Tessa Therapeutics presented positive data from the phase 2 CHARIOT study of TT11 in December 2021.
Tessa Therapeutics has dosed the first patient with relapsed/refractory classical Hodgkin lymphoma (cHL) in its phase 1b ACTION clinical trial (NCT05352828) of TT11, an autologous CD30-targeted chimeric antigen receptor T-cell (CAR-T) therapy in combination with nivolumab.1
“Initiation of this phase 1b clinical trial marks an important milestone for our autologous CD30.CAR-T program as we now have the opportunity to evaluate TT11 in combination with nivolumab as a potential second-line treatment for relapsed or refractory classical Hodgkin lymphoma,” John Ng, chief technology officer and acting chief executive officer, Tessa Therapeutics, said in a statement.1 “Data from our ongoing clinical program investigating TT11 as a monotherapy treatment for later lines of classical Hodgkin lymphoma has demonstrated the CAR-T therapy to be safe with promising measures of efficacy. We now welcome the opportunity to capitalize on this clinical progress by investigating TT11 as a second-line combination therapy, which offers the opportunity to greatly increase the patient population who could potentially benefit from this course of care.”
The ACTION trial will enroll up to 14 patients with relapsed/refractory CD30+ cHL. These participants will receive 2 cycles of nivolumab at 4-week intervals, followed by fludarabine/bendamustine lymphodepleting chemotherapy, a single infusion of TT11, and then another 2 cycles of nivolumab. The trial is primarily updating safety and tolerability of the TT11/nivolumab combination and any dose-limiting toxicities. Secondary endpoints will evaluate efficacy measures such as overall response rate (ORR), duration of response, progression free survival, and complete response (CR) rate. Other outcomes measures include overall survival and pharmacokinetics.
“The current standard of care for relapsed or refractory classical Hodgkin Lymphoma is associated with short-term toxicities and long-term morbidity, with particularly poor tolerability noted among elderly patients,” Ivan Horak, MD, chief medical and scientific officer, Tessa Therapeutics, added to the statement.1 “TT11, Tessa’s CD30 CAR-T therapy, has demonstrated encouraging clinical results as monotherapy, and we believe the combination with nivolumab has the potential to further enhance efficacy and provide patients with a chemotherapy-sparing, second-line treatment option.”
TT11 has been granted Regenerative Medicine Advanced Therapy designation by the FDA and PRIorityMEdicines (PRIME) designation by the EMA. It is currently being evaluated as a monotherapy in later lines of treatment in the phase 2 CHARIOT trial (NCT04268706). Data presented at the 63rd Annual Meeting of the American Society of Hematology in December demonstrated promising safety and efficacy in 14 patients with relapsed/refractory cHL.2 Participants were treated with a median dose of 2.4 x 108 cells/m2 after lymphodepletion.
Investigators observed disease control in 11 patients overall, with 8 CRs, 2 partial responses and one patient with stable disease. Overall, there was a 57.1% CR rate and a 71.4% ORR. The CAR T cells were found to persist for more than 42 days after infusion and showed strong expansion peaking at 7-14 days. The therapy was well-tolerated with no neurotoxicity. There was 1 case of grade 1 cytokine release syndrome which resolved within 5 days.
“These data demonstrate the promise of CD30-CAR-T cell therapy for patients with relapsed or refractory classical Hodgkin lymphoma who have limited treatment alternatives. The therapy demonstrated excellent efficacy in heavily pre-treated patients who had undergone a median of 6 and as many as 18 previous lines of therapy,” principal investigator and presenter Sairah Ahmed, MD, associate professor, The University of Texas MD Anderson Cancer Center, said in a statement at that time.2 “The persistence of the CD30-CAR-T cells, which can play a major role in anti-tumor activity, was also encouraging. We look forward to further clinical development of this therapeutic approach for Hodgkin lymphoma patients.”