acasunlimab (GEN1046) / Genmab - LARVOL DELTA

Molecular profiling of NSCLC patients associates CT-based radiomic features with a tumor microenvironment favorable for immunotherapy (AACR 2025) - P1/2, P2 | "Here, we integrate radiomics with tumor transcriptomic profiles to enhance biological interpretation of CT-based features linked to an immune-responsive tumor microenvironment (TME), in non-small cell lung cancer (NSCLC) treated with acasunlimab, a DuoBody® PD-L1×4-1BB bispecific antibody, +/- pembrolizumab.This study used contrast-enhanced CT images (n=62) and gene expression (HTG EdgeSeq) from tumor biopsies (n=25) of advanced NSCLC subjects in GCT1046-01 (NCT03917381) and GCT1046-04 (NCT05117242). Gabor was negatively correlated with cancer associated fibrosis and extracellular matrix remodeling.These results show that integrating radiomics with tumoral mRNA data identified key characteristics of a TME conducive for immunotherapy, advancing the interpretability of AI-derived imaging features. The composite radiomics score was independent of traditional prognostic factors and reflected immunotherapy-specific mechanisms, highlighting its potential..."

Biomarker • Clinical • IO biomarker • Tumor microenvironment • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

GEN1046 Safety Trial in Patients With Malignant Solid Tumors (clinicaltrials.gov) - P1/2 | N=429 | Active, not recruiting | Sponsor: Genmab | Trial primary completion date: Feb 2026 ➔ Apr 2025

Trial primary completion date • Breast Cancer • Cervical Cancer • Endometrial Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer

Acasunlimab, an Fc-inert PD-L1×4-1BB bispecific antibody, combined with PD-1 blockade potentiates antitumor immunity via complementary immune modulatory effects. (PubMed, J Immunother Cancer) - P2, P3 | "These preclinical results demonstrate that conditional 4-1BB stimulation combined with complete PD-1 blockade enhances antitumor immunity through complementary mechanisms. The acasunlimab and pembrolizumab combination is being evaluated in Phase 2 (NCT05117242) and pivotal Phase 3 (NCT06635824) trials in patients with metastatic non-small cell lung cancer after checkpoint inhibitor therapy failure."

Journal • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • GZMB • IFNG • IL2 • PD-L2

ABBIL1TY NSCLC-06: A global, randomized, open-label, phase III trial of acasunlimab in combination with pembrolizumab (Pembro) vs docetaxel in checkpoint inhibitor (CPI)-experienced patients with PD-L1+ metastatic non-small cell lung cancer (mNSCLC) (ELCC 2025) - P2, P3 | "Secondary endpoints include progression-free survival, objective response rate, duration of response, patient-reported outcomes, and occurrence of AEs. The trial is currently enrolling."

Checkpoint inhibition • Clinical • Combination therapy • IO biomarker • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1 • ROS1

OmniAb Reports Fourth Quarter and Full Year 2024 Financial Results and Business Highlights (Businesswire) - "Acasunlimab: Genmab announced that a Phase 3 trial with acasunlimab as a second-line therapy in non-small cell lung cancer (NSCLC) is now enrolling patients and that they expect to provide an additional Phase 2 data update in NSCLC in 2025."

Enrollment status • P2 data • Non Small Cell Lung Cancer

Acasunlimab Alone or in Combination With Pembrolizumab in Japanese Patients With Advanced or Metastatic Solid Tumors (JSMO 2025) - No abstract available

Clinical • Combination therapy • Metastases • Oncology • Solid Tumor

GEN1046 Safety and PK in Subjects With Advanced Solid Malignancies (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Genmab | Active, not recruiting ➔ Completed | Trial completion date: Aug 2025 ➔ Oct 2024 | Trial primary completion date: Aug 2025 ➔ Oct 2024

Metastases • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Acasunlimab in combination with pembrolizumab reinvigorates anti-tumor immunity in patients with previously treated metastatic non-small cell lung cancer (NSCLC) (SITC 2024) - P2 | "The study was conducted in accordance with the International Council for Harmonisation E6(R2) guidelines on good clinical practice and the principles of the Declaration of Helsinki. All patients provided written informed consent."

Clinical • Combination therapy • IO biomarker • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • HAVCR2

GEN1046 Safety Trial in Patients With Malignant Solid Tumors (clinicaltrials.gov) - P1/2 | N=429 | Active, not recruiting | Sponsor: Genmab | Trial completion date: Oct 2025 ➔ Feb 2026 | Trial primary completion date: Jan 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Breast Cancer • Cervical Cancer • Endometrial Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer

Acasunlimab combined with PD-1 blockade elicits complementary immune-modulatory effects and enhances anti-tumor activity in preclinical models (SITC 2024) - P2 | "Conclusions Our results indicate that combining acasunlimab with additional PD-1 blockade may amplify the anti-tumor immune response by promoting autocrine IL-2–CD25 signaling and increasing the proportion of stem-like CD8+ TILs with effector functions. These results contribute to the growing evidence supporting the potential of combining acasunlimab with pembrolizumab to elicit durable clinical responses.4 Ethics Approval Animal experiments were performed according to the guidelines of the Institutional Animal Care and Use Committee (IACUC) and in accordance with the regulations of the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC)."

IO biomarker • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • FOXP3 • GZMB • HAVCR2 • IL2RA • PD-L2

Acasunlimab combined with PD-1 blockade elicits complementary immune-modulatory effects and enhances anti-tumor activity in preclinical models (SITC 2024) - "Full Regular Abstract, Young Investigator Award (YIA), Immune Engineering Abstracts, and Late-breaking Abstract - Clinical Only (LBA) content will be embargoed until Nov. 5, 2024 at 8 a.m. CT / 9 a.m. ET"

Preclinical • Oncology

Trial to Evaluate Acasunlimab and Pembrolizumab Combination Superiority Over Standard of Care Docetaxel in Non-Small Cell Lung Cancer (ABBIL1TY NSCLC-06) (clinicaltrials.gov) - P3 | N=702 | Recruiting | Sponsor: Genmab

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Dosing Regimen for Acasunlimab (DuoBody-PD-L1x4-1BB) In Combination with Pembrolizumab (IASLC-WCLC 2024) - P2 | "PD results support the hypothesis that intermittent 4-1BB engagement reduces chronic T-cell stimulation, potentially mitigating T-cell dysfunction by allowing a resting interval and resetting of T-cell function. This may improve the magnitude and quality of antitumor immune responses and result in improved durability in the clinical setting."

Combination therapy • IO biomarker • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • CD8 • HAVCR2

Finanshus after accounting from Johnson & Johnson: The focus is on upcoming updates from Genmab's pipeline [Google translation] (MedWatch) - "Jefferies analyst Peter Welford notes that Johnson & Johnson reported second-quarter Darzalex sales of $2.88 billion. dollar is 3-4 per cent. above the consensus estimates and Jefferies' own estimate...But in relation to the share price for Genmab, it is more the company's development pipeline that is in focus, Welford assesses...'In the short term, the focus is on Epkinly (Genmab's cancer drug, ed) maintaining its launch course in the US, updated Acasunlimab lung cancer data at the WCLC lung cancer conference and the first 1042 results.'....The results will probably be available at a scientific meeting in the fourth quarter, Jefferies estimates."

Clinical data • Sales • Follicular Lymphoma • Hematological Malignancies • Lung Cancer • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor

Acasunlimab Alone or in Combination with Pembrolizumab for Previously Treated Metastatic Non-Small Cell Lung Cancer (IASLC-WCLC 2024) - No abstract available

Combination therapy • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Genmab Takes Full Control of Acasunlimab Development Program (GlobeNewswire) - "Genmab A/S...announced today that it will assume sole responsibility for the continued development and potential commercialization of acasunlimab. BioNTech SE (BioNTech) has opted not to participate in the further development of the acasunlimab program under the parties’ existing collaboration agreement. The program will be subject to payment of certain milestones and a tiered single-digit royalty on net sales by Genmab to BioNTech. Genmab plans to initiate the Phase 3 study in the second half of this year....The companies’ long-standing collaboration in antibody science remains in place, and both parties will continue with the existing programs under development under their existing agreements, which were expanded in 2022."

Commercial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

OmniAb Reports Second Quarter 2024 Financial Results and Business Highlights (Businesswire) - "Acasunlimab:....Data from...the Phase 2 GCT1046-04 trial...will inform the planned pivotal Phase 3 trial, which is expected to start before year-end 2024."

New P3 trial • Non Small Cell Lung Cancer

GEN1046 Safety and PK in Subjects With Advanced Solid Malignancies (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Genmab | Trial completion date: Nov 2024 ➔ Aug 2025 | Trial primary completion date: Nov 2024 ➔ Aug 2025

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Safety and Efficacy Study of GEN1046 as a Single Agent or in Combination With Pembrolizumab for Treatment of Recurrent (Non-small Cell) Lung Cancer (clinicaltrials.gov) - P2 | N=125 | Active, not recruiting | Sponsor: Genmab | Recruiting ➔ Active, not recruiting

Checkpoint inhibition • Combination therapy • Enrollment closed • Metastases • Monotherapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

GEN1046 Safety Trial in Patients With Malignant Solid Tumors (clinicaltrials.gov) - P1/2 | N=429 | Active, not recruiting | Sponsor: Genmab | Trial completion date: Dec 2024 ➔ Oct 2025 | Trial primary completion date: Jun 2024 ➔ Jan 2025

Trial completion date • Trial primary completion date • Breast Cancer • Cervical Cancer • Endometrial Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer

Acasunlimab (DuoBody-PD-L1x4-1BB) alone or in combination with pembrolizumab (pembro) in patients (pts) with previously treated metastatic non-small cell lung cancer (mNSCLC): Initial results of a randomized, open-label, phase 2 trial. (ASCO 2024) - P2 | "Given failures of recent trials in this setting, single-agent chemotherapy remains the main tx option despite limited effectiveness (eg, docetaxel ORR 10–14%) and considerable toxicity. In PD-L1+ pts with mNSCLC following progression on prior CPI tx, acasunlimab + pembro combo showed a manageable safety profile and promising efficacy, with deeper responses and durable disease control in pts treated Q6W. Enrollment is ongoing."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Anemia • Fatigue • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • PD-L1

Investigational Acasunlimab (DuoBody -PD-L1x4-1BB) in Combination with Pembrolizumab Demonstrates Meaningful Clinical Activity in Phase 2 Trial in Patients with Previously Treated Metastatic Non-small Cell Lung Cancer (mNSCLC) (GlobeNewswire) - P2 | N=160 | NCT05117242 | Sponsor: Genmab | "The results showed a 12-month overall survival (“OS”) rate of 69%, a median overall survival ('mOS') of 17.5 months, and a 30% overall response rate ('ORR') (confirmed ORR 17%) at the time of data cut-off in patients treated with the combination of acasunlimab and pembrolizumab every six weeks....The OS was evaluated in all centrally confirmed PD-L1-positive patients (n=80). Arm A showed a mOS rate of 5.5 months, a 50% disease control rate (DCR) and a 31% ORR (confirmed ORR 13%) in patients treated with acasunlimab alone....Adverse events were consistent with the safety profiles of the individual drugs and treatment related adverse events ('TRAEs') were primarily grade 1 and 2."

P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Genmab to Showcase Data in Various Patient Populations to be Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - "Genmab A/S...announced today that multiple abstracts evaluating epcoritamab, a T-cell engaging bispecific antibody administered subcutaneously, tisotumab vedotin, an antibody-drug conjugate (ADC), and acasunlimab (also known as GEN1046/BNT311), an investigational bispecific antibody, will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, being held in Chicago, IL and virtually, May 31-June 2, 2024."

Clinical data • Cervical Cancer • Diffuse Large B Cell Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Squamous Cell Carcinoma of Head and Neck

OmniAb Reports First Quarter 2024 Financial Results and Business Highlights (OmniAb) - "Genmab expects to announce acasunlimab (GEN1046: PD-L1 x 4-1BB) Phase 2 data in second-line non-small cell lung cancer (NSCLC) in the first half of 2024; A poster titled 'Acasunlimab (duobody-PD-L1x4-1BB) alone or in combination with pembrolizumab in patients with previously treated metastatic non-small cell lung cancer: Initial results of a randomized, open-label, Phase 2 trial' will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024 at 9:00 a.m. Central time on Saturday, June 1, 2024; In addition, Genmab plans to initiate a Phase 3 study of acasunlimab in second-line NSCLC in 2024."

New P3 trial • P2 data • Non Small Cell Lung Cancer

GEN1046 in Combination With Anticancer Agents for the Treatment of Advanced Endometrial Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Genmab | N=80 ➔ 0 | Initiation date: Apr 2024 ➔ Oct 2023 | Not yet recruiting ➔ Withdrawn

Combination therapy • Enrollment change • Metastases • Trial initiation date • Trial withdrawal • Endometrial Cancer • Oncology • Solid Tumor • MSI • TIGIT