On January 27, 2022 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported the first patient has been dosed in a combination cohort of its anti-CD137 agonist, ADG106, with its anti-CTLA-4 monoclonal antibody (mAb), ADG116, in patients with advanced/metastatic solid tumors (Press release, Adagene, JAN 27, 2022, View Source [SID1234607446]). The dose escalation cohort will evaluate the safety and tolerability of this novel, proprietary combination in patients with advanced/metastatic solid tumors.
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"Existing cancer therapies that target CD137 and CTLA-4 are associated with safety concerns, creating a significant unmet need and high threshold for agents that are both safe and potent. With ADG106 and ADG116, we now have two promising agents to test the therapeutic potential of these two potent pathways together to safely inhibit tumor growth," said Anthony W. Tolcher, M.D., FRCPC, FACP, co-founder of NEXT Oncology and study investigator. "While the oncology community has long known of the compelling preclinical rationale for this intriguing combination, safety has been a barrier to further exploration. Given the encouraging individual safety profiles of both ADG 106 and ADG116 in patients so far, we finally have the rare and exciting opportunity to be the first to move this combination into clinic and improve patient care."
The combination is part of an open-label, global phase 1b/2 clinical trial (ADG116-1003) at multiple sites in the U.S. and Asia Pacific (APAC). The combination part begins with dose-escalation, followed by dose expansion once a recommended dose is established.
"Published research in preclinical models underscores the potential synergistic effect of combining these two potent pathways. We are proud to pioneer exploration of this novel combination, which also demonstrates the translational power of our NEObody platform — targeting unique epitopes with novel mechanisms of action by species cross reactive antibodies that can move directly from preclinical syngeneic mouse models to clinical studies," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. "This innovative clinical research will establish the safety and potential complementary effects of ADG106 and ADG116 against two challenging but orthogonal pathways for T-cell priming by anti-CTLA-4 and proliferation by anti-CD137, respectively, building on the promising preclinical and clinical data on safety and preliminary efficacy from our global trials. This pursuit aligns with our goal to transform the development paradigm of antibody-based immunotherapies for global cancer care."
As single agents, both ADG106 and ADG116 have demonstrated robust safety profiles and early signals of efficacy. In monotherapy trials in 98 patients, ADG106 was well tolerated at doses of 3 mg/kg and 5 mg/kg and at 300mg and 400mg flat doses, with limited liver toxicity or hematologic abnormalities observed. Results showed evidence of efficacy and a potential biomarker associated with tumor shrinkage was identified.
In monotherapy evaluation, ADG116 demonstrated a strong safety profile at doses up to 10 mg/kg, and showed early signals of efficacy, including in treatment-resistant "cold" and "warm" tumors such as ovarian and pancreatic cancers. ADG116 has achieved the recommended dosing range as a single agent and for evaluation in combination therapy.
About ADG116
ADG116 is a fully human ligand-blocking anti-CTLA-4 mAb generated using Adagene’s proprietary NEObody technology and being developed for the treatment of advanced/metastatic solid tumors. ADG116 is designed to enhance efficacy by potent Treg depletion in the tumor microenvironment (TME) and to maintain its physiological function by soft ligand blocking thereby addressing safety concerns associated with existing CTLA-4 therapeutics.
About ADG106
ADG106, is a fully human ligand-blocking, agonistic anti-CD137 IgG4 mAb generated using Adagene’s proprietary NEObody technology and being developed for the treatment of advanced solid tumors and non-Hodgkin’s lymphoma. CD137 stimulates the immune system to attack cancer cells and is a key driver for long-lasting T-cell proliferation and survival. Clinical trials of ADG106 as monotherapy have been conducted in the U.S. and China, and combination trials are underway with multiple anti-PD-1 therapies.