On September 10, 2020 ADC Therapeutics SA (NYSE: ADCT), a late clinical-stage oncology-focused biotechnology company pioneering the development and commercialization of highly potent and targeted antibody drug conjugates (ADCs) for patients with hematological malignancies and solid tumors, reported that preclinical data related to camidanlumab tesirine (Cami, formerly ADCT-301) has been published in the Journal for ImmunoTherapy of Cancer, the online journal of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), in a paper titled, "CD25-targeted antibody-drug conjugate depletes regulatory T cells and eliminates established syngeneic tumors via antitumor immunity (Press release, ADC Therapeutics, SEP 10, 2020, View Source [SID1234564971])."
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The study evaluated the antitumor activity of a pyrrolobenzodiazepine (PBD) dimer-based, CD25-targeted ADC, either alone or in combination with a checkpoint inhibitor, in CD25-negative syngeneic colon cancer models that exhibit tumor infiltration of CD25-expressing regulatory T cells (Tregs). Data demonstrated that single low doses of the CD25-targeted ADC resulted in potent and durable antitumor activity against established CD25-negative solid tumors with infiltrating Tregs, both as a monotherapy and in combination with an anti-PD1 checkpoint inhibitor.
Patrick van Berkel, Ph.D., Senior Vice President of Research and Development at ADC Therapeutics, said, "CD25 is expressed on Tregs that infiltrate the local tumor environment. We were pleased to see that our CD25-targeted ADC depleted CD25-expressing Tregs and not only showed strong anti-tumor activity as a monotherapy in preclinical models, but it also enhanced the activity of anti-PD1 treatment in these models. This study provides proof of concept for a new application of ADCs as immunotherapeutic agents and supports the continued evaluation of Cami in our ongoing Phase 1b clinical trial in patients with selected advanced solid tumors. We look forward to advancing the exploration of Cami as a novel immune-oncology approach for the treatment of solid tumors."
For information about the company’s Phase 1b clinical trial of Cami in solid tumors, visit www.clinicaltrials.gov (identifier NCT03621982).
About Camidanlumab Tesirine (Cami)
Camidanlumab tesirine (Cami, formerly ADCT-301) is an antibody drug conjugate (ADC) comprised of a monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload, tesirine. Once bound to a CD25-expressing cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead killing the cell. This applies to CD25-expressing tumor cells, and also to CD25-expressing Tregs. The intra-tumoral release of its PBD warhead may also cause bystander killing of neighboring tumor cells and PBDs have also been shown to induce immunogenic cell death. All these properties of Cami may enhance immune-mediated anti-tumor activity. Cami is being evaluated in a pivotal Phase 2 clinical trial in patients with relapsed or refractory Hodgkin lymphoma (HL), as well as in a Phase 1a/1b clinical trial in patients with relapsed or refractory HL and non-Hodgkin lymphoma and a Phase 1b clinical trial in solid tumors.