Abstract 87P
Background
Despite being a major cause of early death, concerns over the lack of BBB penetrance result in the exclusion of primary brain tumor patients (Pbt) from early clinical trials (ECT). Moreover, lack of awareness and overly restrictive criteria result in poor accrual.
Methods
We analyzed ECTs opened since 2019 in the VHIO early drug development unit. Trial protocols were reviewed for inclusion and exclusion criteria (IC, EXC) and adhesion to inclusion optimization recommendations for Neuroncology E. Q. Lee et al. (https://doi.org/10.1200/EDBK_349155) and ASCO-FASCO guidelines.
Results
From 181 new early ECT, only 5 (2.7%) trials for solid tumors allowed inclusion of patients with pBT. An additional 18 ongoing trials for solid tumors and 6 specific for pBT were identified. Criteria allowing for ECOG2-KPS 60/80 were implemented in 10 ECT and 4 also allowed 12-18 year-olds. Other recommendations such as allowing patients with mild liver dysfunction (0 ECT), well-controlled HIV (10 ECT), recent malignancy (10 ECT), previous treatment with Bevacizumab (19 ECT), experimental treatment (2 ECT) or TTF (0 ECT) or tumors other than GBM (13). Patients with pBT represented 3.97% of all included patients. The presence of a pBT was not an independent prognostic factor nor led to early discontinuation.
Conclusions
Implementation of recommendations to flexibilize IC is needed, but the main limiting factor is exclusion from trials for “all-solid-tumors”. Exclusion from “all solid tumor” trials should be justified by preclinical evidence of poor brain penetration, and window-of-opportunity trials should confirm brain penetration at therapeutic doses. Enhancing trial designs to increase the accrual of primary brain tumor patients is essential.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
VHIO.
Funding
La Caixa, BBVA, AECC.
Disclosure
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; Other, Personal, Other, Travel expenses: Recordati. A. Hernando Calvo: Financial Interests, Personal, Expert Testimony: Merus; Financial Interests, Institutional, Research Grant: Gilead; Other, Personal, Other, Travel support: Merck Serono, Kyowa Kirin, Bristol Myers Squibb. M.J. Lostes Bardaji: Non-Financial Interests, Personal, Affiliate: SEOM, ESMO. 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 Ingellheim; 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. E. Garralda: Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Anaveon, Hengrui, Sanofi, Incyte, Medscape, Skypta, Sotio, AbbVie, Astex Therapeutics, Alentis Therapeutics, Marengo Therapeutics, Medpace, Pfizer, Amgen, GenMab, GreyWolf, Gilead, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: MSD, Roche, Novartis, SeaGen, PPD, Aran, The Ricky Rubio Fundation, ESMO, Fundación SEOM, CDDF, Springer Nature, Karger, Doctaforum, Tactics, AEFI, Fundación ECO, ESO (European School of Oncology), MeetingPharma, AstraZeneca, Alcura, Horizon CME; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Personal, Stocks/Shares: 1TRIALSP; Financial Interests, Institutional, Research Grant: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho, Beigene, Janssen, Anaveon. M. Vieito: Financial Interests, Personal, Invited Speaker: Novocure; Financial Interests, Personal, Other, Steering committee member: BMS; Non-Financial Interests, Personal, Principal Investigator: Roche, BMS, Taiho, Hutchinson Pharma, Novartis, Mundipharma, Enterome, Debiopharm. All other authors have declared no conflicts of interest.