Final results of a phase II immunotherapy trial for stage III and IV melanoma patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19008-e19008
Author(s):  
Adam Irwin Riker ◽  
Gabriela R. Rossi ◽  
Leonard C Alsfeld ◽  
Fiona Denham ◽  
Lucinda Tennant ◽  
...  
Keyword(s):  
Phase Ii ◽  
Progressive Disease ◽  
Tumor Regression ◽  
Stage Iv ◽  
Pegylated Interferon ◽  
Stage Iii ◽  
Effective Treatment Option ◽  
Autoimmune Antibodies ◽  
Melanoma Patients ◽  
Resected Stage

e19008 Background: Patients with metastatic melanoma have a poor outcome. We hypothesize that combination immunotherapy can synergistically activate host immunity to generate an effective treatment option for high risk, resected stage III, recurrent, refractory or stage IV melanoma patients. Methods: We completed a phase II clinical trial of HyperAcute-Melanoma vaccine (HAM, NLG12036, NewLink Genetics) combined with pegylated interferon (Sylatron, Merck). Trial design was a 12-week regimen with the initial 4 weekly treatments consisting of HAM alone (intradermally) followed by 8 additional treatments of HAM + Sylatron (subcutaneously, 6 µg/kg). Trial endpoints include clinical response, overall safety and correlative findings for observed anti-tumor effect. Results: N=25, median age 60, 68% male with 21 patients completing the trial, 4 stopped due to progressive disease (PD). HAM-related common side effects include erythema and induration at the injection site, without significant grade 3 or 4 toxicities associated with the vaccine. By RECIST criteria, of 16 stage IV patients, there were 2 complete responders (CR), 2 with stable disease (SD) and 3 with no evidence of disease (NED) after resection. For stage III patients, 3/9 remain NED, 1 patient with slowly progressive disease remaining alive for over 30 months. The median overall survival is 29 months, with 50% of the patients surviving for 2 years and 12/25 (48%) still alive. The anti-αGal Ab values increased after vaccination in 24/25 patients by up to 100-fold (median 15, range 3-127). All evaluable patients (21/21) seroconverted, developing autoimmune antibodies. Anti-tyrosinase Ab’s developed in 7/23 correlating with 1 CR and 1 patient NED. Vitiligo developed in 4/25 patients, correlating with 2 CR and 2 NED. Conclusions: Combinatorial immunotherapy with HAM plus Sylatron shows clinical efficacy with tumor regression and concomitant immune activation. Optimization of dosing schedules and addition of other potentially synergistic agents should be explored to further enhance the benefit of this immunotherapeutic approach.

Multi-institutional, prospective, randomized, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine to prevent recurrence in high-risk melanoma patients: A subgroup analysis.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 63-63
Author(s):  
Robert Connor Chick ◽  
Mark B. Faries ◽  
Diane F. Hale ◽  
Phillip M. Kemp Bohan ◽  
Annelies Hickerson ◽  
...  
Keyword(s):  
High Risk ◽  
Subgroup Analysis ◽  
Stage Iv ◽  
Stage Iii ◽  
Tumor Lysate ◽  
High Risk Melanoma ◽  
Risk Melanoma ◽  
Melanoma Patients ◽  
Resected Stage ◽  
Disease Free

63 Background: A novel vaccine strategy may prevent recurrence in high-risk melanoma patients (pts). The TLPLDC vaccine uses yeast cell wall particles (YCWP) to load tumor lysate into autologous dendritic cells (DC). In this phase IIb trial of TLPLDC vs. placebo in resected stage III/IV pts, TLPLDC increased 24 month (mo) disease free survival (DFS) in the per treatment (PT) population. Here, we present a 24mo DFS subgroup analysis and estimated overall 36mo DFS. Methods: Disease-free pts were randomized 2:1 to the TLPLDC vaccine vs. unloaded YCWP+DC at 0, 1, 2, 6, 12, and 18mo. The protocol was amended to allow concurrent adjuvant checkpoint inhibitor (CPI) therapy once approved. The pre-specified PT population included only pts completing the primary vaccine/placebo series (PVS) at 6 mo. Kaplan-Meier estimates of DFS were used to compare treatment arms by stage (III or IV) and CPI therapy (yes/no) in the ITT and PT populations. Results: 144 pts were randomized (103 TLPLDC, 41 placebo); 98 pts (66 TLPLDC, 32 placebo) completed the PVS. There were no clinicopathologic differences between treatment groups. There was no difference in 24mo DFS in stage III pts (n = 112), but in stage IV pts (n = 32), the 24mo DFS was 44% vs 0% (TLPLDC vs placebo) (p = 0.41) in ITT and 73.3% vs. 0% (HR 0.14, p = 0.002) in PT. Stage IV pts were more likely to receive CPI than stage III pts (50% vs. 30%, p = 0.003). There was no difference in 24mo DFS for pts who did not receive CPI (n = 102), but in pts who received CPI (n = 42), the 24mo DFS was 49.3% vs. 31.3% (p = 0.71) in ITT and 68.8% vs. 41.7% (HR 0.46, p = 0.28) in PT, showing a trend toward improved DFS in pts who completed the PVS and received CPI (n = 31). Overall, the 36mo estimated DFS was 34.2% vs. 21.6% (p = 0.89) for ITT and 56.9% vs. 27.9% (p = 0.021) for PT. Conclusions: The TLPLDC vaccine improved DFS in patients completing the PVS at 24 and 36 mos, particularly in the resected stage IV subset. The apparent synergistic effect with TLPLDC + CPI will be confirmed in a phase III study evaluating adjuvant TLPLDC + CPI vs. CPI alone in resected stage IV melanoma pts. Clinical trial information: NCT02301611.

A phase II study of intratumoral application of L19IL2/L19TNF in melanoma patients in clinical stage III or stage IV M1a with presence of injectable cutaneous and/or subcutaneous lesions.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. TPS9103-TPS9103 ◽  
Author(s):  
Riccardo Danielli ◽  
Roberto Patuzzo ◽  
Anna Maria Di Giacomo ◽  
Gianfranco Gallino ◽  
Annabella Di Florio ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Clinical Stage ◽  
Stage Iv ◽  
Stage Iii ◽  
Melanoma Patients

scholarly journals Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial

The Lancet ◽  
2008 ◽  
Vol 372 (9633) ◽  
pp. 117-126 ◽  
Author(s):  
Alexander MM Eggermont ◽  
Stefan Suciu ◽  
Mario Santinami ◽  
Alessandro Testori ◽  
Wim HJ Kruit ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Pegylated Interferon ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Stage Iii ◽  
Phase Iii Trial ◽  
Pegylated Interferon Alfa ◽  
Stage Iii Melanoma ◽  
Resected Stage

scholarly journals 300 Final analysis of a prospective, randomized, double-blind, placebo-controlled phase IIb trial of tumor lysate, particle-loaded, dendritic cell vaccine in stage III/IV melanoma: 36-month analysis

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A327-A327
Author(s):  
Lexy Adams ◽  
Robert Chick ◽  
Guy Clifton ◽  
Timothy Vreeland ◽  
Patrick McCarthy ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Stage Iv ◽  
Standard Of Care ◽  
Stage Iii ◽  
Tumor Lysate ◽  
Double Blind ◽  
Free Survival ◽  
Resected Stage ◽  
Disease Free ◽  
Stage Iv Melanoma

BackgroundThe tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is created ex vivo by loading autologous dendritic cells (DC) with yeast cell wall particles (YCWP) containing autologous tumor lysate, thus delivering tumor antigens to the DC cytoplasm via phagocytosis. TLPLDC then activates a robust T cell response against the unique antigens for each patient. The primary analysis of the prospective, randomized, multi-center, double-blind, placebo-controlled phase IIb trial in patients with resected stage III/IV melanoma showed TLPLDC improved 24-month disease-free survival (DFS) in the per-treatment (PT) analysis (patients completing the 6-month primary vaccine series). Here, we examine the secondary endpoint of 36-month DFS and overall survival (OS).MethodsPatients with resected stage III/IV melanoma were randomized 2:1 to TLPLDC vaccine or placebo (autologous DC loaded with empty YCWP). Treatments were given at 0, 1, 2, 6, 12 and 18 months. The protocol was amended to include patients receiving concurrent checkpoint inhibitors (CPIs) to follow changes in standard of care. The co-primary endpoints were 24-month DFS by intention-to-treat (IT) analysis and per-treatment (PT) analysis, with secondary endpoints including 36-month DFS and OS by ITT and PT analysis, pre-specified analysis by stage, and safety as measured by CTCAE v4.03.ResultsOverall, 103 patients received TLPLDC and 41 placebo. In PT analysis, 65 patients received TLPLDC and 32 placebo. Total adverse events (AEs), grade 3+ AEs, and serious AEs (SAEs) were similar in placebo vs TLPLDC groups, with one related SAE per treatment arm. By ITT analysis, 36-month OS was 76.2% for TLPLDC vs 70.3% for placebo (HR 0.72, p=0.437) and 36-month DFS was 35.6% vs 27.1% (HR 0.95, p=0.841). By PT analysis, 36-month DFS was improved with TLPLDC (57.5% vs 35.0%; HR 0.50, p=0.025, figure 1). This effect was even more dramatic in resected stage IV patients (36-month DFS: 60.9% vs 0%; HR 0.12, p=0.001, figure 2).ConclusionsThis phase IIb trial again demonstrates the safety of the TLPLDC vaccine, and an improved 36-month DFS in patients with resected stage III/IV melanoma who complete the primary vaccine series, particularly in the stage IV subgroup. Next, a phase III trial will evaluate the efficacy of TLPLDC vaccine as adjuvant treatment for resected stage IV melanoma, with patients randomized to receive standard of care PD-1 inhibitors + TLPLDC versus PD-1 inhibitors + placebo.Abstract 300 Figure 136-month disease free survival for patients receiving TLPLDC vs placebo by PT analysisAbstract 300 Figure 236-month disease free survival for subset of stage IV melanoma patients receiving TLPLDC vs placebo by PT analysisTrial RegistrationThis is a phase IIb clinical trial registered under NCT02301611Ethics ApprovalThis study was approved by Western IRB, protocol 20141932.

Phase II study of aflibercept (VEGF trap) in recurrent inoperable stage III or stage IV melanoma of cutaneous or ocular origin

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9028-9028
Author(s):  
A. A. Tarhini ◽  
S. Christensen ◽  
P. Frankel ◽  
K. Margolin ◽  
C. Ruel ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Angiogenesis Inhibitor ◽  
Stage Iv ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Stage Iii ◽  
Unknown Primary ◽  
Vegf Receptor ◽  
Stage Iv Melanoma

9028 Background: Aflibercept is a fusion protein combining the Fc portion of human IgG1with the extracellular ligand-binding domains of human VEGFR1 and VEGFR2, acting as a high-affinity soluble VEGF receptor and potent angiogenesis inhibitor. Methods: Phase II study of aflibercept in patients with inoperable stage III or IV melanoma who had received no prior chemotherapy or hormonal therapy. A 2-stage design was adopted focusing upon response rate (RECIST) and 4-month PFS rate. First stage accrual of 21 patients was specified, while final accrual of 41 is planned, with adequate response/4 month PFSR. Aflibercept was given at 4 mg/kg IV every 2 weeks. Response was assessed every 8 weeks. Results: Twenty seven patients (16 male, 11 female), age 23–83 (median 58) have been enrolled to date. All had AJCC stage IV melanoma (3M1a, 3M1b, 21M1c). Karnofsky PS: 100 (13), 90 (11) or 80 (3). Nine patients had primary ocular melanoma, 16 cutaneous and 2 unknown primary site. A total of 160 cycles have been administered (median 4; range 1–18). Grade 3/4 toxicities included cerebral ischemia (1 patient; 4%), confusion (1; 4%), thrombocytopenia (1; 4%), hypertension (7; 26%), hypotension (1; 4%), left ventricular diastolic dysfunction (1; 4%), fatigue (1; 4%), proteinuria (4; 15%), extraocular muscle paresis (1; 4%), renal failure (1; 4%), back pain (1; 4%), headache (1; 4%). Interim analysis was conducted after the first 21 patients (stage 1). Eight (1 M1a, 1M1b, 6M1c; 4 ocular, 3 cutaneous, 1 unknown primary) of the first 21 patients had at least 4 months of PFS (10 out of 27; 2 additional patients with cutaneous melanoma had SD: 1M1a and 1M1c). One patient (23rd; cutaneous, M1c) had a confirmed complete remission. Four patients were taken off study prior to response evaluation for toxicity (3) or treatment refusal (1). One patient is currently disease free who was not evaluable for response (previous surgery and radiofrequency ablation of measurable disease site). Eleven patients had progression. Conclusions: Aflibercept can be administered with acceptable toxicity, and exhibits promising antitumor efficacy against advanced melanoma. This study continues second stage accrual with anticipated closure before June 2009. [Table: see text]

A phase II single arm study of pazopanib and paclitaxel as first-line treatment for unresectable stage III and stage IV melanoma: Interim analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8524-8524 ◽  
Author(s):  
John P. Fruehauf ◽  
Beverly Alger ◽  
Basmina Parmakhtiar ◽  
James G. Jakowatz ◽  
Claudette Bettis ◽  
...  
Keyword(s):  
Phase Ii ◽  
Interim Analysis ◽  
Cell Cancer ◽  
Stage Iv ◽  
Stage Iii ◽  
First Line ◽  
Open Label ◽  
Unresectable Stage ◽  
Biomarker Analysis ◽  
Stage Iv Melanoma

8524 Background: Metastatic melanoma lacks effective therapy. Pazopanib is a small-molecule inhibitor of VEGFR-1,2,3, PDGFR-B and c-KIT that has antiangiogenic activity in renal cell cancer as well as inhibition of melanoma tumor xenografts. We designed a phase II single arm, open label clinical trial evaluating pazopanib in combination with metronomic paclitaxel as first line therapy for subjects with unresectable stage III and stage IV melanoma. Methods: This protocol utilizes a Simon 2-stage Minimax design, with a planned interim analysis to confirm >3 responders to move to the second stage. To date, 20 eligible patients have been enrolled with 17 evaluable for response. All subjects were treatment naïve and received paclitaxel at 80mg/m2 weekly for three weeks in a 4 week cycle and pazopanib at 800mg as a continuous daily oral dose. The primary endpoint is 6 month progression free survival. Exploratory endpoints include biomarker analysis that may be associated with treatment outcomes (serum VEGF, soluble VEGF R2, serum HIF, serum TSP1 and BRAF mutation status). An additional exploratory endpoint includes the in vitro activity of pazopanib and paclitaxel on patient biopsy material co-cultured with vascular endothelial cells. RECIST criteria were used to define treatment response. Results: For the 17 evaluable patients treated to date the following results were seen: 1 CR, 6 PR’s, 8 SD’s and 2 PD’s. The overall RR (CR+PR) was 40%. Total disease control rate was 80% (PR+SD). The most common AEs/lab abnormalities were nausea (71%), hypertension (57%), fatigue (57%) and vomiting (43%). Grade 3-4 AEs included hypertension (28%), transaminitis (21%) and neutropenia (14%). One patient discontinued for grade 4 transaminitis which subsequently resolved completely. Dose reductions were required for pazopanib in 5 patients and for paclitaxel in one patient. Conclusions: Planned interim analysis of this phase II study demonstrated that pazopanib in combination with paclitaxel was well tolerated and resulted in a 40% response rate, indicating that this combination is of further interest. Accrual will continue to reach a goal of 60 patients.

The efficacy of oxaliplatin-based adjuvant chemotherapy for stage IV colorectal cancer after R0 resection.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 638-638
Author(s):  
Izuma Nakayama ◽  
Mitsukuni Suenaga ◽  
Takeru Wakatsuki ◽  
Mariko Ogura ◽  
Masato Ozaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Adjuvant Chemotherapy ◽  
Stage Iv ◽  
Completion Rate ◽  
Phase Iii ◽  
Stage Iii ◽  
R0 Resection ◽  
Significant Prognostic Factor ◽  
Resected Stage

638 Background: In previous phase III studies (MOSAIC and XELOXA trial), oxaliplatin based chemotherapy was shown to be a standard adjuvant treatment for stage III colorectal cancer (CRC). However, its efficacy for curatively resected stage IV CRC has not yet been clarified. In this retrospective study, we evaluate the efficacy of oxaliplatin based chemotherapy in adjuvant setting for curatively resected stage IV CRC. Methods: Eighty-three patients received adjuvant chemotherapy after R0 resection for Stage IV CRC in our institute between Mar 2007 and Feb 2013. Progression-free survival (PFS), overall survival (OS), completion rate of the treatment and safety were evaluated. Median follow-up time was 33.3 months. Results: Baseline characteristics were as follows (N=83): median age, 61; male/female, 46/37; ECOG PS0, all; colon/rectum, 54/29; synchronous/asynchronous, 41/42. Metastatic sites were liver in 46, lung in 11, peritoneum in 13, lymph node in 12 patients. Median PFS and OS were not reached. Three-year PFS and OS were 67.8% and 88.2%, respectively. Completion rate was 78.6% of the patients. In univariate analysis, completion of treatment, synchronous development and metastasis limited to lung were associated with better PFS, though not statistically significant. Confirmed regional lymph node metastasis of primary tumor showed a trend toward to concern with poor OS. Differences in metastatic site were not observed in both PFS and OS. Multivariate analysis revealed none as a significant prognostic factor. Conclusions: Compared the results to previous trial for stage III CRC, oxaliplatin based adjuvant chemotherapy for stage IV CRC after R0 resection was demonstrated to be consistent in tolerability and efficacy.

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