1101P - Efficacy of anti PD-1 therapy in children and adolescent melanoma patients (MELCAYA study)

Background

The incidence of melanoma in children and adolescents (CA) is reported to be about 5 per million. In these patients (pts), data on the efficacy and safety of anti PD-1 antibodies are lacking. The aim of this study was to determine outcomes of CA melanoma pts receiving anti PD-1 antibodies.

Methods

Melanoma pts ≤ 18 years treated with anti PD-1 based therapy were retrospectively retrieved from 11 academic centers. Information on histopathological diagnosis, surgical treatment, systemic therapy, objective response rate (ORR), safety profile was collected. A central pathology review was carried out in selected cases. Progression-free survival (PFS) and melanoma-specific overall survival (OS) were assessed by Kaplan-Meier method. The study was funded by an EU Horizon Grant (101096667).

Results

Between April 2016 and March 2024, 83 pts treated with systemic therapy were identified and data analysed. Median age was 14 yrs (range 2-18 yrs), 21 pts were ≤ 12 yrs. Overall, 27 CA pts with stage III disease received anti PD-1 antibodies in adjuvant setting, while 48 received anti PD-1-based therapy for advanced disease, and among them 32, 13 and 3 received treatment in 1^st, 2^nd and 3^rd line, respectively. Finally, 2 pts received anti-PD-1 based neoadjuvant treatment. Median follow-up was 5 yrs (IQR 3 – 11 yrs). In CA pts with advanced disease, among the 32 CA pts who received a 1^st line therapy with anti PD-1 the ORR was 37.5%, median PFS and OS were 4.2 months (95%CI: 1.0-7.4) and 27.2 months (95% CI: 6.7-47.7), respectively. Median age of responders vs non responders was 13.5 (3-18) vs 12.0 (0-18), respectively. At 3 years the landmark OS was 41.5%. The ORR was lower in the 2^nd (13.3%) and 3^rd (16.7%) line settings. In CA pts treated with adjuvant anti PD-1 therapy, 3 yrs PFS and 3 yrs OS were 62.1% and 74.2%, respectively. Two pts treated with neoadjuvant PD-1 based therapy achieved pathologic complete response and are still disease free after 36 and 18 months of follow-up, respectively. Toxicities were consistent with previous studies in adult melanoma pts.

Conclusions

Our study provides the first evidence of efficacy of anti PD-1 antibodies in CA melanoma pts, particularly in the first-line setting. Our study supports the use of anti PD-1 therapy in pts < 18 yrs, included those < 12 yrs.

Clinical trial identification

NCT06281912.

Editorial acknowledgement

Legal entity responsible for the study

Mario Mandalà University of Perugia.

Funding

Horizon grant 101096667.

Disclosure

M. Mandalà: Financial Interests, Personal, Advisory Board: MSD, Novartis, Sanofi, BMS, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sun Pharma. I. Brecht: Financial Interests, Institutional, Advisory Board, NF-1-Meeting 11/2023NF-1-Meeting 11/2022: Alexion; Financial Interests, Institutional, Invited Speaker, Neurochirgical Congress - Satellite Symposium Alexion 06/2023: Alexion; Financial Interests, Institutional, Local PI, SPRINKLE Study: Alexion; Financial Interests, Institutional, Funding, Funding for a research project on TAA in pediatric melanoma: Biontech. K. Suijkerbuijk: Financial Interests, Institutional, Advisory Board: Novartis, BMS, AbbVie, Pierre Fabre, MSD; Financial Interests, Institutional, Other, honoraria for Safety Review Committee: sairopa; Financial Interests, Institutional, Research Grant: Novartis, TigaTx, Bristol Myers Squibb, Philips. D. Giannarelli: Financial Interests, Personal, Other, Educational Course in Biostatistics: Amgen; Financial Interests, Personal, Other, Course on GRADE system in Hematology: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisory Board on a Sanofi sponsored study: Sanofi. A. Indini: Financial Interests, Personal, Advisory Board: Novartis, MSD; Financial Interests, Personal, Invited Speaker: Novartis, MSD, BMS, Sanofi, AstraZeneca, Pierre Fabre; Financial Interests, Personal and Institutional, Coordinating PI, Drug-only support by the Merck Investigator Studies Program, for the trial: MSD. V.G. Atkinson: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Pierre Fabre, QBiotics; Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis, Pierre Fabre, Limbic; Financial Interests, Personal, Other, Travel Support: BMS; Financial Interests, Personal, Other, Travel support: Pierre Fabre; Financial Interests, Personal, Other, Advisory Board: Immunocore. H. Helgadottir: Financial Interests, Personal, Invited Speaker: Pierre Fabre, MSD, BMS. C. Robert: Financial Interests, Personal, Advisory Board, Consultancy fees: BMS, Roche, Pierre Fabre, Novartis, Sanofi, MSD, Pfizer, Sun Pharma, Merck, Ultimovacs, Regeneron, EGLE, Philogen, MAAT Pharma; Financial Interests, Personal, Other, Steering Committee: Novartis, Regeneron, Pfizer, IO Biotech; Financial Interests, Personal, Other, IDMC: ULTIMOVACS; Financial Interests, Personal, Invited Speaker: Pierre Fabre, Sanofi, BMS, MSD, Novartis. H.M. Kosela Paterczyk: Non-Financial Interests, Personal, Invited Speaker: MSD, Novartis, BMS, Pierre Fabre, Merck, Sanofi. S. Puig Sarda: Financial Interests, Personal, Advisory Board: Almirall, Isdin, Sanofi, MSD, Pfizer, Novartis, SunPharma, La Roche Posay, Regeneron; Financial Interests, Personal, Invited Speaker: Almirall, Avene, Isdin, Sanofi, Regeneron, Pierre Fabre, SunPharma, La Roche Posay, Cantabria, Eucerin, Bioderma; Financial Interests, Institutional, Other, grants: Almirall; Financial Interests, Institutional, Other, grantts: la roche posay; Financial Interests, Institutional, Funding: Leo Pharma, cantabria; Financial Interests, Institutional, Research Grant: la roche posay; Financial Interests, Institutional, Other, prototypes: Damae medica; Financial Interests, Institutional, Other, Research colaboration: Canfield; Non-Financial Interests, Member of Board of Directors, spin off of the Hospital Clinic and IDIBAPS: Athena Tech. D. Massi: Financial Interests, Personal, Advisory Board: Sakura, Sun Pharma; Financial Interests, Personal, Invited Speaker: Sanofi, Novartis. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, AstraZeneca UK Limited, Bayer Healthcare Pharmaceuticals, BioNTech SE, Boehringer Ingelheim Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG, Highlight Therapeutics S.L, IOBiotech, Immunocore Ireland Limited, Innovent Bioilogics USA Inc, Merck Sharp & Dohme, Novartis Pharma AG, PHMR Limited, Pierre Fabre, Regeneron Pharmaceuticals Inc, Scancell Limited, SkylineDX B.V; Non-Financial Interests, Principal Investigator, GL is PI on over 30 clinical trials: GL is PI on over 30 clinical trials. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, Novartis, Merck Serono, Sun Pharma, Sanofi, Sandoz, Immunocore, Boehringer Ingelheim Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant, Advisory Role and Travel support: MSD, Pierre Fabre; Financial Interests, Personal, Other, Consultant and Advisory Role.Travel support: Pfizer/Array; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Consultant Role: Pfizer, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna; Financial Interests, Personal, Other, Consultant role and travel support: Bio-AI Health; Financial Interests, Personal, Advisory Board, Consultant and Advisory role: ValoTx; Financial Interests, Personal, Advisory Board, Consultant and Advisor role.Travel support: Replimmune; Financial Interests, Personal, Advisory Board, Advisor role: Bayer; Financial Interests, Personal, Other, Consultant and Advisory: Erasca; Financial Interests, Personal, Other, Consultant: Philogen; Financial Interests, Personal, Advisory Board: BionTech, Anaveon; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Member of Board of Directors, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR. A.M.M. Eggermont: Financial Interests, Personal, Advisory Board: Agenus, BioInvent, Boehringer Ingelheim Ingelheim, BioNTech, Brenus, CatalYm, Galecto, Egle, Eikon Therapeutics, Imcheck, IO Biotech, ISA Pharmaceuticals, Merck&Co, MSD, Pfizer, Pierre Fabre, IQVIA, Pierre Fabre, GenOway, Sairopa, Scancell, SkylineDX, Scorpion, TigaTX, Trained Therapeutics DIscovery; Financial Interests, Personal, Stocks/Shares: IO Biotech, Sairopa, SkylineDX. All other authors have declared no conflicts of interest.