A clinical hold has been placed on the phase 1b CYAD-101-002 trial, examining pembrolizumab after treatment with CYAD-101 and folinic acid, fluorouracil, and oxaliplatin preconditioning in metastatic colorectal cancer.
The phase 1b CYAD-101-002 trial (NCT04991948), assessing pembrolizumab (Keytruda) after treatment with CYAD-101 and folinic acid, fluorouracil, and oxaliplatin (FOLFOX) preconditioning in metastatic colorectal cancer (CRC), received a clinical hold following discussion with the FDA due to the need to assess risk in patients, according to a press release from Celyad Oncology.1
The study was paused voluntarily with the intent of examining 2 reported fatalities that took place on the study.
The open label study had an estimated enrollment of 34 patients. The primary end points are occurrence of dose-limiting toxicities and objective response rate. Enrollment required patients to have histologically confirmed metastatic adenocarcinoma of the colon or rectum and an ECOG performance status of 0 or 1. A tumor biopsy at screening and adequate organ, hepatic, renal, pulmonary, and cardiac function were also required.
The first-in-class, non-gene edited allogeneic CAR T-cell product was previously assessed in the phase 1 AlloSHRINK study (NCT03692429) in a population of patients with unresectable metastatic CRC.2 Of the 15 patients who received CYAD-101 after FOLFOX, confirmed partial responses were reported in 2 patients, 1 of whom had a KRAS mutation. Stable disease was reported in 9 patients, with 7 patients having stable disease that lasted for at least 3 months. The median progression-free survival was 3.9 months.
CYAD-101 was administered as 3 infusions following a standard preconditioning cycle of FOLFOX. A 3+3 dose-escalation format was used, with doses including 108, 3x108, and 109 T cells per infusion.
Investigators did not observe any dose-limiting toxicities, grade 3 or higher adverse effects, or graft-versus-host disease following CYAD-101 infusion.
“These clinical results demonstrate the safety and tolerability of a first-in-human non-gene edited allogeneic CAR T-cell treatment with early promising anti-tumor activity in [patients with advanced metastatic] CRC. Preliminary translational analysis present intriguing observations that the modulation of systemic cytokine levels may be associated with dose which is uncommon in CAR T-cell therapies reported to date while limited T-cell clonal diversification in the best responding patient underscores the likely central role of the adoptively transferred T-cell in driving therapeutic response in this particular patient,” the investigators concluded.