GEN1044 / Genmab, AbbVie - LARVOL DELTA

Heat shock factor 1 (HSF1) identified as regulator of resistance to T-cell mediated killing in head and neck cancer cells (CICON 2025) - "In in vitro killing assays, we observed that patient-derived HNSCC cell lines displayed different sensitivities to T-cell mediated killing induced by a CD3-bispecific antibody (CD3-bsAb) targeting the surface protein 5T4 (DuoBody-CD3x5T4), irrespective of the 5T4 levels expressed by these HNSCC-derived cell lines...The exact mode-of-action through which HSF1 promotes resistance to T-cell mediated killing is currently being further investigated, and may vary between individual tumors. Our observations and our experimental approach using CD3-bsAb-CRISPR/Cas9 knockout screens, may be at the basis of developing new (combination) treatment modalities to enhance the efficacy of CD3-bsAb treatments and other immunotherapy approaches that promote anti-tumor T-cell cytotoxicity such as CAR-T cells and immune checkpoint inhibitors."

Head and Neck Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BCL2 • BCL2L1 • HSF1

DuoBody®-CD3x5T4 induces efficient T-cell activation and killing of patient-derived head and neck cancer cells in vitro and ex vivo (SITC 2021) - P1/2 | "In single-cell suspensions from freshly dissociated 5T4+ HNSCC biopsies, DuoBody-CD3x5T4 activated autologous CD4+ and CD8+ TILs, including PD-1+ TILs. This dataset adds to the preclinical evidence for targeting 5T4-expressing solid cancers with DuoBody-CD3x5T4."

IO biomarker • Preclinical • Bladder Cancer • Breast Cancer • Esophageal 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 • CD69 • CD8 • EGFR • GZMB • IL2RA • PTPRC • TNFRSF9 • TPBG

[VIRTUAL] Preclinical mechanism of action and pharmacodynamic biomarker studies of DuoBody®-CD3x5T4 in vitro and in vivo in solid cancer models (SITC 2020) - P1/2 | "In humanized CDX and PDX mouse models, DuoBody-CD3x5T4 showed anti-tumor activity, in addition to PD biomarkers associated with T-cell activation in the tumor and periphery. Currently, DuoBody-CD3x5T4 is being investigated in a first-in-human clinical trial for the treatment of solid tumors (NCT04424641), in which exploratory biomarker analyses to study the clinical MoA and PD are included."

PK/PD data • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Uterine Cancer • CD8 • CXCL8 • IFNG • IL6

[VIRTUAL] Preclinical mechanism of action and pharmacodynamic biomarker studies of DuoBody®-CD3x5T4 in vitro and in vivo in solid cancer models (SITC 2020) - P1/2 | "In humanized CDX and PDX mouse models, DuoBody-CD3x5T4 showed anti-tumor activity, in addition to PD biomarkers associated with T-cell activation in the tumor and periphery. Currently, DuoBody-CD3x5T4 is being investigated in a first-in-human clinical trial for the treatment of solid tumors (NCT04424641), in which exploratory biomarker analyses to study the clinical MoA and PD are included."

PK/PD data • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Uterine Cancer • CD8 • CXCL8 • IFNG • IL6

Mechanistic and pharmacodynamic studies of DuoBody-CD3x5T4 in preclinical tumor models. (PubMed, Life Sci Alliance) - "Lastly, in dissociated patient-derived tumor samples, DuoBody-CD3x5T4 activated tumor-infiltrating lymphocytes and induced tumor-cell cytotoxicity, even when most tumor-infiltrating lymphocytes expressed PD-1. These data provide an in-depth view on the mechanism of action of a CD3 bsAb in preclinical models of solid cancer."

Journal • PK/PD data • Preclinical • Oncology • Solid Tumor • CD4 • CD8 • GZMB • IFNGR1 • PD-1

A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Subjects With Malignant Solid Tumors (clinicaltrials.gov) - P1/2; N=37; Terminated; Sponsor: Genmab; Active, not recruiting ➔ Terminated; Study was terminated due to MTD was reached

Clinical • Trial termination • Bladder Cancer • Breast Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • Uterine Cancer

A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Subjects With Malignant Solid Tumors (clinicaltrials.gov) - P1/2; N=37; Active, not recruiting; Sponsor: Genmab; Recruiting ➔ Active, not recruiting; N=378 ➔ 37; Trial completion date: Jun 2024 ➔ Jan 2022; Trial primary completion date: Mar 2024 ➔ Jan 2022

Clinical • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • Uterine Cancer

Genmab Announces Data to be Presented at SITC 35th Anniversary Annual Meeting (Genmab Press Release) - "Genmab A/S...announced today that multiple abstracts for Genmab programs were accepted for presentation at the Society for Immunotherapy of Cancer’s (SITC) 35th Anniversary Annual Meeting. Accepted abstracts include preliminary data from the first-in-human Phase 1/2a study of DuoBody®-PD-L1x4-1BB (GEN1046), a bispecific antibody in joint development with BioNTech, in patients with advanced solid tumors, which was accepted for e-poster presentation. Pre-clinical data for DuoBody-PD-L1x4-1BB (GEN1046), tisotumab vedotin and DuoBody-CD3x5T4 will also be presented."

P1/2 data • Preclinical • Oncology • Solid Tumor

A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Subjects With Malignant Solid Tumors (clinicaltrials.gov) - P1/2; N=378; Recruiting; Sponsor: Genmab; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Bladder Cancer • Breast Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • Uterine Cancer • F2

"GEN1044 $ABBV $GMAB https://t.co/TD3C8jrMdZ" (@JacobPlieth)

A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Subjects With Malignant Solid Tumors (clinicaltrials.gov) - P1/2; N=378; Not yet recruiting; Sponsor: Genmab

Clinical • New P1/2 trial • Bladder Cancer • Breast Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer • Triple Negative Breast Cancer • Urothelial Cancer • Uterine Cancer