AFM24 / Affimed, Xoma - LARVOL DELTA

AFM24 and atezolizumab combination in patients with advanced epidermal growth factor receptor-expressing (EGFR+) solid tumors: Initial results from the Phase 1 dose-escalation study (SITC 2022) - P1/2 | "Clinical activity was observed in two patients. Dose escalation is proceeding at 480 mg and enrollment has begun."

Clinical • IO biomarker • P1 data • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • EGFR • FCGR3A

Leveraging innate immunity with AFM24, a novel CD16A and epidermal growth factor receptor (EGFR) bispecific innate cell engager: Interim results for the non-small cell lung cancer (NSCLC) cohort. (ASCO 2023) - P1/2 | "AFM24 demonstrated clinical activity and acceptable safety in heavily pretreated patients with EGFR mutant NSCLC. The novel mechanism of action of AFM24 could add to the therapeutic options for patients with EGFR expressing tumors and is under clinical evaluation as a single agent and in combination with atezolizumab or autologous NK cells. Clinical trial information: NCT04259450."

Dermatitis • Dermatology • Immunology • Lung Cancer • Musculoskeletal Pain • Non Small Cell Lung Cancer • Oncology • Pain • Pneumonia • Solid Tumor • EGFR • FCGR3A

Targeting epidermal growth factor receptor (EGFR)-expressing solid tumors with AFM24, a novel CD16A bispecific innate cell engager: Comprehensive correlative science findings from a Phase 1 study (SITC 2022) - P1/2 | "T cells are activated within the periphery, and T cell numbers increase in tumors, which may indicate stimulation of anti-cancer activity of the adaptive immune system as an indirect effect of AFM24. Clinical and correlative science from the escalation phase of the study supports further investigation of AFM24 anti-tumor activity in EGFR-expressing tumor-specific cohorts."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • CD69 • CD8 • EGFR • FCGR3A • KRAS • NRAS

NK cell-mediated tumor cell killing by bispecific innate cell engagers induces ADCC-mediated activation of primary human dendritic cells. (PubMed, Oncoimmunology) - "Nevertheless, ADCC boosted the capacity of cDC1 and DC2 to prime naïve T cell responses but not of DC3. Thus, our data suggests that the therapy with bispecific antibodies targeting NK cells may have the potential to facilitate adaptive antitumor immune responses via activation of cDC1 and DC2."

IO biomarker • Journal • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • CD8 • FCGR3A • PD-L1

The advantages of NK cell vaccines in solid carcinoma clinical trials: conducted by various biology strategy and technology. (PubMed, Front Med (Lausanne)) - "The study illustrated: Dendritic cell-based vaccine platforms (e.g., ilixadencel), cytokine-based vaccine platforms (e.g., ALT-803), NK receptor agonist antibodies (e.g., AFM24) and mRNA/LNP-based vaccine platforms (e.g., BNT116) It has shown early efficacy in solid tumors such as non-small cell lung cancer, triple-negative breast cancer, and glioblastoma (with partial ORR of 30-50% and DCR of 80-100%), and the safety is comparatively manageable (the incidence of grade ≥3 adverse events is less compared to T-cell therapy). In the future, combinatorial regimens (e.g., sequential application of PD-1 inhibitors) need to be optimized, an iPSC-NK universal platform developed, and perioperative application scenarios explored. NK vaccines, by reshaping the immune microenvironment, will be an attractive strategy to break the bottlenecks in the treatment of solid tumors."

Journal • Review • Brain Cancer • Breast Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

AFM24-102: Study to Assess AFM24 in Combination With Atezolizumab in Selected Advanced/Metastatic EGFR-expressing Cancers (clinicaltrials.gov) - P1/2 | N=112 | Terminated | Sponsor: Affimed GmbH | Trial completion date: Nov 2025 ➔ Jun 2025 | Recruiting ➔ Terminated; The trial was prematurely discontinued due to the financial situation of the sponsor and not for safety or efficacy reasons.

Trial completion date • Trial termination • Gastric Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • EGFR

Initial Biomarker Results From the Phase 2A Study of AFM24 With Atezolizumab in Patients With Advanced/Metastatic NSCLC (IASLC-WCLC 2025) - P1/2 | "A DCR of 77%, along with some long, sustained responses, correlates with high numbers of NK cells in the peripheral blood, which potentially leave the periphery and migrate to the tumor upon AFM24 treatment. This combination immunotherapy approach could offer a promising chemotherapy-free alternative, with NK cell frequency as a potential minimally invasive predictive biomarker for treatment response."

Biomarker • Clinical • IO biomarker • Metastases • P2a data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR • FCGR3A

Study to Assess AFM24 in Advanced Solid Cancers (clinicaltrials.gov) - P1/2 | N=85 | Terminated | Sponsor: Affimed GmbH | Completed ➔ Terminated; Enrollment into expansion cohorts in Phase 2 part was terminated due to sponsor decision

Trial termination • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • KRAS

Combination of bispecific innate cell engager (ICE) AFM24 with atezolizumab in patients with advanced/metastatic non-small cell lung cancer (NSCLC) with EGFR kinase domain mutations (EGFRmut): Initial results from a phase 2a study. (ASCO 2025) - P1/2 | "AFM24 combined with atezolizumab demonstrated encouraging clinical efficacy in patients with EGFRmut NSCLC who had exhausted prior lines of therapy. Treatment showed a well-managed safety profile. This approach potentially offers a feasible, chemotherapy-free therapeutic option for the EGFRmut NSCLC patients who have progressed to prior TKIs and platinum-based chemotherapy and warrants further evaluation."

Clinical • IO biomarker • Metastases • P2a data • Infectious Disease • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • FCGR3A

Bispecific innate cell engager (ICE) AFM24 in combination with atezolizumab in patients with advanced/metastatic EGFR-expressing non-small cell lung cancer (NSCLC) without driver mutations: Initial results from a phase 2a study. (ASCO 2025) - P1/2 | "AFM24 in combination with atezolizumab shows promising clinical efficacy in patients who failed prior treatment including platinum-based chemotherapy and CPI. Patients showed a tolerable and well-managed safety profile. A considerable DCR of 77%, with some long, sustained responses was observed."

Clinical • Combination therapy • Metastases • P2a data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • FCGR3A

Affimed Shows Higher Exposure of AFM24 is Associated with Significantly Higher Response Rates and Progression-Free Survival in Refractory NSCLC Patients at AACR Annual Meeting (GlobeNewswire) - P1/2a | N=148 | NCT05109442 | Sponsor: Affimed GmbH | "The analysis is based on post-hoc exposure-response data from 72 NSCLC...Key Findings from the Exposure-Response Analysis: Objective Response Rate (ORR): 33.3% in the high-exposure group vs. 5.6% in the low-exposure group (p=0.0059); Disease Control Rate (DCR): 83.3% vs. 58.3% (p=0.0367); Median Progression-Free Survival (mPFS): 7.33 vs. 2.86 months; Overall Survival (OS): Not yet mature in the high-exposure group vs. 13 months in the low-exposure group....A quartile analysis further confirmed the exposure-efficacy relationship, showing a stepwise increase in ORR from 0% in the lowest quartile to 50% in the highest. Subgroup analysis of 55 patients treated with AFM24 plus atezolizumab showed consistent results: 37.04% ORR in the high-exposure group vs. 7.14% in the low group."

P1 data • Non Small Cell Lung Cancer

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

Dose-optimization using exposure response analysis in AFM24 (in monotherapy and with atezolizumab) in patients with advanced/metastatic non-small cell lung cancer (AACR 2025) - "The data show a strong correlation between exposure and clinical outcome with a significantly increased risk for early tumor progression in the low exposure group. PK modeling suggests that a dose of 720mg AFM24 weekly will result in exposure levels exceeding the cutoff for the high exposure group as early as week 2. The 720mg dose, which has already been established as safe in the phase 1 trial, will be used in future AFM24 studies."

Clinical • Metastases • Monotherapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • FCGR3A

Affimed Announces Acceptance of AFM24 Abstract on Dose Optimization for Presentation at American Association for Cancer Research Annual Meeting (GlobeNewswire) - "Affimed...announced an abstract on AFM24 dose optimization using exposure response analysis has been accepted for presentation as a poster at the Annual Meeting of the American Association for Cancer Research (AACR)....The full abstract will be published online on April 25, 2025."

P1/2 data • Non Small Cell Lung Cancer

First-in-Human Phase 1 study of a CD16A bispecific innate cell engager, AFM24, targeting EGFR-expressing solid tumors. (PubMed, Clin Cancer Res) - "AFM24 was well tolerated with 480 mg established as the RP2D. AFM24 could be a novel therapy for patients with EGFR-expressing solid tumors with suitable tolerability and appropriate pharmacokinetic properties for further development in combination with other immuno-oncology therapeutics."

Journal • P1 data • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • EGFR • FCGR3A

First-in-Human Phase 1 study of a CD16A bispecific innate cell engager, AFM24, targeting EGFR-expressing solid tumors (Clin Cancer Res) - P1/2a | N=85 | NCT04259450 | Sponsor: Affimed GmbH | "In the dose escalation phase, 35 patients received AFM24 weekly across seven dose cohorts (14–720 mg). One patient experienced a DLT of Grade 3 infusion-related reaction (IRR). IRRs were mainly reported after the first infusion; these were manageable with premedication and a gradual increase in infusion rate. Pharmacokinetics were dose-proportional and CD16A receptor occupancy on NK cells approached saturation between 320–480 mg. Paired tumor biopsies demonstrated activation of innate and adaptive immune responses within the tumor. Best objective response was stable disease in 10/35 patients; four had stable disease for 4.3–7.1 months."

P1 data • Solid Tumor

Post-Hoc Exposure-Response Analysis (GlobeNewswire) - "A post-hoc exposure-response analysis was conducted including NSCLC EGFRwt and EGFRmut subjects (n= 44) treated with 480 mg AFM24 in both the AFM24-101 monotherapy study or the AFM24-102 AFM24 combination with atezolizumab study.....The high exposure group showed an ORR of 46% and a PFS of 7.4. A sensitivity analysis using quartiles of exposure supported a clear relationship between exposure and outcome indicating that higher doses of AFM24 will likely result in improved efficacy. The PK profile of 720 mg AFM24 weekly, as tested successfully in the phase 1 trial and further pharmacokinetic modelling indicate that 720 mg will achieve exposure levels that are equal or above the plasma concentrations observed for the high exposure group."

Retrospective data • Non Small Cell Lung Cancer

Affimed Reports Positive Clinical Update on AFM24/Atezolizumab Combination Therapy in Non-Small Cell Lung Cancer (NSCLC) (GlobeNewswire) - P1/2a | N=148 | AFM24-102 (NCT05109442) | Sponsor: Affimed GmbH | "In 33 heavily pretreated NSCLC EGFR wild-type (EGFRwt) patients the combination of AFM24 and atezolizumab shows an overall response rate (ORR) of 21% (6 confirmed responses, 1 response awaiting confirmatory scan) and a disease control rate (DCR) of 76%; tumor shrinkage was observed in 48% of patients; preliminary median progression free survival (PFS) is 5.6 months and 36% of patients remain on treatment; In 17 heavily pretreated NSCLC EGFR mutant (EGFRmut) patients the combination shows an ORR of 24% and a DCR of 71%; tumor shrinkage was observed in 41% of patients; median PFS is 5.6 months and 5 patients (29%) are on treatment for over 10 months; Both cohorts demonstrated a well-manageable side effect profile with no new safety signals identified."

P1/2 data • Non Small Cell Lung Cancer

Affimed to Host Investor Conference Call Highlighting Clinical Data from AFM24 in Combination with Atezolizumab in Non-Small Cell Lung Cancer (GlobeNewswire) - "Affimed N.V...announced today that it will host a conference call on Tuesday, December 17, at 8:30 a.m. EST / 14:30 CET to review clinical data from AFM24-102, the combination trial of its AFM24 innate cell engager ICE with atezolizumab in non-small cell lung cancer."

P1/2 data • Non Small Cell Lung Cancer

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

AFM24-102: Study to Assess AFM24 in Combination with Atezolizumab in Selected Advanced/Metastatic EGFR-expressing Cancers (clinicaltrials.gov) - P1/2 | N=148 | Recruiting | Sponsor: Affimed GmbH | Trial completion date: Jun 2025 ➔ Nov 2025 | Trial primary completion date: Sep 2024 ➔ Feb 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • EGFR

Leveraging innate and adaptive immunity with AFM24 and atezolizumab in metastatic gastric cancer (ESMO 2024) - P1/2 | "AFM24 plus atezolizumab showed early signs of activity in relapsed/refractory mGC/mGEJC pts, including patients with signet ring cell gastric adenocarcinoma. No new or unexpected toxicities were reported. This chemotherapy-free approach could be a therapeutic alternative and warrants further study."

IO biomarker • Metastases • Tumor mutational burden • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR • FCGR3A • TMB

Affimed Reports Second Quarter 2024 Financial Results & Business Update (GlobeNewswire) - P1/2 | N=148 | NCT05109442 | Sponsor: Affimed GmbH | "24 heavily pretreated EGFRmut NSCLC patients are in the trial; in 17 patients that are response evaluable per protocol, 1 CR, 3 PRs and 8 SDs were observed. All responses have been confirmed by follow-up scan. ORR is 23.5% (4/17) and DCR is 70.6% (12/17). Median follow-up is > 7 months and 8 out of the 17 patients continue on treatment. All 4 responders remained on treatment for at least 7 months...Mature PFS data from EGFRmut and EGFRwt cohorts expected to be presented at a future conference in H1 2025."

P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Study to Assess AFM24 in Advanced Solid Cancers (clinicaltrials.gov) - P1/2 | N=85 | Completed | Sponsor: Affimed GmbH | Active, not recruiting ➔ Completed | Trial completion date: Dec 2024 ➔ Jun 2024

Trial completion • Trial completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • KRAS

Preliminary results from the phase 2 study of AFM24 in combination with atezolizumab in patients with EGFR wild-type (EGFR-WT) non-small cell lung cancer (NSCLC). (ASCO 2024) - P1/2 | "AFM24 with atezolizumab shows remarkable signs of clinical efficacy, even in patients with resistance to prior CPI, and a well-tolerated and manageable safety profile in patients with EGFR-WT NSCLC. The study is ongoing and up to 40 patients will be enrolled into this cohort."

Clinical • Combination therapy • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • FCGR3A • PD-1