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Mini Oral session 2

64MO - A phase (ph) II, multi-center study of the safety and efficacy of tebentafusp (tebe) (IMCgp100) in patients (pts) with metastatic uveal melanoma (mUM)

Date

12 Dec 2020

Session

Mini Oral session 2

Presenters

Joseph Sacco

Citation

Annals of Oncology (2020) 31 (suppl_7): S1441-S1451. 10.1016/annonc/annonc392

Authors

J. Sacco1, R. Carvajal2, M. O. Butler3, A. Shoushtari4, J. C. Hassel5

Author affiliations

  • 1 Clatterbridge Cancer Center - NHS Foundation Trust, Wirral/GB
  • 2 Columbia University, New York/US
  • 3 Princess Margaret Centre, Toronto/CA
  • 4 Memorial Sloan Kettering Cancer Center, New York/US
  • 5 University Hospital Heidelberg, Heidelberg/DE
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Abstract 64MO

Background

mUM is a historically treatment-refractory tumor with high expression of gp100 and 12 month (mo) OS rate of 43% (Khoja L, et al. Ann Oncol. 2019; 30(8):1370-1380). Tebe is a bispecific consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target gp100+ cells (melanocytes and melanoma). An intra-patient escalation regimen evaluated in Ph1 of the current study identified 68 μg as the phase 2 dose (Sato T et al. J. Clin. Oncol. 2018; 36(15_suppl): 9521).

Methods

We conducted a Ph2 study of tebe in mUM pts. HLA-A*0201+ pts were treated at 24 centers with a regimen of QW iv dosing (20μg C1D1; 30μg C1D8; 68μg C1D15). 1° objective was ORR by RECIST 1.1 using independent central review (ICR). 2° objectives included safety, OS and PFS.

Results

127 pts were treated (50% male; 70% ECOG 0, 58% LDH >ULN). All pts received ≥1 prior therapy in metastatic setting (34% ≥2 lines; 45% LDT; 73% immunotherapy (65% anti PD1, 31% anti CTLA4)). ORR (all PRs) was 5% (95% CI: 1.8%, 10.0%); median duration of response 8.7 mos. 45% pts achieved stable disease. Of pts with evaluable tumors (n=116), 44% had reduction in target lesions (TL) including immune-related responses. With median follow-up of 19.6 mos, median OS (mOS) was 16.8 mos (95% CI: 12.9, 21.3). 12 mo OS rate was 62%, 18 mo was 45%. 12 mo OS rate of pts with any TL reduction was 86%. Median PFS was 2.8 mos. Most common treatment related AEs (TRAEs) were generally cutaneous (gp100+ melanocytes) or cytokine mediated (T cell activation) and included pyrexia (80%), pruritus (67%), and chills (64%) with Grade ≥3 TRAE of rash maculo-papular (13%), hypotension (8%), increased aspartate aminotransferase (AST), and hypophosphatemia (5% each). TRAEs decreased in frequency and severity after first 3 doses. 86% pts experienced cytokine release syndrome (CRS) by ASTCT criteria (Lee DW, et al. Biol Blood Marrow Transplant. 2019; 25(4): 625-638); 3% Grade 3; 1% Grade 4. There were no grade 5 TRAEs. Pts who developed rash within 7 days of tebe start (64%) had superior mOS, 22.5 mos vs other pts, 10.3 mos.

Conclusions

While the 1° endpoint of ORR was 5%, 44% pts had reduction in TL. 12 mo OS rate (62% all pts, 86% in pts with TL reduction) was promising. Related AEs were generally predictable, manageable, decreased in frequency and severity over first few doses and were consistent with proposed MoA. Tebe is being evaluated in a randomised pivotal trial with 1° endpoint of OS.

Clinical trial identification

NCT02570308.

Legal entity responsible for the study

Immunocore Ltd.

Funding

Immunocore Ltd.

Disclosure

J.J. Sacco: Advisory/Consultancy, Research grant/Funding (institution): Immunocore; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD; Advisory/Consultancy: Delcath; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Speaker Bureau/Expert testimony: Pierre Fabre; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Replimune. R. Carvajal: Advisory/Consultancy: Castle Biosciences; Advisory/Consultancy, Research grant/Funding (institution): Immunocore; Advisory/Consultancy: InxMed; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: PureTech Health; Advisory/Consultancy, Research grant/Funding (institution): Regeneron; Advisory/Consultancy: Sanofi Genzyme; Advisory/Consultancy: Sorrento Therapeutics; Advisory/Consultancy: Trisalus; Shareholder/Stockholder/Stock options: Aura Biosciences; Shareholder/Stockholder/Stock options: Chimeron; Shareholder/Stockholder/Stock options: Rgenix; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Corvus; Research grant/Funding (institution): Ideaya; Research grant/Funding (institution): Iovance; Research grant/Funding (institution): Mirati; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Plexxikon; Research grant/Funding (institution): Roche. M. O. Butler: Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Safety Review Committee: Adaptimmune; Advisory/Consultancy, Safety Review Committee: GSK; Advisory/Consultancy, Research grant/Funding (institution): Immunocore; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Sun Pharma; Research grant/Funding (self): Takara Bio; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): OncoSeq. A.N. Shoushtari: Honoraria (self), Research grant/Funding (institution): Immunocore; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self): Castle Biosciences; Licensing/Royalties: UpToDate; Research grant/Funding (institution): Xcovery; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer. J. C. Hassel: Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: MSD; Advisory/Consultancy: Pierre Fabre; Honoraria (self), Research grant/Funding (institution): BMS; Advisory/Consultancy: Sun Pharma; Honoraria (self), Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Immunocore; Research grant/Funding (institution): Philogen; Research grant/Funding (institution): Sensitize; Research grant/Funding (institution): LIipomerit; Research grant/Funding (institution): Regeneron. A. Ikeguchi: Research grant/Funding (institution): Dynavax; Research grant/Funding (institution): Immunocore; Research grant/Funding (institution): Merck; Research grant/Funding (institution): GSK/Sarah Cannon; Research grant/Funding (institution): Neon Therapeutics/Sarah Cannon. L. Hernandez-Aya: Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: Castle Bioscience; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Immunocore; Research grant/Funding (institution): Merck-EMD; Research grant/Funding (institution): Corvus; Research grant/Funding (institution): Polynoma; Research grant/Funding (institution): Genentech. P. Nathan: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Research grant/Funding (institution): Immunocore; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Incyte; Advisory/Consultancy: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: 4SC; Non-remunerated activity/ies, Uveal melanoma lead: EORTC Melanoma Group; Non-remunerated activity/ies, UK Uveal Melanoma Lead: International Rare Cancer Initiative. O. Hamid: Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Aduro; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Akeso Bio; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution): Array/Pfizer; Advisory/Consultancy: Beigene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Research grant/Funding (institution): BMS; Advisory/Consultancy: Caris; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Genentech; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): GSK; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Immunocore; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Incyte; Advisory/Consultancy: Janssen; Advisory/Consultancy: Jounce; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Nextcure; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Regeneron; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Sanofi; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (self): Tempus; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Zelluna; Research grant/Funding (self): Arcus; Research grant/Funding (self), Research grant/Funding (institution): CytomX; Research grant/Funding (self), Research grant/Funding (institution): Exelixis; Research grant/Funding (self), Research grant/Funding (institution): Iovance; Research grant/Funding (self), Research grant/Funding (institution): Moderna; Research grant/Funding (self), Research grant/Funding (institution): Torque; Research grant/Funding (institution): Arcus. J.M. Piulats Rodriguez: Research grant/Funding (institution): Immunocore. M. Rioth: Advisory/Consultancy: Health Advances. D.B. Johnson: Advisory/Consultancy, Research grant/Funding (institution): Array Biopharma; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy: Catalyst; Advisory/Consultancy: Iovance; Advisory/Consultancy: Janssen; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Research grant/Funding (self): Incyte; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Immunocore; Non-remunerated activity/ies, Melanoma Guideline Committee: NCCN; Non-remunerated activity/ies, Scientific Selection Committee: ASCO; Non-remunerated activity/ies, Immunotherapy Toxicity Guidleines: SITC. J. J. Luke: Honoraria (self), Research grant/Funding (institution): Abbvie; Honoraria (self): Aligos; Honoraria (self), Research grant/Funding (institution): Array; Honoraria (self): Bayer; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (self): Checkmate; Honoraria (self): Cstone; Honoraria (self): Eisai; Honoraria (self), Research grant/Funding (institution): EMD Serono; Honoraria (self): KSQ; Honoraria (self), Travel/Accommodation/Expenses: Janssen; Honoraria (self), Research grant/Funding (institution): Merck; Honoraria (self), Travel/Accommodation/Expenses: Mersana; Honoraria (self): Novartis; Honoraria (self): Partner; Honoraria (self): Pfizer; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Actym; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Alphamab Oncology; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Arch Oncology; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Kanaph; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Mavu; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Onc.AI; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Pyxis; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Tempest; Research grant/Funding (institution): Agios; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Corvus; Research grant/Funding (institution): Immatics; Research grant/Funding (institution): Incyte; Non-remunerated activity/ies: 7 Hills; Research grant/Funding (institution), Non-remunerated activity/ies: Springbank; Advisory/Consultancy: RefleXion; Advisory/Consultancy: Regeneron; Advisory/Consultancy: Ribon; Advisory/Consultancy: Rubius; Advisory/Consultancy: Silicon; Advisory/Consultancy: Tesaro; Advisory/Consultancy: Werewolf; Advisory/Consultancy: Xilio; Advisory/Consultancy, Research grant/Funding (institution): Xencor; Research grant/Funding (institution): Kadmon; Research grant/Funding (institution): Macrogenics; Research grant/Funding (institution): Tizona; Travel/Accommodation/Expenses: Pyxis. E. Espinosa: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Sanofi; Non-remunerated activity/ies, Vice-President: Grupo Espanol Melanoma. S. Leyvraz: Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Immunocore. H.M. Goodall: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Immunocore. C. Holland: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Immunocore. S. Abdullah: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Immunocore. T. Sato: Advisory/Consultancy, Research grant/Funding (institution): Immunocore.

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