KEYNOTE – D36: personalized immunotherapy with a neoepitope vaccine, EVX-01 and pembrolizumab in advanced melanoma.
Abstract Despite improvements made with checkpoint inhibitor (CPI) therapy, a need for new approaches to improve outcomes for patients with unresectable or metastatic melanoma remains. EVX-01, a personalized neoepitope vaccine, combined with pembrolizumab treatment, holds the potential to fulfill this need. Here we present the rationale and novel design behind the KEYNOTE - D36 trial: an open label, single arm, phase II trial aiming to establish the clinical proof of concept and evaluate the safety of EVX-01 in combination with pembrolizumab in CPI naive patients with unresectable or metastatic melanoma. The primary objective is to evaluate if EVX-01 improves [...]
Effect of the SunSafe Training Program on the attitudes, knowledge, and behaviour of Australian high school students towards sun safety: a prospective study
Abstract Background: The SunSafe Student Ambassador Program (SSSAP) in Australia uses the peer-to-peer learning environment to educate high-school students about sun-safety. Aims: To assess whether the SSSAP would improve knowledge, attitudes and behaviours towards sun safety in high-school students and whether this would be sustained at 3 months. Methods: An assessment survey was delivered before, immediately after and 3 months after participation in the SSSAP in 2019. Results: In total, 503 participants completed the pre-presentation survey, 274 completed the post-presentation survey, and 218 completed both. Immediately following presentation, the total composite score for all 18 knowledge questions increased from a mean ± SD [...]
Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma.
Abstract Purpose: The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the efficacy and safety from a phase III, randomized, double-blind, multicenter, international study of T-VEC plus pembrolizumab (T-VEC-pembrolizumab) versus placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma. Methods: Patients with stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were randomly assigned 1:1 to T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was administered at ≤ 4 × 106 plaque-forming unit (PFU) followed by ≤ 4 × 108 PFU 3 [...]
Detailed spatial immunophenotyping of primary melanomas reveals immune cell subpopulations associated with patient outcome.
Abstract While the tumor immune microenvironment (TIME) of metastatic melanoma has been well characterized, the primary melanoma TIME is comparatively poorly understood. Additionally, although the association of tumor-infiltrating lymphocytes with primary melanoma patient outcome has been known for decades, it is not considered in the current AJCC melanoma staging system. Detailed immune phenotyping of advanced melanoma has revealed multiple immune biomarkers, including the presence of CD8+ T-cells, for predicting response to immunotherapies. However, in primary melanomas, immune biomarkers are lacking and CD8+ T-cells have yet to be extensively characterized. As recent studies combining immune features and clinicopathologic characteristics have [...]
Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial
Abstract Background: Pembrolizumab prolongs progression-free and overall survival among patients with advanced melanoma and recurrence-free survival in resected stage III disease. KEYNOTE-716 assessed pembrolizumab as adjuvant therapy in patients with completely resected, high-risk, stage II melanoma. We report results from the planned first and second interim analyses for recurrence-free survival. Methods: In this double-blind, randomised, placebo-controlled phase 3 study, involving 160 academic medical centres and hospitals in 16 countries (Australia, Belgium, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Poland, South Africa, Spain, Switzerland, the UK, and the USA), patients aged 12 years or older with newly diagnosed, completely resected stage [...]
Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination.
Abstract Purpose: Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136). Methods: Eligible patients with unresectable stage III-IV melanoma with confirmed progressive disease (PD) within 12 weeks of the last dose of a PD-1/L1 inhibitor given alone or with other therapies, including cytotoxic T-cell lymphocyte-associated antigen 4 (CTLA-4) inhibitors, received lenvatinib 20 mg orally once daily plus ≤ 35 doses of pembrolizumab 200 mg [...]
Re-induction ipilimumab following acquired resistance to combination ipilimumab and anti-PD-1 therapy.
Abstract Purpose: Combination immunotherapy with nivolumab and ipilimumab has a high initial response rate in advanced melanoma; however, up to 55% of patients later progress. The efficacy and safety of ipilimumab re-induction in the setting of acquired resistance (AR) to combination immunotherapy is unknown. Methods: Patients with advanced melanoma who initially achieved a complete response, partial response or sustained stable disease to induction combination immunotherapy then progressed and were reinduced with ipilimumab (alone or in combination with anti-PD-1) and were analysed retrospectively. Demographics, disease characteristics, efficacy and toxicity were examined. Results: Forty-seven patients were identified from 12 centres. The response rate to [...]
Health-related quality of life (HRQoL) with pembrolizumab (pembro) in resected high-risk stage II melanoma in the phase 3 KEYNOTE-716 study.
Abstract Background: Adjuvant pembro improved RFS vs placebo (HR, 0.61; 95% CI, 0.45-0.82) and had manageable safety in patients (pts) with resected high-risk stage II melanoma at second interim analysis of KEYNOTE-716 (NCT03553836). HRQoL results are presented. Methods: Pts aged ≥12 y with resected stage IIB/C melanoma were randomized 1:1 to adjuvant pembro 200 mg (2 mg/kg for pts ≥12 and < 18 y) Q3W or placebo for ≤17 cycles. Change from baseline in HRQoL was an exploratory end point. EORTC QLQ-C30 and EQ-5D-5L were administered at baseline; cycles 5, 9, 13, and 17 in y 1; every 12 wk [...]
Comprehensive Clinical, Histopathologic, and Molecular Analysis and Long-term Follow-up of Patients With Nodal Blue Nevi
Blue nevi are benign, melanocytic neoplasms that show a range of clinical and morphologic patterns and include common/dendritic, cellular, and atypical cellular subtypes. Like other nevi, they most commonly occur in skin but can occasionally involve lymph nodes where they may be misinterpreted as representing metastatic melanoma. Moreover, whether benign blue nevi can metastasize to lymph nodes and their natural history and prognostic significance has been the subject of great controversy. To date, few cases of nodal blue nevi have been reported in the literature, and those reports have had limited clinical follow-up and supporting molecular data. This study [...]
Association of Antithyroid Antibodies in Checkpoint Inhibitor-Associated Thyroid Immune-Related Adverse Events.
Abstract Context: The significance of thyroid peroxidase (TPOAb) and thyroglobulin antibody (TgAb) in the pathogenesis of thyroid immune-related adverse events (irAEs) is unknown. Objective: To characterize the association of anti-thyroid antibodies with the development of thyroid immune related adverse events. Methods: A retrospective cohort study was conducted of patients with melanoma receiving immune checkpoint inhibitor (ICI) treatment. TPOAb, TgAb, and interleukin-6 (IL-6) were measured retrospectively using tumor-banked samples at baseline and at time of diagnosis of a thyroid irAE. In euthyroid patients (without thyroid irAEs) measures were repeated 30 to 60 days after ICI commencement, which was similar to the median time [...]