By Erin Harris, Editor-In-Chief, Cell & Gene
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At the ASGCT 24th Annual Meeting, Tessa Therapeutics announced its positive, topline data from Its on-going Phase 1 trial in patients with relapsed or refractory CD30-Positive Lymphoma. The data presented at ASGCT 24th Annual meeting demonstrated no dose-limiting toxicity.
While final data readout is expected at the end of this year, I met up with Tessa Therapeutics’ President and CEO Jeffrey H. Buchalter to talk more about the data presented at the event, as it highlights five patients treated with the therapy.
Explain the results for the Phase 1 dose-escalation study that were shared at the ASGCT 24th Annual Meeting.
Our Phase 1 dose-escalation study (NCT04288726) aims to test the safety and efficacy of an allogeneic CD30 CAR Epstein Barr Virus Specific T-cell (EBVST) therapy in patients with relapsed / refractory CD30+ lymphomas at three dose levels - 4 × 107 CD30.CAR EBVSTs, 1 × 108 CD30.CAR EBVSTs and 4 × 108 CD30.CAR EBVSTs. The early results from the ongoing study presented at ASGCT demonstrated an excellent safety profile in 6 patients at two successive dose levels, with no evidence of graft-versus-host disease (GVHD), cytokine release syndrome (CRS), neurotoxicity syndrome or any other severe adverse events associated with allogeneic therapies. What’s more, reported what we believe is encouraging data regarding potential efficacy. Of the 5 patients evaluable for efficacy, 3 patients achieved a partial response. These are early but important results, demonstrating the promise of allogeneic CD30 CAR-EBVST therapy even at lower dose levels, and support the development of Tessa’s allogeneic cell therapy platform.
What should patients with CD30+ lymphomas expect next from early clinical results?
The data presented at ASGCT are interim results from an early-stage clinical study but strongly suggest the promise of safe and efficacious allogeneic cell therapy approaches which could become widely available to CD30+ lymphoma patients. CD30 is a well validated lymphoma target with homogeneous expression in 98% of classical Hodgkin Lymphoma (cHL) and a significant proportion of subsets of non-Hodgkin Lymphomas. Cell therapy represents a significant promise for CD30+ lymphoma patients with limited treatment alternatives in relapsed / refractory (R/R) setting and Tessa is one of the few companies in late-stage clinical development of CD30 directed cell therapy treatments. Tessa’s lead clinical asset, TT11, is an autologous CD30 targeting CAR-T therapy which demonstrated strong clinical response in patients with R/R classical Hodgkin Lymphoma and is currently being investigated in a Phase 2 study. Autologous therapies, however, have limitations in terms of cost and scalability, which can be addressed by allogeneic / ‘donor-derived’ cell therapy treatments. ‘TT11X’ is an allogeneic CD30 CAR-EBVST therapy which is being co-developed by Tessa and Baylor College of Medicine (BCM) in an ongoing Phase 1dose escalation study (NCT04288726).
Explain Tessa’s proprietary allogeneic platform in detail.
Our allogeneic, or “off-the-shelf,” cell therapies have significant advantages and represent the next frontier in cancer treatment. Tessa is developing a unique and potentially transformational allogeneic CD30-CAR EBVST platform that we believe is capable of targeting a broad range of cancers. While allogeneic cell therapies have significant advantages, there are two main challenges to this approach:
- Allogeneic T-cells sourced from healthy donors recognize patient’s cells as foreign and attacks them, thus inducing 'graft‐versus‐host disease (GvHD)' in patients.
- Persistence of infused allogeneic T-cells in patients is often limited as patient’s own immune cells recognize allogeneic T-cells as foreign and attack them resulting in 'graft rejection'.
Tessa’s allogeneic platform tackles these challenges by using Virus-Specific T-cells (VSTs) augmented with CD30-CAR technology. The platform is based on decades-long research and clinical development on unique properties of VSTs by Tessa’s Scientific Co-Founder Malcolm Brenner, M.D., Ph.D., and the team at Baylor College of Medicine. VSTs are highly specialized immune cells produced during a viral infection that have the ability to recognize and kill infected cells while activating other parts of the immune system for a coordinated response. Also, allogeneic VSTs have demonstrated a strong safety profile and efficacy in early trials with minimal risk of graft versus host disease and graft rejection. Less than 1% Grade 3+ GvHD has been observed in > 400 patients over 25+ years across various malignancies. These qualities of VSTs may enable broad application in the allogeneic setting. CD30 CAR-Ts have the potential to further augment Virus Specific T cells (VSTs). Preclinical studies have demonstrated that CD30 targeting potentially helps improve allogeneic VST expansion and persistence.
With this platform approach, Tessa aims to overcome the current challenges faced by allogeneic cell therapies and create more efficacious, reliable, and scalable therapies capable of targeting a broad range of cancers.
What is next for the study?
The Phase 1 study aims to enroll 12-18 patients at three escalating dose levels - 4 × 10^7 CD30.CAR EBVSTs, 1 × 10^8 CD30.CAR EBVSTs and 4 × 10^8 CD30.CAR EBVSTs and the dataset presented at ASGCT includes three patients dosed at the lowest dosing level (4 × 10^7 CD30.CAR EBVSTs) and three at the second level (1 × 10^8 CD30.CAR EBVSTs). Patient enrollment continues with the aim to assess safety and efficacy at the highest dose cohort. We expect to report full findings from the trial by the end of 2021. Additional steps in the development of allogeneic CD30 CAR-EBVSTs will be assessed after completion of the dose-escalation portion of Phase 1. We may evaluate multiple doses to increase cell persistence and further improve patient outcomes, given the excellent safety profile. Longer term, we aim to develop this platform with dual CAR targeting to tackle other hematological malignancies and solid tumors where there is significant patient need.