whose disease progressed on Tagrisso®, two HER3-directed ADCs beat platinum chemotherapy in Phase 3 trials.
SystImmune and Bristol Myers Squibb’s izalontamab brengitecan nearly doubled median progression-free survival (PFS), 11.1 vs 5.7 months (HR=0.40).
Hengrui’s ruzaltatug rezetecan had PFS of 8.3 vs 5.4 months (HR 0.47).10 Both trials ran in China, and survival data are immature.11 Kelun-Biotech’s sacituzumab tirumotecan, licensed to Merck, reported median survival of 25.9 vs 17.4 months (HR=0.69) in the same setting.12
Data from global studies mainly showed encouraging results with one exception:
In Merck’s TroFuse-005 trial with 776 patients with previously treated endometrial cancer, sacituzumab tirumotecan reduced the risk of death by 32% compared with chemotherapy (HR 0.68), although severe side effects were more frequent.13
Zai Lab’s DLL3 ADC with atezolizumab produced an 81.8% confirmed response rate (27 of 33) in first-line small cell lung cancer.14
ArriVent’s CDH17 ADC produced a 44.8% response rate (13 of 29) in colorectal cancer, though 6 of those 13 responses were unconfirmed.15
AstraZeneca’s sonesitatug vedotin cut the risk of death by 42% versus investigator’s choice of therapy in second-line and later gastric cancer (median survival 10.6 vs 6.4 months), though its progression-free survival endpoint did not reach statistical significance.16
Pfizer’s sigvotatug vedotin did not significantly improve survival over docetaxel in previously treated non-squamous lung cancer (HR=0.93).17
Are T-Cell Engagers and Bispecifics Working in Solid Tumors?
Yes, in several tumors, and durability is the next question.
Amgen’s tarlatamab plus durvalumab as first-line maintenance in small cell lung cancer cut the risk of death by 58% (median survival 21.1 vs 12.7 months, HR 0.42). Cytokine release syndrome, an inflammatory immune reaction, occurred in 49.6% of patients, almost all grade 1 or 2.18
Xencor’s XmAb819 produced confirmed response rates of 30%, 44% and 45.5% (5 of 11) at three doses in kidney cancer, with grade 3 or higher related events in 72.1% of patients.19
Immatics’ IMA402 produced a 25% response rate (10 of 40) and 32% in PRAME-high melanoma.20
Akeso’s ivonescimab, a PD-1 and VEGF bispecific, extended median survival to 14.9 from 12.1 months in biliary tract cancer (HR 0.75) in a China-only trial.21
Promising Early Data for a New Small Molecule
A Phase 1 trial with Johnson & Johnson’s oral small molecule RIPTAC JNJ-6143 produced a 75% response rate (12 of 16 patients with measurable disease) in prostate cancer patients who had a median of four prior therapies, although follow-up was only 5.6 months.22 The 50 mg dose is moving into a Phase 2 study.
What Is RTW’s Take on ESMO 2026?
For investors, the signal is breadth, not the headline endpoint. A few programs with very high expectations, including Moderna’s, did not clear the bar investors had set, and two ADCs missed an endpoint. The programs most likely to become standards of care are the ones whose results survive larger samples and earlier lines of treatment.
What to Watch Next
Merck and Moderna are engaging regulators on intismeran; full INTerpath-001 results are slated for The New England Journal of Medicine on November 11, 2026.23
Three Phase 3 lung cancer trials will test whether intismeran works beyond melanoma.24
Tango plans its Phase 3 start in the first half of 202725 ; Zai Lab plans a global Phase 3 by the end of 2026.26
Xencor plans to discuss an accelerated approval path with the FDA in the first half of 2027 and a registration-enabling study by the end of 2027.27
Erasca, which did not present at ESMO, reported in July that its pan-RAS molecular glue ERAS-0015 produced a 57% response rate (4 of 7 patients, including unconfirmed responses) in second-line or later KRAS G12X pancreatic cancer at the 32 mg dose, and it will update the data in November.28
Statements reflect RTW’s views and opinions as of the date hereof. All expressions of opinion are subject to change without notice and are not intended to be a forecast of future events or results. This material is for informational purposes only and does not constitute investment advice or a recommendation to buy or sell any security. As of the publication date, funds and accounts managed by RTW Investments, LP hold investments in Tango Therapeutics, Erasca, ArriVent Biopharma, Immatics, Xencor, and Keymed Biosciences and Zai Labs, and RTW has a financial interest in their success. These holdings do not represent all RTW investments. Views and holdings may change without notice.
Endnotes
1 Merck and Moderna, "Merck and Moderna Will Present Results From Landmark Phase 3 INTerpath-001 Trial for Intismeran Autogene Plus KEYTRUDA® (pembrolizumab) at ESMO 2026 Presidential Symposium," press release, October 22, 2026. Presentation LBA1.
2 Merck and Moderna, press release, October 22, 2026, cited above. See also David Berman, "IR Insights: Recapping the Phase 3 INTerpath-001 Results," Moderna, October 24, 2026.
3 Merck and Moderna, press release, October 22, 2026, cited above.
4 Merck and Moderna, press release, October 22, 2026, cited above.
5 Tango Therapeutics, "Tango Presents Promising Results from Phase 1/2 Study of Vopimetostat and Daraxonrasib in Pancreatic Cancer and Provides Updates to Development Strategy," press release, October 23, 2026, data cutoff August 20, 2026.
6Tango Therapeutics, press release, October 23, 2026, cited above.
7 Incyte, "Incyte Highlights New Data Advancing its Gastrointestinal Cancer Portfolio at ESMO 2026," press release, October 26, 2026.
8 Roche, "Roche’s divarasib demonstrated best-in-class efficacy, advancing the standard of care in previously treated KRAS G12C-mutated lung cancer," press release, October 25, 2026. See also MD Anderson Cancer Center, "ESMO 2026: New targeted therapy improved survival for patients with KRAS-mutated lung cancer," news release.
9 GenFleet Therapeutics, "Initial Clinical Readout of GFH276 (an Oral Molecular-glue Pan RAS Inhibitor) Presented as Late-breaking Abstract (LBA) at 2026 ESMO Annual Meeting, Demonstrating Promising Clinical Potential and Favorable Safety in Pretreated RAS-mutant Solid Tumors," press release, October 26, 2026.
10 Ayisha Sharma, "EGFR-mutant lung cancer is an ADC battleground, with China leading the charge," Endpoints News, October 26, 2026.
11 Endpoints News, "EGFR-mutant lung cancer is an ADC battleground," cited above.
12 Kelun-Biotech, "Final OS Analysis Results from Phase III OptiTROP-Lung04 Study of Sacituzumab Tirumotecan (sac-TMT) Presented at 2026 ESMO," press release, October 25, 2026, abstract LBA67, data cutoff August 6, 2026.
13 Merck, "Sacituzumab Tirumotecan (Sac-TMT) Reduced the Risk of Death by 32% and the Risk of Disease Progression or Death by 41% Compared to Chemotherapy in Certain Patients With Advanced or Recurrent Endometrial Cancer," press release, October 26, 2026. Presentation LBA11; published simultaneously in The Lancet.
14 Zai Lab, "Zai Lab’s Zocilurtatug Pelitecan (Zoci, Formerly ZL-1310) Demonstrates High Response Rates, Encouraging Durability and Well-Tolerated Safety Profile in First-Line Extensive-Stage Small Cell Lung Cancer," press release, October 23, 2026, September 2026 data cutoff.
15 ArriVent BioPharma, "ArriVent Announces Initial Phase 1 Data for CDH17-targeted ADC ARR-217 in Patients with Gastrointestinal Cancers at ESMO Congress 2026," press release, October 25, 2026, data cutoff August 5, 2026.
16 AstraZeneca, "Sonesitatug vedotin reduced the risk of death by 42% in 2nd- and later-line CLDN18.2-positive advanced gastric/GEJ cancers in CLARITY-Gastric01," press release, October 25, 2026.
17 OncoDaily, "SigVie-002: Sigvotatug Vedotin Misses OS Endpoint Versus Docetaxel in Previously Treated NSCLC," October 25, 2026. See also Reynald Castaneda and Nicole DeFeudis, "#ESMO26: Pfizer looks beyond lung cancer flop as BioNTech, Bristol Myers show early activity," Endpoints News, October 25, 2026.
18 Pérol M, Yoshida T, Ahn MJ, et al. Tarlatamab–durvalumab maintenance for extensive-stage small-cell lung cancer. N Engl J Med. Published online October 24, 2026. doi:10.1056/NEJMoa2609482. Presented at ESMO Congress 2026, abstract LBA3. Secondary source: Amgen, "IMDELLTRA® in Combination With IMFINZI® Reduced Risk of Death by an Unprecedented 58% in First-Line Extensive Stage Small Cell Lung Cancer," press release, October 24, 2026.
19 Xencor, "Xencor Presents Phase 1 Dose Selection Data for XmAb819, a Potential First-in-Class ENPP3 x CD3 Bispecific T-Cell Engager, in Development for Patients With Advanced Clear Cell Renal Cell Carcinoma and ENPP3+ Tumors," press release, October 25, 2026, data cutoff September 1, 2026, presented by Sumanta Pal, M.D.
20 Immatics, "Immatics Presents Clinical Activity of IMA402 PRAME Bispecific and IMA203CD8 PRAME Cell Therapy across Advanced Solid Tumors in Two Oral Presentations at 2026 ESMO Annual Meeting," press release, October 24, 2026, data cutoff June 1, 2026, presentation 1955RO.
21 Akeso, "Positive Overall Survival Results from the Phase III HARMONi-GI1 Trial of Ivonescimab Plus Chemotherapy Versus Durvalumab Plus Chemotherapy in First-Line Biliary Tract Cancer Presented at the ESMO 2026 Presidential Symposium," press release, October 25, 2026. See also Cancer Network Staff, "Ivonescimab Combo Improves Survival in Advanced Biliary Tract Cancer," CancerNetwork, October 25, 2026.
22 Johnson & Johnson, “Johnson & Johnson reports 75% tumor response rate in advanced prostate cancer with JNJ-6143, a first-in-class RIPTAC™ molecule,” press release, October 25, 2026.
23 Merck and Moderna, press release, October 22, 2026, cited above.
24 Merck and Moderna, press release, October 22, 2026, cited above.
25 Tango Therapeutics, press release, October 23, 2026, cited above.
26 Zai Lab, press release, October 23, 2026, cited above.
27 Xencor, press release, October 25, 2026, cited above.
28 Erasca, “Erasca Announces Updated Preliminary Phase 1 Data and Registration-Enabling Plans for Potentially Best-in-Class Pan-RAS Molecular Glue ERAS-0015 in KRAS-Mutant Solid Tumors,” press release, July 13, 2026.
