Investigators plan to initiate a phase 2 study evaluating AFM13 plus AB-101 in patients with relapsed/refractory classical Hodgkin lymphoma in the first half of 2024.
The FDA has cleared an investigational new drug application (IND) for AFM13 plus AB-101 in the treatment of patients with relapsed/refractory classical Hodgkin lymphoma, according to a press release from Affimed N.V.
Clearance of the IND allows investigators to initiate the open-label, multi-center, multi-cohort phase 2 AFM13-203 (LuminICE-203) study, which will evaluate the efficacy and safety of AFM13 plus AB-101 in those with relapsed/refractory classical Hodgkin lymphoma and CD30-positive peripheral T-cell lymphoma (PTCL). Investigators plan to begin the study in the third quarter of 2023 and expect to report early data from the safety run-in portion in the first half of 2024.
The AFM13-203 trial will build upon findings from the phase 1/2 AFM13-104 trial (NCT04074746), in which investigators assessed AFM13 in combination with cord blood-derived natural killer (cbNK) cells for treating those with pretreated CD30-positive Hodgkin lymphoma and non-Hodgkin lymphoma.
Of 35 patients with heavily pre-treated, CD30-positive disease who enrolled on the AFM13-104 trial, the objective response rate (ORR) was 94%, and the complete response (CR) rate was 71%. Additionally, 63% of patients receiving the recommended phase 2 dose (RP2D) remained in CR for at least 6 months. The study regimen was also well tolerated and produced no instances of cytokine release syndrome, immune effector cell-associated neurotoxicity, or graft-versus-host-disease.
“We are excited to have received FDA clearance of our IND application for this promising combination therapy of AFM13 and AB-101, which has the potential to provide a new treatment option for Hodgkin Lymphoma and PTCL,” Wolfgang Fischer, chief operating officer at Affimed, said in the press release.
AFM13 is a first-in-class tetravalent bispecific innate cell engager designed to activate the innate immune system to destroy CD30-positive hematologic tumors. Moreover, AB-101 is a cord-blood derived, allogeneic, cryopreserved NK cell therapy designed to be administered in combination with monoclonal antibodies or innate-cell engagers in the out-patient setting.
Investigators of the phase 2 AFM13-203 trial plan to enroll up to 134 patients with relapsed/refractory classical Hodgkin lymphoma, including 24 in the safety run-in portion, and between 68 to 110 in the dose optimization and expansion phases. The study will also include an exploratory cohort with an additional 20 patients with PTCL.
The primary end point of the AFM13-203 trial is anti-tumor activity based on ORR, which includes CRs and partial responses (PRs). Secondary end points include duration of response (DOR), safety and tolerability, and the immunogenicity of AFM13 plus AB-101.
Patients who have received at least 2 lines of therapy for relapsed/refractory classical Hodgkin lymphoma, including 1 line of combination chemotherapy, are eligible to enroll on the AFM13-203 trial. Patients must have also received prior therapy with brentuximab vedotin (Adcetris) and a PD-1 checkpoint inhibitor to enroll.
Investigators of the AFM13-104 trial evaluated the safety and RP2D of cbNK cells preloaded with AFM13 (AFM13-NK) followed by intravenous AFM13 in those with refractory/relapsed CD30-positive lymphoid malignancies. Patients received standard-of-care fludarabine intravenously over 1 hour plus cyclophosphamide intravenously over 30 to 60 minutes, 5 and 3 days prior to intravenous AFM13-NK which was given over 4 hours on day 0 followed by intravenous AFM13 over 4 hours on days 7, 14, and 21 of treatment.
The primary end point of the AFM13-104 trial was the incidence of adverse effects. Secondary end points included overall survival, event-free survival, ORR, CR rate, PR rate, and DOR.
Patients 15 to 75 years old with a diagnosis of relapsed/refractory classical Hodgkin lymphoma, anaplastic large cell lymphoma, PTCL not otherwise specified, mycosis fungoides, or B-cell non-Hodgkin lymphoma were eligible for enrollment on the AFM13-104 trial. Additional eligibility criteria included having a Karnofsky performance status of at least 60% and no uncontrolled arrhythmias or symptomatic cardiac disease.
Affimed announces IND clearance for a phase 2 clinical trial investigating AFM13 and AB-101 combination therapy. News release. May 23, 2023. Accessed May 23, 2023. bit.ly/3IDn4Rj