1316 Initial monotherapy clinical activity of invikafusp alfa, a first-in-class TCR β-chain-targeted bifunctional antibody, in tissue-agnostic, TMB-H patients from STARt-001, a phase 1/2 trial
Notice bibliographique
Résumé
Background Invikafusp alfa (STAR0602), a selective, dual T cell agonist targeting Vβ6/10 TCRs, is being evaluated as monotherapy in the Phase 2 expansion of START-001, a multicenter Phase 1/2 trial in patients with tissue-agnostic TMB-H (≥ 10 mut/Mb) and/or microsatellite instability (MSI)-H solid tumors.Methods Ongoing Phase 2 expansion enrolls patients with TMB-H/MSI-H solid tumors to 3 separate cohorts: tissue-agnostic TMB-H or MSI-H, and colorectal cancer. All patients receive recommended Phase 2 dose of 0.08 mg/kg i.v. invikafusp, Q2W. Here we report the first pooled results ever presented for tissue-agnostic, TMB-H patients from Phase 2 and Phase 1 who received optimal biological dose (range 0.08 to 0.12 mg/kg).Results As of 30 June 2025, 47 patients across 17 different TMB-H solid tumors were enrolled: 33% received ≥ 4 lines of prior therapy; 70% received prior immune checkpoint blockade (ICB) and 30% were ICB-naïve because ICB were either not standard of care or not approved for the condition.Of 47 patients, 33 had ≥ 1 post treatment tumor assessment. Overall, invikafusp showed tissue-agnostic, anti-tumor activity (partial response [PR] and tumor regression) in 10 different TMB-H tumor types (table 1). Specifically, 16 patients (49%) had target lesion reduction with 8 (24%) PR and 19 (58%) stable disease (82% disease control) per RECIST. PR and tumor regression were seen in both ICB-resistant (primary and secondary) and ICB-naive patients, suggesting invikafusp’s tissue-agnostic anti-tumor activity is independent of prior ICB treatment.Invikafusp’s overall safety profile was consistent with its mechanism of action (MoA) of selective, dual T cell activation via both TCR and IL-2 co-stimulation. The most common TEAEs were low-grade, well managed with supportive care.Nanostring on 20 paired blood and tumor specimens showed: 1) unequivocal expansion of Vb6/10 T cells post treatment across all tumor types tested, confirming invikafusp’s MoA of selective expansion of in vivo tumor-infiltrating lymphocytes (TILs); 2) significant upregulation of pathways of cytotoxicity, TCR and chemokine signaling, and costimulatory molecules in TILs post treatment; and 3) downregulation of gene expressions of immune suppression (e.g., PD-1 and FOXP3) in TILs of patients with tumor reduction.Conclusions As a first-in-class, dual T cell agonist, invikasfusp showed clinically meaningful anti-tumor activity in TMB-H patients with potential to overcome ICB resistance, offering them a new class of immune-oncology therapeutics. FDA has granted a Fast Track Designation for invikafusp in TMB-H CRC. Phase 2 expansion is ongoing to further investigate the efficacy of invikafusp.Trial Registration NCT05592626Ethics Approval STARt-001 obtained ethics approval, including the following names of the ethics committee(s) or institutional review board(s), the number/ID of the approval(s). In addition,participants gave informed consent before taking part. The list of the names of the ethics committee(s) or institutional review board(s): Comite de Protection des Personnes Sud-Est III (CT # 2023-505334-10-01) CEIm HM Hospitales (CT # 2023-505334-10-01) Dana Farber Cancer Institute IRB (22-577) Comite de Protection des Personnes Sud-Est III (CT # 2023-505334-10-01) Institutional Review Board/Privacy Board/Memorial Sloan Kettering Cancer Center (23-239) CEIm HM Hospitales (CT # 2023-505334-10-01) WCG IRB (Inst Tracking #: NCT05592626) University of Miami Human Subject Research Office (HSRO) (IBIS# 20231136) NIH Office of IRB Operations (23-5345) AdventHealth Orlando IRB (2052490-3) WCG IRB (Inst Tracking #: STUDY00019146) WCG IRB (Inst. Tracking #: 24-11-7340)Abstract 1316 Table 1Invikafusp showed tissue-agnostic anti-tumor activity (partial responses and tumor regression) in 10 different tumor types with high tumor mutational burden (TMB-H*)*TMB-H defined as ≥ 10 mut/Mb per local testing #n = number of patients
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».