Slide 1: Lifileucel (LN-144), a Cryopreserved Autologous TIL Therapy in Advanced Melanoma
Lifileucel (LN-144), a Cryopreserved Autologous Tumor Infiltrating Lymphocyte (TIL) Therapy in Patients with Advanced Melanoma: Evaluation of Impact of Prior Anti–PD-1 Therapy James M. G. Larkin,1 Amod Sarnaik,2 Jason Alan Chesney,3 Nikhil I. Khushalani,2 John M. Kirkwood,4 Jeffrey S. Weber,5 Karl D
Slide 2: Background
Background • Currently, no treatment is approved for patients with advanced melanoma whose disease progresses while on or after treatment with ICI and BRAF/MEK inhibitors • In patients with advanced melanoma who are either primary refractory or develop resistance to ICI, retreatment with ICI or trea
Slide 3: C-144-01 Study Design
C-144-01 Study Design Phase 2, multicenter study to assess the efficacy and safety of autologous TIL (lifileucel) for treatment of patients with metastatic melanoma (NCT02360579) Cohort 1 Cohort 2 Endpoints Non-cryopreserved • Primary: Efficacy per investigator-assessed ORR using RECIST 1.1 TIL prod
Slide 4: Patient Journey and TIL Manufacturing
Patient Journey and TIL Manufacturing 1 2 3 4 5 6 Patient Intake Tumor Tissue Procurement Non-myeloablative Lifileucel Infusion IL-2 Administration Discharge • Surgical resection of a tumor lesion Lymphodepletion • One time treatment • Up to 6 doses (~1.5 cm in diameter) • Cyclophosphamide • Lifileu
Slide 5: Baseline Patient and Disease Characteristics
Baseline Patient and Disease Characteristics Characteristic N=66 Characteristic N=66 Gender, n (%) BRAF Mutation Status, n (%) Female 27 (41) Mutated V600E or V600K 17 (26) Male 39 (59) Wild type 45 (68) Age, years Unknown 3 (5) Median 55 Other 1 (2) Min, max 20, 79 Tumor PD-L1 Expression, n (%) Pri
Slide 6: Safety
Safety AEs Over Time TEAEs Reported in ≥30% of Patients Preferred Term, n (%) Any Grade Grade 3/4 Grade 5 Any TEAE* 66 (100) 64 (97.0) 2 (3.0)† Thrombocytopenia 59 (89.4) 54 (81.8) 0 Chills 53 (80.3) 4 (6.1) 0 Anemia 45 (68.2) 37 (56.1) 0 Pyrexia 39 (59.1) 11 (16.7) 0 Neutropenia 37 (56.1) 26 (39.4)
Slide 7: Objective Response Rate
Objective Response Rate Response, n (%) N=66 • Mean number of TIL cells infused: 27.3 × 109 Objective Response Rate 24 (36.4) Complete response 3 (4.5) After a median study follow-up of 33.1 months, median DOR was not reached Partial response 21 (31.8) (range 2.2, 38.5+ months) Stable disease 29 (43
Slide 8: Best Overall Response
Best Overall Response 81% (50/62) of patients had a reduction in tumor burden 11 patients (17.7%) had further SOD reduction since April 2020 datacut *Patients with BRAF V600 mutation. 3 patients had no post-TIL disease assessment due to early death, and 1 due to start of new anticancer therapy. DOR,
Slide 9: Time to Response for Evaluable Patients (PR or Better)
Time to Response for Evaluable Patients (PR or Better) • 79% of responders received prior ipilimumab − 46% of responders received prior anti–PD-1 / anti–CTLA-4 combination • Responses continued to deepen over time − 1 PR converted to CR after 24 months post- lifileucel *BOR is best overall response
Slide 10: Early and Sustained CR in a Patient with Multiple Failed Prior Therapies
Early and Sustained CR in a Patient with Multiple Failed Prior Therapies Patient Narrative • 44-year-old male • Initial diagnosis in 2016 • Superficial spreading melanoma • Prior systemic therapies: − Ipilimumab + nivolumab − Dabrafenib + trametinib − TLR9 agonist + pembrolizumab − TVEC + pembrolizu
Slide 11: Site of Tumor Resection and Infused Cell Dose
Site of Tumor Resection and Infused Cell Dose Total Cell Dose Site of Tumor Resection R2=0.0248 Ratio CD4+ / CD8+ TIL R2=0.0074 Appropriate amount of TIL was manufactured Target lesion SOD reductions were seen across the range regardless of tumor resection site of total TIL cell doses and CD4+ / CD8
Slide 12: Univariable Analyses: ORR of Lifileucel
Univariable Analyses: ORR of Lifileucel ORR was not predicted by any patient or clinical characteristics analyzed, including: • Baseline LDH (≤ULN vs >ULN) • Baseline ECOG performance status (0 vs ≥1) • Baseline brain / liver lesions (yes vs no) • Cumulative duration on anti–CTLA-4 (≤median vs >medi
Slide 13: Univariable Analyses: DOR of Lifileucel
Univariable Analyses*: DOR of Lifileucel Although cumulative duration on prior anti–PD-1 / anti–PD-L1 was not associated with achieving a response to lifileucel (ORR), it was associated with DOR *Univariable Cox proportional hazards regression model was used to estimate hazard ratios with 95% confid
Slide 14: Multivariable Model: Independent Predictors for DOR of Lifileucel
Multivariable Model*: Independent Predictors for DOR of Lifileucel • Variables from the univariable analyses were examined using the best subset approach • Two parameters were identified: – Baseline LDH – Cumulative duration of prior anti–PD-1 / anti–PD-L1 Responders (N=24) Parameter Comparison HR (
Slide 15: Conclusions
Conclusions • In heavily pretreated patients with advanced or metastatic melanoma who progressed on or after multiple prior therapies, including anti–PD-1 / anti–PD-L1 and BRAF/MEK inhibitors (if BRAF V600 mutant), lifileucel treatment resulted in: – 36.4% ORR – Median DOR not reached at median 33.1
Slide 16: Acknowledgments
Acknowledgments Thank you to all of the patients and their families who participated in this study C-144-01 Cohort 2 Investigators Iovance Contributors • Ana Arance Fernandez, MD, PhD1 • Omid Hamid, MD14 • Anna C. Pavlick, DO, MBA5 • Cecile Chartier • Hendrik-Tobias Arkenau, MD, PhD2 • Amy Harker-Mu