Featured Clinical Trial: Immunotherapy for Patients with Metastatic Melanoma

2004 ◽  
Author(s):  
Keyword(s):  
Clinical Trial ◽  
Metastatic Melanoma

scholarly journals Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial

2012 ◽  
Vol 28 (4) ◽  
pp. 1131-1138 ◽  
Author(s):  
CHIE OSHITA ◽  
MASAKO TAKIKAWA ◽  
AKIKO KUME ◽  
HARUO MIYATA ◽  
TADASHI ASHIZAWA ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Dendritic Cell ◽  
Metastatic Melanoma ◽  
Phase Ii ◽  
Phase Ii Clinical Trial ◽  
Melanoma Patients

Phase 1 study to evaluate safety and efficacy of ipilimumab + nivolumab + external beam radiotherapy in patients with metastatic melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS9591-TPS9591
Author(s):  
Michael Andrew Postow ◽  
Susan Jane Knox ◽  
Danielle McCabe ◽  
Mary J. Macri ◽  
Paul Schwarzenberger ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Metastatic Melanoma ◽  
Phase 1 ◽  
External Beam Radiotherapy ◽  
Objective Response ◽  
Palliative Therapy ◽  
Dose Fractionation ◽  
High Dose ◽  
Melanoma Metastasis ◽  
Open Label

TPS9591 Background: Immunotherapy (IMT) with checkpoint blocking antibodies has led to progress in metastatic melanoma with 3 FDA-approved drugs, including the combination of ipilimumab (IPI), a CTLA-4 antibody, and nivolumab (NIVO), a PD-1 antibody. Although radiotherapy (RT) is primarily used as local palliative therapy in metastatic melanoma, it also possibly affects systemic antitumor immunity. Preclinical data suggest RT alters the tumor microenvironment and renders tumor cells more susceptible to immunologically-mediated disease regression. These preclinical immunologic effects of RT have been shown to vary by RT dose and fractionation. We are now conducting the first clinical trial in patients to evaluate the triple combination of IPI + NIVO + RT using 2 different dose/fractionation schemes of RT. Methods: This ongoing Phase 1, open-label, multicenter study (NCT02659540) evaluates safety, efficacy, and immunologic effects of IPI + NIVO + RT in 18 patients with unresectable stage IV melanoma. Patients must have 1 melanoma metastasis that can be safely irradiated for palliative purposes and at least 1 measurable lesion that will not be irradiated. Patients receive concurrent IPI (3 mg/kg) and NIVO (1 mg/kg) every 3 weeks (Q3W) x 4, followed by NIVO monotherapy (240 mg Q2W), with RT initiated between the first and second doses of IPI + NIVO. In Cohort A, the irradiated metastasis receives a conventionally fractionated low dose of 30 Gy in 10 fractions of 3 Gy each over 2 weeks. If ≤7 of 9 patients (78%) in Cohort A have Grade 3/4 drug- or radiation-related adverse events, safety is deemed acceptable and Cohort B enrollment opens. In Cohort B, the irradiated metastasis receives a hypofractionated high dose of 27 Gy in 3 fractions of 9 Gy each over 2 weeks. The primary endpoint is safety. Secondary endpoints are objective response rate and disease control rate by RECIST and immune-related RECIST measured at Weeks 12 and 18, duration of response, progression-free survival, and overall survival. Exploratory endpoints include correlative studies of immunological effects. Enrollment opened on 05 Aug 2016. As of 31 Dec 2016, 4 patients are enrolled in Cohort A; enrollment is ongoing. Clinical trial information: NCT02659540.

Salvage chemotherapy in the treatment of metastatic melanoma after progression on immunotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22019-e22019
Author(s):  
Payal Shah ◽  
Patrick Boland ◽  
Anna C. Pavlick
Keyword(s):  
Clinical Trial ◽  
Metastatic Melanoma ◽  
Retrospective Analysis ◽  
Checkpoint Inhibitors ◽  
Small Sample Size ◽  
Single Agent ◽  
Complete Response ◽  
Salvage Chemotherapy ◽  
Small Sample ◽  
Clinical Trial Evidence

e22019 Background: Immune-checkpoint inhibitors (ICI) have dramatically altered the prognosis of metastatic melanoma (MM); however, fifty percent of patients will not respond to ICI. For these patients, the next choice of treatment includes targeted therapy or a clinical trial if eligible. If these treatment choices have already been utilized or are not available to the patient, there may be value in attempting a course of salvage chemotherapy (CTX). Limited clinical trial evidence has demonstrated unexpected efficacy of CTX after prior progression on ipilimumab, offering higher disease control rates than expected from what is seen in first-line chemotherapy. The phenomenon of a “priming” effect of ICI on CTX efficacy has been shown in patients of various solid tumors after progression on anti-PD1/PD-L1 therapy. The purpose of this retrospective analysis is to evaluate the efficacy of salvage CTX after prior ICI therapy for patients with MM. Patients with ocular melanoma were excluded, as this tumor subtype is known to have reduced response to immunotherapy. Methods: By retrospective analysis, patients were included under an IRB approved waiver of consent. We identified patients with MM treated with ICI therapy between Jan, 2011 and July, 2019 who were subsequently treated with salvage CTX as a result of progression of disease (POD). Salvage CTX included dacarbazine, carboplatin, temozolomide, paclitaxel, or a combination. We assessed response rate, duration of response, and time to progression (TTP) from the onset of salvage CTX. Results: A total of 22 patients who satisfied the above criteria were identified. The majority of this population had a course of single agent ICI as well as a course of combination ICI prior to salvage CTX (72.7%, n = 16/22). 13 (59.1%) patients had POD on salvage CTX with a median TTP of 10.9 weeks. 9 (40.9%) patients responded to salvage CTX. 3 (13.6%) patients achieved a complete response, 4 (18.2%) patients achieved a partial response and 2 (9.1%) patients achieved stable disease. Mean durability of response was 53.6 weeks, ranging from 7-194 weeks. Conclusions: ICI “priming” prior to salvage CTX efficacy may improve disease responsiveness to CTX. This sequence of therapy may offer patients another reasonable treatment option. Despite the small sample size of this study, a prospective clinical trial in MM exploring CTX following ICI progression should be considered.

A phase II study of anti-PD1 monoclonal antibody (Nivolumab) administered in combination with anti-LAG3 monoclonal antibody (Relatlimab) in patients with metastatic melanoma naive to prior immunotherapy in the metastatic setting.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS10085-TPS10085
Author(s):  
Anjali Rohatgi ◽  
Ryan Campbell Massa ◽  
William E. Gooding ◽  
Tullia C. Bruno ◽  
Dario Vignali ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
Metastatic Melanoma ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Disease Assessment ◽  
Survival Duration ◽  
Metastatic Setting

TPS10085 Background: Novel checkpoint inhibitors are a promising treatment for advanced melanoma, as only a fraction of patients have durable responses to current FDA-approved immunotherapy. Lymphocyte activation gene 3 (LAG3) is an inhibitory checkpoint receptor on CD4+ and CD8+ T cells, where engagement results in suppression of T cell activation and proliferation. LAG3 and PD1 are co-expressed on T cells during T cell receptor signaling and are down-regulated after antigen clearance. Persistent stimulation leads to prolonged LAG3 and PD1 expression and to T cell exhaustion, a possible mechanism of resistance to immunotherapy. Both LAG3 and PD1 are expressed on tumor-infiltrating T cells in melanoma. Murine tumors treated with both anti-LAG3 and anti-PD1 have demonstrated increased tumor regression than tumors in mice treated with either single agent. Further, a phase I trial has demonstrated safety of combined anti-LAG3 monoclonal antibody, relatlimab and anti-PD1 monoclonal antibody, nivolumab. Methods: This phase II, single-center clinical trial is designed to enroll treatment naive patients with unresectable or metastatic melanoma to ultimately receive combined relatlimab and nivolumab after a lead-in arm where patients are randomized to receive relatlimab, nivolumab, or the combination for the first 4 week cycle. For the lead-in phase, patients will have baseline and post-treatment blood and tumor sampling. Disease assessment by imaging will occur after the lead-in phase at 4 weeks. After completion of the lead-in phase, all patients proceed to combination therapy with disease assessment at 12-week intervals. The primary endpoint for the lead-in phase is to evaluate changes in immune cell populations in peripheral blood and tumor with the single agents and combination treatment. The primary endpoint for the combination phase is best overall anti-tumor response. Secondary clinical endpoints include progression-free survival, overall survival, duration of response and toxicity. Exploratory endpoints are to determine the mechanistic effects of anti-LAG3 and anti-PD1 on the blood and tumor microenvironment, cytokine signatures, and correlation of these with clinical response. The study is currently accruing with enrollment of 9 out of 42 patients. Clinical trial information: NCT03743766.

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