88P - Evaluation of trending drug targets and technologies in current drug development

Background

Novel investigational agents (IAs) aim to exploit new mechanisms and cancer vulnerabilities, expanding our arsenal of anticancer drugs. Recently, highly selective biomarker-directed IAs have allowed advancements in the precision treatment of oncogene-driven cancers by decreasing toxicity and increasing activity. In phase I drug development, a global problem of unknown magnitude is the multiplicity of similar drugs being investigated against the same target, colloquially known as the ‘me too’ phenomenon.

Methods

The Clinicaltrials.gov online database was queried for phase I clinical trials active during a two-year timeframe from December 2020 to December 2022. Natural language processing was employed to extract IAs from experimental interventions. Autoritative sources (Cancer.gov, Pubmed, et similia) were queried to classify IAs based on target and drug class/structure. Whenever data was unavailable from these websites, lower tier sources were employed. Overall target frequency and co-occurrence analyses were subsequently evaluated.

Results

By surveying the current landscape of phase I clinical trials for a two-year timeframe (December 2020 to December 2022), we identified 4480 distinct IAs. Excluding agents without direct mechanistic targets, non-human genome encoded targets (such as viral proteins, metabolites, carbohydrates et similia) or undisclosed data, 1016 gene targets and 3495 investigational agents were identified. While only a minority of gene targets had 4 or more IAs directed against them (26.7%) the majority of IA, 83.3% of single-target and 92.5% of multi-targeted, were directed against this minority of gene targets. The most frequent IA classes were Inhibitors(1105), Cell products(933), Monospecific-monoclonal antibodies(488) and Vaccines(252). The most frequent gene targets by number of IA were: CD19(316), EGFR(131), CD3(126), ERBB2(125), BCMA(108) and PD-1(106), CTLA4-PD1 and PDL1-CTLA4 were the most frequent cooccurring target pairs.

Conclusions

Only a minority (9.3%) of phase I IAs were explored against a target without a competitive agent; Unfortunately, the majority of IAs (86%) shared targets with at least 3 other agents. We argue that these duplicative efforts could be redirected toward unmet needs instead.

Clinical trial identification

Editorial acknowledgement

This abstract did not receive any editorial assistance.

Legal entity responsible for the study

M. Repetto.

Funding

Has not received any funding.

Disclosure

M. Repetto: Financial Interests, Personal, Funding: Sanofi. A. Drilon: Financial Interests, Personal, Advisory Board: Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millennium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, BeiGene, BerGenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem Oncology, MORE Health, AbbVie, 14ner/Elevation Oncology, Remedica, ArcherDX, Monopteros, Novartis, EMD Serono, Melendi, Liberum, Repare RX, Amgen, Janssen, EcoR1, Monte Rosa; Financial Interests, Personal, Other, CME: Medscape, Onclive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, PeerView Institute, Paradigm Medical Communications, WebMD, MJH Life Sciences, Med Learning, Imedex, Answers in CME, Medscape, Clinical Care Options, AiCME; Financial Interests, Personal, Other, CME, Consulting: Axis; Financial Interests, Personal, Other, Consulting: Nuvalent, Merus, EPG Health, mBrace, Harborside Nexus, Ology, TouchIME, Entos, Treeline Bio, Prelude, Applied Pharmaceutical Science, Inc; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Remedica Ltd, RV More; Financial Interests, Personal, Stocks/Shares: Treeline Biosciences; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Personal, Other, stocks: mBrace; Financial Interests, Institutional, Funding, Research funding: Pfizer, Exelixis, GlaxoSmithKline, Teva, Taiho, PharmaMar; Financial Interests, Personal, Funding, Research: Foundation Medicine; Non-Financial Interests, Personal, Member: ASCO, AACR, IASLC; Other, Personal, Other, Food/Beverage: Merck, PUMA, Merus; Other, Personal, Other, Other: Boehringer Ingelheim. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Pfizer; Financial Interests, Personal, Advisory Board: Ellipsis, Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Personal, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Personal, Advisory Role, Member of the Scientific Council. Patient Advocacy Association: Europa Donna; Non-Financial Interests, Personal, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Personal, Invited Speaker, No compensation for this role, This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Personal, Officer, Member of the Advisory Council: EUSOMA. All other authors have declared no conflicts of interest.