Integrating Early-Stage Drug Development with Clinical Networks; Challenges and Opportunities: The City of Hope Developing Experience
Abstract
:1. Introduction
2. Current Challenges for Early-Stage Clinical Trials
3. City of Hope (COH) Community Oncology Practice Network
4. Clinical Research Integration Opportunities
5. Ongoing COH Phase 1 Program Integrative Initiatives
5.1. Development of a Virtual “Refractory Disease” Phase 1 Trial—Matching Tele-Medicine Oncology Clinic
5.2. Expansion of Phase 1 Trials to City of Hope—Orange County
5.3. Precision Medicine Network Initiative
6. The City of Hope Center for Precision Medicine
6.1. COH-CPM Clinical Case Conferences
6.2. Precision Oncology Tumor Board
7. Centralized Logistical Operation of COH-INSPIRE
8. Expansion of INSPIRE to the COH Community Oncology Network
9. Leveraging INSPIRE to Accelerate Early Drug Development across the COH Community Oncology Network
10. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Dickson, M.; Gagnon, J.P. Key factors in the rising cost of new drug discovery and development. Nat. Rev. Drug Discov. 2004, 3, 417–429. [Google Scholar] [CrossRef]
- DiMasi, J.A.; Grabowski, H.G.; Hansen, R.W. Innovation in the pharmaceutical industry: New estimates of R&D costs. J. Health Econ. 2016, 47, 20–33. [Google Scholar] [PubMed] [Green Version]
- Mak, K.-K.; Pichika, M.R. Artificial intelligence in drug development: Present status and future prospects. Drug Discov. Today 2019, 24, 773–780. [Google Scholar] [CrossRef] [PubMed]
- Ingber, D.E. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat. Rev. Genet. 2022, 23, 467–491. [Google Scholar] [CrossRef] [PubMed]
- Mennen, S.M.; Alhambra, C.; Allen, C.L.; Barberis, M.; Berritt, S.; Brandt, T.A.; Campbell, A.D.; Castañón, J.; Cherney, A.H.; Christensen, M.; et al. The evolution of high-throughput experimentation in pharmaceutical development and perspectives on the future. Org. Process Res. Dev. 2019, 23, 1213–1242. [Google Scholar] [CrossRef]
- Parasrampuria, D.A.; Benet, L.Z.; Sharma, A. Why drugs fail in late stages of development: Case study analyses from the last decade and recommendations. AAPS J. 2018, 20, 46. [Google Scholar] [CrossRef]
- Lin, A.; Giuliano, C.J.; Palladino, A.; John, K.M.; Abramowicz, C.; Yuan, M.L.; Sausville, E.L.; Lukow, D.A.; Liu, L.; Chait, A.R.; et al. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci. Transl. Med. 2019, 11, eaaw8412. [Google Scholar] [CrossRef]
- Unger, J.M.; Vaidya, R.; Hershman, D.L.; Minasian, L.M.; Fleury, E.M. Systematic review and meta-analysis of the magnitude of structural, clinical, and physician and patient barriers to cancer clinical trial participation. JNCI J. Natl. Cancer Inst. 2019, 111, 245–255. [Google Scholar] [CrossRef]
- Levit, L.A.; Byatt, L.; Lyss, A.P.; Paskett, E.D.; Levit, K.; Kirkwood, K.; Schenkel, C.; Schilsky, R.L. Closing the rural cancer care gap: Three institutional approaches. JCO Oncol. Pract. 2020, 16, 422–430. [Google Scholar] [CrossRef]
- Decoster, G.; Stein, G.; Holdener, E.E. Responses and toxic deaths in phase I clinical trials. Ann. Oncol. 1990, 1, 175–181. [Google Scholar] [CrossRef]
- Von Hoff, D.D.; Turner, J. Response rates, duration of response, and dose response effects in phase I studies of antineoplastics. Investig. New Drugs 1991, 9, 115–122. [Google Scholar] [CrossRef]
- Chihara, D.; Lin, R.; Flowers, C.R.; Finnigan, S.R.; Cordes, L.M.; Fukuda, Y.; Huang, E.P.; Rubinstein, L.V.; Nastoupil, L.J.; Ivy, S.P.; et al. Early drug development in solid tumours: Analysis of National Cancer Institute-sponsored phase 1 trials. Lancet 2022, 400, 512–521. [Google Scholar] [CrossRef] [PubMed]
- Chakiba, C.; Grellety, T.; Bellera, C.; Italiano, A. Encouraging Trends in Modern Phase 1 Oncology Trials. N. Engl. J. Med. 2018, 378, 2242–2243. [Google Scholar] [CrossRef] [PubMed]
- Schwaederle, M.; Zhao, M.; Lee, J.; Lazar, V.; Leyland-Jones, B.; Schilsky, R.; Mendelsohn, J.; Kurzrock, R. Association of Biomarker-Based Treatment Strategies with response rates and progression free survival in refractory malignant neoplasms: A meta-analysis. JAMA Oncol. 2016, 2, 1452–1459. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mackley, M.; Fernandez, N.R.; Fletcher, B.; Woolcott, C.G.; Fernandez, C.V. Revisiting risk and benefit in early oncology trials in the era of precision medicien: A systematic review and meta-analysis of phase 1 trials of targeted single-agent anticancer therapies. JCO Precis. Oncol. 2021, 5, 17–26. [Google Scholar] [CrossRef]
- Von Hoff, D.D.; Stephenson, J.J.S., Jr.; Rosen, P.; Loesch, D.M.; Borad, M.J.; Anthony, S.; Jameson, G.S.; Brown, S.; Cantafio, N.; Richards, D.A.; et al. Pilot study using molecular profiling of patients’tumors to find potential targets and select treatments for their refractory cancers. J. Clin. Oncol. 2010, 28, 4877–4883. [Google Scholar] [CrossRef]
- Sathian, B.; Asim, M.; Banerjee, I.; Pizarro, A.B.; Roy, B.; Van Teijlingen, E.R.; Nascimento, I.J.B.D.; Alhamad, H.K. Impact of COVID-19 on clinical trials and clinical research: A systematic review. Nepal. J. Epidemiol. 2020, 10, 878–887. [Google Scholar] [CrossRef] [PubMed]
- Lasch, F.; Psarelli, E.; Herold, R.; Mattsson, A.; Guizzaro, L.; Pétavy, F.; Schiel, A. The Impact of COVID-19 on the Initiation of Clinical Trials in Europe and the United States. Clin Pharm. Ther. 2022, 111, 1093–1102. [Google Scholar] [CrossRef]
- Lee, C.; Werner, T.L.; Deal, A.M.; Krise-Confair, C.J.; Bentz, T.A.; Cummings, T.M.; Grant, S.C.; Lee, A.B.; Moehle, J.; Moffett, K.; et al. Clinical trial metrics: The complexity of conducting clinical trials in North American Cancer Centers. JCO Oncol. Pract. 2021, 17, e77–e93. [Google Scholar] [CrossRef]
- Mendelsohn, J.; Moses, H.L.; Nass, S.J. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program; National Academies Press: Washington, DC, USA, 2010. [Google Scholar]
- Goodsaid, F. Challenges of biomarkers in drug discovery and development. Expert Opin. Drug Discov. 2012, 7, 457–461. [Google Scholar] [CrossRef] [Green Version]
- Rothwell, D.G.; Ayub, M.; Cook, N.; Thistlethwaite, F.; Carter, L.; Dean, E.; Smith, N.; Villa, S.; Dransfield, J.; Clipson, A.; et al. Utility of ctDNA to support patient selection for early phase clinical trials: The TARGET study. Nat. Med. 2019, 25, 738–743. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dienstmann, R.; Serpico, D.; Rodon, J.; Saura, C.; Macarulla, T.; Elez, E.; Alsina, M.; Capdevila, J.; Perez-Garcia, J.; Sánchez-Ollé, G.; et al. Molecular profiling of patients with colorectal cancer and matched targeted therapy in phase I clinical trials. Mol. Cancer Ther. 2012, 11, 2062–2071. [Google Scholar] [CrossRef] [Green Version]
- Siu, L.L.; Conley, B.A.; Boerner, S.; LoRusso, P.M. Next-Generation Sequencing to Guide Clinical Trials. Clin. Cancer Res. 2015, 21, 4536–4544. [Google Scholar] [CrossRef] [Green Version]
- Mateo, J.; Steuten, L.; Aftimos, P.; André, F.; Davies, M.; Garralda, E.; Geissler, J.; Husereau, D.; Martinez-Lopez, I.; Normanno, N.; et al. Delivering precision oncology to patients with cancer. Nat. Med. 2022, 28, 658–665. [Google Scholar] [CrossRef] [PubMed]
- Kaminski, A.; Szamreta, E.A.; Shah, R.; Ning, N.; Aggarwal, J.; Hussain, A.; Adeboyeje, G. Barriers to next-generation sequencing despite increased utilization: U.S. physician survey results. J. Clin. Oncol. 2021, 39 (Suppl. 15), e18754. [Google Scholar] [CrossRef]
- Johansen Taber, K.A.; Dickinson, B.D.; Wilson, M. The promise and challenges of next-generation genome sequencing for clinical care. JAMA Intern. Med. 2014, 174, 275–280. [Google Scholar] [CrossRef]
- Moor, J.; Gray, S.W.; Mitchell, S.A.; Klabunde, C.N.; Freedman, A.N. Oncologist Confidence in Genomic Testing and Implications for Using Multimarker Tumor Panel Tests in Practice. JCO Precis. Oncol. 2020, 4, 620–631. [Google Scholar] [CrossRef]
- Roberts, M.C.; Spees, L.P.; Freedman, A.N.; Klein, W.M.P.; Das, I.P.; Butler, E.N.; de Moor, J.S. Oncologist-Reported Reasons for Not Ordering Multimarker Tumor Panels: Results from a Nationally Representative Survey. JCO Precis. Oncol. 2021, 5, 701–709. [Google Scholar] [CrossRef]
- Ashbury, F.D.; Thompson, K.; Williams, C.; Williams, K. Challenges adopting next-generation sequencing in community oncology practice. Curr. Opin. Oncol. 2021, 33, 507–512. [Google Scholar] [CrossRef]
- Bedard, P.L.; Hyman, D.M.; Davids, M.S.; Siu, L.L. Small molecules, big impact: 20 years of targeted therapy in oncology. Lancet 2020, 395, 1078–1088. [Google Scholar] [CrossRef]
- Precision Medicine for All: Cancer Centre Makes Genomic Analysis a Top Priority. Available online: https://www.nature.com/articles/d42473-022-00259-y (accessed on 1 March 2023).
- Solomon, I. INSPIRE Study (Implementing Next-generation Sequencing for Precision Intervention and Risk Evaluation): Scaling Return of Genomic Results. In Proceedings of the Conference: Precision Prevention, Early Detection, and Interception of Cancer, Austin, TX, USA, 1 January 2022. [Google Scholar]
- McDonnell, K.; Hong, C.; Bonner, J.D.; Lindsey, S.S.; Solomon, I.; Hampel, H.; Park, W.; Idos, G.; Gray, S.W.; Gruber, S.B. Germline mutational landscape of non-highly penetrant Fanconi anemia genes unveiled from sequencing of 5,044 patients with solid tumor cancer. J. Clin. Oncol. 2022, 40 (Suppl. 16), 10521. [Google Scholar] [CrossRef]
- Kruper, L. Reappraising the Fanconi Anemia DNA repair pathway in breast cancer risk and precision intervention: Insights and opportunities from the City of Hope INSPIRE study. In Proceedings of the San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 6–10 December 2022. [Google Scholar]
- Courdy, S.; Hulse, M.; Nadaf, S.; Mao, A.; Pozhitkov, A.; Berger, S.; Chang, J.; Achuthan, S.; Kancharla, C.; Kunz, I.; et al. The City of Hope POSEIDON enterprise-wide platform for real-world data and evidence in cancer. J. Clin. Oncol. 2021, 39 (Suppl. 15), e18813. [Google Scholar] [CrossRef]
- Vadas, A.; Bilodeau, T.J.; Oza, C. Special Report: The Evolution of Biomarker Use in Clinical Trials for Cancer Treatments. Available online: https://www.thejournalofprecisionmedicine.com/the-journal-of-precision-medicine/special-report-the-evolution-of-biomarker-use-in-clinical-trials-for-cancer-treatments/ (accessed on 1 March 2023).
- Goulart, B.H.; Clark, J.W.; Pien, H.H.; Roberts, T.G.; Finkelstein, S.N.; Chabner, B.A. Trends in the use and role of biomarkers in phase I oncology trials. Clin. Cancer Res. 2007, 13 Pt 1, 6719–6726. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Malone, E.R.; Oliva, M.; Sabatini, P.J.B.; Stockley, T.; Siu, L.L. Molecular profiling for precision cancer therapies. Genome Med. 2020, 12, 8. [Google Scholar] [CrossRef] [Green Version]
- Jardim, D.L.; Schwaederle, M.; Hong, D.S.; Kurzrock, R. An appraisal of drug development timelines in the Era of precision oncology. Oncotarget 2016, 7, 53037–53046. [Google Scholar] [CrossRef] [Green Version]
- Collins, F.S.; Varmus, H. A new initiative on precision medicine. N. Engl. J. Med. 2015, 372, 793–795. [Google Scholar] [CrossRef] [Green Version]
- Hamburg, M.A.; Collins, F.S. The path to personalized medicine. N. Engl. J. Med. 2010, 363, 301–304. [Google Scholar] [CrossRef]
- Kelloff, G.J.; Sigman, C.C. Cancer biomarkers: Selecting the right drug for the right patient. Nat. Rev. Drug Discov. 2012, 11, 201–214. [Google Scholar] [CrossRef]
- Kiriiri, G.K.; Njogu, P.M.; Mwangi, A.N. Exploring different approaches to improve the success of drug discovery and development projects: A review. Future J. Pharm. Sci. 2020, 6, 27. [Google Scholar] [CrossRef]
- Giri, V.N.; Shimada, A.; Leader, A.E. Predictors of Population Awareness of Cancer Genetic Tests: Implications for Enhancing Equity in Engaging in Cancer Prevention and Precision Medicine. JCO Precis Oncol. 2021, 5, 1699–1708. [Google Scholar] [CrossRef]
- Catz, D.S.; Green, N.S.; Tobin, J.N.; Lloyd-Puryear, M.A.; Kyler, P.; Umemoto, A.; Cernoch, J.; Brown, R.; Wolman, F. Attitudes about genetics in underserved, culturally diverse populations. Community Genet. 2005, 8, 161–172. [Google Scholar] [CrossRef] [PubMed]
- Khoury, M.J.; Bowen, S.; Dotson, W.D.; Drzymalla, E.; Green, R.F.; Goldstein, R.; Kolor, K.; Liburd, L.C.; Sperling, L.S.; Bunnell, R. Health equity in the implementation of genomics and precision medicine: A public health imperative. Genet. Med. 2022, 24, 1630–1639. [Google Scholar] [CrossRef] [PubMed]
- Elwyn, G.; Cochran, N.; Pignone, M. Shared Decision Making-The Importance of Diagnosing Preferences. JAMA Intern. Med. 2017, 177, 1239–1240. [Google Scholar] [CrossRef] [PubMed]
- Blasimme, A.; Vayena, E. Becoming partners, retaining autonomy: Ethical considerations on the development of precision medicine. BMC Med. Ethics 2016, 17, 67. [Google Scholar] [CrossRef] [Green Version]
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Villalona-Calero, M.A.; Malhotra, J.; Chung, V.; Xing, Y.; Gray, S.W.; Hampel, H.; Gruber, S.; McDonnell, K. Integrating Early-Stage Drug Development with Clinical Networks; Challenges and Opportunities: The City of Hope Developing Experience. J. Clin. Med. 2023, 12, 4061. https://doi.org/10.3390/jcm12124061
Villalona-Calero MA, Malhotra J, Chung V, Xing Y, Gray SW, Hampel H, Gruber S, McDonnell K. Integrating Early-Stage Drug Development with Clinical Networks; Challenges and Opportunities: The City of Hope Developing Experience. Journal of Clinical Medicine. 2023; 12(12):4061. https://doi.org/10.3390/jcm12124061
Chicago/Turabian StyleVillalona-Calero, Miguel A., Jyoti Malhotra, Vincent Chung, Yan Xing, Stacy W. Gray, Heather Hampel, Stephen Gruber, and Kevin McDonnell. 2023. "Integrating Early-Stage Drug Development with Clinical Networks; Challenges and Opportunities: The City of Hope Developing Experience" Journal of Clinical Medicine 12, no. 12: 4061. https://doi.org/10.3390/jcm12124061
APA StyleVillalona-Calero, M. A., Malhotra, J., Chung, V., Xing, Y., Gray, S. W., Hampel, H., Gruber, S., & McDonnell, K. (2023). Integrating Early-Stage Drug Development with Clinical Networks; Challenges and Opportunities: The City of Hope Developing Experience. Journal of Clinical Medicine, 12(12), 4061. https://doi.org/10.3390/jcm12124061