Navigating biometrics complexity in a pivotal CAR T-cell therapy submission
Case study
Overview
A biotechnology sponsor was progressing a pivotal Phase II randomised, multi-centre, open-label study evaluating a chimeric antigen receptor (CAR) T therapy against standard of care in participants with relapsed or refractory diffuse large B-cell lymphoma who were not eligible for high-dose chemotherapy and autologous stem cell transplantation.
The study reflected a highly relevant development challenge for cell and gene therapy sponsors: generating robust
evidence for a CAR T-cell product in a treatment area where approved CAR T-cell therapies already exist. The study demonstrated ICON’s ability to operationalise a complex pivotal CAR T-cell trial and support the biometrics activities required for regulatory submission.
Challenge
The sponsor needed to demonstrate a significant treatment effect and safety profile versus standard of care within a complex, randomised CAR T-cell trial design. This required careful handling of differing treatment pathways, visit schedules and analysis considerations between the CAR T-cell and standard of care arms, with the added complexity of permitted crossover.
CAR T-cell studies bring specific operational and analytical challenges, including multiple stages of administration such as leukapheresis, lymphodepletion, bridging therapy and product administration. They also require detailed safety reporting for adverse events of special interest, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and cytopenias.
Solution
ICON applied specialist cell and gene therapy biometrics expertise to support the study’s complex safety, efficacy
and regulatory requirements.
- Delivered detailed reporting of adverse events of special interest, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and cytopenias
- Distinguished adverse events from signs and symptoms to support accurate safety reporting
- Adapted to updated CTCAE safety reporting requirements and reported outcomes for leukapheresed
participants who were not treated - Supported complex efficacy analyses, including non-proportional hazards, primary and sensitivity analyses,
and estimand frameworks for key endpoints - Accounted for differences between investigator-assessed efficacy data and independent review committee
findings - Applied appropriate blinding controls for restricted-access results in an open-label study
- Responded to post-submission regulatory analysis requests
Outcome
With ICON’s biostatistics and programming support, the sponsor was able to submit the program for FDA biologics
licence application review and to the European Medicines Agency for marketing authorisation. ICON’s contribution
helped support the level of analytical quality and regulatory readiness required for a pivotal CAR T-cell submission.
Following this work, the sponsor awarded ICON additional activity related to a protocol amendment, including TFL
production for a newly added Part II FIT component of the study.
ICON’s value add
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Regulatory-ready submission support
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Confidence in complex study delivery
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CAR T-cell specific biometrics expertise
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Responsive post-submission support
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Robust safety and efficacy analyses