Treatment with CD30 chimeric antigen receptor T-cell therapy combined with a monoclonal antibody has begun in the phase 1b ACTION study of patients with relapsed or refractory classical Hodgkin lymphoma.
The first of approximately 97 patients with classical Hodgkin lymphoma (cHL) has been administered the combination of TT11 and nivolumab (Opdivo) in the phase 1b ACTION study (NCT05352828).1
TT11 is an experimental autologous CD38-chimeric antigen receptor (CAR) T-cell therapy that is being developed for the potential treatment of relapsed or refractory cHL as a single agent and in combination with other therapies. The agent had been granted a regenerative medicine advanced therapy designation by the FDA and the PRIME scheme by European Medicines Agency.
Trial Name: A Phase 2 Multi-Center Study Evaluating the Safety and Efficacy of CD30-Directed Genetically Modified Autologous T Cells (CD30.CAR-T) in Adult and Pediatric Patients With Relapsed or Refractory Classical Hodgkin Lymphoma
ClinicalTrials.gov Indentifier: NCT04268706
Sponsor: Tessa Therapeutics
Completion Date: March 2037
“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,” stated John Ng, chief technology officer and acting chief operating office and of Tessa Therapeutics,” in a press release.
Dosing in the study comes after single-agent results were reported from the phase 2 CHARIOT study (NCT04268706). In heavily-pretreated patients with cHL, promising efficacy and tolerable was shown with TT11 monotherapy. The overall response rate observed was 71.4% with a complete response rate of 57.1% In terms of safety, the most common toxicities were hematologic toxicities.2
“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,” added Ng.1
In the multicenter, open-label, single arm ACTION study, patients will receive 4 cycles of TT11 at 2 x 108 cells/m2 in combination with nivolumab 480 mg or 6 mg/kg 4 times per week, fludarabine 30 mg/m2/day for 3 days, and bendamustine 70 mg/m2/day for 3 days after a successful leukapheresis to produce CD30 CAR T cells.3
The primary end point being explored in the study is the safety of autologous CD30 CAR T cells determined by dose-limiting toxicities. The secondary end points of the study include anti-tumor activity, overall response rate, duration of response, and progression-free survival. Other outcome being investigated include overall survival and pharmacokinetics.
Male or female patient aged 12 years or older are eligible to enroll if they have relapsed/refractory cHL following failure on standard frontline therapy, at least 1 measurable lesion, and adequate hematologic, renal, hepatic function and other laboratory tests. Patients are required to have an ECOG performance status of 0 or, a life expectancy of > 12 weeks, and no active infection at the time of screening.
Patients are excluded from the study if they have received prior treatment with salvage therapy for relapsed/refractory cHL, investigational CD30 CAR T cells. Moreover, patients receiving other investigational therapies, live vaccines, or immunosuppressive agents are not eligible for the study. Comorbidities that may interfere with study treatment and hypersensitivity to study drugs are also mentioned in the exclusion criteria.
The ACTION study is actively recruiting patients with relapsed/refractory cHL at study sites in California, Florida, North Carolina, and Texas.
REFERENCES:
1. Tessa Therapeutics doses first patient in phase 1b clinical trial investigating TT11 in combination with nivolumab for the treatment of relapsed/refractory classical hodgkin lymphoma (cHL). News release. August 17, 2022. Accessed August 18, 2022. https://bit.ly/3AteZem
2. Tessa Therapeutics announces positive data from phase 2 trial of autologous cd30-car-t therapy (TT11) in relapsed or refractory classical hodgkin lymphoma at 2021 ASH Annual Meeting. News release. August 14, 2021. Accessed August 18, 2022. https://bit.ly/3Qy0OKL
3. Phase 2 study evaluating autologous CD30.CAR-T cells in patients with relapsed/refractory hodgkin lymphoma (CHARIOT). Clinicaltrials.gov. Updated April 5, 2022. Accessed August 18, 2022.
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