First-in-Class Anti-immunoglobulin-like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance Mechanism in Patients with Advanced Solid Tumors.

PURPOSE: In this first-in-human study (NCT03564691) in advanced solid tumors, we investigated a novel first-in-class human IgG4 monoclonal antibody targeting the immunoglobulin-like transcript 4 (ILT4) receptor, MK-4830, as monotherapy and in combination with pembrolizumab. PATIENTS AND METHODS: Patients with histologically/cytologically confirmed advanced solid tumors, measurable disease by RECIST v1.1, and evaluable baseline tumor sample received escalating doses of intravenous MK-4830 every 3 weeks as monotherapy (parts A and B) and in combination with pembrolizumab (part C). Safety and tolerability were the primary objectives. Pharmacokinetics, objective response rate per RECIST v1.1, and molecular biomarkers were also evaluated. RESULTS: Of 84 patients, 50 received monotherapy and 34 received combination therapy. No dose-limiting toxicities were observed; maximum tolerated dose was not reached. MK-4830 showed dose-related target engagement. Eleven of 34 patients in the dose-escalation phase who received combination therapy achieved objective responses; 5 previously had progressive disease on anti-PD-1/PD-L1 therapies. Exploratory evaluation of the association between response and pretreatment gene expression related to interferon-gamma signaling in tumors suggested higher sensitivity to T-cell inflammation with combination therapy than historically expected with pembrolizumab monotherapy, with greater response at more moderate levels of inflammation. CONCLUSIONS: This first-in-class MK-4830 antibody dosed as monotherapy and in combination with pembrolizumab was well tolerated with no unexpected toxicities, and demonstrated dose-related evidence of target engagement and antitumor activity. Inflammation intrinsic to the ILT4 mechanism may be facilitated by alleviating the myeloid-suppressive components of the tumor microenvironment, supporting the target of ILT4 as a potential novel immunotherapy in combination with an anti-PD-1/PD-L1 agent.

Testing For SARS-CoV-2: The Day the World Turned its Attention to the Clinical Laboratory.

In the last few months, an unprecedented number of laboratory tests for coronavirus disease 2019 (COVID-19) have been developed at a remarkable speed. With the rapid adoption of these tests into clinical practice, combined with the widespread publicity they received, questions arose related to the different types of tests, their utility, performance, and regulatory approval status. The aim of this publication is to provide a general landscape of laboratory testing for COVID-19 and offer a historical and regulatory perspective associated with them. Specifically, we aim to elaborate on the regulatory complexities of diagnostic testing in the United States and its implications to the present outbreak, as well as provide a synopsis of laboratory tests that have been developed for COVID-19. We will first address the detection of severe acute respiratory syndrome-coronavirus 2 directly by either nucleic acid amplification tests or by the detection of the viral protein for active infections. Subsequently, we will provide an overview of serological tests that can aid not only in diagnosis but additionally help to identify prior infections and potential immunity.