Leveraging Cell Therapy Advances for Treating Hodgkin Lymphoma, Other Cancers

Tessa Therapeutics recently dosed the first patient with relapsed/refractory classical Hodgkin lymphoma (cHL) in the phase 1b ACTION clinical trial (NCT05352828) of TT11, an autologous CD30-targeted chimeric antigen receptor T-cell (CAR-T) therapy being developed as a second-line treatment in combination with nivolumab. The therapy is also being evaluated as a monotherapy in later lines of treatment for cHL in the phase 2 CHARIOT trial (NCT04268706). In addition to TT11, Tessa’s technologies include allogeneic CAR-oncolytic virus combinations and bispecific antibodies the company is developing toward the treatment of both hematological malignancies and solid tumors.

CGTLive spoke with Ivan Horak, MD, chief medical and scientific officer, Tessa Therapeutics, to learn more about Tessa’s technologies and platforms and the advantages they confer in oncologic indications. He also discussed progress with the ACTION study of TT11.

CGTLive: What are the advantages of Tessa’s technologies and platforms in oncologic indications?

Ivan Horak, MD: First off, bispecific T-cell technology - I think it's a very exciting platform with a very good track record. With this platform, over 400 patients were treated in post-transplant setting for viral diseases and it was very well tolerated with no cytokine release syndrome, no graft-versus-host disease. Importantly, there is no need for gene editing. Gene editing induces double strand DNA breaks that ultimately may lead to chromosomal instability. It's a bit of a nightmare for both clinical and manufacturing: manufacturing has to establish that you don't have chromosome instability in your batches, and clinicians have to follow these patients very closely. So bispecific T-cells bring some unique opportunities.

Another advantage we have is with antibodies. We have access to LlaMABody™ VHH antibodies which are very convenient for CAR technology. Plus, we have a good understanding of signaling and how to modify the T cells and keep them fully functional. These are unique strengths. Last but not least is the combination of the allogeneic cell therapy with oncolytic viruses. This is a replicative deficient adenovirus, which has to be injected locally, and carries a helper virus that can carry multiple payloads, in our cases, IL-12 and PD-L1 mini body. really can help to change the ecosystem for T-cell technology. We have very good data from clinic already, with responses purely from injection of the adenovirus, not only locally but in visceral metastases. We change the immunologic profile of the patient to be much more favorable for T cell therapy. So, with all of that, I would say that we are probably one of the first companies to combine oncolytic virus with T cell therapy, and that with our bispecific T-cell technologies puts Tessa into a really unique orbit.

Can you discuss the ongoing ACTION trial of TT11?

First off, one of the hallmarks of cHL is a Pd-L1 amplification, which explains why the patient is immunocompromised. So we tried to benefit from this knowledge and combining the PD-1 with CAR T as again, probably one of the very early companies to do this combination. So, the role of the PD-1 here is really to neutralize PD-L1 to neutralize the immunosuppressive factor. Second, it's very important to protect T-cells from exhaustion not only in the cHL field but in the whole field of cell therapy. So, we have already started dosing patients and we are getting close to completing enrollment of the study. All of this is very exciting and they expect to present the early data of primarily safety but definitely with a significant portion of efficacy at the International Conference on Malignant Lymphoma in 2023.

We originally opened the study in 3 centers, now we’ve extended to 5. The trial opened in the middle of Summer 2022 and nobody wants to go in a clinical trial then but in spite of that, we'll be done hopefully very soon with enrollment. We're enrolling patients who failed primary treatment. These are new patients just diagnosed with advanced stages of cHLand did not respond to the treatment, which is a very small fraction, or who relapses or progressed, which is around 15 to 25% of the advanced stages of cHL. Obviously, the primary endpoint is safety but our goal is really induction of complete remission. Second line therapy is really the holy grail in cHL, a lot of stuff is going on there.

The trial design is 2 cycles of the anti PD-1, lymphocyte depletion, and cell therapy, during which patients will be scanned multiple times to really understand where the complete remission happens. In addition, we are going to measure circulating tumor DNA. This is a technology which came from Ash Alizadeh at Stanford, and we believe that looking at the comparison between the circulating tumor DNA and PET scanning is going to provide Tessa with early signatures with at least a prediction of who is going to do well and how well. I think this is a very interesting strategy that hopefully will be even more relevant in second-line treatment.

This transcript has been edited for clarity.