Phase 1/2 study of IMC-C103C, a T cell receptor bispecific (MAGE-A4xCD3) ImmTAC targeting MAGE-A4-expressing malignancies

Purpose
IMC-C103C is an ImmTAC bispecific (MAGE-A4xCD3) T cell engager targeting a peptide from the cancer-testis antigen MAGE-A4 presented by HLA-A*02:01. This phase 1/2 study in advanced solid tumors (IMC-C103C-101; NCT03973333) investigated the saf…

BCL-2/BCL-xL inhibitor pelcitoclax with osimertinib for EGFR-mutated advanced non-small-cell lung cancer: a phase 1b trial

Background
Overcoming tyrosine kinase inhibitor (TKI) resistance improves survival in advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). We therefore examined the safety and preliminary efficacy of pelcitoclax…

Adjuvant penpulimab in very-high risk clear cell renal cell carcinoma: a prospective, non-randomized, controlled phase II trial with integrated plasma multi-omics analyses

Purpose
Patients with very-high risk clear cell renal cell carcinoma (ccRCC) remain at substantial risk of recurrence after nephrectomy. However, heterogeneity in benefit from adjuvant immunotherapy observed in the KEYNOTE-564 trial, together with lim…

Pharmacologic activity, safety, and preliminary efficacy of GEN3009, a CD37-targeting DuoHexaBody, in relapsed or refractory B-cell non-Hodgkins lymphoma

Background
Tetraspanin CD37, highly expressed in mature B-cells, represents an opportunity for therapeutic targeting in B-cell malignancies. GEN3009 (DuoHexaBody-CD37), a humanized biparatopic IgG1 antibody with an E430G hexamerization-enhancing mutat…

Long-term follow-up from the OMNIVORE trial: response-adaptive nivolumab and ipilimumab in advanced renal cell carcinoma

Background
Immune checkpoint inhibitor-based combinations represent the standard of care for advanced renal cell carcinoma. The OMNIVORE trial investigated a response-adaptive strategy, including treatment discontinuation in early nivolumab responders…

Sequential involvement of hypoxia and anti-PD-1 treatment in shaping tumor-regional CD39+CD8+ T cells highlights immunotherapy-resistant features in NSCLC

Background
Understanding resistance to anti-programmed cell death protein 1 (PD-1) therapy is critical for developing reversal strategies. Although ectonucleotidase CD39 (ENTPD1) (CD39)+ cluster of differentiation 8 (CD8)+ T cells have been associated…

Immune checkpoint inhibitor therapy after tumor-infiltrating lymphocytes in unresectable melanoma

Purpose
Treatment strategies for patients with advanced melanoma resistant to adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) remain undefined. The efficacy of immune checkpoint inhibitors (ICIs) after TIL has not been previously desc…

COVID-19 mRNA vaccination and immune-related adverse events in patients with cancer receiving immune checkpoint inhibitors: a target trial emulation study

Background
COVID-19 messenger RNA (mRNA) vaccines enhance immune checkpoint inhibitor (ICI) efficacy through type I interferon responses, but may theoretically increase the burden of immune-related adverse events (irAEs). This study aimed to determine…

Immune checkpoint inhibitor neurotoxicity: long-term outcomes with focus on 1-year neurological sequelae

Background
Data on the long-term course of neurological immune-related adverse events (n-irAEs) are limited by the size of studies as well as short and heterogeneous follow-up durations. Herein, we assessed the risk and predictors of 1-year neurologic…

VEGF-A blockade overcomes liver metastases resistance to chemoimmunotherapy in patients with advanced non-squamous NSCLC

Purpose
Liver metastases (LMs) confer resistance to immune checkpoint blockade in advanced non-squamous non-small cell lung cancer (ns-NSCLC), likely through an immunosuppressive tumor microenvironment (TME). We hypothesized that vascular endothelial …

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