Abstract 823P
Background
Tebentafusp (tebe) demonstrated an overall survival (OS) benefit, HR 0.51, compared to investigator choice (IC) in a Ph3 trial in untreated metastatic uveal melanoma (mUM). 82% of the IC arm was pembrolizumab (pembro); ipilimumab + nivolumab (ipi + nivo) was not studied. The 1-yr OS rate for tebe and pembro were 73% and 59%, respectively, while the 1-yr OS rate for ipi + nivo in GEM-1402 was 52%. Using individual patient data (IPD), we conducted a propensity score (PS) weighted analysis to compare OS on tebe or pembro (IMCgp100-202) to ipi+nivo (GEM-1402) in untreated mUM.
Methods
Two analyses were conducted: 1) an initial match-adjusted indirect comparison (MAIC) of tebe or pembro with ipi+nivo and 2) a PS analysis of tebe with ipi+nivo. To adjust for differences in patient characteristics, PS from a logistic regression model were used to generate inverse probability of treatment weights (IPTW). OS was compared using weighted Cox models and Kaplan-Meier curves. The primary analysis was complete case with ATT (average treatment effect of the treated) weights. Sensitivity analyses used alternative missing data methods and weights.
Results
MAICs favored tebe vs ipi+nivo (HR 0.51, 95% CI 0.32-0.79) with no significant difference for pembro vs ipi+nivo (HR 0.74, 95% CI 0.45-1.21). 237 tebe and 45 ipi + nivo patients were included in the primary IPTW analysis. Key baseline covariates including LDH, ALP and ECOG were generally well balanced across treatments, with some differences in disease location. After IPT weighting, all key baseline characteristics were balanced. The IPTW adjusted OS favored tebe, HR 0.43 (95% CI 0.29-0.64); 1-yr OS 74% vs 50%, respectively. Sensitivity analyses showed consistent superior OS for tebe with all IPTW HRs <0.48. An IPTW analysis of pembro vs ipi + nivo based on full IPD will be presented.
Conclusions
Tebentafusp is the only therapy to demonstrate an OS benefit in previously untreated mUM against an IC arm that was mostly pembro. A patient-level propensity analysis comparison to ipi + nivo demonstrates a similarly strong OS benefit for tebentafusp. These data support initial use of tebentafusp in previously untreated HLA-A*0201+ mUM patients as the standard of care.
Clinical trial identification
NCT03070392, NCT02626962.
Editorial acknowledgement
Legal entity responsible for the study
Immunocore Ltd.
Funding
Immunocore Ltd.
Disclosure
J.M. Piulats Rodriguez: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Roche, BMS, MSD, BeiGene, VCN, AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: BMS, Pfizer, Janssen, BeiGene, Mirati. S. Piperno-Neumann: Financial Interests, Personal, Advisory Board: Immunocore. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfzer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Invited Speaker: Polish Society of Surgical Oncology; Non-Financial Interests, Officer: ASCO; Non-Financial Interests, Invited Speaker, President Elect: Polish Oncological Society. P. Nathan: Financial Interests, Personal, Advisory Board: BMS, Immunocore, Novartis, Merck, Pfizer, 4SC; Financial Interests, Institutional, Other, research support: Immunocore; Financial Interests, Personal, Invited Speaker: novartis, 4SC; Financial Interests, Institutional, Invited Speaker: BMS, Novartis, Ipsen, Immunocore, Merck, Pfizer. J.C. Hassel: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Sanofi, MSD, Sunpharma, Almirall, Roche, Amgen, GSK, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, Pierre Fabre, Sunpharma, GSK; Financial Interests, Institutional, Advisory Board: Novartis, BMS, Immunocore, Nektar, Philogen; Financial Interests, Institutional, Research Grant: BMS, Sunpharma; Financial Interests, Institutional, Invited Speaker: Philogen, BMS, Genentech, Immunocore, Immunocore, 4SC, Novartis, BioNTech, Idera, Iovance, Nektar, Pierre Fabre, Regeneraon, Sanofi; Non-Financial Interests, Leadership Role: DeCOG; Non-Financial Interests, Member: ASCO. E. Espinosa: Financial Interests, Personal, Advisory Role: BMS, MSD, Novartis, Pierre Fabre, Roche, Sanofi; Financial Interests, Personal, Speaker’s Bureau: BMS, MSD, Novartis, Pierre Fabre, Roche; Non-Financial Interests, Personal, Member, Vice President: Grupo Espanol Melanoma. L. de la Cruz Merino: Other, Personal, Advisory Board: MSD-Merck, Roche Farma, Bristol Myers Squibb, Pierre-Fabre, Amgen, Novartis; Financial Interests, Personal, Funding: MSD-Merck, Roche Farma, Celgene. S. Ochsenreither: Financial Interests, Personal, Advisory Board: MSD, Merck, BMS, AstraZeneca, Janssen, CureVac, Ipsen; Financial Interests, Personal, Invited Speaker: MSD, Merck, BMS; Financial Interests, Personal, Invited Speaker, Patent of T-cell therapy target: Fred Hutchinson cancer Research Center. A.N. Shoushtari: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Immunocore; Financial Interests, Personal, Royalties: UptoDate; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Immunocore, Polaris, Xcovery, Pfizer, Novartis, Targovax ASA, Checkmate Pharmaceuticals; Non-Financial Interests, Member: ASCO. M. Orloff: Financial Interests, Personal, Advisory Role: Immunocore, TriSalus Life Sciences, IDEAYA Biosciences; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Immunocore, Delcath Systems, Plexxikon, IDEAYA Biosciences, Linnaeus Therapeutics. A.K.S. Salama: Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Merck; Financial Interests, Personal, Advisory Role: Iovance, Novartis, Pfizer, Regeneron Pharmaceuticals. C. Watkins: Financial Interests, Personal, Advisory Role: Immunocore, Celgene/Bristol Myers Squibb, AstraZeneca, Actinium Pharmaceuticals, Ascelia, Humanigen, Nobelpharma, Evgen, Astellas Pharma, F2G, Amylyx, Kite/Gilead; Financial Interests, Personal, Sponsor/Funding: Roche. H. Goodall: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. All other authors have declared no conflicts of interest.