INTerpath-009 establishes a phase 3 NSCLC program testing pembrolizumab with or without intismeran autogene (V940), with platinum-doublet chemotherapy listed in the protocol. No efficacy readout is supplied.
NCT06623422
Immunopeptidomics-guided selection is the strongest translational enablement signal. In 24 NSCLC tumors, donor-specific HLA presentation filtering generated functional responses in 5/6 tested patients and strong responses to 9/70 putative neoantigens.
PMID:42270771
Antigen presentation competence is a gating variable. NSCLC ICI resistance is associated with MHC-I, TAP2, B2M, IFN/JAK-STAT defects, neoantigen loss, and immune-excluded states; vaccine-induced T cells will not overcome absent presentation alone.
PMID:42495623
Neoantigen mRNA vaccine reviews identify manufacturing timeline, HLA diversity, tumor heterogeneity, and immune editing as implementation constraints; these are not resolved by the current clinical registry record.
PMID:41984335
```json
{
"leads": [
{
"id": "v940-nsclc-phase3",
"title": "Intismeran autogene (V940) in phase 3 NSCLC",
"claim": "INTerpath-009 is a recruiting phase 3 NSCLC study of pembrolizumab with or without intismeran autogene (V940); the listed protocol includes platinum-doublet chemotherapy options and has primary completion projected for 2033.",
"citations": [
"
NCT06623422"
],
"status": "opened"
},
{
"id": "immunopeptidomics-neoantigen-selection-nsclc",
"title": "Immunopeptidomics-guided neoantigen selection",
"claim": "In 24 NSCLC tumors, HLA-presentation-informed neoantigen selection produced functional responses in 5 of 6 tested patients; 9 of 70 putative neoantigens elicited strong responses.",
"citations": [
"
PMID:42270771"
],
"status": "opened"
},
{
"id": "antigen-presentation-gating-nsclc-vaccines",
"title": "Antigen-presentation competence as a vaccine-response gate",
"claim": "NSCLC immune resistance includes MHC-I, TAP2, B2M, and IFN/JAK-STAT defects, neoantigen loss, and immune-excluded states; these mechanisms constrain neoantigen-vaccine activity.",
"citations": [
"
PMID:42495623"
],
"status": "opened"
},
{
"id": "mrna-neoantigen-vaccine-operational-barriers",
"title": "Operational constraints on personalized neoantigen mRNA vaccination",
"claim": "Personalized neoantigen mRNA vaccine implementation is constrained by manufacturing timelines, HLA diversity, tumor heterogeneity, and immune editing.",
"citations": [
"
PMID:41984335"
],
"status": "opened"
}
],
"candidates": [],
"dossiers": [],
"retired": [],
"ledger_moves": [
{
"action": "open",
"target": "v940-nsclc-phase3",
"note": "Phase 3 NSCLC registry program identified; no outcome data supplied.",
"citations": [
"
NCT06623422"
]
},
{
"action": "open",
"target": "immunopeptidomics-neoantigen-selection-nsclc",
"note": "Patient-level functional neoantigen-selection evidence supports pipeline prioritization.",
"citations": [
"
PMID:42270771"
]
},
{
"action": "open",
"target": "antigen-presentation-gating-nsclc-vaccines",
"note": "Resistance biology defines a selection and combination constraint.",
"citations": [
"
PMID:42495623"
]
},
{
"action": "open",
"target": "mrna-neoantigen-vaccine-operational-barriers",
"note": "Review identifies translational constraints relevant to personalized mRNA deployment.",
"citations": [
"
PMID:41984335"
]
}
],
"next_queries": [
"\"intismeran autogene\" OR V940 AND non-small cell lung cancer",
"\"personalized mRNA neoantigen vaccine\" AND NSCLC AND clinical trial",
"NSCLC neoantigen vaccine immunopeptidomics HLA presentation"
],
"summary_line": "Phase 3 V940 NSCLC development is active; immunopeptidomics improves neoantigen selection, while presentation defects remain a hard gate."
}
```