Phase I dose-escalation trial of AMXT 1501 dicaprate plus difluoromethylornithine: a dual-agent approach targeting immunosuppressive polyamine metabolism.

Background: Dysregulation of polyamine synthesis has been observed in various cancer cell types. A novel approach to depriving cancer cells of polyamines involves the use of difluoromethylornithine (DFMO) to block polyamine biosynthesis in combination with AMXT 1501, a potent inhibitor of polyamine transport. Preclinical mouse tumor models showed that the combination of AMXT 1501 plus DFMO had strong antitumor activity, together with evidence of a stimulated immune response against tumors.

Modulating Treatment Outcomes of Patients with Solid Tumors in Immunotherapy Trials: A Drug Interaction Analysis from a Phase 1 Unit.

Concurrent use of medications can modulate the effectiveness of immunotherapy. Although this interaction is well documented for immune checkpoint inhibitors, whether this occurs with new experimental compounds has not been evaluated. A computerized data extraction tool was used to collect clinical data and identify the prescription of a predefined set of medications within 30 days of immunotherapy infusion in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center.

Molecular characterization of NUT carcinoma: a report from the NUT carcinoma registry.

Purpose: NUT carcinoma (NC) is an underdiagnosed, poorly differentiated squamous cell cancer with a median survival of 6.7 months. Defined by NUTM1 fusions, NC enhances oncogene transcription, including MYC.

Safety and Tolerability of Berzosertib, an Ataxia-Telangiectasia-Related Inhibitor, and Veliparib, an Oral Poly (ADP-ribose) Polymerase Inhibitor, in Combination With Cisplatin in Patients With Refractory Solid Tumors.

Purpose: We conducted a phase I trial of the combination of cisplatin with the ataxia-telangiectasia-related protein kinase inhibitor berzosertib and the poly (ADP-ribose) polymerase inhibitor (PARPi) veliparib, with the objective of creating a DNA damage response (DDR)-impaired, BRCA null-like phenotype to potentiate the antitumor activity of cisplatin.

Patients And Methods: In this open label, 3 + 3 trial design, cisplatin and berzosertib were administered intravenously on day 1 (D1) and D8, and D2 and D9, respectively, together with twice-daily oral veliparib on D1-D3 and D8-D10 in 21-day cycles. Previous platinum and PARPi therapy were permitted.

Phase Ib Study of Pembrolizumab in Combination with Intratumoral Injection of Clostridium novyi-NT in Patients with Advanced Solid Tumors.

Purpose: Intratumoral injection of Clostridium novyi-NT, lacking alpha toxin, germinates and subsequently replicates in the tumor hypoxic regions, causing cell lysis and inflammation. This phase 1b study investigated the safety and synergistic effects of pembrolizumab and C. novyi-NT in advanced solid tumors.