The Challenge 

Sponsored by the biotechnology company Zelluna Immunotherapy (‘Zelluna’) based in Norway, ZIMA-101 is a complex first-in-human, first-in-class Phase I clinical trial evaluating ZI-MA4-1, an allogeneic TCR-NK cell therapy targeting MAGE-A4 positive solid tumours.  

As Zelluna’s first clinical trial and the first clinical translation of its TCR-NK platform, establishing ZIMA-101 presented a number of novel operational challenges. These included establishing the appropriate UK drug-supply and importation pathway for an off-the-shelf, cryopreserved cell therapy, and developing the pharmacy, storage, handling and clinical processes required to deliver multiple doses safely and effectively within an NHS research setting. 

Addressing these requirements at pace required close coordination between Zelluna, The Christie and the wider ATTC network. Through this collaborative approach, The Christie became the first site globally to open the ZIMA-101 clinical trial and consented the first patient 89 days after HRA approval and 126 days from application submission. This timeline comfortably met the UK Government’s target for clinical trials to open and recruit their first participant within 150 days. 

The Solution 

Connections built through the ATTC network 

Zelluna identified The Christie as a potential lead site based on the site’s experience in cell therapy and the delivery of first-in-human phase 1 studies across multiple cancer indications, engaging with Professor Fiona Thistlethwaite. As both the iMATCH ATTC Director and head of the AICT team at The Christie, Professor Thistlethwaite was able to understand the company’s support needs and connect Zelluna with the CGT Catapult.  

The CGT Catapult was then able to support Zelluna during preparation for ZIMA-101, Zelluna’s first clinical trial, including development of the  protocol and review of the briefing package prepared for scientific advice with the Medicines and Healthcare products Regulatory Agency (MHRA). The CGT Catapult also provided specific support on chemistry manufacturing and controls (CMC) considerations associated with the novel cell therapy product.  

Agile clinical trial set up at site 

Successful initiation of this clinical trial required early strategic alignment and collaborative expertise across multiple disciplines. As the investigational product was an off-the-shelf Advanced Therapy Investigational Medicinal Product (ATIMP), the requirements for handling, oversight and local implementation differed from those associated with conventional autologous ATIMPs. The Christie established a tailored investigational product pathway and supporting local processes to ensure the site was appropriately equipped to deliver the trial effectively.  

To achieve the National Institute for Health and Care Research (NIHR) 150-day study set-up timelines, key preparatory activities were undertaken in parallel with regulatory review, allowing operational requirements, governance arrangements and documentation to be developed concurrently. Early and sustained engagement between the pharmacy, stem cell laboratory, clinical and sponsor teams enabled timely decision-making, proactive identification and management of potential risks, and effective resolution of trial-specific requirements.  

The Results 

With Professor Thistlethwaite acting as the Global Chief Investigator, The Christie became the first research site worldwide to open the ZIMA-101 clinical trial and recruit a patient. Through the expertise and agility of the AICT team, the first global patient provided consent 126 days from submission of the regulatory approval application, demonstrating the capability of The Christie to support efficient delivery of complex ATMP clinical trials.  

The key factors enabling this achievement included: 

• Early engagement between Zelluna, as a new trial sponsor, and The Christie as the lead research site 

• Establishment of a strong link between Zelluna and the ATTC network 

• Targeted support provided to Zelluna through the CGT Catapult 

• The highly specialist ATMP clinical trial expertise of the multidisciplinary AICT team at The Christie 

• The AICT team’s proactive patient pre-screening, enabling rapid identification and recruitment of eligible patients 

Wider Impact 

Early engagement between Zelluna and The Christie in turn enabled rapid connection to the ATTC network and the CGT Catapult, which was essential to progressing the novel operational aspects that were needed to initiate this first clinical trial for Zelluna. Through clear and efficient communication, Zelluna was supported to achieve key milestones in establishing and initiating the ZIMA-101 clinical trial. 

Building these early connections ensured that the right clinical, regulatory and manufacturing expertise was accessed quickly. This powerful example of collaborative working demonstrates the ATTC network’s mission: to make the UK the leading environment for ATMP clinical trials and to keep the UK as a location of choice for advanced therapy research.