Merck-Moderna melanoma vaccine cuts recurrence risk 42% at ESMO 2026

A personalized mRNA cancer vaccine from Merck and Moderna reduced the risk of melanoma recurrence by 42% when combined with the immunotherapy Keytruda, compared with Keytruda alone. The phase 3 result, presented to a packed auditorium at the European Society for Medical Oncology (ESMO) congress in Madrid — a conference that closed on October 27 after roughly 164 presentations, more than 6,300 submitted abstracts and over 37,000 attendees — anchors a meeting heavy with late-stage oncology data.

The vaccine, Intismeran, is built from a patient's own tumor sample. Sequencing identifies the specific mutations in that cancer, and a synthetic mRNA coding for up to 34 neoantigens (new proteins produced by tumor mutations) is administered so the body translates those sequences and presents them to the immune system, generating targeted T-cell responses against cancer cells.

What did AbbVie show in lung cancer?

AbbVie reported phase 1 data for its antibody-drug conjugate (ADC, an antibody linked to a cell-killing payload) Temab-A in solid tumors. Combined with the antibody bevacizumab, it produced a 30% overall response rate (ORR, the share of patients whose tumors shrank) after a median follow-up of 18.2 months. In non-small cell lung cancer (NSCLC) with epidermal growth factor receptor mutations, ORR reached 50% with median overall survival of 13.8 months in unselected patients. The FDA granted Temab-A two breakthrough therapy designations this month.

A second AbbVie candidate, ABBV-706, achieved a 56% ORR and 12.4-month median overall survival in second-line-plus small-cell lung cancer; in the second-line-only cohort, ORR rose to 82% with median overall survival of 14.4 months.

Hutchmed, a Hong Kong-based drug discovery company, presented phase 3 data for Orpathys, an FDA-approved small molecule, combined with AstraZeneca's Tagrisso — both tyrosine kinase inhibitors blocking abnormal MET receptor pathway activation. In patients whose cancer progressed after Tagrisso, the combination cut the risk of disease progression or death by 45% and the risk of death by 32%, extending median overall survival from 12.9 to 17.8 months. In a separate first-line trial with high MET overexpression, the risk of progression or death fell by 44% and 55%. Hutchmed argues the data support an all-oral, biomarker-driven frontline standard of care.

Accord Healthcare's monoclonal antibody serplulimab also featured, though in a descriptive bridging study rather than a superiority trial. Despite a higher proportion of liver metastases in the serplulimab group, one-year overall survival rates were 52.4% versus 41.4% for atezolizumab, and two-year rates were 32.2% versus 17.6%.

Taiho's small molecule zipalertinib, a tyrosine kinase inhibitor, produced a 30% ORR in 43 NSCLC patients with EGFR mutations and cancer spread to the central nervous system. Intracranial disease control reached 72%, with a median intracranial duration of response of 9.7 months.

"Patients with NSCLC harboring EGFR exon 20 insertion mutations or other uncommon EGFR mutations and active CNS metastases have a significant need for therapies that can effectively address disease in the brain," said Helena Yu, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center and study investigator. "The intracranial responses observed with zipalertinib in REZILIENT2 are encouraging and support continued evaluation."

Which early-stage assets stood out?

Montreal-based Kainova Therapeutics presented DT-7012, a monoclonal antibody that depletes regulatory T cells (Tregs, immune cells that suppress anticancer responses) by binding CCR8, a G protein-coupled receptor on their surface. "It's like we tag these T regulatory cells and then the immune system can better remove or deplete those T regulatory cells from the tumor microenvironment," said CEO Sean MacDonald. The antibody both blocks receptor internalization and carries a modified FC region triggering two clearance mechanisms: antibody-dependent cellular cytotoxicity and phagocytosis.

In an ongoing phase 1/2 trial, as monotherapy and combined with Keytruda, the drug showed a consistent safety profile with mild, manageable adverse events that "reversed swiftly," according to CMO Jean-Marie Cuillerot. One uveal melanoma patient whose cancer progressed on Keytruda developed a partial response and has remained in the trial over seven months; a pancreatic cancer patient with no prior Keytruda response also achieved a partial response. "The data set is still small. We are working on increasing the data set, but we have demonstrated that the drug can be active in settings where anti-PD-1s are inactive," Cuillerot said.

London-based Avacta Therapeutics presented phase 1 data for faridoxorubicin, a peptide-drug conjugate and prodrug linking doxorubicin to a peptide that keeps the chemotherapy silent until it reaches fibroblast activation protein in the tumor microenvironment. In salivary gland cancer — 6% to 8% of head and neck cancers — severe neutropenia occurred in 16.7% of patients versus 49% on standard doxorubicin, and median progression-free survival nearly doubled to 11.4 months against traditional benchmarks of six to 6.7 months. "We've shown a dramatic reduction in the hematologic toxicities," said CEO Christina Coughlin. Cohorts in soft tissue sarcoma and triple-negative breast cancer follow.

Oslo-based Oncoinvent previewed its phase 1/2 trial of Radspherin in HR-proficient ovarian cancer, where intact DNA repair makes PARP inhibitors and chemotherapy less effective. The therapy delivers billions of radium-224-containing calcium carbonate microparticles into the peritoneum. Safety data arrive in December, with efficacy data at the nine-month follow-up due in the first quarter of 2027.

Genmab, defending its $8 billion acquisition of Merus, reported that the phase 3 trial of its ovarian cancer ADC Rina-S hit its primary endpoint: a 71% reduction in the risk of disease progression or death in platinum-resistant ovarian cancer versus chemotherapy, with overall survival hazard ratios of 0.43 overall and 0.44 in the high folate receptor alpha group. Merus-derived bispecific antibody petosemtamab induced an 82% ORR in 17 first-line colorectal cancer patients and 70% in second-line.

Agenus reported phase 2 colon cancer data for botensilimab: in 18 patients, 72% achieved a pathologic complete response, 83% a major pathologic response, 94% a pathologic response at surgery, all patients were alive at a median 15-month follow-up, and 89% had no recurrence. One patient with colon and rectal tumors had a complete rectal response and preserved the rectum, with no regrowth at seven months. In prostate cancer, Syncromune's SV-102, combining a CD40 agonist and a TLR9 agonist, kept roughly 80% of participants alive after two years, building on a previously reported 87% ORR.

With pivotal vaccine data, multiple ADC readouts and a pending December safety readout from Oncoinvent, the Madrid congress sets a crowded near-term agenda for oncology portfolio decisions.