Slide 1: A Pilot Trial of Lifileucel for Melanoma Brain Metastases: Feasibility and Safety
A Pilot Trial of Lifileucel for Melanoma Brain Metastases: Feasibility and Safety Allison Betof Warner1, JW Smithy2, MA Postow2, K Panageas2, JP Das2, A Holodny2, AJ Schoenfeld2, JD Wolchok3, AN Shoushtari2 1Stanford University School of Medicine, Stanford, CA, USA; 2Memorial Sloan Kettering Cancer
Slide 2: Disclosures
Disclosures Consulting: Adaptimmune, Bristol Myers Squibb, BluePath Solutions, Genmab, Immatics, Instil Bio, IO Biotech, Iovance Biotherapeutics, Novartis, Merck, Pfizer, Replimune Research Funding (Institutional): Bristol Myers Squibb, Iovance Biotherapeutics, Lyell Immunopharma, Obsidian Therapeut
Slide 3: Background: Melanoma Brain Metastasis (MBM)
Background: Melanoma Brain Metastasis (MBM) Melanoma is the solid tumor with highest propensity for brain metastasis 1 Approximately 40-75% of patients with metastatic melanoma develop MBM 2,3 CheckMate 2044 and the ABC trial5 established ipilimumab + nivolumab as first- line therapy for patients wi
Slide 4: Background: Melanoma Brain Metastasis (MBM)
Background: Melanoma Brain Metastasis (MBM) Melanoma is the solid tumor with highest propensity for brain metastasis 1 Approximately 40-75% of patients with metastatic melanoma develop MBM 2,3 CheckMate 2044 and the ABC trial5 established ipilimumab + nivolumab as first- line therapy for patients wi
Slide 5: Background: TIL Therapy for PD-1 Refractory Melanoma
Background: TIL Therapy for PD-1 Refractory Melanoma (www.tilworkinggroup.com) PRESENTED BY: Allison Betof Warner, MD, PhD @DrBetofMDPhD
Slide 6: Background: TIL Therapy for PD-1 Refractory Melanoma
Background: TIL Therapy for PD-1 Refractory Melanoma ORR: 31.4% DCR: 77.7% n=153 (Chesney et al. JITC 2022) PRESENTED BY: Allison Betof Warner, MD, PhD @DrBetofMDPhD
Slide 7: Background: TIL Therapy for PD-1 Refractory Melanoma
Background: TIL Therapy for PD-1 Refractory Melanoma ORR: 31.4% DCR: 77.7% n=153 C-144-01 trial: excluded symptomatic and/or untreated brain metastases M14TIL trial: allowed up to 2 asymptomatic brain metastases of <1 cm with no edema (Chesney et al. JITC 2022) PRESENTED BY: Allison Betof Warner, MD
Slide 8: Background: TIL for MBM
Background: TIL for MBM NCI Experience1,2 18 patients with untreated MBM 4 CR, 1 PR (ORR 28%) 1 symptomatic intracranial hemorrhage AACR Case Report3 16M with bulky nodal disease and MBM, progressed s/p ipilimumab and dabrafenib PR at 3 months, CR confirmed at 60 months, ongoing >7 years post-treatm
Slide 9: Background: TIL for MBM
Background: TIL for MBM NCI Experience1,2 18 patients with untreated MBM 4 CR, 1 PR (ORR 28%) 1 symptomatic intracranial hemorrhage AACR Case Report3 16M with bulky nodal disease and MBM, progressed s/p ipilimumab and dabrafenib PR at 3 months, CR confirmed at 60 months, ongoing >7 years post-treatm
Slide 10: Background: TIL for MBM
Background: TIL for MBM NCI Experience1,2 18 patients with untreated MBM 4 CR, 1 PR (ORR 28%) 1 symptomatic intracranial hemorrhage AACR Case Report3 16M with bulky nodal disease and MBM, progressed s/p ipilimumab and dabrafenib PR at 3 months, CR confirmed at 60 months, ongoing >7 years post-treatm
Slide 11: Pilot Trial of Lifileucel for Patients with Asymptomatic Melanoma Brain Metastases and Progression on Prior PD-1 Therapy
Pilot Trial of Lifileucel for Patients with Asymptomatic Melanoma Brain Metastases and Progression on Prior PD-1 Therapy Objectives Key inclusion criteria Primary Metastatic non-uveal melanoma Feasibility of treatment asymptomatic intracranial lesion 5-30mm ( extracranial resectable lesion harvest r
Slide 12: Treatment Schema for TIL Therapy
Treatment Schema for TIL Therapy PRESENTED BY: Allison Betof Warner, MD, PhD @DrBetofMDPhD
Slide 13: Treatment Schema Modified for MBM
Treatment Schema Modified for MBM PRESENTED BY: Allison Betof Warner, MD, PhD @DrBetofMDPhD
Slide 14: Treatment Schema Modified for MBM
Treatment Schema Modified for MBM PRESENTED BY: Allison Betof Warner, MD, PhD @DrBetofMDPhD
Slide 15: Patient and Disease Characteristics
Patient and Disease Characteristics Characteristic All Patients (N=10) Age, yr median (range) 43 (32-71) Female n (%) 3 (30%) ECOG status 0 n (%) 3 (30%) Melanoma subtype Cutaneous n (%) 6 (60%) Acral n (%) 3 (30%) Mucosal n (%) 1 (10%) Prior systemic therapy # lines median (range) 2 (1-6) Anti-PD-1
Slide 16: Patient and Disease Characteristics
Patient and Disease Characteristics Characteristic All Patients (N=10) Age, yr median (range) 43 (32-71) Site for TIL Harvest Female n (%) 3 (30%) Lymph node (n=5) ECOG status 0 n (%) 3 (30%) Skin/subcutaneous (n=3) Melanoma subtype Lung (n=1) Cutaneous n (%) 6 (60%) Liver (n=1) Acral n (%) 3 (30%)
Slide 17: Lifileucel infusion was feasible in patients with MBM after progression on anti-PD-1
Lifileucel infusion was feasible in patients with MBM after progression on anti-PD-1 Enrolled 10 patients from December 2022 to January 2024 8/10 patients received lifileucel infusion 2 patients not infused due to clinical progression/rapid deterioration Both received bridging therapy Both had >20 b
Slide 18: Lifileucel infusion was feasible in patients with MBM after progression on anti-PD-1
Lifileucel infusion was feasible in patients with MBM after progression on anti-PD-1 Enrolled 10 patients from December 2022 to January 2024 Days from consent to lifileucel infusion: median (range) 58 (49-76) 8/10 patients received lifileucel infusion Days from TIL harvest surgery to lifileucel 2 pa
Slide 19: Safety
Safety Nonhematologic TEAE in >1 patienta Any Grade Grade 3/4 Grade 3/4 hematologic lab abnormalitiesb Grade 3/4 N (%) (N=8) N (%) N=8 Febrile neutropenia 5 (63%) 5 (63%) Neutropenia 8 (100%) Chills 5 (63%) 0 Lymphopenia 8 (100%) Fever 3 (38%) 0 Leukopenia 8 (100%) Fatigue 3 (38%) 0 Thrombocytopenia
Slide 20: Lifileucel can produce extracranial and intracranial responses after progression on anti-PD-1
Lifileucel can produce extracranial and intracranial responses after progression on anti-PD-1 Intracranial BOR PRESENTED BY: Allison Betof Warner, MD, PhD @DrBetofMDPhD
Slide 21: Lifileucel can produce extracranial and intracranial responses after progression on anti-PD-1
Lifileucel can produce extracranial and intracranial responses after progression on anti-PD-1 Best Overall Response Efficacy (RECIST) Cohort Intracranial BOR Global BOR (n=8) Objective response rate, n (%) Partial response 2 (25%) Stable disease 2 (25%) Progressive disease 4 (50%) Disease control ra
Slide 22: Patient Case
Patient Case 40 year old man with BRAF wildtype cutaneous melanoma with disease progression following treatment with nivolumab and ipilimumab+pembrolizumab. Cerebellar metastasis previously treated with SRS then progressed. Baseline PRESENTED BY: Allison Betof Warner, MD, PhD @DrBetofMDPhD
Slide 23: Patient Case
Patient Case 40 year old man with BRAF wildtype cutaneous melanoma with disease progression following treatment with nivolumab and ipilimumab+pembrolizumab. Cerebellar metastasis previously treated with SRS then progressed. Lifileucel Baseline Month 9 PRESENTED BY: Allison Betof Warner, MD, PhD @DrB
Slide 24: Patient Case
Patient Case 40 year old man with BRAF wildtype cutaneous melanoma with disease progression following treatment with nivolumab and ipilimumab+pembrolizumab. Cerebellar metastasis previously treated with SRS then progressed. Lifileucel Baseline Month 12 PRESENTED BY: Allison Betof Warner, MD, PhD @Dr
Slide 25: Patient Case
Patient Case 40 year old man with BRAF wildtype cutaneous melanoma with disease progression following treatment with nivolumab and ipilimumab + pembrolizumab. Cerebellar metastasis previously treated with SRS then progressed. Month 14 Growth of previously radiated cerebellar lesion Surgical resectio
Slide 26: Overall Survival
Overall Survival Intention to Treat Cohort Patients who Received Lifileucel Infusion PRESENTED BY: Allison Betof Warner, MD, PhD @DrBetofMDPhD
Slide 27: Conclusions
Conclusions In patients with asymptomatic melanoma brain metastases following progression on an anti-PD-1 containing regimen and (if appropriate) BRAF+MEKi therapy: Lifileucel administration is feasible Lifileucel can produce extracranial and intracranial responses, including the potential for durab
Slide 28: Thank You!
Thank You! Thank you to all patients, their families, and their caregivers. Alex Shoushtari, MD Jim Smithy, MD Charlotte Ariyan, MD, PhD Jannakie Joseph, NP Elizabeth Cathcart Alec Lynch Deanna Cogswell Justina Morgan Isabel Concepcion, NP Kathy Panageas, DrPH Jeeban Das, MBBCh Mike Postow, MD Camer