AFM13 Plus AB-101 to Be Tested in Phase 2 Study

Lymphomas: © immimagery - stock.adobe.com

The ongoing LuminICE phase 2 study demonstrated that AFM13 in combination with AB-101 may hold promise for the treatment of patients with relapsed or refractory CD30-positive lymphomas, according to data presented at the 2023 American Society of Hematology (ASH) Annual Meeting.

As there are limited treatment options for this patient population, with no standard of care, so finding efficacious treatment options is needed, according to the study authors.

“Although brentuximab vedotin [Adcetris] and PD-1 inhibitors have dramatically impacted the treatment for patients with Hodgkin lymphoma, there is still a need to develop novel agents for patients either with inadequate response to these agents or who are unable to tolerate them,” stated the study’s primary investigator, Allison J. Moskowitz, MD, a lymphoma specialist at Memorial Sloan Kettering Cancer Center.

The main objective of the study is to determine the objective response rate (ORR), the secondary response being safety and immunogenicity (striking an immune response), complete response rate, duration of response, and progression-free survival (PFS).

AFM13 is a bispecific cell engager that interacts with natural killer cells (NK) such as CD16A and CD30 within Hodgkin lymphoma (HL) and peripheral T-cell lymphoma (PTCL) cells. Through this, AFM13 is able to increase NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC).

AB-101 is a non-genetically modified, off-the-shelf NK cell product that came from cord blood. This source of treatment is used to improve ADCC through choice of KIR-B haplotype and CD16 F158V polymorphism.

Prior studies evaluated AM13 in patients with R/R Hodgkin lymphoma and PTCL, concluding that the drug shows positive clinical effects and an efficient safety record. Within a recent phase 1/2 study, AFM13 was administered in combination with cord blood-derived cells in patients with R/R CD30-positive lymphomas. The requested phase 2 dose was given (n=35) and led to an ORR of 94% and a complete response rate (CR) of 71%.

Regarding AB-101, previous studies resulted in strong efficiency against tumor cell lines, and a phase 1/2 trial with AB-101 as monotherapy and in combination with rituximab (Rituxan) concluded that the drug remained well tolerated.

The phase 2 trial (NCT05883449) plans to focus on the efficiency and safety of AFM13 plus AB-101 used for the treatment of patients with R/R HL and certain R/R CD30-positive PTCL subtypes. The subtypes that were accepted were angioimmunoblastic T-cell lymphoma, and ALK-positive, and -negative anaplastic large cell lymphoma (ALCL).

“The primary endpoint of the study is to establish overall response rate by PET assessed by an independent radiology committee. Secondary endpoints include safety, overall survival and progression-free survival,” Moskowtiz said.

The includes patients aged ≥18 years, with R/R HL, who have received two prior lines of therapy (which include combination chemotherapy, brentuximab vedotin and checkpoint inhibitors). Furthermore, patients with R/R PTCL possess the CD30 expression of ≥1% by immunohistochemistry and have underwent one line of combination chemotherapy. Patients with ALCL must be intolerant to brentuximab vedotin, while treatment with an anti-cancer agent ≤21 days prior to enrolment, the continuation of toxicity from therapy, central nervous system involvement, and previous treatment with AFM13 or NK cells were excluded.

For the upcoming study, patients will be given the drugs intravenously within the span of 48-day cycles for 3 cycles. A run-in phase was announced as well, which will give patients both AFM13 and AB-101 in 4 cohorts. Fludarabine (30 mg/m 2/day) and cyclophosphamide (300 mg/m 2/day) will be given through an IV from Day −5 to Day −3 at the start of each treatment cycle. Next, AFM13 (200 mg or 300 mg once weekly) will be given, with AB-101 (dose level 1 or 2, see Figure) given 1 hour later per cycle, while being given 6 ×10 6 IU of IL-2 subcutaneously at least 1 hour after each AB-101 dose.1

Cohorts 1 and 2 will begin, following 3 and 4 if the starting cohorts produce accurate conclusions. After cycle 1 is completed, safety and efficiency responses to treatment will be evaluated to determine the dose level to be used within the main study.

An exploratory cohort (cohort 5) will begin enrolment of patients with CD30 + PTCL, and alongside this, efficiency and screening reports will be evaluated on Day 43 (± 3 days) of each cycle.

“If the running cohort in Hodgkin lymphoma meets the protocol safety criteria and exploratory cohort 5 will begin enrollment of patients with CD30+ peripheral T-cell lymphoma. Disease assessment will be conducted at baseline and on day 43 of each cycle and patients will receive up to 3 cycles of treatment,” Moskowitz noted.




REFERENCE:
1. Moskowitz A, Harstrick A, Emig M, , etl al. AFM13 in Combination with Allogeneic Natural Killer Cells (AB-101) in Relapsed or Refractory Hodgkin Lymphoma and CD30 + Peripheral T-Cell Lymphoma: A Phase 2 Study (LuminICE). Presented at: ASH Annual Meeting. December 9-12, 2023. Abstract: 4855.