scholarly journals 49P A phase II randomized trial with adjuvant autologous tumor lysate-pulsed dendritic cells (DC) in resected stage III-IV melanoma patients: Preliminary immunological results

2021 ◽  
Vol 32 ◽  
pp. S1394
Author(s):  
L. Ridolfi ◽  
J. Bulgarelli ◽  
C. Piccinini ◽  
S. Carloni ◽  
A. Granato ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Randomized Trial ◽  
Phase Ii ◽  
Stage Iii ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Melanoma Patients ◽  
Resected Stage

A prospective, randomized, blinded, placebo-controlled, phase IIb trial of an autologous tumor lysate + yeast cell wall particles (YCWP) + dendritic cells (DC) vaccine vs unloaded YCWP + DC and embedded phase I/IIa trial with tumor lysate particle only (TLPO) vaccine in stage III and stage IV (resected) melanoma to prevent recurrence.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. TPS201-TPS201 ◽  
Author(s):  
John W Myers ◽  
Garth S Herbert ◽  
Guy T Clifton ◽  
Timothy J Vreeland ◽  
Tommy A Brown ◽  
...  
Keyword(s):  
Cell Wall ◽  
Dendritic Cells ◽  
High Risk ◽  
Yeast Cell ◽  
Yeast Cell Wall ◽  
Stage Iii ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Risk Of Recurrence ◽  
Disease Free

TPS201 Background: Melanoma is a potentially lethal skin malignancy; patients with stage III/IV resected disease have a recurrence rate of 50-90%. Adjuvant checkpoint inhibitor immunotherapy decreases the risk of recurrence but also causes significant immune-related toxicity. Vaccines are a promising strategy for patients with high risk melanoma. The optimal time to intervene may be in the adjuvant setting after attaining a disease-free state through standard of care therapies. Our strategy uses autologous tumor lysate (TL) in a yeast cell wall particle (YCWP) to load dendritic cells (DC) ex vivo. The tumor lysate particle loaded dendritic cell (TLPLDC) vaccine is then given to prevent melanoma recurrences. An alternate vaccine delivery method that we are evaluating utilizes the tumor lysate particle-only (TLPO) technique, in which tumor lysate is loaded into capped YCWP and injected intradermally, allowing an in vivo uptake by the patient’s dendritic cells. Methods: We are performing a prospective, randomized, blinded, placebo-controlled phase IIb trial in patients with resected stage III/IV melanoma who have been rendered disease-free but remain at high risk of recurrence. The study will utilize the TLPLDC strategy vs placebo (2:1) in 120 patients, followed by a bridging study of TLPO vs TLPLDC (2:1) in 60 patients. Both TLPLDC and TLPO inoculations will be monthly x3, followed by boosters at 6, 12, and 18 months. Primary endpoints will be disease free survival (DFS) at 24 months in the TLPLDC arm, and overall safety in the TLPO arm. We have completed enrollment in the phase IIb portion of the study. Clinical trial information: NCT02301611.

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.

Preliminary results of a phase II-study: Vaccination therapy of pancreatic carcinoma patients with autologous, tumor lysate pulsed dendritic cells

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14102-14102
Author(s):  
C. Bauer ◽  
M. Dauer ◽  
M. Schnurr ◽  
J. Junkmann ◽  
F. Bauernfeind ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Pancreatic Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Dendritic Cell Vaccination ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Local Disease ◽  
Vaccination Therapy

14102 Background: Vaccination trials in the experimental and in the clinical setting have shown that it is possible to use dendritic cells (DC) to induce a specific antitumoral immune response. In this study, a protocol for the treatment of patients with metastasised pancreatic carcinoma with autologous, tumor-lysate pulsed dendritic cells was established. Methods: Patients with strong suspicion of pancreatic carcinoma receiving abdominal surgery are recruited to the study. Tumor-lysate is derived by freeze-taw-cycles from surgically derived tissue specimens. After recurrence of histologically verified pancreatic carcinoma or in a primarily palliative situation, patients are eligible for DC vaccination. DC are derived from PBMC according to a six-day protocol, loaded with tumor lysate and stimulated with TNF-alpha and PgE2. DC are applicated intracutaneously into the groin region three times in twice weekly cycles, then in monthly cycles. Immune response is controlled by DTH skin testing. Samples of non adherent cells are frozen for future MLR and ELISPOT assays. Main study end point is partial or complete remission four months after the start of vaccination. Alternative end points are adverse effects, quality of life, one-year survival and immuno-monitoring. Results: Tumor material of 49 patients has been worked up to tumor lysate and stored for future vaccinations. Four patients have received dendritic cell vaccination. Two of these patients have received their four months staging CT. In one case local disease was stable. The other patient showed progressive disease. A more pronounced proliferation of specific T cells compared to the control setting could be demonstrated by MLR assay. Discussion: A protocol for vaccination with tumor lysate pulsed dendritic cells of patients with pancreatic carcinoma has been established. Four patients have been vaccinated with dendritic cells according to a phase II study protocol. Vaccination was tolerated well. Because of a severe adverse reaction after the beginning of gemcitabine therapy, vaccination had to be omitted intercurrently with this patient. Results of most immuno monitoring assays are pending. One patient receiving DC vaccination therapy showed stable local disease. No significant financial relationships to disclose.

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.

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