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Updated: Jan 30, 2026
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Predicting Successful Phase Advancement and Regulatory Approval in Multiple Myeloma From Phase I Overall Response
Ehsan Malek1, Caner Saygin1, Rebecca Ye1
1Ehsan Malek, Fahrettin Covut, Neal J. Meropol, and Marcos De Lima, University Hospitals Seidman Cancer Center; Ehsan Malek, Byung-Gyu Kim, Fahrettin Covut, Neal J. Meropol, and Marcos De Lima, Case Western Reserve University Case Comprehensive Cancer Center; Caner Saygin, Taussig Cancer Institute; Rebecca Ye, Case Western Reserve University, Cleveland; Jeffrey Welge, University of Cincinnati; and James J. Driscoll, The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, OH.
Purpose:
Drug development in oncology is resource intensive, time consuming, and frequently unsuccessful. Here, we hypothesized that therapeutic benefit of published phase I studies of antimyeloma investigational agents was associated with advancement to phase II and future regulatory approval.
Patients And Methods:
Seventy four phase I trials that treated patients with multiple myeloma (n = 2,408) conducted from 2004 to 2015 were analyzed to assess drug safety, efficacy, phase advancement, and regulatory approval.
Results:
The median overall response rate (ORR) for all single-agent trials evaluated was 13.2%. However, the ORR in trials that advanced to phase II was 19%, whereas it was only 4% in trials that failed to advance. The median ORR was 23% for trials testing agents that were ultimately approved by the US Food and Drug Administration compared with only 8% for trials testing agents that were not approved (hazard ratio, 2.21; 95% CI, 2.01 to 2.61; P = .012). Importantly, the absolute number of phase I trials in multiple myeloma, but not the success rate, significantly increased over the period studied. The proportion of industry-sponsored trials also steadily increased over that same period. The ratio of initial dose to maximum tolerated dose was 0.29, suggesting that many patients were undertreated.
Conclusion:
Investigational agents with higher ORRs in phase I trials were more likely to advance to phase II trials and achieve US Food and Drug Administration approval. Our results suggest that designing phase I trials to maximize the antimyeloma efficacy of a given compound may lead to more successful and cost-effective drug development.
Insights
Higher overall response rates in early phase trials for antimyeloma agents predict advancement to phase II and US Food and Drug Administration approval, improving drug development efficiency.
Area of Science:
- Oncology
- Clinical Pharmacology
- Drug Development
Background:
- Oncology drug development is costly, lengthy, and often fails.
- Early phase trials are critical for assessing investigational agents.
Purpose of the Study:
- To determine if therapeutic benefit in phase I trials correlates with phase II advancement and regulatory approval for antimyeloma agents.
- To analyze factors influencing the success of early phase oncology drug development.
Main Methods:
- Analysis of 74 phase I trials (n=2,408) for multiple myeloma from 2004-2015.
- Assessment of drug safety, efficacy (overall response rate - ORR), phase advancement, and US Food and Drug Administration (FDA) approval.
Main Results:
- Trials advancing to phase II had a higher median ORR (19%) than those that did not (4%).
- FDA-approved agents showed higher median ORRs (23%) compared to non-approved agents (8%).
- The number of phase I trials increased, but success rates did not; many patients appeared undertreated.
Conclusions:
- Higher ORRs in phase I trials predict successful phase II advancement and FDA approval.
- Optimizing phase I trial design to maximize efficacy can enhance drug development success and cost-effectiveness.
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