Phase II study of retifanlimab in patients with recurrent locally advanced or metastatic Merkel cell carcinoma (POD1UM-201).

Background: POD1UM-201, an open-label, single-arm, phase II multiregional study, evaluated efficacy and tolerability of retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in chemotherapy-naive patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).

Methods: Patients were enrolled across 34 sites in the USA, Canada, and Europe. Eligible patients were ≥18 years with confirmed recurrent advanced locoregional or metastatic MCC not amenable to surgery or radiation therapy, had not received previous systemic treatment, had measurable disease, and Eastern Cooperative Oncology Group performance status 0-1.

Brain metastases from Merkel cell carcinoma: A nationwide retrospective study.

Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer causing distant metastases in 30 % of cases but rarely involving the brain. PD-1/PD-L1 inhibitors constitute the standard treatment of advanced MCC but their impact on brain metastases is unknown.

Methods: This retrospective study included MCC patients with central nervous system (CNS) metastases from the French CARADERM registry and the Groupe de Cancérologie Cutanée network.

Neoadjuvant immune checkpoint inhibitors for patients with resectable stage III/IV melanoma: A nationwide real-life study in France (NEOMEL).

Background: Despite the clear therapeutic benefits of neoadjuvant treatment (NT) with immune checkpoint inhibitors (ICIs) in clinical trials, the efficacy of NT ICIs (NT-ICI) and the optimal regimen for patients (pts) with resectable metastatic melanoma (RMM) remain to be confirmed in real life.

Objective: To assess the efficacy and safety of NT-ICI among pts with RMM in real life.

Methods: NEOMEL is a French retrospective multicentric cohort study.

RP1 Combined With Nivolumab in Advanced Anti-PD-1-Failed Melanoma (IGNYTE).

Purpose: Effective treatment options for melanoma after immune checkpoint blockade failure are limited. RP1 (vusolimogene oderparepvec) is a herpes simplex virus type 1-based oncolytic immunotherapy, here evaluated in combination with nivolumab in anti-PD-1-failed melanoma.

Methods: Patients had advanced melanoma that had confirmed progression on anti-PD-1 (≥8 weeks, last prior treatment).

MelanoDB: A dataset of clinical and molecular features of patients with advanced melanoma treated with MAPK inhibitors.

MAPK inhibitors (MAPKi) have revolutionized the treatment of patients with advanced melanoma. However, primary and acquired resistance mechanisms limit their efficacy. Predicting MAPKi response from the tumor baseline features remains challenging due to the limited size of patient cohorts.

Administration of nivolumab plus ipilimumab: Infusion of the fixed-ratio combination versus sequential infusions in two randomized controlled trials of metastatic melanoma (CheckMate 742) and renal cell carcinoma (CheckMate 800).

Background: Immune checkpoint inhibitors can be coadministered as a fixed-ratio combination (FRC) or administered as sequential infusions (ASI). Two randomized, open-label trials compared nivolumab + ipilimumab as a FRC versus ASI in patients with melanoma or renal cell carcinoma.

Methods: CheckMate 742 was a Phase 3b study in patients with advanced or metastatic melanoma who received nivolumab 1 mg/kg and ipilimumab 3 mg/kg either concurrently as an FRC or sequentially as ASI every 3 weeks.

Combination of encorafenib and binimetinib followed by ipilimumab and nivolumab versus ipilimumab and nivolumab in patients with advanced melanoma with BRAF or BRAF mutations (EBIN): an international, open-label, randomised, controlled, phase 2 study.

Background: Current first-line treatment for patients with metastatic melanoma with BRAF or BRAF mutations includes immunotherapy with immune checkpoint inhibitors and targeted therapy; however, the optimal sequencing of these treatments is unclear. We aimed to investigate the use of a targeted-therapy induction regimen before treatment with immune checkpoint inhibitors.

Methods: This open-label, randomised, controlled, phase 2 trial (EBIN) was conducted at 37 centres in eight European countries.

The CD70-CD27 Axis in Cancer Immunotherapy: Predictive Biomarker and Therapeutic Target.

The CD27-CD70 interaction is recognized as a positive costimulatory pathway for T-cell priming and expansion. However, recent studies showed that chronic CD27-CD70 interaction in cancer can lead to apoptosis of T cells, rendering them dysfunctional. CD70 is expressed not only by hematologic tumors but also by solid tumor cells.

Harnessing nutrient scarcity for enhanced CAR-T-cell potency and safety in solid tumors.

Despite significant advancements, the effectiveness of chimeric antigen receptor (CAR)-T-cell-based therapies in solid tumors remains limited. Key challenges include on-target effects, off-tumor toxicity and reduced CAR-T-cell function within the tumor microenvironment, which is often characterized by metabolic stress triggered by factors such as amino acid scarcity. Activating transcription factor-4 (ATF4) and its upstream regulator GCN2 play crucial roles in the metabolic reprogramming and functionality of CD4 and CD8 T cells.

Cutaneous melanoma.

Cutaneous melanoma is a common cancer in Australia and New Zealand, Europe, and North America, and its incidence is still increasing in many regions. Ultraviolet (UV) radiation exposure (for example, through excessive sunlight exposure) remains the primary risk factor for melanoma; however, public awareness campaigns have led to a marked reduction in mortality. In addition to genetic damage from UV radiation, specific genetic alterations have been linked to melanoma.

A Phase I, First-in-Human, Dose-Escalation, Expansion Trial of Cytokine-Encoding Synthetic mRNA Mixture Alone or with Cemiplimab in Advanced Solid Tumors.

Purpose: We investigated SAR441000 (mixture of four mRNAs encoding IL-12, single-chain IFN-α-2b, GM-CSF, and IL-15 sushi domain) alone or in combination with cemiplimab in patients with advanced solid tumors.

Patients And Methods: SAR441000 was intratumorally administered weekly in a 4-week cycle in monotherapy and in a 3-week cycle at a predefined dose level with 350 mg cemiplimab (intravenously) every 3 weeks in combination therapy. The primary objective was to determine MTD or maximum administered dose, overall safety, tolerability, and objective response rate of SAR441000.

Soluble CD27 differentially predicts resistance to anti-PD1 alone but not with anti-CTLA-4 in melanoma.

Metastatic melanoma can be treated with anti-PD-1 monotherapy or in combination with anti-CTLA-4 or anti-Lag3. However, combination therapy is associated with a high risk of toxicity. Recently, we reported that high plasma soluble CD27 (sCD27) levels reflect the intratumoral interaction of CD70-CD27 and dysfunctional T cells in the tumor microenvironment of renal cell carcinoma.

Modern Approach to Manage Patients With Kaposi Sarcoma.

Kaposi sarcoma (KS) is a malignancy associated with Kaposi's sarcoma-associated herpesvirus (KSHV), primarily affecting immunocompromised individuals, such as those with HIV or those receiving immunosuppressive treatments. Immunocompetent individuals may also be affected, illustrating the disease's heterogeneity. KS manifests in different forms-classic, endemic, epidemic, iatrogenic, and in men having sex with men-each with distinct clinical features depending on immune status and geographic area of origin.

Immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD-1 treatment. A EUMelaReg real-world evidence study.

Background: Adjuvant immune checkpoint inhibition (ICI) with anti-PD-1 antibodies in high-risk resected melanoma has been shown to improve recurrence-free survival. It is unclear whether prior adjuvant anti-PD-1 therapy is associated with altered response to subsequent ICI treatment in the metastatic setting.

Methods: Using data from the European Melanoma Registry (EUMelaReg), we analyzed the efficiency of first-line (1L) ICI in non-resectable or metastatic melanoma after failure from prior adjuvant anti-PD-1 treatment.

Randomized, Open-Label, Phase III Study of Tilsotolimod in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced Refractory Melanoma (ILLUMINATE-301).

Purpose: There are limited treatment options for advanced melanoma that have progressed during or after immune checkpoint inhibitor therapy. Intratumoral (IT) immunotherapy may improve tumor-specific immune activation by promoting local tumor antigen presentation while avoiding systemic toxicities. The phase 3 ILLUMINATE-301 study (ClinicalTrials.

Phase I study of intratumoral administration of CV8102 in patients with advanced melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck, or adenoid cystic carcinoma.

Background: CV8102, a toll-like receptor 7/8 and RIG I agonist, has demonstrated antitumor immune responses in preclinical studies. We investigated intratumoral (IT) administration of CV8102 in patients with anti-programmed cell death protein-1 (PD-1) therapy-naïve or anti-PD-1 therapy-refractory cutaneous melanoma (cMEL) and in patients with advanced cutaneous squamous cell carcinoma, head and neck squamous cell carcinoma and adenoid cystic carcinoma.

Methods: This open-label, cohort-based, phase I dose escalation study aimed to establish the maximum tolerated dose (MTD), recommended dose (RD), safety and preliminary efficacy of CV8102 as monotherapy or in combination with a PD-1 inhibitor.

Diagnosis and treatment of dermatofibrosarcoma protuberans. European interdisciplinary guideline - update 2024.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous fibroblastic tumour that is locally aggressive, with a tendency for local recurrence, but rarely metastasizes. A collaboration of multi-disciplinary experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Union of Medical Specialists (UEMS) and the European Academy of Dermatology and Venereology (EADV) was formed to update recommendations on DFSP diagnosis and treatment, based on current literature reviews and the experts' consensus. Diagnosis is suspected clinically and confirmed by pathology report, which should specify whether a transformation in higher-grade fibrosarcoma occurred.

Clinical outcomes and management following progressive disease with anti-PD-(L)1 therapy in patients with advanced Merkel Cell Carcinoma.

Aim: Merkel Cell Carcinoma (MCC) is a rare skin cancer with a rising incidence worldwide. Anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies are effective for the treatment of advanced MCC. This study examines patterns of response / progression of advanced MCC to anti-PD-(L)1 therapies and describes subsequent management.

BRAF and MEK inhibitors rechallenge after an adverse drug reaction in patients with cancer: A pharmacovigilance cohort study.

Importance: The safety profile of a rechallenge with BRAF inhibitors (BRAFi) or a combination of BRAF and MEK inhibitors (MEKi) following an adverse drug reaction (ADR) remains largely unexplored.

Objective: To identify the reported recurrence rate of the same ADR after a BRAFi±MEKi targeted therapy (TT) rechallenge in patients with cancer and to identify factors associated with recurrence.

Design, Setting, And Participants: In this observational, pharmacovigilance study, ADR reports were sourced from VigiBase, the World Health Organization database.

Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial.

Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy.

When to stop immunotherapy for advanced melanoma: the emulated target trials.

Background: Immune checkpoint inhibitors (ICIs) have demonstrated their efficacy with a 7.5-year overall survival (OS) close to 50% for advanced stages. The design of clinical trials provides for treatment until progression or toxicity, or for a maximum duration of two years.