Matteo S Carlino

• BMedSc MBBS FRACP
• Staff Specialist at Westmead Hospital

Introduction mRNA-4157 is a novel mRNA-based individualized neoantigen therapy (INT) designed to enhance endogenous antitumor T-cell responses by targeting unique patient-specific tumor mutations. In the phase 2 mRNA-4157-P201 (KEYNOTE-942) trial, patients with completely resected high-risk stage IIIB-IV melanoma receiving mRNA-4157 + pembrolizumab...

Background Neoadjuvant immunotherapy has become the new standard of care for stage III melanoma. This study sought to describe the metabolic changes seen with fludeoxyglucose-18-positron emission tomography (FDG-PET) following neoadjuvant immunotherapy in patients with melanoma and explore associations with pathological response and recurrence-free...

Glioblastoma (GBM) is an aggressive primary adult brain tumor that rapidly recurs after standard-of-care treatments, including surgery, chemotherapy and radiotherapy. While immune checkpoint inhibitor therapies have transformed outcomes in many tumor types, particularly when used neoadjuvantly or as a first-line treatment, including in melanoma bra...

Previous results from the KEYNOTE-716 trial demonstrated significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) with adjuvant pembrolizumab versus placebo in patients with resected stage IIB or IIC melanoma. We present a post hoc analysis of efficacy according to primary tumor location. KEYNOTE-716 (NCT035...

Purpose: To evaluate linrodostat mesylate, a selective, oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, combined with nivolumab ± ipilimumab in advanced solid tumors and hematologic malignancies. Patients and methods: In this phase 1/2 study, patients received once-daily (QD) linrodostat (part 1 [escalation], 25-400 mg; part 2 [expansion],...

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer with low survival probability as it is generally diagnosed at later stages. Using a combination of immune-checkpoint inhibitors (ICIs) Ipilimumab (IPI) + Nivolumab (NIVO) as a first line treatment for unresectable MPM, the CheckMate 743 trial reported higher overall survival (OS)...

Disclosure: L. Wu: None. J. Wentworth: None. C. Liddle: None. M. Carlino: Consulting Fee; Self; Amgen Inc, Bristol-Myers Squibb, Novartis Pharmaceuticals, Pierre Fabre, Regeneron Pharmaceuticals, Roche Pharmaceuticals, Merck, Sanofi. D. Brown: None. R.J. Clifton-Bligh: None. G. Long: Consulting Fee; Self; Amgen Inc, AstraZeneca, Boehringer Ingelhei...

Background: Previous results from this trial showed longer overall survival after treatment with nivolumab plus ipilimumab or with nivolumab monotherapy than with ipilimumab monotherapy in patients with advanced melanoma. Given that patients with advanced melanoma are living longer than 7.5 years, longer-term data were needed to address new clinic...

Background: Following major achievements seen with drug therapies for the treatment of advanced melanoma in the last decade, they now also have an ever-increasing role for the treatment of earlier stage disease. This review outlines the current drugs used to treat melanoma, and how general practitioners (GPs) can assist in the management of patien...

Free access of the article until 30 September 2024 via this link: https://authors.elsevier.com/a/1jaye5EIIgPe0t Summary Background In the European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 study, adjuvant pembrolizumab improved recurrence-free survival and distant-metastasis-free survival in patients with res...

Immune checkpoint inhibitors and BRAF-targeted therapy each improve survival in melanoma. Immune changes early during targeted therapy suggest the mechanisms of each drug class could work synergistically. In the non-comparative, randomized, phase 2 NeoTrio trial, we investigated whether targeted therapy could boost the proportion of patients achiev...

LBA2 Background: Standard of care (SOC) for resectable, macroscopic stage III melanoma is therapeutic lymph node dissection (TLND) followed by adjuvant (adj) therapy with nivolumab (NIVO), pembrolizumab (PEM) or, in BRAFmut melanoma, dabrafenib + trametinib (DAB/TRAM). The recent phase 2 SWOG S1801 trial showed superior event-free survival (EFS) of...

LBA9512 Background: mRNA-4157 is a novel, mRNA-based individualized neoantigen therapy designed to increase endogenous antitumor T-cell responses by targeting unique patient (pt) tumor mutations. In the primary analysis of the Ph 2 mRNA-4157-P201 (KEYNOTE-942) trial (median planned follow-up, 23 mo), pts with completely resected high-risk stage III...

LBA9584 Background: Neoadjuvant (neoadj) ipilimumab (IPI) + nivolumab (NIVO) showed improved event-free survival compared to adjuvant (adj) NIVO, but at the cost of increased immune related toxicity (irAEs). In the PRADO trial, impairment of health-related quality of life (HRQoL) was predominantly driven by the extent of the surgery and not by irAE...

Background: Phase 1-2 trials involving patients with resectable, macroscopic stage III melanoma have shown that neoadjuvant immunotherapy is more efficacious than adjuvant immunotherapy. Methods: In this phase 3 trial, we randomly assigned patients with resectable, macroscopic stage III melanoma, in a 1:1 ratio, to receive two cycles of neoadjuv...

TPS9616 Background: The anti−PD-1 antibody pembrolizumab is approved as adjuvant therapy for stage IIB-C and stage III melanoma by AJCC 8th ed, following complete resection. Adjuvant pembrolizumab has improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with high-risk melanoma, but many patients experience...

9523 Background: This study sought to describe the changes seen with FDG-PET following neoadjuvant immunotherapy in melanoma patients (pts), and explore associations with pathological response and recurrence-free survival (RFS). Methods: Two prospective clinical trial cohorts of stage III pts with RECIST measurable nodal melanoma were included; 1)...

9579 Background: NeoIT with anti-PD-1 (PD1) showed better event-free survival than adjuvant (adj)IT and is standard of care for pts with stage IIIB–D melanoma. Many pts achieve a Major Pathological Response with neoIT (MPR; complete [pCR] or near-complete [near-pCR] pathological response) and may not require additional Tx; pts with non-MPR (partial...

9520 Background: Immune checkpoint inhibitors (ICI) targeting PD-1 and CTLA-4 can achieve durable responses. Historically, therapies in advanced malignancies were considered palliative, however long-term results from ICI melanoma studies suggest cure may be possible for some patients (pts). Despite clinical trial data, little is known about the ris...

9581 Background: The identification of risk factors for CNS met in stage III melanoma pts will facilitate the development of personalized surveillance strategies. Previously we characterized the incidence (3.6%, 9.6%, and 15.8% at 1, 2, and 5 yrs) and risk factors for CNS met in pts diagnosed with stage III melanoma from 1998 to 2014. It is unknown...

Background. The recent implementation of immune-checkpoint inhibitors (ICIs) has markedly changed the management and clinical outcomes for patients with advanced non-small cell lung cancer (NSCLC). Despite higher efficacy, ICIs are associated with a range of immune-related adverse events (irAEs). This retrospective study aimed to investigate the in...

The biological underpinnings of therapeutic resistance to immune checkpoint inhibitors (ICI) in adolescent and young adult (AYA) melanoma patients are incompletely understood. Here, we characterize the immunogenomic profile and spatial architecture of the tumor microenvironment (TME) in AYA (aged ≤ 30 years) and older adult (aged 31–84 years) patie...

Background: The clinical efficacy of immune-checkpoint inhibitors is complicated by the risk for immune-related adverse events (irAEs) that can involve any organ systems. To date, (1) we cannot predict irAE risk reliably at patient level and (2) irAEs remain a diagnosis of exclusion as there are no specific clinical or biological markers. The goal...

Background: Approximately 1 in 3 pts with PD1-resistant MM will benefit from IPI+PD1, but the role of adding IPI in this context is unclear. We sought to (a) identify biomarkers and (b) determine mechanisms of response to IPI+PD1 in PD1 resistant pts. Methods: Pts with PD1-resistant MM subsequently treated with IPI+PD1 were included. We performed m...

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO...

Immune checkpoint blockade (ICB) targeting programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte protein 4 (CTLA-4) can induce remarkable, yet unpredictable, responses across a variety of cancers. Studies suggest that there is a relationship between a cancer patient’s gut microbiota composition and clinical response to ICB; however, def...

Background Adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) versus placebo in the phase 3 KEYNOTE-716 study of resected stage IIB or IIC melanoma. At the prespecified third interim analysis (data cut-off, January 4, 2022), the HR for RFS in the overall population was 0.64 (95%...

Protein kinase C (PKC) is activated downstream of gain-of-function GNAQ or GNA11 (GNAQ/GNA11) mutations in over 90% of uveal melanoma (UM). Phase I clinical trials of PKC inhibitors have shown modest response rates with no survival benefit in metastatic UM. Although PKC inhibitors actively suppress mitogen-activated protein kinase (MAPK) signalling...

Background Immune checkpoint inhibitor (ICI) gastrointestinal toxicity (gastritis, enteritis, colitis) is a major cause of morbidity and treatment-related death. Guidelines agree steroid-refractory cases warrant infliximab, however best management of infliximab-refractory ICI gastrointestinal toxicity (IRIGItox) is unknown. Methods We conducted an...

Background: The clinical efficacy of immune-checkpoint inhibitors is complicated by the risk for immune-related adverse events (irAEs) that can involve any organ systems. Among the most frequently observed irAEs are gastrointestinal and respiratory complications, which can significantly impact patients’ quality of life and treatment outcomes. Under...

The authors present a striking case of a patient experiencing a lichenoid drug eruption secondary to immunotherapy, curiously sparing scarred skin from past burns. We observed vastly higher amounts of inflammatory lymphoid cells staining for PD‐1; 70% in skin with a lichenoid drug reaction and 50% in scarred skin. The lack of a lichenoid reaction a...

Purpose In sentinel node-positive (SN+ve) melanoma patients, active surveillance with regular ultrasound examination of the node field has become standard, rather than completion lymph node dissection (CLND). A proportion of these patients now receive adjuvant systemic therapy and have routine cross-sectional imaging (computed tomography [CT] or po...

Introduction The COVID‐19 pandemic caused rapid implementation of telehealth for melanoma follow‐up care in Australia. This study explores Australian melanoma patients and clinicians' level of satisfaction with telehealth. Methods A cross‐sectional study was conducted across three specialist melanoma centres in Sydney, Australia. Melanoma patients...

Background Tumor microenvironment (TME) characteristics are potential biomarkers of response to immune checkpoint inhibitors in metastatic melanoma. This study developed a method to perform unsupervised classification of TME of metastatic melanoma. Methods We used multiplex immunohistochemical and quantitative pathology-derived assessment of immun...

Background: Liver metastases are associated with poor prognosis across cancers. Novel treatment strategies to treat patients with liver metastases are needed. This meta-analysis aimed to assess the efficacy of vascular endothelial growth factor inhibitors in patients with liver metastases across cancers. Methods: A systematic search of PubMed, C...

Importance: Anti-programmable cell death-1 (anti-PD-1) improves relapse-free survival when used as adjuvant therapy for high-risk resected melanoma. However, it can lead to immune-related adverse events (irAEs), which become chronic in approximately 40% of patients with high-risk melanoma treated with adjuvant anti-PD-1. Objective: To determine...

Background and Aim: Immune checkpoint inhibitors (ICIs) have heralded a new era in clinical oncology. These drugs selectively inhibit checkpoint molecules on T and antigen-presenting cells, thus boosting the proliferation and activation of cytotoxic T cells. In 2016, the programmed cell death antigen-1 inhibitor pembrolizumab was approved for first...

Background: Immune checkpoint inhibitors (ICIs) have revolutionized management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increa...

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO...

LBA9515 Background: The combination of mRNA-4157/V940 and pembrolizumab improved recurrence free survival (RFS) compared to pembrolizumab monotherapy in patients with resected high-risk stage III/IV cutaneous melanoma in the randomized Phase 2 mRNA-4157-P201/KEYNOTE-942 trial (RFS event rate of 22.4% (24/107) versus 40% (20/50); HR = 0.561; 95% CI:...

LBA9503 Background: mRNA-4157 is a novel mRNA-based personalized cancer vaccine which encodes up to 34 patient-specific tumor neoantigens. The open-label randomized Phase 2 mRNA-4157-P201/Keynote-942 trial met its primary endpoint of recurrence free survival (RFS) in patients with resected high-risk stage IIIB/C/D and IV melanoma. The study has sho...

LBA9505 Background: Adjuvant pembrolizumab significantly improved distant metastasis-free survival (DMFS) and recurrence-free survival (RFS) in patients with resected stage IIB or IIC melanoma versus placebo. We present the protocol-specified final DMFS analysis from KEYNOTE-716 (NCT03553836). Methods: Eligible patients were ≥12 years old with rese...

9591 Background: Adjuvant anti-PD1 improves relapse-free survival in high-risk, resected melanoma, but can lead to irAEs, which become chronic in up to 41% of patients (Patrinely et al, JAMA Onc 2021). Given the expanding use of anti-PD-1 in earlier settings in many tumors, it is imperative to assess their long-term effects. We aimed to determine t...

TPS9611 Background: Pembrolizumab is an anti−PD-1 monoclonal antibody that has been shown to significantly improve recurrence-free survival and distant metastasis-free survival when used as adjuvant therapy in patients with high-risk resected melanoma (Long GV, et al. Lancet Oncol. 2022;23:1378-88; Eggermont AMM, et al. Lancet Oncol. 2021;22:643-54...

Background: The open-label randomized Phase 2 mRNA-4157-P201/Keynote-942 trial met its primary endpoint of prolonged recurrence free survival (RFS) in patients with resected high-risk stage III/IV melanoma. Tumor immunogenicity provides a favorable landscape for inflammatory processes associated with clinical benefit to checkpoint inhibitors (ICI)...

BACKGROUND Checkpoint inhibitor–associated autoimmune diabetes mellitus (CIADM) is a distinct form of autoimmune diabetes that is a rare complication of immune checkpoint inhibitor therapy. Data regarding CIADM are limited. PURPOSE To systematically review available evidence to identify presentation characteristics and risk factors for early or se...

Increasing evidence strongly supports the key role of the tumour microenvironment in response to systemic therapy, particularly immune checkpoint inhibitors (ICIs). The tumour microenvironment is a complex tapestry of immune cells, some of which can suppress T-cell immunity to negatively impact ICI therapy. In this paper, we describe a protocol bui...

Background Gene expression profiling is increasingly being utilised as a diagnostic, prognostic and predictive tool for managing cancer patients. Single-sample scoring approach has been developed to alleviate instability of signature scores due to variations from sample composition. However, it is a challenge to achieve comparable signature scores...

Background: Different metastatic sites have distinct response rates to immune checkpoint inhibitors (ICI), suggesting that anatomical locations play a role in treatment response and survival. This project investigated the impact that sites of metastases present at baseline - ie. before starting treatment - have on the anatomical patterns of progres...

Purpose Patients with melanoma liver metastases have significantly reduced overall response and survival when treated with immune checkpoint inhibitors (ICI) compared to those without liver metastases. Melanoma liver metastases are less likely to respond to ICI compared to other sites of metastases, and the presence of liver metastases has also bee...

Background: While immune checkpoint inhibitors (ICI) have become the standard-of-care for advanced melanoma patients, only half of treated patients will survive beyond 5-years and many develop significant toxicity. The PIP study is combining pre-treatment clinical, molecular, and immunological profiles of melanoma patients to provide accurate predi...

Background: Metastatic Merkel cell carcinoma (mMCC) is highly responsive to immune checkpoint inhibitors (ICIs); however, durability of response after treatment cessation and response to retreatment in the setting of progression is unknown. Methods: Patients (pts) having mMCC from 10 centres who discontinued ICI treatment for a reason other than...

Background: Metformin is a commonly prescribed and well-tolerated medication. In laboratory studies, metformin suppresses BRAF wild-type melanoma cells but accelerates the growth of BRAF-mutated cells. This study investigated the prognostic and predictive value of metformin, including with respect to BRAF mutation status, in the European Organisat...

Increasing evidence strongly supports the key role of the tumour microenvironment in response to systemic therapy, particularly immune checkpoint inhibitors (ICIs). The tumour microenvironment is a complex tapestry of immune cells, some of which can suppress T-cell immunity to negatively impact ICI therapy. The immune component of the tumour microe...

Resistance to immune checkpoint inhibitor therapies in melanoma is common and remains an intractable clinical challenge. In this study, we comprehensively profile immune checkpoint inhibitor resistance mechanisms in short-term tumor cell lines and matched tumor samples from melanoma patients progressing on immune checkpoint inhibitors. Combining ge...

Late-Breaking Research Session

Immune-related adverse events (irAEs) are side effects of immune checkpoint inhibitor therapy (ICI). While common irAEs have been well characterized, there are more limited data on rare immune related adverse events (RirAEs) due to low incidence. Lack of characterization of these entities has led to difficulties in accurate diagnosis and management...

Background In patients with stage III melanoma, despite surgical resection and adjuvant systemic therapy, locoregional recurrences still occur. The randomized, phase III Trans-Tasman Radiation Oncology Group (TROG) 02.01 trial demonstrated that adjuvant radiotherapy (RT) after complete lymphadenectomy (CLND) halves the incidence of melanoma recurre...

The prognostic value of sentinel node biopsy (SNB) is well established and SNB was therefore adopted as a requirement for pathological staging of melanomas>1 mm thick in the American Joint Committee on Cancer (AJCC) 8th edition. Consequently, a negative SNB status became an eligibility criterion for clinical trials of adjuvant systemic therapy in r...

Purpose: This study characterizes intratumoural macrophage populations within baseline melanoma biopsies from patients with advanced melanoma who received either anti-PD-1 monotherapy or combination with anti-CTLA-4. Particularly, FcγRIIIa (CD16) expressing macrophage densities were investigated for associations with response and progression-free...

Immunotherapy targeting PD1 and/or CTLA4 leads to durable responses in a proportion of melanoma patients. However, many patients will not respond to these immune checkpoint inhibitors and up to 60% of responding patients will develop treatment resistance. We describe a vulnerability in melanoma driven by immune cell activity that provides a pathway...