Unpacking the Approval: How a Single-Arm Trial Led to ROS1 Lung Cancer Drug's Green Light
Recent approval of repotrectinib for ROS1-positive non-small cell lung cancer brings some notable details. (https://lnkd.in/gGT4zAtC)
?? The decision was based on a single-arm, open-label trial with 127 patients, including 71 ROS1 TKI-na?ve and 56 ROS1 TKI-pretreated patients.
??ORR (overall response rate) and DOR (duration of response) as the endpoints
?? Notably, this is a full approval, not accelerated. No additional confirmatory studies are required, though the ongoing TRIDENT-1 study is expected to enroll around 500 patients (source: clinicaltrials.gov)
?? No CDx (Companion Diagnostics) required, although "availability of an IVD" is committed.
? This decision initially puzzled me in the context of FDA's emphasis on confirmatory trials, especially randomized ones. However, clarity emerged at the ODAC meeting on Nov 16. Dr. Pazdur highlighted the challenges in molecularly heterogeneous diseases like lung cancer, especially for rare biomarker subsets (like ROS1). In such cases, high response rates and extensive patient enrollment in single-arm trials can suffice for approval, given the impracticality of large randomized trials. (This rationale can be found in Dr. Pazdur's remarks at 1:18:00 of the ODAC meeting https://lnkd.in/gFMa5_q7 thx! Sutan Wu)
??Kudos to the FDA/OCE and Dr. Pazdur for their pragmatic and balanced approach to regulatory requirements.
Biostatistics Strategy | NGS Algorithms | Precision Oncology | Data-Driven Insights
1 年Kudos to the team! The omission of a requirement for CDx is noteworthy – does it suggest flexibility in identifying ROS1+ patients, such as through LDTs? It's highly notable that a CDx is committed for availability though.
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1 年A good friend of mine was an early patient enrolled on this trial and is still thriving today! 10.5 years since his original metastatic lung cancer diagnosis!