Mesothelin-Targeting T Cell Receptor Fusion Construct Cell Therapy in Refractory Solid Tumors: Phase 1/2 Trial Interim Results

Authors

Raffit Hassan
Marcus Butler
Roisin E O'Cearbhaill
David Y Oh
Melissa Johnson
Kevin Zikaras
Munisha Smalley
Michael Ross
Janos L Tanyi
Azam Ghafoor
Nirali N Shah
Babak Saboury
Liang Cao
Alfonso Quintás-Cardama
David Hong

Publication Date

8-1-2023

Journal

Nature Medicine

Abstract

The T cell receptor fusion construct (TRuC) gavocabtagene autoleucel (gavo-cel) consists of single-domain anti-mesothelin antibody that integrates into the endogenous T cell receptor (TCR) and engages the signaling capacity of the entire TCR upon mesothelin binding. Here we describe phase 1 results from an ongoing phase1/2 trial of gavo-cel in patients with treatment-refractory mesothelin-expressing solid tumors. The primary objectives were to evaluate safety and determine the recommended phase 2 dose (RP2D). Secondary objectives included efficacy. Thirty-two patients received gavo-cel at increasing doses either as a single agent (n = 3) or after lymphodepletion (LD, n = 29). Dose-limiting toxicities of grade 3 pneumonitis and grade 5 bronchioalveolar hemorrhage were noted. The RP2D was determined as 1 × 10

Keywords

Humans, Neoplasms, Receptors, Antigen, T-Cell, Cell- and Tissue-Based Therapy

DOI

10.1038/s41591-023-02452-y

PMID

37501016

PMCID

PMC10427427

PubMedCentral® Posted Date

7-27-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes