Cell therapy weekly: Phase III trial comparing large B-cell lymphoma CAR T-cell therapies
This week: Lyell Immunopharma (CA, USA) initiated its Phase III head-to-head comparison of CAR T-cell therapies in large B-cell lymphoma (LBCL) – the first trial of its kind, and BlueWhale Bio (PA, USA) dosed its first patient with a cell therapy using company’s flagship technology, Synecta™ T1 CDNPs (cell-derived nanoparticles). Plus, Mytos (London UK) announced three new manufacturing collaborations.
The news highlights:
- Three new cell manufacturing collaborations
- CAR T-cells manufactured with cell-derived nanoparticle technology
- Phase III head-to-head trial comparing CAR T-cell therapies
Three new cell manufacturing collaborations
Mytos, a biotechnology company specializing in automated cell manufacturing, has announced new manufacturing collaborations with three biotech companies. Each company will integrate Mytos’ iDEM automated cell manufacturing platform to scale varying cell types for therapeutic use.
The companies involved in this new collaboration and their usage are as follows:
- StemSight (Tampere, Finland) will use the platform to advance its induced pluripotent stem cell-derived corneal stem cell therapies for limbal stem cell deficiency.
- Rinri Therapeutics (Sheffield, UK) will be incorporating the iDEM platform to support the production of their otic neural progenitor cell therapy addressing sensorineural hearing loss.
- Novadip (Mont-Saint-Guibert, Belgium) will be evaluating the platform to scale production of its autologous adipose-derived stem cell products for bone defects.
“Mytos enables us to increase the output of our existing facilities, without having to delay scaling to build out new capacity,” said Neil Johnson, Chief Technical Offiecer at Novadip. “This partnership is an important step as we move closer to delivering regenerative bone therapies to patients who currently have few treatment options.”
CAR-T cells manufactured with cell-derived nanoparticle technology
BlueWhale Bio has dosed the first patient in a clinical trial at the University of Pennsylvania (USA), evaluating the safety and feasibility of huCART19-IL18 cells in patients with relapsed or refractory CD19+ cancers. These specialized CAR-T cells are manufactured using the company’s flagship technology, Synecta™ T1 CDNPs (cell-derived nanoparticles), which aims to enhance therapeutic efficacy while streamlining the production process.
Synecta™ T1 CDNPs mimic natural T-cell stimulation through membrane-bound signals, cytokines and adhesion molecules, offering a scalable alternative to synthetic activators. Synecta has received US Food and Drug Administration (MD, USA) clearance as the first regulatory-approved CDNPs for T-cell activation. Preclinical studies have demonstrated their enhanced capabilities over commercially available methods where they achieved target dose levels faster and more consistently, even with exhausted T cells.
“This pioneering trial of huCART19-IL18, manufactured in just 3 days, showed durable complete responses in patients with refractory lymphoma,” said Jim Riley, Professor of Microbiology at the University of Pennsylvania and Scientific Co-founder of BlueWhale Bio. “With BlueWhale’s cell-derived nanoparticle activation and expansion technology, we aim for more consistent and scalable manufacturing results to accelerate the growth and adoption of cell-based therapies.”
Phase III head-to-head trial comparing CAR T-cell therapies
Lyell Immunopharma has initiated PiNACLE-H2H, a Phase III head-to-head randomized controlled trial. The trial will compare their dual-targeting CD19/CD20 CAR T-cell therapy, rondecabtagene autoleucel (ronde-cel), against standard-of-care single-targeting therapies (lisocabtagene maraleucel or axicabtagene ciloleucel) for patients with relapsed or refractory LBCL in the second-line treatment setting.
PiNACLE-H2H will enroll approximately 400 patients across the United States and Australia, with the first patient expected by early 2026.
Ronde-cel, which has received both Regenerative Medicine Advanced Therapy and Fast Track designations from the US Food and Drug Administration, is designed to target B cells expressing either CD19, CD20, or both. The CAR-T therapy is manufactured to contain higher proportions of naïve and central memory T cells – features designed to improve complete response rates and durability compared to currently approved therapies.
This trial is the first Phase III head-to-head comparison of CAR T-cell therapies in LBCL and will run alongside Lyell’s other pivotal trial, PiNACLE, a single-arm study of ronde-cel in third-line or later treatment settings.