City of Hope Leads Phase II Clinical Trial for Efficacy & Safety of ADCT-301 in Patients with Relapsed or Refractory Hodgkin Lymphoma

City of Hope Leads Phase II Clinical Trial for Efficacy & Safety of ADCT-301 in Patients with Relapsed or Refractory Hodgkin Lymphoma

City of Hope Medical Center’s Alex Herrera, MD, leads a Phase II clinical trial assessing the efficacy and safety of ADCT-301 (camidanlumab tesirine) in patients with relapsed or refractory Hodgkin lymphoma (HL). Sponsored by Swiss emerging biotech ADC Therapeutics SA, the team has treated the first patients for testing a highly potent and targeted antibody drug conjugates (ADCs) for patients suffering from malignancies and solid tumors.

The Mission

The business stakes are big for this study. Sponsor ADC Therapeutics SA will seek to use the clinical trial results to support the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration—and of course if approved by the agency the company can commercialize ADCT-301 by offering a new option for the Hodgkin lymphoma community. The personal stakes—there are north of 15,000 patients that this drug could potentially help if this study results go well.

The Study

The study evaluates the clinical efficacy and safety of Camidanlumab Tesirine (ADCT-301) in participants with relapsed or refractory Hodgkin Lymphoma (HL), as published in Seeking 100 patients, the study team led by Dr. Herrera have dosed the first patients in the pivotal Phase II clinical trial. An open-label, single-arm study uses the 2014 Lugano Classification Criteria. The study centers on patients with pathologically confirmed relapsed or refractory HL who have failed three prior  lines of therapy, including brentuximab vedotin (Adcetris/Seattle Genetics) and checkpoint inhibitor approved for HL such as nivolumab (Opdivo/BMS) or pembrolizumab (Keytruda/Merck).

The Disease

Dr. Herrera reported in the sponsor’s press release that “approximately 15 to 25 % of the 16,500 patients diagnosed with HL each year in the U.S. and Europe have relapsed or refractory HL. While advances have been made in the treatment of HL, a significant unmet need remains in the relapsed or refractory HL patient population, especially patients who have progressed following treatment with other novel agents. I believe ADCT-301 has the potential to fill this important medical need.”

What is ADCT-301? (camidanlumab tesirine)

An antibody-drug conjugate (ADC) composed of a human antibody that binds to the protein CD25,(HuMax®-TAC, licensed from Genmab A/S) conjugated to a pyrrobenzodiazepine dimer (PD) toxin. Once bound to a CD25-expressing tumor cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead killing the cell with an immunogenic cell death. The intra-tumoral release of its PBD warhead may also cause bystander killing of neighboring tumor cells. The ADCT also depletes CD25-positive regulatory T cells in the tumor environment. All of these properties ADCT-301 may enhance immune-mediated anti-tumor activity.

ADCT-301 is being evaluated in a pivotal Phase 2 clinical trial in patients with relapsed or refractory Hodgkin lymphoma; as well as ongoing Phase 1a/1b clinical trials in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma and a Phase Ib clinical trial in solid tumors.

The Sponsor

ADC Therapeutics, based in Lausanne,  Switzerland, was founded in 2011. Since then through at least 5 funding rounds they have raised approximately $531 million according to their websiteThey develop ADCs and non-antibody drug conjugate products. They have operations in London (R&D), New Jersey (Clinical) and the San Francisco Bay Area (CMC). 

Their clinical programs include ADCT-402, ADCT-301, ADCT-602 and ADCT-601 and seek to advance them through clinical trials in multiple hematological and solid tumor indications. They have numerous preclinical ADCs they work to bring to the clinic.

They tout that they have deep knowledge and understanding of ADCs and the oncology treatment landscape. They are dedicated to developing best-in-class PBD-armed ADCs to address unmet medical needs and improve outcomes for people with difficult-to-treat cancer. Chris Martin, CEO and Jay Feingold, MD, PhD, CMO lead the venture.

The Research Site

City of Hope is a NCI-designated Comprehensive Cancer Center—they are considered a worldwide leader in administering clinical trials with a focus on advanced investigational treatments.  City of Hope is currently conducting more than 500 clinical trials, enrolling more than 6,200 patients.

The Principal Investigator

Alex Herrera, MD, is an assistant professor at Department of Hematology & Hematopoietic Cell Transplantation and a Hematologist and Oncologist. His areas of focus include immunotherapy and hematopoietic stem cell transplantation in patients with lymphoma. A member of the Toni Stephenson Lymphoma Center, he has received many honors, grants and awards relating to leukemia and lymphoma as well as other areas of interest.

Call to Action: If you or a loved one have relapsed or refractory Hodgkin lymphoma (HL), this is a study to track. Also, if you are in California or have means to travel, consider City of Hope for an opinion.