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Optimizing the FDA’s Project Optimus: opportunities and challenges

Nature Reviews Clinical Oncology volume 21, pages 165–166 (2024)Cite this article

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Through Project Optimus, the FDA calls for radical changes in the design of early phase trials to identify the optimal doses of oncology drugs to achieve maximal efficacy with better tolerability and patient acceptability. Herein, we discuss approaches that will enable the implementation of this initiative as well as some concerns that the draft guidance has raised in the oncology community.

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References

  1. FDA. Optimizing the dosage of human prescription drugs and biological products for the treatment of oncologic diseases. fda.gov, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/optimizing-dosage-human-prescription-drugs-and-biological-products-treatment-oncologic-diseases (FDA, 2023).

  2. Roda, D., Jimenez, B. & Banerji, U. Are doses and schedules of small-molecule targeted anticancer drugs recommended by phase I studies realistic? Clin. Cancer Res. 22, 2127–2132 (2016).

    Article  CAS  PubMed  Google Scholar 

  3. Hong, D. S. et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N. Engl. J. Med. 383, 1207–1217 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hennessy, B. T., Gauthier, A. M., Michaud, L. B., Hortobagyi, G. & Valero, V. Lower dose capecitabine has a more favorable therapeutic index in metastatic breast cancer: retrospective analysis of patients treated at M. D. Anderson Cancer Center and a review of capecitabine toxicity in the literature. Ann. Oncol. 16, 1289–1296 (2005).

    Article  CAS  PubMed  Google Scholar 

  5. Brose, M. S. et al. A randomized study of lenvatinib 18 mg vs 24 mg in patients with radioiodine-refractory differentiated thyroid cancer. J. Clin. Endocrinol. Metab. 107, 776–787 (2022).

    Article  PubMed  Google Scholar 

  6. Yap, T. A. et al. Phase I trial of the PARP inhibitor olaparib and AKT inhibitor capivasertib in patients with BRCA1/2- and non-BRCA1/2-mutant cancers. Cancer Discov. 10, 1528–1543 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yuan, Y., Lin, R., Li, D., Nie, L. & Warren, K. E. Time-to-event Bayesian optimal interval design to accelerate phase I trials. Clin. Cancer Res. 24, 4921–4930 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Banerji, U. & Workman, P. Critical parameters in targeted drug development: the pharmacological audit trail. Semin. Oncol. 43, 436–445 (2016).

    Article  CAS  PubMed  Google Scholar 

  9. Blagden, S. P. et al. Effective delivery of complex innovative design (CID) cancer trials–a consensus statement. Br. J. Cancer 122, 473–482 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Araujo, D. et al. Oncology phase I trial design and conduct: time for a change - MDICT Guidelines 2022. Ann. Oncol. 34, 48–60 (2023).

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Drug Development Unit, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK

    Simon Rodney & Udai Banerji

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  1. Simon Rodney
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  2. Udai Banerji
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Correspondence to Simon Rodney or Udai Banerji.

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Competing interests

The Drug Development Unit is a joint department of the Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. The Institute of Cancer Research has research and commercial interests in licensed drugs such as abiraterone and capivasertib, and classes of drugs such as inhibitors of HSP90, HDAC, PI3K, alpha folate targeted thymidylate synthase, CHK1, MPS-1, GSPT-1 degraders and HSF-1 pathway. The unit receives funding from the Cancer Research UK Convergence Science Centre and the Experimental Cancer Centre and Biomedical Research Centre initiatives. The opinions expressed are personal. U.B. has received honoria for participation in advisory boards from Ellipsis Pharma, PharmEnable, Carrick Therapeutics and Pegasy, has received funding for preclinical research from Avacta and Verastem Oncology and clinical trial funding from Verastem Oncology. S.R. declares no competing interests.

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Rodney, S., Banerji, U. Optimizing the FDA’s Project Optimus: opportunities and challenges. Nat Rev Clin Oncol 21, 165–166 (2024). https://doi.org/10.1038/s41571-023-00853-z

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