Abstract 93P
Background
Although most academic molecular prescreening programs have been designed to facilitate enrollment of patients (pts) in EPCT, the real-world impact of precision oncology remains largely unknown across tumor types.
Methods
The 360R is a prospective observational study evaluating the efficacy and mechanisms of resistance of TT in pts treated with EPCT at Vall d´Hebron Institute of Oncology. The main inclusion criteria for 360R included pts ≥18 years old, ECOG of 0-1 eligible for EPCT. EPCT included phase 1,2 and master protocols. Primary endpoint was objective response rate (ORR) by RECIST 1.1. Secondary endpoints were progression free survival (PFS) and PFS2/PFS1 ratio. 360R PFS (PFS2) was compared with the PFS in the prior line of treatment before enrollment (PFS1) using 1.3 as a threshold for treatment benefit (Massard C. et al. Cancer Discovery. 2017).
Results
Between 2015 and 2023, 265 pts received treatment with TT in EPCT: ECOG 1 (N=143; 54%), female (N=133; 50%). Median age was 61 (range 20-83). Tumor types included: colorectal (N=53; 20%), head and neck (N=42; 16%) and other (N=170; 64%). Treatment regimens included TT monotherapy (85%) or combination (15%). One hundred seven pts (40%) were treated with non-matched TT (NMTT) and 158 (60%) with matched TT (MTT) based on immunohistochemistry or DNA NGS assays. Among pts treated with MTT, 135 (85%) were genomically matched (GMTT) and 23 (15%) non-genomically matched (NGMTT). The most frequent targets for NMTT were SHP2 (19%), BET (18%) and PRMT5 (10%) inhibitors while for MTT FGFR (24%), KRAS G12C (12%) and NTRK (6%). In the overall population, ORR=19%. Median PFS and OS were 3.5 (95%CI 2.9-4.1) and 12.4 months (95%CI 9.0-15.8) respectively. ORR varied according to time of enrollment: ORR=6% in 2015-2016, 13% in 2017-2018, 18% in 2019-2020 and 25% in 2021-2023. PFS2/PFS1≥1.3=36%. Notably, a numerically higher PFS2/PFS1≥1.3 was observed in MTT vs NMTT (40 vs 29% respectively). Among pts receiving MTT, PFS2/PFS1≥1.3 was observed in 41% for GMTT as compared to 36% in NGMTT.
Conclusions
Promising trends are observed in efficacy data for EPCT testing TT. The PFS1/PFS2 ratios observed, especially in the GMTT population, support the clinical utility of molecular prescreening programs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Vall d'Hebron Institute of Oncology.
Funding
Has not received any funding.
Disclosure
I. Braña: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, eTheRNA Immunotherapies, Merck Sharp & Dohme (MSD), Rakuten Pharma, PCI Biotech, Guidepoint; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Personal, Expert Testimony: Cancer Expert Now, Merck Serono, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GSK, Gliknik, Incyte, ISA Pharmaceuticals, Janssen Oncology, Kura, Merck Serono, Debiopharm, Merck Sharp & Dohme (MSD), Nanobiotix, Novartis, Northern Biologics, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences, Roche, Immutep, MacroGenics, Sanofi, PharmaMar, Odonate Therapeutics, Bicycle Therapeutics, Dragonfly therapeutics, Gilead; Non-Financial Interests, Personal, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Personal, Member, Head and Neck Group: EORTC; Non-Financial Interests, Personal, Member: SEOM, ASCO. M. Vieito Villar: Non-Financial Interests, Personal, Principal Investigator: Roche, BMS, Taiho, Hutchinson Pharma, Novartis, Mundipharma, Enterome, Debiopharm. O. Mirallas: Financial Interests, Personal, Invited Speaker: ROVI; Financial Interests, Institutional, Invited Speaker: Roche, Merck; Other, Personal, Other, Travel Expenses: Kyowa Kirin, Almirall; Other, Personal, Other, Travel Expenses and Conference Fee: Sanofi. R. Dienstmann: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, Ipsen, Libbs, Lilly, Merck Sharp & Dohme, Roche, Sanofi, Servier, GSK, Takeda, Janssen, Gilead, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Roche, Foundation Medicine; Financial Interests, Personal, Full or part-time Employment, Oncoclínicas is a private healthcare provider in Brazil. I work part time as Medical Director of the Precision Medicine and Big Data Initiative. We develop molecular tests (pathology and genomics) that are offered to patients treated in the organisation as part of support programs sponsored by pharmaceutical companies and I coordinate research activities with real-world clinico-genomics cohorts: Oncoclínicas; Financial Interests, Personal, Stocks/Shares: Trialing; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Novartis, AstraZeneca, Daiichi-Sankyo, GSK. A. Vivancos: Financial Interests, Personal, Advisory Board: Roche, Bristol Meyers Squibb, Guardant Health, Bayer, Incyte; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Bristol Meyers Squibb, Roche, Incyte. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd., Genentech Inc., Ikena Oncology, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc, Scorpion Therapeutics, Tolremo Therapeutics, CARsgen Therapeutics, hC Bioscience Inc, Takeda Pharmaceuticals International AG; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex/HMP; Financial Interests, Personal, Advisory Board: Cardiff Oncology; Financial Interests, Personal, Stocks/Shares: Oniria Therapeutics, 1TRIALSP, Alentis Therapeutics, Pangaea Oncology; 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, 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, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Personal, Member of Board of Directors, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Personal, Member of Board of Directors, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Personal, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Personal, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Personal, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Personal, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Personal, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Personal, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Personal, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Personal, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer-EORTC; Non-Financial Interests, Personal, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Personal, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Personal, 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., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Personal, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Personal, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Personal, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, Personal, Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Personal, Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. E. Garralda: Financial Interests, Personal, Invited Speaker: MSD, Roche, Thermo Fisher, Novartis, Seagen; Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, F-Star Therapeutics, Sanofi, Incyte, Medscape; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Personal, Stocks/Shares: 1TRIALSP; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho; Financial Interests, Institutional, Research Grant: Beigene, Janssen. A. Hernando Calvo: Other, Personal, Other, Travel support: Merck Serono, Kyowa Kirin. All other authors have declared no conflicts of interest.