Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study
Background Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 pati...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
December 13, 2022
|
| In: |
Journal for ImmunoTherapy of Cancer
Year: 2022, Jahrgang: 10, Heft: 12, Pages: 1-14 |
| ISSN: | 2051-1426 |
| DOI: | 10.1136/jitc-2022-005755 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1136/jitc-2022-005755 Verlag, lizenzpflichtig, Volltext: https://jitc.bmj.com/content/10/12/e005755 
|
| Verfasserangaben: | Jason Chesney, Karl D. Lewis, Harriet Kluger, Omid Hamid, Eric Whitman, Sajeve Thomas, Martin Wermke, Mike Cusnir, Evidio Domingo-Musibay, Giao Q. Phan, John M. Kirkwood, Jessica C. Hassel, Marlana Orloff, James Larkin, Jeffrey Weber, Andrew J. S. Furness, Nikhil I. Khushalani, Theresa Medina, Michael E. Egger, Friedrich Graf Finckenstein, Madan Jagasia, Parameswaran Hari, Giri Sulur, Wen Shi, Xiao Wu, Amod Sarnaik |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1837268851 | ||
| 003 | DE-627 | ||
| 005 | 20230831095311.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230222s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1136/jitc-2022-005755 |2 doi | |
| 035 | |a (DE-627)1837268851 | ||
| 035 | |a (DE-599)KXP1837268851 | ||
| 035 | |a (OCoLC)1389535490 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Chesney, Jason |e VerfasserIn |0 (DE-588)141991364 |0 (DE-627)704114844 |0 (DE-576)327250747 |4 aut | |
| 245 | 1 | 0 | |a Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies |b pooled analysis of consecutive cohorts of the C-144-01 study |c Jason Chesney, Karl D. Lewis, Harriet Kluger, Omid Hamid, Eric Whitman, Sajeve Thomas, Martin Wermke, Mike Cusnir, Evidio Domingo-Musibay, Giao Q. Phan, John M. Kirkwood, Jessica C. Hassel, Marlana Orloff, James Larkin, Jeffrey Weber, Andrew J. S. Furness, Nikhil I. Khushalani, Theresa Medina, Michael E. Egger, Friedrich Graf Finckenstein, Madan Jagasia, Parameswaran Hari, Giri Sulur, Wen Shi, Xiao Wu, Amod Sarnaik |
| 264 | 1 | |c December 13, 2022 | |
| 300 | |a 14 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 22.02.2023 | ||
| 520 | |a Background Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma. - Methods Eligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing practice facility for 22-day lifileucel manufacturing. Patients received a non-myeloablative lymphodepletion regimen, a single lifileucel infusion, and up to six doses of high-dose interleukin-2. The primary endpoint was IRC-assessed ORR (Response Evaluation Criteria in Solid Tumors V.1.1). - Results The Full Analysis Set consisted of 153 patients treated with lifileucel, including longer-term follow-up on the 66 patients previously reported. Patients had received a median of 3.0 lines of prior therapy (81.7% received both anti-programmed cell death protein 1 and anti-cytotoxic lymphocyte-associated protein 4) and had high disease burden at baseline (median target lesion sum of diameters (SOD): 97.8 mm; lactate dehydrogenase (LDH) >upper limit of normal: 54.2%). ORR was 31.4% (95% CI: 24.1% to 39.4%), with 8 complete responses and 40 partial responses. Median duration of response was not reached at a median study follow-up of 27.6 months, with 41.7% of the responses maintained for ≥18 months. Median overall survival and progression-free survival were 13.9 and 4.1 months, respectively. Multivariable analyses adjusted for Eastern Cooperative Oncology Group performance status demonstrated that elevated LDH and target lesion SOD >median were independently correlated with ORR (p=0.008); patients with normal LDH and SOD <median had greater likelihood of response than those with either (OR=2.08) or both (OR=4.42) risk factors. The most common grade 3/4 treatment-emergent adverse events (≥30%) were thrombocytopenia (76.9%), anemia (50.0%), and febrile neutropenia (41.7%). - Conclusions Investigational lifileucel demonstrated clinically meaningful activity in heavily pretreated patients with advanced melanoma and high tumor burden. Durable responses and a favorable safety profile support the potential benefit of one-time lifileucel TIL cell therapy in patients with limited treatment options in ICI-refractory disease. | ||
| 650 | 4 | |a Clinical Trials, Phase II as Topic | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Immunotherapy, Adoptive | |
| 650 | 4 | |a Lymphocytes, Tumor-Infiltrating | |
| 650 | 4 | |a Melanoma | |
| 700 | 1 | |a Lewis, Karl D. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kluger, Harriet |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hamid, Omid |e VerfasserIn |0 (DE-588)1300402733 |0 (DE-627)1858210348 |4 aut | |
| 700 | 1 | |a Whitman, Eric |e VerfasserIn |4 aut | |
| 700 | 1 | |a Thomas, Sajeve |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wermke, Martin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Cusnir, Mike |e VerfasserIn |4 aut | |
| 700 | 1 | |a Domingo-Musibay, Evidio |e VerfasserIn |4 aut | |
| 700 | 1 | |a Phan, Giao Q. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kirkwood, John M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hassel, Jessica C. |d 1975- |e VerfasserIn |0 (DE-588)129790702 |0 (DE-627)480399069 |0 (DE-576)29783715X |4 aut | |
| 700 | 1 | |a Orloff, Marlana |e VerfasserIn |4 aut | |
| 700 | 1 | |a Larkin, James |e VerfasserIn |4 aut | |
| 700 | 1 | |a Weber, Jeffrey |e VerfasserIn |4 aut | |
| 700 | 1 | |a Furness, Andrew J. S. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Khushalani, Nikhil I. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Medina, Theresa |e VerfasserIn |4 aut | |
| 700 | 1 | |a Egger, Michael E. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Finckenstein, Friedrich Graf |e VerfasserIn |4 aut | |
| 700 | 1 | |a Jagasia, Madan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Hari, Parameswaran |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sulur, Giri |e VerfasserIn |4 aut | |
| 700 | 1 | |a Shi, Wen |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wu, Xiao |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sarnaik, Amod |e VerfasserIn |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal for ImmunoTherapy of Cancer |d London : BioMed Central, 2013 |g 10(2022), 12, Artikel-ID e005755, Seite 1-14 |h Online-Ressource |w (DE-627)750086335 |w (DE-600)2719863-7 |w (DE-576)383767369 |x 2051-1426 |7 nnas |a Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies pooled analysis of consecutive cohorts of the C-144-01 study |
| 773 | 1 | 8 | |g volume:10 |g year:2022 |g number:12 |g elocationid:e005755 |g pages:1-14 |g extent:14 |a Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies pooled analysis of consecutive cohorts of the C-144-01 study |
| 856 | 4 | 0 | |u https://doi.org/10.1136/jitc-2022-005755 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://jitc.bmj.com/content/10/12/e005755 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20230222 | ||
| 993 | |a Article | ||
| 994 | |a 2022 | ||
| 998 | |g 129790702 |a Hassel, Jessica C. |m 129790702:Hassel, Jessica C. |d 50000 |d 910000 |d 911300 |e 50000PH129790702 |e 910000PH129790702 |e 911300PH129790702 |k 0/50000/ |k 0/910000/ |k 1/910000/911300/ |p 12 | ||
| 999 | |a KXP-PPN1837268851 |e 427548424X | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"recId":"1837268851","relHost":[{"disp":"Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies pooled analysis of consecutive cohorts of the C-144-01 studyJournal for ImmunoTherapy of Cancer","origin":[{"publisher":"BioMed Central","dateIssuedDisp":"2013-","dateIssuedKey":"2013","publisherPlace":"London"}],"part":{"issue":"12","text":"10(2022), 12, Artikel-ID e005755, Seite 1-14","volume":"10","pages":"1-14","extent":"14","year":"2022"},"pubHistory":["1.2013 -"],"type":{"bibl":"periodical","media":"Online-Ressource"},"physDesc":[{"extent":"Online-Ressource"}],"recId":"750086335","language":["eng"],"title":[{"title":"Journal for ImmunoTherapy of Cancer","title_sort":"Journal for ImmunoTherapy of Cancer","subtitle":"official journal of the Society for Immunotherapy of Cancer (SITC)"}],"note":["Gesehen am 29.06.20"],"id":{"issn":["2051-1426"],"eki":["750086335"],"zdb":["2719863-7"]}}],"note":["Gesehen am 22.02.2023"],"title":[{"title":"Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies","subtitle":"pooled analysis of consecutive cohorts of the C-144-01 study","title_sort":"Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies"}],"language":["eng"],"person":[{"display":"Chesney, Jason","family":"Chesney","role":"aut","given":"Jason"},{"family":"Lewis","display":"Lewis, Karl D.","given":"Karl D.","role":"aut"},{"family":"Kluger","display":"Kluger, Harriet","given":"Harriet","role":"aut"},{"role":"aut","given":"Omid","display":"Hamid, Omid","family":"Hamid"},{"given":"Eric","role":"aut","family":"Whitman","display":"Whitman, Eric"},{"role":"aut","given":"Sajeve","display":"Thomas, Sajeve","family":"Thomas"},{"given":"Martin","role":"aut","family":"Wermke","display":"Wermke, Martin"},{"display":"Cusnir, Mike","family":"Cusnir","role":"aut","given":"Mike"},{"display":"Domingo-Musibay, Evidio","family":"Domingo-Musibay","role":"aut","given":"Evidio"},{"display":"Phan, Giao Q.","family":"Phan","role":"aut","given":"Giao Q."},{"role":"aut","given":"John M.","display":"Kirkwood, John M.","family":"Kirkwood"},{"given":"Jessica C.","role":"aut","family":"Hassel","display":"Hassel, Jessica C."},{"family":"Orloff","display":"Orloff, Marlana","given":"Marlana","role":"aut"},{"role":"aut","given":"James","display":"Larkin, James","family":"Larkin"},{"family":"Weber","display":"Weber, Jeffrey","given":"Jeffrey","role":"aut"},{"given":"Andrew J. S.","role":"aut","family":"Furness","display":"Furness, Andrew J. S."},{"family":"Khushalani","display":"Khushalani, Nikhil I.","given":"Nikhil I.","role":"aut"},{"family":"Medina","display":"Medina, Theresa","given":"Theresa","role":"aut"},{"family":"Egger","display":"Egger, Michael E.","given":"Michael E.","role":"aut"},{"display":"Finckenstein, Friedrich Graf","family":"Finckenstein","role":"aut","given":"Friedrich Graf"},{"role":"aut","given":"Madan","display":"Jagasia, Madan","family":"Jagasia"},{"role":"aut","given":"Parameswaran","display":"Hari, Parameswaran","family":"Hari"},{"role":"aut","given":"Giri","display":"Sulur, Giri","family":"Sulur"},{"family":"Shi","display":"Shi, Wen","given":"Wen","role":"aut"},{"role":"aut","given":"Xiao","display":"Wu, Xiao","family":"Wu"},{"display":"Sarnaik, Amod","family":"Sarnaik","role":"aut","given":"Amod"}],"physDesc":[{"extent":"14 S."}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"name":{"displayForm":["Jason Chesney, Karl D. Lewis, Harriet Kluger, Omid Hamid, Eric Whitman, Sajeve Thomas, Martin Wermke, Mike Cusnir, Evidio Domingo-Musibay, Giao Q. Phan, John M. Kirkwood, Jessica C. Hassel, Marlana Orloff, James Larkin, Jeffrey Weber, Andrew J. S. Furness, Nikhil I. Khushalani, Theresa Medina, Michael E. Egger, Friedrich Graf Finckenstein, Madan Jagasia, Parameswaran Hari, Giri Sulur, Wen Shi, Xiao Wu, Amod Sarnaik"]},"id":{"eki":["1837268851"],"doi":["10.1136/jitc-2022-005755"]},"origin":[{"dateIssuedKey":"2022","dateIssuedDisp":"December 13, 2022"}]} | ||
| SRT | |a CHESNEYJASEFFICACYAN1320 | ||