Following promising preclincial findings, acimtamig (AFM13) plus allogenic natural killer cells (AB-101) will be examined for the treatment of patients with relapsed/refractory Hodgkin lymphoma and CD30-positive peripheral T-cell lymphoma in the phase 2 LuminICE-203 clinical trial (NCT05883449), according to a presentation during the 

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,” Allison J. Moskowitz, MD, a lymphoma specialist at Memorial Sloan Kettering Cancer Center in New York, New York, said during the presentation.

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 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 end point of the study is to establish overall response rate by PET assessed by an independent radiology committee. Secondary end points 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.

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.

Moskowitz A, Harstrick A, Emig M, , et 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). 

. 2023;142(suppl 1):4885. doi:10.1182/blood-2023-174250

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Following promising preclincial findings, acimtamig plus allogenic natural killer cells will be examined for the treatment of patients with relapsed/refractory Hodgkin lymphoma and CD30-positive peripheral T-cell lymphoma.

Acimtamig Plus Allogeneic Natural Killer Cells Under Phase 2 Evaluation in R/R Hodgkin Lymphoma and CD30+ PTCL 

Real-world data support the use of the MammaPrint (MP) index as a predictor of neoadjuvant chemosensitivity in patients with hormone receptor (HR)–positive, HER2-negative early-stage breast cancer, according to findings that were shared at the 2023 San Antonio Breast Cancer Symposium.

Neoadjuvant chemotherapy produces low rates of pathologic complete response (pCR; ypT0/is ypN0) in patients with HR-positive, HER2-negative early-stage breast cancer (ESBC). The genomic MP test detects gene activity and classifies patients with breast cancer into high and low risk of cancer recurrence, as genomic signatures have potential to predict chemosensitivity and advanced treatment compared to standard clinical subtypes. In past trials, MP-determined high-risk subtypes tended to have higher pCR rates when using specific treatments.

“The real-world data demonstrate [that] MP and BluePrint [(BP) have] clinical utility to predict the likelihood of achieving pCR after neoadjuvant chemotherapy in HR-positive, HER2-negative ESBC,” the researchers stated in their poster presentation.

The observational FLEX trial (NCT03053193) consists of 12,328 patients, all with ESBC, who were tested by MP with or without BP. This study focuses on MP High 1 (H1) and High 2 (H2) statuses as biomarkers for neoadjuvant chemosensitivity within the patient population (patients with HR-positive, HER2-negative ESBC) who had been enrolled in the FLEX study (n = 214).

Within the study, MP identified 2 subtypes, H1 (n=142) and H2 (n = 72), in patients with ESBC. Characteristics such as age, menopausal status, race, tumor stage, and lymph node status were also analyzed.

MP, H1, H2, BP, and pCR were adjusted and analyzed through age, race, grade, T stage, N stage, and neoadjuvant chemotherapy regimen, according to findings from the study.

Fifty-nine percent of grade 3 tumors were categorized in the H2 tumor subgroup, and 98% of H1 tumors were Luminal B. Within the Luminal B (a type of breast cancer that responds to the hormone estrogen that also harbors the HER2 gene) subgroup, only 51% were H2 tumors and 49% were basal-type (an aggressive molecular subtype of breast cancer), according to BP.

The H2 tumor subgroup had a higher pCR rate, at 29.2%, in comparison with H1 tumors, at 6.3% (

 < 0.01). Among the 35 patients within the basal-type H2 subgroup the pCR rate was 37.1% (

“Although both MP high-risk groups exhibit chemosensitivity, High 2 tumors have higher chemosensitivity than High 1 tumors. Future studies will evaluate the correlation between neoadjuvant chemotherapy regimens (TC vs AC-T) pCR, and whole transcriptome changes to understand the underlying biology of treatment response,” the researchers noted.

Within BP Luminal B tumors, patients with MP H2 tumors had a higher pCR rate (21.6%) compared with those who had MP H1 tumors (5.8%; 

 = 0.03) tumors were also associated with a chance of pCR.

“Response to neoadjuvant immunotherapy is currently being evaluated in patients with HR-positive, HER2-negative, stage II to III, MP High 2 breast cancer in the SWOG 2206 trial [NCT06058377] that is open to accrual,” the researchers said.

O'Shaughnessy J, Pusztai L, Graham C, etl al. MammaPrint index predicts neoadjuvant chemosensitivity in patients with HR+HER2- early-stage breast cancer in the real-world evidence FLEX study. Presented at: San Antonio Breast Cancer Conference; December 5-9, 2023; San Antonio, TX. Abstract: PO5-15-04.

Real-world data support the use of the MammaPrint index as a predictor of neoadjuvant chemosensitivity in patients with hormone receptor–positive, HER2-negative early-stage breast cancer. 

Rylan DeStefano

Articles

Acimtamig Plus Allogeneic Natural Killer Cells Under Phase 2 Evaluation in R/R Hodgkin Lymphoma and CD30+ PTCL

MammaPrint Predicts Likelihood of pCR With Neoadjuvant Chemo in HR+/HER2– Early Breast Cancer