Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10006-10006 ◽  
Author(s):  
Amod Sarnaik ◽  
Nikhil I. Khushalani ◽  
Jason Alan Chesney ◽  
Karl D. Lewis ◽  
Theresa Michelle Medina ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Adoptive Cell Therapy ◽  
Advanced Melanoma ◽  
Autologous Tumor ◽  
Mek Inhibitors ◽  
High Baseline ◽  
Heavily Pretreated ◽  
Melanoma Patients

10006 Background: Treatment options are limited for patients with advanced melanoma who have progressed on checkpoint inhibitors and targeted therapies. Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) leverages and enhances the body’s natural defense against cancer and has shown durable responses in heavily pretreated melanoma patients. Methods: C-144-01 is a global Phase 2 open-label, multicenter study of efficacy & safety of lifileucel in patients with unresectable metastatic melanoma who have progressed on checkpoint inhibitors and BRAF/MEK inhibitors, if BRAFv600 mutant. We report on Cohort 2 (N = 66) patients who have received TIL. Tumors were resected at local institutions, processed in central GMP facilities for TIL production, manufactured, cryopreserved & shipped back to sites in a 22-day process. Therapy consisted of one week of lymphodepletion, a single lifileucel infusion, and up to 6 IL-2 doses. ORR was based on RECIST v1.1 by investigator assessment. Data cutoff was Feb 2, 2020. Results: Baseline characteristics: 3.3 mean prior therapies (anti-PD1 100%; anti-CTLA-4 80%; BRAF/MEK inhibitor 23%), high baseline tumor burden (106 mm mean target lesion sum of diameters), 44% liver/brain lesions, 40.9% LDH > ULN. ORR by investigator was 36.4% (2 CR, 22 PR) and DCR was 80.3%. Mean time to response was 1.9 months (range: 1.3-5.6). After a median study follow-up of 17.0 months, median DOR (mDOR) was still not reached. Six responders have progressed, 2 have died and 2 started other anti-cancer therapy without progression. The adverse event profile was consistent with the underlying advanced disease and the lymphodepletion and IL-2 regimens. Additional follow-up data will be available for presentation. Conclusions: Lifileucel treatment results in a 36.4% ORR and mDOR was not reached at 17.0 months of median study follow up in a heavily pretreated metastatic melanoma patients with high baseline disease burden who progressed on multiple prior therapies, including anti-PD1 and BRAF/MEK inhibitors, if BRAFv600 mutant. Clinical trial information: NCT02360579.

Safety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients who progressed on multiple prior therapies including anti-PD-1.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2518-2518 ◽  
Author(s):  
Amod Sarnaik ◽  
Nikhil I. Khushalani ◽  
Jason Alan Chesney ◽  
Harriet M. Kluger ◽  
Brendan D. Curti ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Adoptive Cell Therapy ◽  
Mek Inhibitor ◽  
Braf V600e ◽  
Autologous Tumor ◽  
Safety And Efficacy ◽  
High Baseline ◽  
Heavily Pretreated ◽  
Melanoma Patients

2518 Background: Treatment options are limited for patients with advanced melanoma who have progressed on checkpoint inhibitors and targeted therapies such as BRAF/MEK inhibitors (if BRAF-V600E mutated). Adoptive cell therapy utilizing tumor-infiltrating lymphocytes (TIL) has shown antitumor efficacy with durable long-term responses in heavily pretreated melanoma patients. Safety and efficacy of lifileucel (LN-144), a centrally manufactured autologous TIL therapy are presented. Methods: C-144-01 is a global Phase 2 open-label, multicenter study of the efficacy and safety of lifileucel in patients with unresectable metastatic melanoma. We report on Cohort 2 (N = 55) patients who received cryopreserved lifileucel. Tumors resected at local institutions were processed in central GMP facilities for TIL production in a 22-day process. Final TIL infusion product was cryopreserved and shipped to sites. Patients received one week of cyclophosphamide/fludarabine preconditioning lymphodepletion, a single lifileucel infusion, followed by up to 6 doses of IL-2. Results: In 55 patients with Stage IIIC/IV unresectable melanoma, 3.1 mean prior therapies (anti-PD1 100%; anti-CTLA-4 80%; BRAF/MEK inhibitor 24%), high baseline tumor burden (110 mm mean target lesion sum of diameters), ORR was 38% (2 CR, 18 PR, 1 uPR). Of 21 responders, 4 have progressed to date with median follow up of 7.4 months. Overall disease control was 76%. Improved responses in some patients were observed with longer follow up. Most (54) patients progressed on prior anti-PD1 and those with PD-L1 negative status (TPS < 5%) were among responders. Mean cells infused was 28 x109. Median IL-2 doses administered was 6.0. Adverse events resolved to baseline, 2 weeks post TIL infusion, a potentially important benefit of one-time TIL therapy. Conclusions: Lifileucel treatment results in 38% ORR in heavily pretreated metastatic melanoma patients with high baseline disease burden who received prior anti-PD1 and BRAF/MEK inhibitor if BRAF mutated. Based on these data, a new Cohort 4 in C-144-01 has been initiated to support lifileucel registration. Clinical trial information: NCT02360579.

Safety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients previously treated with at least one prior systemic therapy.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 136-136
Author(s):  
Amod Sarnaik ◽  
Sajeve Samuel Thomas ◽  
Diwakar Davar ◽  
John M. Kirkwood ◽  
Harriet M. Kluger ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Preliminary Data ◽  
Checkpoint Inhibitors ◽  
Therapeutic Option ◽  
Adoptive Cell Therapy ◽  
High Dose ◽  
Autologous Tumor ◽  
Mek Inhibitors ◽  
Melanoma Patients

136 Background: While immunotherapies including checkpoint inhibitors and targeted therapies (BRAF/MEK inhibitors) are options for patients with metastatic melanoma, many patients still develop progressive disease. These patients have few treatment options available including high dose IL-2 and chemotherapy with reported second line response rates of 4-10%. Adoptive cell therapy utilizing tumor-infiltrating lymphocytes (TIL) is recognized as an effective treatment in metastatic melanoma, able to elicit durable and complete responses in even heavily pretreated patients. We provide preliminary data for lifileucel TIL (LN-144) in heavily pre-treated metastatic melanoma patients who progressed on multiple checkpoint and BRAF/MEK inhibitors. Methods: C-144-01 is an ongoing global Phase 2, open-label, multicenter study of efficacy and safety of lifileucel in patients with unresectable metastatic melanoma. We report on Cohort 2 (N = 47) patients who received cryopreserved lifileucel. Tumors resected at local institutions were processed at central GMP facilities in a 22-day manufacturing process. The final product was cryopreserved and shipped to sites. Patients received a one week cyclophosphamide/fludarabine preconditioning lymphodepletion regimen, a single lifileucel infusion, followed by up to 6 doses of iv IL-2 (600,000 IU/kg). Results: Patients with Stage IIIC/IV melanoma had 3.3 mean prior therapies (range: 1-9) and high baseline tumor burden, reflected by a mean sum of diameters of target lesions of 112 mm. Preliminary efficacy results: ORR = 38% (1 CR, 13 PR, 4 uPR), DCR = 77%, and median DOR 6.4 mo (range: 1.3 to 13.7) with median follow-up 6.0 mo. Longer follow-up led to improved responses in some patients including the CR. Frequency of AEs decreased over time, a potentially important benefit of one-time TIL treatment. Conclusions: Preliminary data support lifileucel TIL as an efficacious and well-tolerated therapeutic option for patients with metastatic melanoma who have failed multiple lines of prior therapies including checkpoint inhibitors and BRAF/MEK inhibitors. Clinical trial information: NCT02360579.

scholarly journals P865 Safety & efficacy of lifileucel (LN-144) tumor infiltrating lymphocyte therapy in metastatic melanoma patients after progression on multiple therapies – independent review committee data update

2020 ◽  
Vol 8 (Suppl 1) ◽  
pp. A12-A12
Author(s):  
Amod Sarnaik ◽  
Nikhil Khushalani ◽  
Jason Chesney ◽  
Harriet Kluger ◽  
Brendan Curti ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Advanced Melanoma ◽  
Review Committee ◽  
Safety And Efficacy ◽  
Mek Inhibitors ◽  
Tumor Infiltrating Lymphocyte ◽  
Heavily Pretreated ◽  
Independent Review ◽  
Melanoma Patients

BackgroundTreatment options are limited for patients with advanced melanoma who have progressed on checkpoint inhibitors and targeted therapies such as BRAF/MEK inhibitors (if BRAF-V600E mutated). Adoptive cell therapy utilizing tumor-infiltrating lymphocytes (TIL) has shown antitumor efficacy with durable responses in heavily pretreated melanoma patients. Safety and efficacy of lifileucel, a centrally manufactured cryopreserved autologous TIL therapy assessed by both investigator and an independent review committee (IRC), are presented.MethodsC-144-01 is a global Phase 2 open-label, multicenter study of the safety and efficacy of lifileucel in patients with unresectable metastatic melanoma. We report on Cohort 2 (N = 66) patients with Stage IIIC/IV unresectable melanoma who received lifileucel. Tumors resected at local institutions were processed in central GMP facilities for TIL production in a 22-day process. Final TIL infusion product was cryopreserved and shipped to sites. Patients received one week of cyclophosphamide/fludarabine preconditioning lymphodepletion, a single lifileucel infusion, followed by up to 6 doses of IL-2. All responses were assessed by RECIST 1.1.Results66 patients had the following baseline characteristics: 3.3 mean prior therapies (anti-PD1 100%; anti-CTLA-4 80%; BRAF/MEK inhibitor 23%), relatively high tumor burden (106 mm mean target lesion sum of diameters), 44% with liver and/or brain lesions, median LDH 244 U/L. Objective Response Rate (ORR) by investigator was 36.4% (2 CR, 22 PR, 1 previously confirmed PR is now changed to SD) and Disease Control Rate (DCR) of 80.3%. At a median follow up of 9.7 months, median Duration of Response (DOR) has not been reached. The adverse event profile was generally consistent with the underlying advanced disease and the profile of the lymphodepletion and IL-2 regimens.The ORR per IRC was 34.8% (2 CR, 21 PR) and DCR was 72.7%. At a median follow up of 6.9 months, the median IRC DOR has not been reached. Overall concordance rate of investigator and IRC read of response was 89.4%. The concordance compares favorably with literature reports in a metastatic disease.1ConclusionsLifileucel treatment resulted in a 36.4% ORR in heavily pretreated metastatic melanoma patients with high baseline disease burden who had received prior anti-PD1 and BRAF/MEK inhibitors, if tumor BRAF mutated. The high concordance of 89.4% between investigator and IRC confirms the original assessment of lifileucel efficacy in metastatic melanoma.2AcknowledgementsThe authors would like to thank the patients and their families for participation in the study.The authors would also like to acknowledge the support and dedication of all investigators and site team members from all participating clinical trial institutions.Trial RegistrationClinicalTrials. gov Identifier: NCT02360579Ethics ApprovalEthics Approval This trial was approved by Western Institutional Review Board - IRB Tracking Number: 20160198.ReferencesGhiorghiu DC, et al. Comparison of central and site review of RECIST data in an open randomised phase II trial in advanced melanoma. 10.1594.ecr 2009/C-075.Sarnaik A, et al. Safety and efficacy of cryopreserved autologous tumor infiltrating lymphocyte therapy (LN-144, lifileucel) in advanced metastatic melanoma patients who progressed on multiple prior therapies including anti-PD-1. J Clin Oncol 2019;37:2518–2518.

scholarly journals Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Mélanie Saint-Jean ◽  
Anne-Chantal Knol ◽  
Christelle Volteau ◽  
Gaëlle Quéreux ◽  
Lucie Peuvrel ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Adoptive Cell Therapy ◽  
Interleukin 2 ◽  
Tumor Infiltrating Lymphocytes ◽  
Advanced Melanoma ◽  
Autologous Tumor ◽  
Unresectable Stage ◽  
Melanoma Patients ◽  
Infiltrating Lymphocytes

Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs). This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2) regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous metastasis, TILs were produced according to a previously described method and then infused into the patient who also received a complementary subcutaneous IL-2 regimen. Nine women and 1 man were treated for unresectable stage IIIC (n=4) or IV (n=6) melanoma. All but 1 patient with unresectable stage III melanoma (1st line) had received at least 2 previous treatments, including anti-CTLA-4 antibody for 4. The number of TILs infused ranged from 0.23 × 109 to 22.9 × 109. Regarding safety, no serious adverse effect was reported. Therapeutic responses included a complete remission, a partial remission, 2 stabilizations, and 6 progressions. Among these 4 patients with clinical benefit, 1 is still alive with 9 years of follow-up and 1 died from another cause after 8 years of follow-up. Notably, patients treated with high percentages of CD4 + CD25 + CD127lowFoxp3+ T cells among their TILs had significantly shorter OS. The therapeutic effect of combining TILs with new immunotherapies needs further investigation.

Complete responses to two different anti-PD1 agents in a metastatic melanoma patient

2019 ◽  
Vol 26 (2) ◽  
pp. 496-499 ◽  
Author(s):  
Saadettin Kilickap ◽  
Deniz C Guven ◽  
Oktay H Aktepe ◽  
Burak Y Aktas ◽  
Omer Dizdar
Keyword(s):  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Real Life ◽  
Complete Response ◽  
Duration Of Treatment ◽  
Treatment Protocols ◽  
Real Life Data ◽  
Heavily Pretreated ◽  
Drug Free

In the last decade, immune checkpoint inhibitors changed the landscape of metastatic melanoma. However, the optimal duration of treatment and treatment cessation in responders is largely unknown. Herein, we represent a heavily pretreated metastatic melanoma case who had a complete response to pembrolizumab and also a complete response with nivolumab after progression during drug-free follow-up. We think that reinduction with a different anti-PD1 antibody may be used in patients with metastatic melanoma responders. Clinical trials with prespecified sequential treatment protocols and large real-life data can further delineate this subject.

scholarly journals CEACAM1: Expression and Role in Melanocyte Transformation

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Gabriela Turcu ◽  
Roxana Ioana Nedelcu ◽  
Daniela Adriana Ion ◽  
Alice Brînzea ◽  
Mirela Daniela Cioplea ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Adhesion Molecule ◽  
Checkpoint Inhibitors ◽  
Advanced Melanoma ◽  
Melanoma Treatment ◽  
Melanoma Patients ◽  
New Biomarkers ◽  
Cell Adhesion Molecule 1

Metastases represent the main cause of death in melanoma patients. Despite the current optimized targeted therapy or immune checkpoint inhibitors the treatment of metastatic melanoma is unsatisfactory. Because of the poor prognosis of advanced melanoma there is an urgent need to identify new biomarkers to differentiate melanoma cells from normal melanocytes, to stratify patients according to their risk, and to identify subgroups of patients that require close follow-up or more aggressive therapy. Furthermore, melanoma progression has been associated with the dysregulation of cell adhesion molecules. We have reviewed the literature and have discussed the important role of the expression of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in the development of melanoma. Thus, novel insights into CEACAM1 may lead to promising strategies in melanoma treatment, in monitoring melanoma patients, in assessing the response to immunotherapy, and in completing the standard immunohistochemical panel used in melanoma examination.

scholarly journals 153 NEO-PTC-01 (BNT-221), an autologous neoantigen-specific T-cell product for adoptive cell therapy of metastatic melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A167-A167
Author(s):  
Divya Lenkala ◽  
Jessica Kohler ◽  
Brian McCarthy ◽  
Michael Nelson ◽  
Jonathan McGee ◽  
...  
Keyword(s):  
T Cell ◽  
Metastatic Melanoma ◽  
Ex Vivo ◽  
Adoptive Cell Therapy ◽  
T Cell Responses ◽  
Process Engineering ◽  
High Quality ◽  
Cell Product ◽  
Cell Responses ◽  
Melanoma Patients

BackgroundNeoantigens are tumor-specific antigens that are important in the anti-tumor immune response. These antigens are not subject to central immune tolerance and are therefore potentially more immunogenic than tumor-associated antigens. NEO-STIM®, our propriety ex vivo induction process, was developed to generate T-cell products specific to these neoantigens from the peripheral blood of patient. Here, we present the results of a proof of concept, pre-clinical study with multiple successful process engineering runs generating a neoantigen-specific T-cell product (NEO-PTC-01) using leukaphereses from metastatic melanoma patients. These products contain specific T-cell responses targeting multiple neoantigens from each individual patient‘s tumor.MethodsPatient-specific neoantigens were predicted using our RECON® bioinformatics platform. Predicted high-quality neoantigens were utilized in our ex vivo stimulation protocol, NEO-STIM, in the process engineering runs of NEO-PTC-01. NEO-STIM is used to prime, activate and expand memory and de novo T-cell responses from both the CD4+ and the CD8+ compartment. High throughput flow cytometric analysis was performed to characterize the specificity and functionality (cytokine production and cytolytic capacity) of the induced T-cell responses.ResultsHere we present the successful induction of 4–5 CD8+ and 4–7 CD4+ T-cell responses per patient, generated using peripheral blood mononuclear cells from multiple melanoma patients during these successful process engineering runs. We then extensively characterized these T-cell responses and demonstrate that these responses are functional, specific and have cytolytic capacity. Moreover, the induced T cells can recognize autologous tumor.ConclusionsNEO-STIM is a novel platform that generates ex vivo T-cell responses to high-quality neoantigen targets. NEO-PTC-01, the neoantigen-specific T cell product generated from this process, is a potent adoptive cell therapy targeting multiple immunogenic neoantigens in patients with metastatic melanoma.

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