Personalized neoantigen vaccine combined with precision critical lesion radiotherapy (CLERT) in advanced solid tumors: Updated results from the iNATURE phase II trial

iNATURE

Paciente / Población Intervención / Exposición Comparación Desenlace

In patients with metastatic solid tumours progressing after at least one line of treatment, a personalised neoantigen peptide vaccine plus critical-lesion radiotherapy improved progression-free survival compared with placebo plus critical-lesion radiotherapy.

N

35pacientes

Diseño

Randomised 1:1, placebo-controlled phase II trial (GCOG0028; NCT06314087) stratified by tumour type in patients with metastatic solid tumours progressing after at least one line of treatment, comparing a personalised neoantigen peptide vaccine (BXP-001) with placebo, with all patients receiving critical-lesion immuno-preserving radiotherapy (CLERT).

Desenlace

Progression-free survival.

ResultadoMedian PFS 10.3 months (95% CI 6.2-not reached) with the neoantigen vaccine vs 3.1 months (95% CI 2.0-6.4) with placebo (P = 0.0045), HR 0.29 (95% CI 0.12-0.71; P = 0.007), with no significant difference across cancer types (P = 0.651). The vaccine induced neoantigen-specific T-cell responses in 83.3% of evaluable patients and antibody responses in 100%. In the vaccine arm, 2/16 patients had more than 30% shrinkage of liver or mediastinal metastases. No grade ≥3 vaccine-related adverse events occurred in either arm, and quality of life did not change significantly in either arm.

Kong FP, Zhang Y, Hu Y, et al. Presented at ESMO Congress 2026, abstract LBA52, 24 October. Not yet published.

Discusión y crítica

This small randomised trial shows a large progression-free survival benefit when a personalised neoantigen vaccine was added to critical-lesion radiotherapy in heavily pretreated patients, with no grade 3 or higher vaccine-related toxicity. Only 35 of 114 screened patients were randomised and three quarters had lung cancer, so the confidence intervals are wide and the claim of no difference by tumour type has little power. The abstract does not report follow-up duration, overall survival, objective response rates across both arms or whether patients and investigators were blinded. Because every patient received radiotherapy, the trial tests the vaccine as an add-on and cannot show what the radiotherapy contributes.