acimtamig (AFM13) / Affimed, Xoma - LARVOL DELTA

RESULTS FROM THE DOSE-FINDING PART OF LuminICE-203 PHASE 2 STUDY: ACIMTAMIG (AFM13) IN COMBINATION WITH AlloNK (AB-101) IN PATIENTS WITH RELAPSED/ REFRACTORY HODGKIN LYMPHOMA (ICML 2025) - P2 | "Introduction: New therapeutic options are needed for patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) who progress following standard systemic therapies including chemotherapy, brentuximab vedotin (BV), and checkpoint inhibitors. The combination of acimtamig and AlloNK has shown promising efficacy with a well-managed safety profile, indicating potential therapeutic benefits and offering hope for patients with R/R cHL who have exhausted standard-of-care treatment options."

Clinical • Combination therapy • P2 data • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • FCGR3A • TNFRSF8

INITIAL RESULTS OF THE LUMINICE-203 STUDY INVESTIGATING ACIMTAMIG WITH OFF-THE-SHELF ALLOGENEIC NATURAL KILLER CELLS (ALLONK®) IN RELAPSED OR REFRACTORY CLASSICAL HODGKIN LYMPHOMA (EBMT 2025) - P2 | "Background: Patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) who progress following chemotherapy, brentuximab vedotin (BV) and PD-1 inhibitors require novel treatment options...After lymphodepletion treatment with fludarabine/cyclophosphamide (Days −5 to −3) AlloNK and acimtamig are co-administered on Days 1, 8, and 15, followed by acimtamig only on Days 22, 29 and 36 of a 58-day cycle, for up to 3 cycles... Acimtamig plus AlloNK exhibits promising efficacy and tolerability in heavily pretreated patients. Combining acimtamig with a scalable, off-the-shelf NK-cell product has the potential to address a high unmet need in patients with R/R cHL who otherwise have no SOC option. The study is ongoing"

Classical Hodgkin Lymphoma • Cytomegalovirus Infection • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Infectious Disease • Lymphoma • Oncology • FCGR3A • TNFRSF8

AFM13 IN PATIENTS WITH CD30 POSITIVE RELAPSED OR REFRACTORY (R/R) PERIPHERAL T CELL LYMPHOMA (PTCL): RESULTS FROM THE PHASE 2 REDIRECT STUDY (ICML 2023) - P2 | "Patients had received a mean of 2.7 prior treatment lines; 46.3% received prior brentuximab vedotin (BV), 17.6% received prior auto-transplant. AFM13 monotherapy demonstrated robust clinical activity in heavily pretreated patients with R/R PTCL. The safety profile of AFM13 was well managed and consistent with previously reported data from prior and ongoing clinical studies with AFM13. These data support future evaluation of AFM13 in combination with other immunotherapies, including allogeneic NK cells, to further potentiate anti-tumor immune responses to CD30+ lymphomas."

Clinical • IO biomarker • P2 data • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • FCGR3A • TNFRSF8

Innate Cell Engager AFM13 Combined with Preactivated and Expanded Cord Blood-Derived NK Cells for Patients with Double Refractory CD30+ Lymphoma (ASH 2022) - P1/2 | "Patients aged 15–75 years with R/R CD30+ lymphomas refractory to brentuximab vedotin are enrolled...Each treatment cycle consisted of fludarabine/cyclophosphamide (days −5 to −3), followed by infusion of the AFM13-NK cells, cultured for 14 days as described above (day 0), and three weekly IV infusions of AFM13 (200 mg, days 7, 14 and 21)... This is the first clinical trial to date using an ICE® construct precomplexed with cytokine-induced memory-like CB-NK cells to treat patients with CD30+ R/R HL and NHL. Our preliminary results indicate that this ICE® precomplexed CB-NK cell therapy has an excellent tolerability profile and is highly active in patients with heavily pretreated R/R CD30+ lymphomas and warrants further investigation."

Clinical • IO biomarker • Graft versus Host Disease • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • FCGR3A • IL12A • IL15 • IL18 • IL21 • TNFRSF8

ACIMTAMIG (AFM13) IN COMBINATION WITH ALLONK® (AB-101) IN PATIENTS WITH RELAPSED OR REFRACTORY CLASSICAL HODGKIN LYMPHOMA: RESULTS FROM THE DOSE FINDING PHASE OF THE LUMINICE-203 PHASE 2 STUDY (EHA 2025) - P2 | "Patients have exhausted standard of care therapies, including chemotherapy, brentuximab vedotin and PD-1 inhibitors. The combination of acimtamig and AlloNK® therapy demonstrates promising efficacy and a manageable safety profile, offering a potential benefit to patients with R/R cHL who have exhausted standard-of-care treatments"

Clinical • Combination therapy • P2 data • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • FCGR3A • TNFRSF8

Investigating the Novel Combination of the Innate Cell Engager (ICE®) Acimtamig with Off-the-Shelf Allogeneic Natural Killer Cells AlloNK® in Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL): Initial Results of the Phase 2 Luminice-203 Study (ASH 2024) - P1/2, P2 | "Introduction : Patients (pts) with R/R cHL are in need of new treatment options, especially after failure of standard treatments including brentuximab vedotin (BV) and PD-1 inhibitors...After a standard lymphodepletion treatment regimen with fludarabine/cyclophosphamide (Days -5 to -3) pts receive AlloN- and acimtamig coadministered on days 1,8,15 followed by acimtamig only on days 22,29 and 36 of a 48-day cycle for up to 3 cycles...These early results are in line with previous data from study NCT04074746 which used fresh allogeneic NK cells thereby validating the co-administration approach of acimtamig with an off-the-shelf, allogeneic, cryopreserved NK cell product (AlloNK) in R/R cHL. This treatment has the potential to address a high unmet need in R/R cHL pts who have otherwise no SOC option."

P2 data • Classical Hodgkin Lymphoma • Cytomegalovirus Infection • Graft versus Host Disease • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Infectious Disease • Lymphoma • Oncology • FCGR3A • TNFRSF8

Allogeneic NK cells with a bispecific innate cell engager in refractory relapsed lymphoma: a phase 1 trial. (PubMed, Nat Med) - P1/2 | "Outcomes of patients with CD30-positive (CD30+) lymphomas have improved with the advent of brentuximab vedotin (BV) and, in Hodgkin lymphoma, anti-PD1 checkpoint inhibitors (CPI)...AFM13-a CD30/CD16A bispecific antibody-activates natural killer (NK) cells to kill CD30+ cells...This therapy showed encouraging preliminary safety and efficacy. ClinicalTrials.gov Identifier: NCT04074746 ."

Journal • P1 data • Graft versus Host Disease • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Lymphoma • Oncology • FCGR3A • TNFRSF8

Results from the completed dose-finding part of phase 2 study of the innate cell engager acimtamig (AFM13) in combination with AlloNK (AB-101) in relapsed or refractory classical Hodgkin lymphoma (LuminICE-203). (ASCO 2025) - P2 | "All pts in the study were heavily pretreated with chemotherapy, brentuximab vedotin and PD-1 inhibitors; median (range) prior treatment lines was 4.5 (2–13), including previous stem cell transplant in 14 (58%) pts. Acimtamig in combination with AlloNK shows promising efficacy with a well-managed safety profile with the potential to address an unmet need in pts with R/R HL who have exhausted standard-of-care treatment options. Efficacy results of acimtamig plus AlloNK in pts with R/R HL."

Combination therapy • P2 data • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • FCGR3A • TNFRSF8

Innate cell engager (ICE®) AFM13 combined with preactivated and expanded cord blood (CB)-derived NK cells for patients with refractory/relapsed CD30+ lymphoma (AACR 2022) - P1 | "Pts receive 2 cycles of fludarabine/cyclophosphamide (days −5 to −3) followed by AFM13-CB NK cells (day 0) and 3 weekly intravenous infusions of AFM13 (200 mg, days 7, 14 and 21). In conclusion, the preliminary results of this first clinical trial of ICE®-precomplexed NK cells for R/R CD30+ lymphoma indicate excellent tolerability and high activity and warrant further investigation of this approach. >"

Clinical • Hematological Malignancies • Lymphoma • Oncology • FCGR3A • IL12A • IL15 • IL18 • TNFRSF8

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) (ASH 2023) - P2 | "AB-101 has demonstrated potent killing of tumor cell lines in vitro and in vivo, and preliminary results of a Phase 1/2 trial of AB-101 alone and in combination with rituximab in patients with R/R B cell non-Hodgkin lymphoma demonstrated AB-101 is well tolerated (Khanal et al...Patients aged ≥18 years are planned for enrolment and patients with R/R HL must have received at least two prior lines of therapy including prior combination chemotherapy, brentuximab vedotin (BV) and a checkpoint inhibitor...A run-in phase will assess two dose levels of AFM13 and AB-101 in 4 cohorts (Figure). A standard lymphodepletion regimen of fludarabine (30 mg/m2/day) and cyclophosphamide (300 mg/m2/day) will be administered IV from Day −5 to Day −3 at the start of each treatment cycle...In addition, an exploratory cohort (cohort 5) will begin enrolment of patients with CD30+ PTCL. Disease and efficacy assessments will be conducted at screening and on Day 43 (± 3 days) of each cycle."

Combination therapy • P2 data • B Cell Non-Hodgkin Lymphoma • Bone Marrow Transplantation • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Transplantation • ALK • FCGR3A • TNFRSF8

Innate Cell Engager (ICE®) AFM13 Combined with Preactivated and Expanded (P+E) Cord Blood (CB)-Derived Natural Killer (NK) Cells for Patients with Refractory CD30-Positive Lymphomas: Final Results (ASH 2023) - P1/2 | "Pts ages 15–75 with CD30+ lymphomas refractory to brentuximab vedotin were enrolled...Each treatment cycle consisted of fludarabine/cyclophosphamide (days −5 to −3) followed by infusion (day 0) of the AFM13-precomplexed CB NK cells, cultured for 14 days as described above, and three weekly IV infusions of AFM13 (200 mg, days 7, 14 and 21)... CB-derived cytokine-induced memory-like NK cells precomplexed with AFM13 have excellent tolerability and activity for pts with heavily pretreated and refractory CD30+ lymphoma."

Clinical • IO biomarker • Graft versus Host Disease • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Lymphoma • Oncology • CD48 • FCGR3A • IL12A • IL15 • IL18 • IL2 • IL21 • TNFRSF8

CD16A Shedding Regulates Innate Cell Engager-Induced Serial Killing by Natural Killer Cells. (PubMed, Eur J Immunol) - "The bispecific innate cell engager acimtamig (AFM13) was superior to IgG1 monoclonal antibodies in ADCC and in increasing the fraction of cytotoxic NK cells and serial killers...These results demonstrate that CD16A shedding represents an intrinsic feature of NK cell biology that is critical to sustain the antitumoral cytotoxicity of NK cells. This has implications for CD16A engineering of NK cell products and their combination with CD16A-directed NK cell engagers."

Journal • Oncology • FCGR3A

NCI-2019-03536: Modified Immune Cells (AFM13-NK) and A Monoclonal Antibody (AFM13) in Treating Patients With Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1/2 | N=45 | Completed | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Completed | N=30 ➔ 45 | Trial completion date: Apr 2027 ➔ Sep 2025 | Trial primary completion date: Apr 2027 ➔ Sep 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • TNFRSF8

LuminICE-203: Phase 2 Study of AFM13 in Combination With AB-101 in Subjects With R/R HL and CD30+ PTCL (clinicaltrials.gov) - P2 | N=25 | Terminated | Sponsor: Affimed GmbH | N=154 ➔ 25 | Trial completion date: Nov 2027 ➔ Jun 2025 | Recruiting ➔ Terminated | Trial primary completion date: Apr 2026 ➔ Nov 2024; Due to sponsor decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • TNFRSF8

COMPARATIVE EFFICACY OF THERAPEUTIC APPROACHES IN RELAPSED/REFRACTORY PERIPHERAL T-CELL LYMPHOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2025) - "This meta-analysis evaluates the efficacy of various therapies for RR-PTCL, including Epigenetic modifiers (HDIs, DNA methyltransferase inhibitors, EZH1/2 inhibitors), Small molecule inhibitors (targeting PI3K/AKT/mTOR, JAK/STAT, ALK, aurora kinase, farnesyl transferase), Combination therapies (various multi-class drug combinations), Pralatrexate-based regimens, monoclonal antibodies (e.g., Pembrolizumab, Alemtuzumab, Zanolimumab, etc.) and Others (Acimtamig, CAR T-cell therapy, etc.). This analysis suggests that combination therapies had the highest response rates, with SMI and pralatrexate-based therapies showing the longest OS. Other cytotoxic chemotherapy-based regimens had the lowest effectiveness, which suggests that combined targeted no-cytotoxic treatment regimens should be further studied in R/R PTCL. Outcomes continue to be poor, and clinical trials with novel treatment strategies should be prioritized"

Retrospective data • Review • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • EZH2

TRANSLATIONAL FINDINGS FROM THE PHASE 2 LUMINICE-203 STUDY OF ACIMTAMIG (AFM13) IN COMBINATION WITH ALLONK® (AB-101) IN PATIENTS WITH RELAPSED OR REFRACTORY CLASSICAL HODGKIN LYMPHOMA (R/R CHL) (EHA 2025) - P2 | "The correlative science analysis of acimtamig and AlloNK® combination showed a high CD16 RO and a PK profile as expected and comparable to acimtamig monotherapy. Furthermore, changes in cytokine levels and NK cell phenotype suggest an immune activation trend with potential therapeutic benefits for patients with R/R HL that encourages further investigation."

Clinical • Combination therapy • P2 data • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • FCGR3A • IL5 • NKG2D • TNFRSF8

Combination of Acimtamig and AlloNK Effective in R/R Classical Hodgkin Lymphoma (Hematology Advisor) - P2 | N=154 | LuminICE-203 (NCT05883449) | Sponsor: Affimed GmbH | "Acimtamig combined with AlloNK is associated with an objective response rate (ORR) as high as 100% in heavily pretreated patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (HL), according to research presented at the ASCO Annual Meeting 2025. The findings are from the phase 2, open-label LuminICE-203 study (NCT05883449), which assessed the efficacy and safety of acimtamig combined with AlloNK in patients with R/R HL....Among all 4 patient cohorts, the ORR was 87.5%, with 14 (58.3%) complete responses. The AlloNK DL1 + 200 mg acimtamig cohort, AlloNK DL1 + 300 mg acimtamig cohort, and AlloNK DL2 + 300 mg acimtamig cohorts each had an ORR of 83.3%. The AlloNK DL2 + 200 mg acimtamig cohort had an ORR of 100%. Ten patient responses were ongoing, the researchers reported. The estimated 6-month progression-free survival rate was 61%."

P2 data • Hodgkin Lymphoma

Affimed Announces Acceptance of Three Abstracts for Presentation at the American Society for Clinical Oncology Annual Meeting (GlobeNewswire) - "Affimed...announced an abstract on the phase 2 LuminICE-203 study of its innate cell engager (ICE) acimtamig in combination with AlloNK (AB-101) has been accepted for an oral presentation at the Annual Meeting of the American Society for Clinical Oncology (ASCO)....In addition, two abstracts on AFM24 in combination with atezolizumab in non-small cell lung cancer (NSCLC) have been accepted as poster presentations."

P2 data • Hodgkin Lymphoma • Non Small Cell Lung Cancer

NCI-2019-03536: Modified Immune Cells (AFM13-NK) and A Monoclonal Antibody (AFM13) in Treating Patients With Recurrent or Refractory CD30 Positive Hodgkin or Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1/2 | N=30 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Apr 2025 ➔ Apr 2027 | Trial primary completion date: Apr 2025 ➔ Apr 2027

Trial completion date • Trial primary completion date • B Cell Non-Hodgkin Lymphoma • Classical Hodgkin Lymphoma • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • TNFRSF8

Bispecific Antibody Boosts NK Cell Response in Lymphoma (Mirage News) - P1/2 | N=30 | NCT04074746 | "A novel cell therapy approach using cord blood-derived natural killer (NK) cells pre-complexed with AFM13, or acimtamig, a CD30/CD16A bispecific antibody, was safe and generated strong response rates for patients with refractory CD30-positive lymphomas , according to a new study from The University of Texas MD Anderson Cancer Center....The overall response rate (ORR) and complete response (CR) in study patients was 92.9% and 66.7%, respectively. Among patients with Hodgkin lymphoma, the ORR and CR were 97.3% and 73%, respectively. At a median follow-up of 20 months, the two-year event-free survival (EFS) and overall survival (OS) rates for all participants were 26.2% and 76.2%, respectively, which is encouraging given the heavily pretreated and refractory nature of the patients' tumors."

P1/2 data • Hodgkin Lymphoma

Acimtamig Plus AlloNK Elicits Responses in Heavily Pretreated R/R Hodgkin Lymphoma (OncLive) - P2 | N=154 | LuminICE-203 (NCT05883449) | Sponsor: Affimed GmbH | "The addition of the innate cell engager acimtamig (AFM13) to AlloNK (AB-101) generated high objective and complete response (CR) rates in heavily pretreated patients with relapsed/refractory Hodgkin lymphoma who had exhausted standard-of-care treatment options, according to preliminary findings from the run-in portion of the phase 2 LuminICE-203 trial (NCT05883449). Early data presented at the 51st Annual EBMT Meeting demonstrated that at a data cutoff of November 14, 2024, among all 4 cohorts of patients with heavily pretreated relapsed/refractory Hodgkin lymphoma (n = 22), the objective response rate (ORR) was 86%, which included 12 complete responses (55%) and 12 partial responses. Responses were ongoing in 15 patients. The remaining 3 patients had progressive disease."

P2 data • Hodgkin Lymphoma

Affimed Announces Positive Results Demonstrating Safety and Efficacy of Acimtamig and AlloNK Combination in Relapsed/Refractory Classical Hodgkin Lymphoma (R/R cHL) Patients (GlobeNewswire) - P2 | N=154 | LuminICE-203 (NCT05883449) | Sponsor: Affimed GmbH | "Affimed N.V...today announced the presentation of data in a poster session at the 66th ASH Annual Meeting and Exposition. The dataset includes 22 patients from the run-in phase of the LuminICE-203 (AFM13-203) phase 2 open-label, multicenter, multi-cohort study. The trial evaluates the safety and efficacy of the combination of acimtamig (AFM13) with Artiva Biotherapeutics’ allogeneic NK cell AlloNK® in patients with R/R cHL. Acimtamig in combination with AlloNK demonstrated a high overall response rate (ORR) of 86% with complete response (CR) of 55%. All patients in the study were heavily pretreated with a median of 5 (range: 2-13) prior therapies."

P2 data • Hodgkin Lymphoma • Peripheral T-cell Lymphoma

Affimed Announces Acimtamig and AlloNK Combination Granted Regenerative Medicine Advanced Therapy (RMAT) Designation by the U.S. Food and Drug Administration (FDA) (GlobeNewswire) - "Affimed N.V...today announced that the U.S. FDA has granted RMAT designation to the combination therapy of Affimed’s innate cell engager (ICE) acimtamig and Artiva Biotherapeutic’s AlloNK (AB101) for the treatment of relapsed or refractory Hodgkin Lymphoma (R/R HL)....Data from all four cohorts of the run-in phase of the LuminICE-203 trial will be featured in a poster session at the 66th ASH Annual Meeting and Exposition on December 8, 2024."

FDA event • Hodgkin Lymphoma

A Phase 2 study of acimtamig (AFM13) in patients with CD30-positive, relapsed or refractory peripheral T-cell lymphomas. (PubMed, Clin Cancer Res) - "The promising clinical efficacy observed warrants further investigation, and development of acimtamig for patients with R/R CD30+ lymphomas continues in combination with allogeneic natural killer cells."

Journal • P2 data • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • FCGR3A • TNFRSF8

Affimed Reports Third Quarter 2024 Financial Results & Business Update (GlobeNewswire) - "Upcoming Milestones: i) LuminICE-203: Efficacy update of four cohorts to be presented at ASH 2024. ii) AFM24-102: ORR and safety data from the EGFRwt cohort to be presented at a Company conference call on December 17, 2024. iii) AFM28-101: Updated data from the dose escalation to be presented at ASH 2024."

P1 data • P1/2 data • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Hodgkin Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor