Pharmacology-based ranking of anti-cancer drugs to guide clinical development of cancer immunotherapy combinations.
| Title: | Pharmacology-based ranking of anti-cancer drugs to guide clinical development of cancer immunotherapy combinations. |
|---|---|
| Authors: | Lemaire V; Department of Clinical Pharmacology, Genentech Inc, 1 DNA Way, South San Francisco, CA, 94080, USA. lemaire.vincent@gene.com.; Shemesh CS; Department of Clinical Pharmacology, Genentech Inc, 1 DNA Way, South San Francisco, CA, 94080, USA. shemesh.colby@gene.com.; Rotte A; Independent Consultant, Santa Clara, USA.; Current address: Clinical and Regulatory Affairs, Arcellx, Gaithersburg, USA. |
| Source: | Journal of experimental & clinical cancer research : CR [J Exp Clin Cancer Res] 2021 Oct 01; Vol. 40 (1), pp. 311. Date of Electronic Publication: 2021 Oct 01. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: BioMed Central Country of Publication: England NLM ID: 8308647 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-9966 (Electronic) Linking ISSN: 03929078 NLM ISO Abbreviation: J Exp Clin Cancer Res Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2009- : London : BioMed Central; Original Publication: [Roma] : APSIT |
| MeSH Terms: | Antineoplastic Agents/*therapeutic use ; Immunotherapy/*methods ; Neoplasms/*drug therapy ; Pharmaceutical Preparations/*administration & dosage; Neoplasms/immunology ; Neoplasms/pathology ; Pharmaceutical Preparations/chemistry ; Animals ; Drug Therapy, Combination ; Humans |
| Abstract: | The success of antibodies targeting Programmed cell death protein 1 (PD-1) and its ligand L1 (PD-L1) in cancer treatment and the need for improving response rates has led to an increased demand for the development of combination therapies with anti-PD-1/PD-L1 blockers as a backbone. As more and more drugs with translational potential are identified, the number of clinical trials evaluating combinations has increased considerably and the demand to prioritize combinations having potential for success over the ones that are unlikely to be successful is rising. This review aims to address the unmet need to prioritize cancer immunotherapy combinations through comprehensive search of potential drugs and ranking them based on their mechanism of action, clinical efficacy and safety. As lung cancer is one of the most frequently studied cancer types, combinations that showed potential for the treatment of lung cancer were prioritized. A literature search was performed to identify drugs with potential in combination with PD-1/PD-L1 blockers and the drugs were ranked based on their mechanism of action and known clinical efficacy. Nineteen drugs or drug classes were identified from an internal list of lead molecules and were scored for their clinical potential. Efficacy and safety data from pivotal studies was summarized for the selected drugs. Further, overlap of mechanisms of action and adverse events was visualized using a heat map illustration to help screen drugs for combinations. The quantitative scoring methodology provided in this review could serve as a template for preliminary ranking of novel combinations.; (© 2021. The Author(s).) |
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| Contributed Indexing: | Keywords: Cancer; Cancer immunotherapy; Clinical trials; Combination development; Pharmacology |
| Substance Nomenclature: | 0 (Antineoplastic Agents); 0 (Pharmaceutical Preparations) |
| Entry Date(s): | Date Created: 20211002 Date Completed: 20220131 Latest Revision: 20240403 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8485537 |
| DOI: | 10.1186/s13046-021-02111-5 |
| PMID: | 34598713 |
| Database: | MEDLINE |
Journal Article; Review