Earlier this week the U.S. Food and Drug Administration (FDA) lifted a partial clinical hold on the pivotal Phase II clinical study of camidanlumab tesirine (formerly known as ADCT-301) in patients with relapsed or refractory Hodgkin lymphoma. The drug is being developed by ADC Therapeutics.

Camidanlumab tesirine is an antibody-drug conjugate or ADC comprised of a monoclonal antibody that binds to CD25 (HuMax®-TAC, licensed from Genmab), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload tesirine (SG3249), which has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death.

Once bound to a CD25-expressing cell, camidanlumab tesirine is internalized into the cell where enzymes release the PBD-based warhead killing the cell with immunogenic cell death. The intra-tumoral release of its PBD warhead may also cause bystander killing of neighboring tumor cells. The ADC also depletes CD25-positive regulatory T-cells in the tumor environment.

Enhance immune-mediated anti-tumor activity
Based on these properties of camidanlumab tesirine is believed to enhance immune-mediated anti-tumor activity.

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The investigational drug is being evaluated in a pivotal Phase II clinical trial in patients with relapsed or refractory Hodgkin lymphoma, as well as in a Phase Ia/Ib clinical trial in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma and a Phase Ib clinical trial in solid tumors.

Information request
“We’ve worked diligently to provide a thorough and prompt response to the FDA following its request for information about our pivotal Phase II clinical trial of camidanlumab tesirine,” said Jay Feingold, M.D., Ph.D., Senior Vice President and Chief Medical Officer of ADC Therapeutics.

“During the partial clinical hold we continued to treat patients benefiting from camidanlumab tesirine, and now look forward to resuming the enrollment of new patients in the trial as soon as possible.”

The 100-patient Phase II, multi-center, open-label, single-arm clinical trial is evaluating the safety and efficacy of camidanlumab tesirine in patients with relapsed or refractory HL. Patients with pathologically confirmed relapsed or refractory Hodgkin lymphoma who have failed three prior lines of therapy, including brentuximab vedotin and a checkpoint inhibitor approved for HL such as nivolumab or pembrolizumab, are eligible for enrollment in the clinical trial.

The trial is intended to support the submission of a Biologics License Application (BLA) to the FDA.

ADC Therapeutics is located in Lausanne, Switzerland, and utilizes laboratory facilities at Queen Mary Bioenterprises Innovation Centre, London, UK (Featured image: Courtesy: 2016 QMB Innovation Center; used with permission).

Clinical Trials
Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma – NCT02432235
Study of ADCT-301 in Patients With Selected Advanced Solid Tumors  – NCT03621982
Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) in Patients With Relapsed or Refractory Hodgkin Lymphoma – NCT04052997
Study of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL) – NCT02588092

Reference
Hofland P. 15th ICML: Camidanlumab Tesirine Shows High Overall Response Rate in R/R Classical Hodgkin Lymphoma. ADC Review | Journal of Antibody-drug conjugates ADCR 2019 (6).29 [Artricle]