tumor lysate particle loaded dendritic cell vaccine (TL-YCWP-DC) / Orbis Health Solutions - LARVOL DELTA

WIRB Protocol: 20141932: Phase IIB TL + YCWP + DC in Melanoma (clinicaltrials.gov) - P2 | N=187 | Completed | Sponsor: Elios Therapeutics, LLC | Phase classification: P2b ➔ P2

Metastases • Phase classification • Melanoma • Oncology • Solid Tumor

Tumor lysate particle only vaccine (TLPO) vs. Tumor lysate particle-loaded, dendritic cell vaccine (TLPLDC) to prevent recurrence in resected stage III/IV melanoma patients: Results of a phase I/IIa trial. (PubMed, Cancer Treat Res Commun) - "In a randomized, double-blind Phase I/IIa trial, there were no differences in DFS or OS in resected Stage III/IV melanoma patients receiving adjuvant TLPO versus TLPLDC vaccines. Given manufacturing advantages, further efficacy testing of TLPO is warranted in a Phase III trial."

Clinical • Journal • P1/2 data • Melanoma • Oncology • Solid Tumor

Multi-center Phase I/IIa Trial of an Autologous Tumor Lysate (TL) + Yeast Cell Wall Particles (YCWP) + Dendritic Cells (DC) Vaccine in Addition to Standard of Care Checkpoint Inhibitor of Choice in Metastatic Melanoma Patients With Measurable Disease. (clinicaltrials.gov) - P1/2 | N=26 | Completed | Sponsor: Elios Therapeutics, LLC | N=45 ➔ 26

Checkpoint inhibition • Enrollment change • Metastases • Melanoma • Oncology • Solid Tumor

Prospective, randomized, double-blind phase 2B trial of the TLPO and TLPLDC vaccines to prevent recurrence of resected stage III/IV melanoma: a prespecified 36-month analysis. (PubMed, J Immunother Cancer) - P2b | "The TLPO and TLPLDC (without G-CSF) vaccines were associated with improved DFS and OS in this clinical trial. Given production and manufacturing advantages, the efficacy of the TLPO vaccine will be confirmed in a phase 3 trial."

Clinical • Journal • P2b data • Immune Modulation • Melanoma • Oncology • Solid Tumor

[VIRTUAL] The effect of pretreatment with G-CSF prior to dendritic cell collection during the phase IIb trial of an autologous DC-based vaccine for advanced, resectable melanoma (SITC 2020) - P2b | "Similarly, the DFS survival benefit of TLPLDC–G-CSF was enhanced in patients who received prior immunotherapy (IO) (61.9% vs. 11.5% and 35.7% respectively, p=0.007) or checkpoint inhibitors (CPI) (48.5% vs. 10.6% and 37.5% respectively, p=0.039).Conclusions TLPLDC vaccine created without G-CSF pretreatment significantly improved 36-month DFS and OS compared to TLPLDC+G-CSF or placebo in stage III/IV (resected) melanoma patients...Ongoing evaluation will determine if G-CSF mobilization leads to collection of phenotypically different DCs. Based on these results, we are planning a phase III trial of TLPLDC–G-CSF + CPI vs. placebo + CPI in advanced melanoma post-resection."

P2b data • Melanoma • Oncology • Solid Tumor • CSF3

[VIRTUAL] 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 (SITC 2020) - P2b | "Conclusions This 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."

Clinical • P2b data • Melanoma • Oncology • Solid Tumor

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. (ASCO-SITC 2020) - P2b; "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 • P2b data

WIRB Protocol: 20141932: Phase IIB TL + YCWP + DC in Melanoma (clinicaltrials.gov) - P2b | N=184 | Completed | Sponsor: Cancer Insight, LLC | Active, not recruiting ➔ Completed | Trial primary completion date: Jul 2021 ➔ May 2022

Trial completion • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Divergent clinical outcomes in a phase 2B trial of the TLPLDC vaccine in preventing melanoma recurrence and the impact of dendritic cell collection methodology: a randomized clinical trial. (PubMed, Cancer Immunol Immunother) - "Patients receiving TLPLDC vaccine without G-CSF had improved OS and DFS. Outcomes remained similar between patients receiving TLPLDC + G and placebo. Direct DC harvest without G-CSF had higher expression of genes linked to DC maturation, likely improving clinical efficacy."

Clinical • Clinical data • Journal • P2b data • Melanoma • Oncology • Solid Tumor

Initial analysis of open-label administration of autologous tumor lysate (TL) + dendritic cells (DC) vaccine (TLPLDC) in melanoma patients who recurred during a phase IIb adjuvant vaccine trial (AACR 2018) - "Of these 8 pts, 3 were treated with pembrolizumab, 1 BRAF/MEK inhibition, and 1 TVEC. On initial analysis, open label administration of the TLPLDC vaccine after recurrence may have benefit when combined with SOC therapy in the adjuvant setting and in patients with measurable metastatic disease. Additional follow up and controlled trials are needed to confirm benefit in this setting."

Clinical • P2b data • Melanoma

[VIRTUAL] Prospective, randomized trial of the tumor lysate, particle only vaccine compared to the tumor lysate, particle-loaded, dendritic cell vaccine to prevent recurrence for resected stage III/IV melanoma (SITC 2020) - No abstract available

Clinical • Melanoma • Oncology • Solid Tumor

[VIRTUAL] 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 (SITC 2020) - P2b | "Conclusions This 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."

Clinical • P2b data • Melanoma • Oncology • Solid Tumor

[VIRTUAL] The effect of pretreatment with G-CSF prior to dendritic cell collection during the phase IIb trial of an autologous DC-based vaccine for advanced, resectable melanoma (SITC 2020) - P2b | "Similarly, the DFS survival benefit of TLPLDC–G-CSF was enhanced in patients who received prior immunotherapy (IO) (61.9% vs. 11.5% and 35.7% respectively, p=0.007) or checkpoint inhibitors (CPI) (48.5% vs. 10.6% and 37.5% respectively, p=0.039).Conclusions TLPLDC vaccine created without G-CSF pretreatment significantly improved 36-month DFS and OS compared to TLPLDC+G-CSF or placebo in stage III/IV (resected) melanoma patients...Ongoing evaluation will determine if G-CSF mobilization leads to collection of phenotypically different DCs. Based on these results, we are planning a phase III trial of TLPLDC–G-CSF + CPI vs. placebo + CPI in advanced melanoma post-resection."

P2b data • Melanoma • Oncology • Solid Tumor • CSF3

[VIRTUAL] Impact of disease-free interval on recurrence in high-risk melanoma patients in a phase IIb trial of the tumor lysate particle loaded dendritic cell (TLPLDC) vaccine (AACR-II 2020) - "The TLPLDC vaccine improved overall survival in patients with DFI >3 months prior to recurrence. These patients have more indolent disease biology and a less immunosuppressive tumor microenvironment, where monotherapy with a cancer vaccine is thought to be more effective. Further study is required to identify patients at initial presentation who are more likely to benefit from the TLPLDC vaccine."

Clinical • IO Biomarker • P2b data • Melanoma • Oncology • Solid Tumor • BRAF

Interim analysis of a prospective, randomized, double blind, placebo controlled, phase IIb trial of the TLPLDC vaccine to prevent recurrence in resected stage III or IV melanoma patients. (ASCO 2018) - P2b; "The TLPLDC vaccine is safe with minimal toxicity. Among pts completing the PVS period (6 mos), there is a strong trend toward fewer recurrences in the TLPLDC arm. This benefit will be confirmed at the primary analysis of 2 yr DFS; however, these early data provide an encouraging signal that a phase III trial for efficacy may be warranted."

Clinical • P2b data • Melanoma

[VIRTUAL] The influence of harvest method on dendritic cell function and clinical outcomes in a randomized trial of a dendritic cell vaccine to prevent recurrences in high-risk melanoma. (ASCO 2021) - P2b | "Pts receiving TLPLDC vaccine had significantly improved OS and DFS, while outcomes remained similar between those who received TLPLDC+G vs placebo . Pts who did not receive G-CSF had higher expression of genes linked to DC maturation and antigen processing and presentation, likely explaining the improvement in clinical efficacy . A phase III trial to further assess the TLPLDC vaccine to prevent recurrence is planned."

Clinical • Clinical data • IO biomarker • Melanoma • Oncology • Solid Tumor • CD14 • CD27 • CD74 • HLA-DQA1 • IFIT1 • IL10 • ITGA4 • SERPINA1

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. (ASCO-SITC 2020) - P2b; "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 • P2b data

Clinical efficacy of vaccination with the autologous tumor lysate particle loaded dendritic cell (TLPLDC) vaccine in metastatic melanoma. (ASCO 2019) - P1/2; "Vaccination with the TLPLDC vaccine in combination with systemic approved therapies in MM pts is well tolerated and may provide clinical benefit in patients with and without measurable disease. Clinical trial information: NCT02678741"

Clinical

Safety and efficacy of autologous tumor lysate particle-loaded dendritic cell vaccination in combination with systemic therapies in patients with recurrent and metastatic melanoma. (PubMed, Melanoma Res) - "The TLPLDC vaccine is well-tolerated and safe in combination with SoC therapies. Future trials will determine the efficacy of TLPLDC in combination with SoC therapies in metastatic melanoma."

Clinical • Combination therapy • Journal • Melanoma • Oncology • Solid Tumor

Safety and efficacy of autologous tumor lysate particle-loaded dendritic cell vaccination in combination with systemic therapies in patients with recurrent and metastatic melanoma. (PubMed, Melanoma Res) - "The TLPLDC vaccine is well-tolerated and safe in combination with SoC therapies. Future trials will determine the efficacy of TLPLDC in combination with SoC therapies in metastatic melanoma."

Clinical • Combination therapy • Journal • Melanoma • Oncology • Solid Tumor

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. (PubMed, Cancer Med) - "The TLPLDC vaccine improved DFS in patients completing the primary vaccine series, particularly in the resected stage IV patients. The efficacy of the TLPLDC vaccine will be confirmed in a phase III study evaluating adjuvant TLPLDC + CPI versus Placebo + CPI in resected stage IV melanoma patients."

Clinical • Journal • P2b data • Melanoma • Oncology • Solid Tumor

Multi-center Phase I/IIa Trial of an Autologous Tumor Lysate (TL) + Yeast Cell Wall Particles (YCWP) + Dendritic Cells (DC) Vaccine in Addition to Standard of Care Checkpoint Inhibitor of Choice in Metastatic Melanoma Patients With Measurable Disease. (clinicaltrials.gov) - P1/2; N=45; Completed; Sponsor: Cancer Insight, LLC; Active, not recruiting ➔ Completed

Checkpoint inhibition • Clinical • Trial completion • Melanoma • Oncology • Solid Tumor

Multi-center Phase I/IIa Trial of an Autologous Tumor Lysate (TL) + Yeast Cell Wall Particles (YCWP) + Dendritic Cells (DC) Vaccine in Addition to Standard of Care Checkpoint Inhibitor of Choice in Metastatic Melanoma Patients With Measurable Disease. (clinicaltrials.gov) - P1/2; N=45; Active, not recruiting; Sponsor: Cancer Insight, LLC; Trial completion date: Dec 2020 ➔ Oct 2021

Checkpoint inhibition • Clinical • Trial completion date • Melanoma • Oncology • Solid Tumor

Phase IIB TL + YCWP + DC in Melanoma (clinicaltrials.gov) - P2b; N=184; Active, not recruiting; Sponsor: Cancer Insight, LLC; Trial primary completion date: Jul 2022 ➔ Jul 2021

Clinical • Trial primary completion date • Melanoma • Oncology • Solid Tumor

A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis. (PubMed, Ann Surg Oncol) - P2b | "This phase IIb trial of TLPLDC vaccine administered to patients with resected stage III/IV melanoma shows TLPLDC is well-tolerated and improves DFS in patients who complete the primary vaccine series. This suggests patients who do not recur early benefit from TLPLDC in preventing future recurrence from melanoma. A phase III trial of TLPLDC + checkpoint inhibitor versus checkpoint inhibitor alone in patients with advanced, surgically resected melanoma is under development."

Clinical • Journal • P2b data • Melanoma • Oncology • Solid Tumor