benufutamab (GEN1029) / Genmab - LARVOL DELTA

HexaBody-DR5/DR5 (GEN1029) shows potent preclinical antitumor activity in a variety of patient-derived xenograft (PDX) tumor models (AACR-NCI-EORTC 2019) - P1/2; "A Phase 1/2 clinical trial to determine the RP2D and assess clinical safety of HexaBody-DR5/DR5 in cancer patients is currently ongoing (NCT03576131), from which a case study will be presented. Conclusion Potent anti-tumor activity of HexaBody-DR5/DR5 was observed in large and diverse panels of CRC, gastric and urothelial PDX models, providing preclinical rationale for the clinical evaluation of HexaBody-DR5/DR5 in these indications."

Potent preclinical activity of HexaBody-DR5/DR5 in relapsed and/or refractory multiple myeloma. (PubMed, Blood Adv) - "Supporting this, bortezomib combined with HexaBody-DR5/DR5 synergistically increased cytotoxicity in MM cells in 7 of 11 newly diagnosed patients. Lenalidomide also synergized with HexaBody-DR5/DR5, but only via its immunomodulatory effects, presumably by enhancing the antibody-dependent cellular cytotoxicity activity of HexaBody-DR5/DR5. Daratumumab showed additive effects when combined with HexaBody-DR5/DR5. In conclusion, the results of this preclinical study indicate a therapeutic potential for HexaBody-DR5/DR5, especially in recently treated relapsed/refractory MM patients."

Journal • Preclinical • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology • Solid Tumor

GEN1029 (HexaBody®-DR5/DR5) Safety Trial in Patients With Malignant Solid Tumors (clinicaltrials.gov) - P1/2; N=48; Terminated; Sponsor: Genmab; N=520 ➔ 48; Trial completion date: Mar 2022 ➔ Oct 2021; Recruiting ➔ Terminated; Sponsor decision

Clinical • Enrollment change • Trial completion date • Trial termination • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer

Dual epitope targeting and enhanced hexamerization by DR5 antibodies as a novel approach to induce potent anti-tumor activity through DR5 agonism. (PubMed, Mol Cancer Ther) - "We observed potent anti-tumor activity in vitro and in vivo in large panels of patient-derived xenograft models representing various solid cancers. The results of our preclinical studies provided the basis for an ongoing clinical trial exploring the activity of HexaBody-DR5/DR5 (GEN1029) in patients with malignant solid tumors."

Journal • Oncology • Solid Tumor

GEN1029 (HexaBody®-DR5/DR5) Safety Trial in Patients With Malignant Solid Tumors (clinicaltrials.gov) - P1/2; N=520; Recruiting; Sponsor: Genmab; N=188 ➔ 520

Clinical • Enrollment change

DR5 agonist activity of HexaBody®-DR5/DR5 (GEN1029) is potentiated by C1q and independent of Fc-gamma receptor binding in preclinical tumor models (AACR 2019) - "Cytotoxicity of Hx-DR5-01/05 was most optimal in the presence of C1q and completely independent of FcγR-mediated antibody crosslinking or effector functions in vitro and in vivo. A clinical trial to assess clinical safety of Hx-DR5-01/05 in patients is currently ongoing."

Preclinical