1056P - Efficacy of spartalizumab across multiple cancer types in patients with PD1-high mRNA expressing tumors (SOLTI-1904 ACROPOLI)

Background

Building upon our earlier findings (Paré et al. Ann Oncol 2019 ), we hypothesized that anti-PD1 monotherapy is active across multiple cancer-types in PD1-high mRNA expressing tumors.

Methods

ACROPOLI is a phase II, open-label, non-randomized, multicentric trial in Spain, evaluating the efficacy of spartalizumab (anti-PD1) monotherapy for advanced PD1-high mRNA expressing solid tumors. PD1-high was defined by a pre-specified cutoff from FFPE tumor samples. Pts received spartalizumab 400 mg 4-weekly, and the primary objective was overall response rate (ORR) according to RECIST v1.1. Secondary objective was clinical benefit rate (CBR), defined as non-progressive disease for ≥6 months. Here, we report the early efficacy results of a prespecified interim analysis (IA) after the first 50 pts enrolled. A succesfull IA was defined as an ORR of ≥14%. Additionally, we report updated efficacy and safety data (n=58).

Results

From Apr2021 to May2022, 916 tumors were analyzed and 10.8% were PD1-high. Median of TILs in PD1-high tumors was significantly higher than in the rest of tumors (15% vs. 4%, p<0.001). Across 10 clinical sites, 58 pts (35 women) were enrolled with 20 different tumor histologies and a median of 2 prior treatments for advanced disease (range 0-13). Regarding the IA (data cutoff Apr2022), the ORR was 16% (8/50) and the Clinical Benefit Rate (CBR) was 28% (14/50). Regarding the updated efficacy results (data cutoff May2023), ORR was 17.2% (10/58) and CBR 29.3% (17/58). Clinical responses were observed in different cancer-types, including mesothelioma, sarcoma, carcinoma of primary unknown, cholangiocarcionoma, colorectal, ovarian, gastric and pancreatic cancers. 5 patients (8.6%) experienced grade 3-4 toxicities related to spartalizumab, with one fatal event.

Conclusions

Spartalizumab monotherapy demonstrated promising efficacy data and a favorable safety profile in heavily treated patients with immune-inflamed solid tumors expressing high levels of PD1 mRNA. Premature discontinuation of the trial's recruitment occurred due to the termination of the spartalizumab development program. Nevertheless, the trial will begin enrolling a new cohort of 111 patients with PD1-high tumors with tislelizumab.

Clinical trial identification

NCT04802876.

Editorial acknowledgement

Legal entity responsible for the study

SOLTI.

Funding

Novartis Pharma AG.

Disclosure

A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, Oncolytics Biotech, Guardant Health, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca, 1TRIALSP, S.L.; Financial Interests, Personal, Member of Board of Directors, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics, INTERNATIONAL ONCOLOGY BUREAU, S.L.; Financial Interests, Institutional, Local PI: Roche, AstraZeneca; Financial Interests, Personal and Institutional, Steering Committee Member: Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Novartis; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation; Non-Financial Interests, Personal, Other, Asociación Española de Investigación sobre el Cáncer: ASEICA. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer/ AstraZeneca / Veracyte / Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech, Novartis. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daichii, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-cilag international NV, NOvartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President. ASEICA (Spanish Association of Cancer Research): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, Glaxo Smith Kline, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., Glaxo Smith Kline Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. E. Garralda: Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, F-Star Therapeutics, Sanofi, Incyte; Financial Interests, Personal, Invited Speaker: MSD, Lilly, Roche, Thermo Fisher, Novartis, Seagen; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho; Financial Interests, Institutional, Research Grant: BeiGene, Janssen. A.M. Arance Fernandez: Financial Interests, Personal, Advisory Board, Consultant /Advisory/ Speaker / Travel, Accomodations, Expenses/: Pierre Fabre, Novartis, Roche, BMS, MSD, Merck, Sanofi; Financial Interests, Institutional, Other, Research Funding: Pierre Fabre, Novartis, MSD, BMS, Merck, Roche, Sanofi, Amgem. J. Martin-Liberal: Financial Interests, Personal, Invited Speaker: Astellas, Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, Pierre Fabre, Roche, Sanofi, Highlight Therapeutics; Financial Interests, Personal, Other, Travel grant: Bristol Myers Squibb, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Ipsen. Y. Izarzugaza Peron: Financial Interests, Personal, Invited Speaker: Novartis, pfizer, Gilead; Financial Interests, Personal, Advisory Board: Daiichi. C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Meyers Squibb, Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann - La Roche Ltd, Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Piere Fabre, PintPharma, Puma, Roche Farma, Sanofi-Aventis, Seagen, Zymeworks, Genentech, Innoup, Millenium, Pharmalex Spain SLU; Financial Interests, Personal, Other, SC: Byondis B.V., Glaxo, Macrogenics, Menarini, Merus, Synthon Biopharpaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La RocheLtd, Genentech, GSK, Immunomedics, Innoup Farma, Macrogenics, Menarini Ricerche, Merus, Novartis, Pfizer, Puma, Roche, Sanofi-Aventis, Seattle Genetics; Financial Interests, Institutional, Coordinating PI: Byondis B.V.; Non-Financial Interests, Member: Spanish Society of Medical Oncology (SEOM), American Society for Clinical Oncology (ASCO), Geicam (Spanish Breast Cancer Research Group), European Society for Medical Oncology (ESMO), Sinology Society of the Official College of Physicians of Barcelona (COMB); Non-Financial Interests, Member, Junta Directiva y Comité Científico: SOLTI group (Academic research group in breast cancer). C. Hierro: Financial Interests, Personal, Invited Speaker: MSD, Lilly; Financial Interests, Personal, Research Grant, Principal Investigator of Merck Research Grant in Personalized Medicine 2020 : Merck; Non-Financial Interests, Principal Investigator, Clinical Trial: BMS, Zymeworks, ALX Oncology, AstraZeneca; Other, Other, Travel fees: BMS, Amgen, Roche, Merck. R. Mesia Nin: Financial Interests, Personal, Advisory Board: Merck, MSD, Bayer, Seattle Genetics, Nanobiotix, Boehringer, Segean; Financial Interests, Personal, Invited Speaker: Merck, MSD, BMS; Non-Financial Interests, Principal Investigator, Clinical Trial PI: BMS; Non-Financial Interests, Principal Investigator, Observational trial PI: Merck. A. Cervantes: Financial Interests, Institutional, Advisory Board: MerckSerono, Amgen, Roche, Transgene, AnHeart Therapeutics, AbbVie, GSK; Financial Interests, Institutional, Invited Speaker: Amgen, Roche, Merck Serono, Foundation Medicine; Financial Interests, Personal, Other, Associate Editor: Annals of Oncology, ESMO Open; Financial Interests, Personal, Other, Editor in Chief: Cancer Treatment Reviews; Financial Interests, Institutional, Research Grant, Principal Investigator: Actuate Therapeutic, Amgen, Astellas Pharma, BeiGene, Bayer, AstraZeneca, BMS, Amcure, FibroGen, Lilly, Genentech, MedImmune, Merck Serono, Novartis, Natera, MSD, Servier, Sierra Oncology, Adaptimmune, Takeda, Affimed, Roche, Seamless, Gilead, Janssen, F. STAR Therapeutics, Ribon Therapeutics; Non-Financial Interests, Other, Scientific Director: INCLIVA Biomedical Research Institute. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, TheraMyc, Hutchinson MediPharma International, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc, Scorpion Therapeutics, Tolremo Therapeutics; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex / HMP; Financial Interests, Personal, Invited Speaker, educacional collaboration: MJH Life Sciences; Financial Interests, Personal, Advisory Board: Cardiff Oncology; Financial Interests, Personal, Stocks/Shares: Oniria Therapeuics; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, Janssen-Cilag International NV, Merck Health KGAA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc, BeiGene, Boehringer Ingelheim, HalioDX SAS, Hutchinson Medipharma, MedImmune, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Member of Board of Directors, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Member of Board of Directors, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc.; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc.; Non-Financial Interests, : HalioDX SAS. All other authors have declared no conflicts of interest.