Innovations in clinical trial design have significantly shortened development timelines for oncology drugs. The 21st Century Cures Act (Cures Act), enacted in 2016, sought to accelerate medical innovation by updating regulatory frameworks, advancing patient-focused research, and enhancing data sharing.¹

One major component of the act allows the US Food and Drug Administration (FDA) to drive modern clinical trial methodologies that improve efficiency and reduce costs.² The Act promotes the use of adaptive designs, which provides flexibility to modify the trial sample size, treatment arms, or randomization ratios based on interim analyses without compromising validity or integrity.¹˒² The FDA has released several guidance documents to propel adaptive designs.  One example is the 2019 guidance to industry for the use of adaptive clinical trial design to support drug effectiveness and safety.³

The Cures Act has significantly shaped oncology clinical trials, especially for targeted drugs used in precision medicine.⁴ Designs such as master protocols, including umbrella trials that test multiple targeted therapies within a single cancer type and basket trials that evaluate one therapy across multiple cancer types sharing a biomarker are increasingly common.⁴˒⁵ This and other novel trial designs mark the movement away from fixed design protocols to a more dynamic structure.⁴   

Drugs that have gained approvals using the adaptive design facilitated by the Cures Act include PD-1/PD-L1 such as pembrolizumab (Keytruda), CAR T such as tisagenlecleucel (Kymriah) and most recently, zongertinib (Hernexeos). Zongertinib received accelerated FDA approval in August 2025 for the treatment of HER2-mutated non-small cell lung cancer using Phase 1a/1b clinical trial results.⁶⁻⁸  

The zongertinib clinical trial used an adaptive Phase 1 multiple cohort design, meaning several patient groups with different characteristics were studied at the same time.⁸˒⁹ Among 71 patients previously treated with platinum-based chemotherapy but without HER2-targeted tyrosine kinase inhibitor or antibody-drug conjugates (ADC), the trial reported an objective response rate (ORR) of 75%, with 58% maintaining a response for at least six months. In contrast, among 34 patients who had prior platinum chemotherapy and a HER2-targeted ADC, ORR was 44%, with 27% achieving a DOR of ≥ six months. The annual wholesale acquisition cost for zongertinib is $263,615.¹⁰ 

Key questions to ask from the managed care perspective as adaptive trial designs become more common include but are not limited to: 

• What evidence exists regarding long-term outcomes, including durability of response and overall survival benefits, for these novel therapies? 
• What potential strategies could enable risk-sharing or outcomes-based agreements to manage the high costs of these treatments? 
• How can real-world evidence be leveraged to validate clinical value and support decision-making? 

The Cures Act has changed cancer trials by promoting adaptive designs, master protocols, and patient-focused research. It has increased the speed to market for many innovative therapies while challenging the system to manage costs and evidence gaps.