P1152: RESULTS FROM A PHASE I PHARMACOKINETIC (PK) AND SAFETY STUDY OF TRPH-222, A NOVEL CD22-TARGETING ANTIBODY-DRUG CONJUGATE, IN PATIENTS WITH RELAPSED/REFRACTORY B-CELL NON-HODGKIN LYMPHOMA (R/R NHL)
Notice bibliographique
Résumé
Background: TRPH-222 is a novel antibody-drug conjugate (ADC) comprised of a humanized anti-CD22 monoclonal antibody and maytansine, a potent microtubule inhibitor, joined by a novel third-generation linker-conjugation technology (SMARTag®). This approach enables site-specific conjugation of the maytansine payload while tightly controlling drug:antibody ratio (DAR), resulting in a highly stable anti-CD22 ADC with a non-cleavable linker designed to widen the therapeutic window. Aims: The primary objectives of this first in human study are to determine the safety, tolerability and pharmacokinetics (PK) of TRPH-222 monotherapy in patients with R/R NHL. Methods: TRPH-222-100 is an open-label, multicenter study comprised of dose-escalation and dose-expansion stages. TRPH-222 was administered IV once every 3 weeks. 22 patients were enrolled in dose-escalating cohorts of TRPH-222 (0.6 mg/kg to 10 mg/kg) from DLBCL, FL, TFL, MCL and MZL histologies, and 10 patients in a dose-expansion cohort (7.5 mg/kg) focusing on DLBCL and FL histologies. Results: As of January 7, 2022, 32 NHL patients have been enrolled: 15 indolent (14 FL and 1 MZL) and 17 aggressive histologies (15 DLBCL, 1 TFL and 1 MCL). Patients had a median age of 64.5 years, a median of 4 prior lines of therapy including 7 patients receiving prior CAR-T treatment. Three DLTs occurred in 2 patients during the study and comprised Grade 3 and 4 transaminase elevations; one each at 4.2 and 10 mg/kg and one Grade 3 thrombocytopenia at 4.2 mg/kg. Treatment-related serious adverse events (AEs) occurred in 2 patients (6.3%), caused by thrombocytopenia and pyrexia (both at 7.5 mg/kg TRPH-222). AEs were more prevalent at doses ≥7.5 mg/kg and less prevalent at lower doses. There was a trend to higher grade AEs in patients with aggressive histologies, compared to indolent ones. The most frequent (≥ 5%) treatment-emergent related AEs (Grade ≥3) included thrombocytopenia (34%), neutropenia (22%), ALT/AST elevation (6%), dry eye (6%) and blurred vision (6%). Cytopenias were non-febrile, infrequent, asymptomatic and resolved without significant intervention. Ocular findings were consistent with known epithelial keratopathy of ADCs and were generally low grade and resolved to ≤ Grade 1 with dose interruptions and/or reductions. Overall, TRPH-222 demonstrated a favourable safety profile with most AEs being predominantly low grade, tolerable, easily managed and reversible. Preliminary efficacy results suggest evidence of anti-tumor activity, most notably in patients with R/R FL. Of the 13 response-evaluable FL patients, 4 complete responses (CR) and 2 partial responses (PR) were observed, with an overall response rate (ORR) of 46% and a complete response rate (CRR) of 31%. Four patients with metabolic CRs maintained these CRs for long periods off treatment; 3 patients remain in CR with responses maintained for up to 25 months. Responses were generally early, durable and CRs were maintained off-therapy. Beyond FL, CRs were also observed in 1 DLBCL patient and in 1 MCL patient. Summary/Conclusion: TRPH-222 was found to be well tolerated at higher dose levels than evaluated for other ADCs. TRPH-222 monotherapy resulted in robust and durable CRs in FL across dose levels where patients were able to discontinue TRPH-222 while remaining in remissions. Collectively, these characteristics of TRPH-222 are favorable for further development in the indolent lymphoma setting either as monotherapy or in combination with other anti-tumor agents in B-cell lymphoma 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 | 0,001 | 0,001 |
| 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 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».