Title |
Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 and 4-1BB (GEN1046) in Patients with Advanced Refractory Solid TumorsGEN1046, a Bispecific Antibody Targeting PD-L1 and 4-1BB
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Published in |
Cancer Discovery, February 2022
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DOI | 10.1158/2159-8290.cd-21-1345 |
Pubmed ID | |
Authors |
Alexander Muik, Elena Garralda, Isil Altintas, Friederike Gieseke, Ravit Geva, Eytan Ben-Ami, Corinne Maurice-Dror, Emiliano Calvo, Patricia M. LoRusso, Guzman Alonso, Maria E. Rodriguez-Ruiz, Kristina B. Schoedel, Jordan M. Blum, Bianca Sänger, Theodora W. Salcedo, Saskia M. Burm, Eliana Stanganello, Dennis Verzijl, Fulvia Vascotto, Angelica Sette, Juliane Quinkhardt, Theo S. Plantinga, Aras Toker, Edward N. van den Brink, Mark Fereshteh, Mustafa Diken, David Satijn, Sebastian Kreiter, Esther C.W. Breij, Gaurav Bajaj, Eleni Lagkadinou, Kate Sasser, Özlem Türeci, Ulf Forssmann, Tahamtan Ahmadi, Uğur Şahin, Maria Jure-Kunkel, Ignacio Melero |
Abstract |
Checkpoint inhibitors (CPIs) have revolutionized the treatment paradigm for advanced solid tumors; however, there remains an opportunity to improve response rates and outcomes. In preclinical models, 4-1BB costimulation synergizes with CPIs targeting the PD-1/PD-L1 axis by activating cytotoxic T-cell-mediated antitumor immunity. DuoBody®-PD-L1x4-1BB (GEN1046) is an investigational, first-in-class, bispecific immunotherapy agent designed to act on both pathways by combining simultaneous and complementary PD-L1 blockade and conditional 4-1BB stimulation in one molecule. GEN1046 induced T-cell proliferation, cytokine production, and antigen-specific T-cell-mediated cytotoxicity superior to clinically approved PD-(L)1 antibodies in human T-cell cultures and exerted potent antitumor activity in transplantable mouse tumor models. In dose escalation of the ongoing first-in-human study in heavily pretreated patients with advanced refractory solid tumors (NCT03917381), GEN1046 demonstrated pharmacodynamic immune effects in peripheral blood consistent with its mechanism of action, manageable safety, and early clinical activity (disease control rate: 65.6% [40/61]), including patients resistant to prior PD-(L)1 immunotherapy. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 16 | 28% |
Spain | 4 | 7% |
Dominican Republic | 3 | 5% |
Germany | 3 | 5% |
Canada | 2 | 4% |
United Kingdom | 2 | 4% |
China | 1 | 2% |
Austria | 1 | 2% |
Belgium | 1 | 2% |
Other | 0 | 0% |
Unknown | 24 | 42% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 39 | 68% |
Scientists | 13 | 23% |
Science communicators (journalists, bloggers, editors) | 4 | 7% |
Practitioners (doctors, other healthcare professionals) | 1 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 67 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 16 | 24% |
Student > Ph. D. Student | 9 | 13% |
Unspecified | 4 | 6% |
Student > Doctoral Student | 3 | 4% |
Student > Bachelor | 3 | 4% |
Other | 11 | 16% |
Unknown | 21 | 31% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 17 | 25% |
Biochemistry, Genetics and Molecular Biology | 8 | 12% |
Medicine and Dentistry | 6 | 9% |
Unspecified | 4 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 4% |
Other | 6 | 9% |
Unknown | 23 | 34% |