Amivantamab with or without chemotherapy in right-sided metastatic colorectal cancer: Updated results from OrigAMI-1, an open-label, phase 1b/2 study.
Notice bibliographique
Résumé
197 Background: Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity and is FDA approved in EGFR -mutated advanced non-small cell lung cancer. High MET expression is observed in ~68% of patients (pts) with metastatic colorectal cancer (mCRC). Additionally, MET amplification occurs in up to 23% of EGFR-resistant mCRC and is implicated in driving resistance to EGFR-targeting antibodies (EGFRi). Compared to left (L)-sided disease, right (R)-sided disease is less responsive to EGFRi and associated with poorer outcomes. We present longer follow-up data among pts with R-sided mCRC. Methods: OrigAMI-1 (NCT05379595) is assessing ami as monotherapy and combined with chemotherapy in mCRC. All pts were wild-type for KRAS , NRAS , BRAF , and EGFR ectodomain by central ctDNA testing, without ERBB2 / HER2 amplification. One ami monotherapy cohort (Cohort C) enrolled only pts with R-sided disease (all pts must have 2-3 prior lines; prior EGFRi allowed). The ami plus chemotherapy cohorts (Cohorts D [with FOLFOX] and E [with FOLFIRI) enrolled both L- and R-sided disease (1 prior line max; prior EGFRi use was exclusionary). Primary tumor locations of cecum, ascending colon, hepatic flexure, and transverse colon were considered R-sided. Response was assessed by the investigator per RECIST v1.1. Results: As of 26-Aug-2024, 23 pts with R-sided mCRC received ami monotherapy (median follow-up of 8.1 months [mo]). Median number of prior lines was 2, and 43% had prior EGFRi. There were 7 pts with R-sided disease who received ami plus FOLFOX or FOLFIRI (median follow-up of 6.5 mo); all 7 had received 1 prior line. Among pts receiving ami monotherapy, objective response rate (ORR) was 22% (5/23) and disease control rate (DCR) was 78% (18/23), with 1 achieving a complete response. Median duration of response (DoR) is 7.4 mo; response and treatment are ongoing for 3 of the 5 responders. In pts receiving ami plus FOLFOX or FOLFIRI, ORR was 43% (3/7) and DCR was 86% (6/7). Median DoR is 5.8 mo, with all 3 responders on treatment, of which 2 are ongoing response. Additional details are in the Table. Biomarker data will be presented at the meeting. Safety profile among R-sided disease was consistent with prior reports, with the most common ami-related grade 3+ AEs being rash and hypoalbuminemia (2 pts each). Conclusions: Ami monotherapy or combined with FOLFOX or FOLFIRI demonstrated durable antitumor activity in R-sided mCRC. Clinical trial information: NCT05379595 . Efficacy. Ami monotherapy (n=23) Ami + FOLFOX or FOLFIRI (n=7) Median follow-up, mo (range) 8.1 (0.6–17.5) 6.5 (3.2–8.8) Median number prior lines 2 1 Prior EGFRi, n (%) 10 (43) 0 ORR, % (95% CI) 22 (8–44) 43 (10–82) Median DoR, mo (95% CI) 7.4 (3.7–NE) 5.8 (NE–NE) a DCR, % (95% CI) 78 (56–93) 86 (42–100) Median progression-free survival, mo (95% CI) 3.7 (3.4–5.5) 7.4 (1.8–NE) a All 3 responders remain on treatment; 2 of 3 responders are ongoing response.
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 | 0,003 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».