Phase 1 study of latozinemab in progranulin-associated frontotemporal dementia.

Introduction: Heterozygous mutations in the gene lead to reduced progranulin (PGRN) levels in plasma and cerebrospinal fluid (CSF) and are causative of frontotemporal dementia (FTD) with > 90% penetrance. Latozinemab is a human monoclonal immunoglobulin G1 antibody that is being developed to increase PGRN levels in individuals with FTD caused by heterozygous loss-of-function mutations.

Methods: A first-in-human phase 1 study was conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple-dose intravenous administration of latozinemab in eight symptomatic participants with FTD caused by a heterozygous loss-of-function mutation (FTD-).

AL008 Enhances Myeloid Antitumor Function by Inhibiting SIRPα Signaling and Activating Fc Receptors.

Antagonizing the CD47-signal regulatory protein (SIRP)α pathway, a critical myeloid checkpoint, promotes antitumor immunity. In this study, we describe the development of AL008, a pan-allelic, SIRPα-specific Ab that triggers the degradation of SIRPα and, concurrently, stimulates FcγR activation of myeloid cells through an engineered Fc domain. AL008 showed superior enhancement of phagocytosis of tumor cells opsonized with antitumor Ag Abs compared with another SIRPα Ab tested.

Targeting the Siglec-Sialic Acid Immune Axis in Cancer: Current and Future Approaches.

The sialic acid-binding immunoglobulin-like lectin (Siglec)-sialic acid immune axis is an evolutionarily conserved immunoregulatory pathway that provides a mechanism for establishing self-recognition and combatting invasive pathogens. Perturbations in the pathway lead to many immune dysregulated diseases, including autoimmunity, neurodegeneration, allergic conditions, and cancer. The purpose of this review is to provide a brief overview of the relationship between Siglecs and sialic acid as they relate to human health and disease, to consider current Siglec-based therapeutics, and to discuss new therapeutic approaches targeting the Siglec-sialic acid immune axis, with a focus on cancer.

Phase 1b study of anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) in patients with platinum-sensitive recurrent ovarian cancer.

Objective: This study investigated the safety and tolerability of lifastuzumab vedotin (DNIB0600A) (LIFA), an antibody-drug conjugate, in patients with recurrent platinum-sensitive ovarian cancer (PSOC).

Methods: In this open-label, multicenter phase 1b study, LIFA was administered intravenously once every 3 weeks (Q3W) with starting dose 1.2 mg/kg in a 3 + 3 dose-escalation scheme.

Antitumor activity of ipatasertib combined with chemotherapy: results from a phase Ib study in solid tumors.

Background: This phase Ib study evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of the oral AKT inhibitor ipatasertib and chemotherapy or hormonal therapy in patients with advanced or metastatic solid tumors to determine combined dose-limiting toxicities (DLTs), maximum tolerated dose, and recommended phase II doses and schedules.

Patients And Methods: The clinical study comprised four combination treatment arms: arm A (with docetaxel), arm B [with mFOLFOX6 (modified leucovorin, 5-fluorouracil, and oxaliplatin)], arm C (with paclitaxel), and arm D (with enzalutamide). Primary endpoints were safety and tolerability; secondary endpoints were pharmacokinetics, clinical activity per Response Evaluation Criteria in Solid Tumors v1.