Phase Ib multicenter study of anti-TIM-3 (S095018/Sym023) in combination with anti-PD-1 (Sym021) in patients with advanced/metastatic recurrent biliary tract cancer

Background
T-cell immunoglobulin and mucin-domain containing 3 (TIM-3) is an inhibitory receptor linked to decreased antitumor activity of immune cells. S095018 is a human anti-TIM-3 IgG2 antibody that blocks the binding of phosphatidyl serine to TIM-…

Evaluation of mixed response in tumor size and survival in patients with rare cancers treated with dual checkpoint inhibitor therapy (DART SWOG S1609)

Background
Mixed response, where different lesions within the same patient show discordant responses to treatment, remains poorly understood. To better understand the complex effects of mixed response on patient survival, we devised three different de…

First-in-human phase 1 study of RO7119929, an oral TLR7 agonist prodrug, in patients with advanced primary or metastatic liver cancers

Background
The orally available toll-like receptor 7 (TLR7) agonist prodrug RO7119929 is converted to active drug predominantly in the liver, where it is hypothesized to reprogram the local immune microenvironment. We aimed to explore the safety, phar…

Prospective study of patients with immune checkpoint inhibitor-induced hepatitis; characterization of liver injury, outcome of therapy, and management of steroid-unresponsive and steroid-dependent hepatitis

Background
Immune-related hepatitis (ir-hepatitis) ranks among the most frequent adverse events of immune checkpoint inhibitors (ICIs). Limited knowledge exists regarding the incidence, characteristics, and treatment of patients having an inadequate r…

Resistance to anti-PD-1 immunotherapy for stage III and IV melanoma: a global chart review study

Background
Anti-programmed cell death protein 1 (PD-1) immunotherapy has revolutionized the treatment of stage III and IV melanoma. Real-world data on its resistance is needed to facilitate the development of combinatorial approaches to overcome anti-…

Androgen deprivation, androgen receptor-targeted vaccination, and nivolumab in patients with high-risk localized prostate cancer

Background
In murine studies, we demonstrated that a DNA vaccine encoding the androgen receptor (pTVG-AR) given prior to androgen deprivation elicited prostate tumor-infiltrating lymphocytes and an antitumor response. The current trial evaluated this …

Influence of body composition on the efficacy of nivolumab plus ipilimumab for metastatic clear cell renal cell carcinoma

Background
Immune checkpoint inhibitor therapy (ICI) with nivolumab+ipilimumab is a first-line (1L) standard for metastatic clear cell renal cell carcinoma (ccRCC), yet outcomes remain heterogeneous. Increasing evidence suggests that host factors infl…

Phase I/II clinical trial of a melanoma vaccine targeting shared non-mutated antigens and a shared mutated BRAF neoantigen with an agonistic CD40 antibody (CDX-1140) plus TLR3 agonist (poly-ICLC)

Background
For patients with high-risk melanoma who are unresponsive or intolerant to immune checkpoint inhibitors, cancer vaccines may provide benefit with a favorable toxicity profile. CD4+ T cells provide essential help to dendritic cells (DCs) for…

Clinical and translational results from a phase 1 trial of gemcitabine/nab-paclitaxel with nivolumab/ipilimumab or hydroxychloroquine/ipilimumab in untreated metastatic pancreatic adenocarcinoma

Background
Patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) often respond to cytotoxic therapy, but early disease progression is typical. Responses to immunotherapy alone are rare. Recent advances in chemoimmunotherapy combinations of…

Caninized PD-1 monoclonal antibody in oral malignant melanoma: efficacy and exploratory biomarker analysis

Background
Canine oral malignant melanoma (OMM) is a highly aggressive tumor, with several available treatment options, though few achieve durable response or complete remission. Because of its biological similarity to human mucosal melanoma, canine O…

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