Pilot trial of the hu14.18-IL2 immunocytokine in patients with completely resectable recurrent stage III or stage IV melanoma

AbstractPhase I testing of the hu14.18-IL2 immunocytokine (IC) in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5  mg/m2/day. Preclinical data in IC-treated tumor-bearing mice with low tumor burden documented striking antitumor effects. Patients with completely resectable recurrent stage III or stage IV melanoma were scheduled to receive 3 courses of IC at 6  mg/m2/day i.v. on days 1, 2 and 3 of each 28-day course. Patients were randomized to complete surgical resection either following neoadjuvant (Group A) or prior to adjuvant (Group B) IC course 1. Primary objectives were to: (1) evaluate histological evidence of anti-tumor activity and (2) evaluate recurrence-free survival (RFS) and OS. Twenty melanoma patients were randomized to Group A (11 patients) or B (9 patients). Two Group B patients did not receive IC due to persistent disease following surgery. Six of 18 IC-treated patients remained free of recurrence, with a median RFS of 5.7 months (95% confidence interval (CI) 1.8-not reached). The 24-month RFS rate was 38.9% (95% CI 17.5 –60.0%). The median follow-up of surviving patients was 50.0 months (range: 31.8–70.4). The 24-month OS rate was 65.0% (95% CI 40.3–81.5%). Toxicities were similar to those previously reported. Exploratory tumor-infiltrating lymphocyte (TIL) analyses suggest prognostic value of TILs from Group A patients. Prolonged tumor-free survival was seen in some melanoma ...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

Related Links:

CONCLUSION: irPR features are consistent across tumor types and treatment settings. Standardized, pan-tumor immune-mediated pathologic response criteria (irPRC) are defined and associated specimen-handling considerations are described. Future, prospective studies are merited to validate irPRC in larger datasets and to associate pathologic features with long-term patient outcomes. PMID: 31672770 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Purpose of review The aim of this review is to provide an overview of the current development of immuno-oncology in the (neo)adjuvant setting. Recent findings Several checkpoint inhibitors (CPis) have been approved for the treatment of advanced solid cancers, mostly for unresectable metastatic setting. Thus, the next logical step is to explore the potential of CPi in earlier stages of the disease. Summary There are currently many ongoing trials investigating immunotherapy agents in the early setting in various tumor types, involving various CPis and other innovative immunotherapies, as well as combinations with eit...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: INNOVATIVE AGENTS AND TREATMENT MODALITIES: Edited by Ahmad Awada and Steven T. Rosen Source Type: research
Abstract Immunotherapy has led to unprecedented improvement in the treatment and prognosis of high-risk resectable and metastatic disease across cancer types. Nowhere is this better highlighted than in the management of advanced and metastatic melanoma with the introduction of molecularly targeted therapies and immune checkpoint inhibitors. Following their success in melanoma, immunotherapies have also been evaluated and their use approved in the management across a variety of other solid malignancies in the neoadjuvant, adjuvant, and advanced/metastatic setting. This review provides an overview of the current lan...
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Tags: Surg Oncol Clin N Am Source Type: research
Immunotherapy has led to unprecedented improvement in the treatment and prognosis of high-risk resectable and metastatic disease across cancer types. Nowhere is this better highlighted than in the management of advanced and metastatic melanoma with the introduction of molecularly targeted therapies and immune checkpoint inhibitors. Following their success in melanoma, immunotherapies have also been evaluated and their use approved in the management across a variety of other solid malignancies in the neoadjuvant, adjuvant, and advanced/metastatic setting. This review provides an overview of the current landscape of immune c...
Source: Surgical Oncology Clinics of North America - Category: Surgery Authors: Source Type: research
Abstract Cancer immunotherapies utilizing immune checkpoint inhibitors (ICIs) have demonstrated durable efficacy in a proportion of patients with advanced/metastatic cancers. More recently, the use of ICIs for the adjuvant treatment of patients with surgically resectable melanoma have also demonstrated efficacy by improving relapse-free survival and in the case of ipilimumab (anti-CTLA-4) also improving overall survival. While promising, the effective scheduling of surgery and immunotherapy and its duration is not well elucidated. Recent preclinical studies suggest that surgery followed by adjuvant therapy might b...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Michal Yalon1†, Amos Toren1,2†, Dina Jabarin2, Edna Fadida3, Shlomi Constantini3 and Ruty Mehrian-Shai1* 1Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel 2The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel 3Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, we evaluated the therapeutic benefit of combining the TAB004 antibody with Liposomal-MSA-IL-2 in immune competent and human MUC1 transgenic (MUC1.Tg) mouse models of PDA and investigated the associated immune responses. Treatment with TAB004 + Lip-MSA-IL-2 resulted in significantly improved survival and slower tumor growth compared to controls in MUC1.Tg mice bearing an orthotopic PDA.MUC1 tumor. Similarly, in the spontaneous model of PDA that expresses human MUC1, the combination treatment stalled the progression of pancreatic intraepithelial pre-neoplastic (PanIN) lesion to adenocarcinoma. Treatment with t...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Ginevra Doglioni1,2†, Sweta Parik1,2† and Sarah-Maria Fendt1,2* 1Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium 2Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute, Leuven, Belgium Metastasis formation is the leading cause of death in cancer patients. Thus, understanding and targeting this process is an unmet need. Crucial steps during the establishment of metastases include the (pre)metastatic niche formation. This process relies on the interaction of th...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Seon Ah Lim1†, Jungwon Kim1†, Seunghyun Jeon1†, Min Hwa Shin1, Joonha Kwon1, Tae-Jin Kim1, Kyungtaek Im1, Youngmin Han2, Wooil Kwon2, Sun-Whe Kim2, Cassian Yee3, Seong-Jin Kim4*, Jin-Young Jang2* and Kyung-Mi Lee1,3,5* 1Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, South Korea 2Department of Surgery and Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea 3Department of Melanoma Medical Oncology and Immunology, MD Anderson Cancer Center, Houston, TX, United States 4Prec...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
More News: Allergy & Immunology | Cancer | Cancer & Oncology | Immunotherapy | Melanoma | Neoadjuvant Therapy | Skin Cancer | Toxicology