Chimeric Antigen Receptor T Cells Targeting CD19 and GCC in Metastatic Colorectal Cancer: A Nonrandomized Clinical Trial.

Importance: Chimeric antigen receptor (CAR) T-cell therapy (CART) has transformed the treatment landscape of hematologic cancer, but has negligible effects for adult solid cancers. In this trial, an autologous CAR T-cell product demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer (mCRC).

Objective: To evaluate the safety and efficacy of guanylate cyclase-C (GCC19) CART in participants with metastatic colorectal cancer (mCRC).

LOAd703, an oncolytic virus-based immunostimulatory gene therapy, combined with chemotherapy for unresectable or metastatic pancreatic cancer (LOKON001): results from arm 1 of a non-randomised, single-centre, phase 1/2 study.

Background: Pancreatic ductal adenocarcinoma is characterised by low immunogenicity and an immunosuppressive tumour microenvironment. LOAd703, an oncolytic adenovirus with transgenes encoding TMZ-CD40L and 4-1BBL, lyses cancer cells selectively, activates cytotoxic T cells, and induces tumour regression in preclinical models. The aim of this study was to evaluate the safety and feasibility of combining LOAd703 with chemotherapy for advanced pancreatic ductal adenocarcinoma.

Safety, pharmacokinetics, and pharmacodynamics in healthy Chinese volunteers treated with SC0062, a highly selective endothelin-A receptor antagonist.

This study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and food effects (FE) of SC0062, a highly active endothelin-A (ET ) receptor antagonist, in healthy subjects. The primary objectives of this first-in-human phase I study, comprised of single-ascending-dose, multiple-ascending-dose, and FE parts, were to characterize the safety and tolerability of SC0062, and FE. The secondary objectives were to determine the PK behavior of SC0062 and its major active metabolite M18, whereas exploratory objectives focused on PD effects, principally effects on endothelin-1 (ET-1) and total bile acids (TBA).

Phase 1 study of the protein deubiquitinase inhibitor VLX1570 in patients with relapsed and/or refractory multiple myeloma.

This phase 1 study sought to characterize the safety, tolerability, and pharmacokinetic behavior of VLX1570, a small molecule inhibitor of the deubiquitinases (DUBs) that remove sterically bulky ubiquitin chains from proteins during processing in the19S regulatory subunit of the proteasome, in patients with relapsed and refractory multiple myeloma (MM). Fourteen patients were treated with escalating doses of VLX1570 ranging from 0.05 to 1.

A Phase 1 Trial of CNDO-109-Activated Natural Killer Cells in Patients with High-Risk Acute Myeloid Leukemia.

Natural killer (NK) cells are an emerging immunotherapy approach to acute myeloid leukemia (AML); however, the optimal approach to activate NK cells before adoptive transfer remains unclear. Human NK cells that are primed with the CTV-1 leukemia cell line lysate CNDO-109 exhibit enhanced cytotoxicity against NK cell-resistant cell lines. To translate this finding to the clinic, CNDO-109-activated NK cells (CNDO-109-NK cells) isolated from related HLA-haploidentical donors were evaluated in a phase 1 dose-escalation trial at doses of 3 × 10 (n = 3), 1 × 10 (n = 3), and 3 × 10 (n = 6) cells/kg in patients with AML in first complete remission (CR1) at high risk for recurrence.