Why do ADCs treat their support poorly

ADC Therapeutics treats first patient with ADCT-402 in key study in patients with relapsed or refractory diffuse large B-cell lymphoma

Phase II study to evaluate the efficacy and safety of the CD19 antibody-drug conjugate in support of the biologics license application

First results expected in the third quarter of 2019

LAUSANNE, Switzerland, Aug. 08, 2018 (GLOBE NEWSWIRE) - ADC Therapeutics, a company that researches and develops oncological drugs and specializes in the development of proprietary antibody-drug conjugates (ADCs), announced today that im The first patient was dosed as part of the phase II study. The study is intended to support the application for a biologics license (BLA) with the US Food and Drug Administration (FDA). The clinical study evaluates the efficacy and safety of ADCT-402 (loncastuximab tesirine ) in patients with relapsed or refractory diffuse large B-cell lymphoma (DGBZL).

At the 2017 American Society of Hematology (ASH) annual meeting, the company presented phase I data for ADCT-402 from 138 evaluable patients with extensive pretreatment who had failed or did not tolerate established therapies with known clinical benefits had. The median was three previous therapies. At this point in time, in Part 1 of the study (dose escalation), the overall response rate (ORR) among the 49 evaluable responsive DGBZL patients who received ADCT in doses of at least 120 μg / kg was 55 percent (27/49). 18 patients showed a complete response (37 percent), 9 a partial response (18 percent).

The primary endpoint of the multicenter, open-label, single-arm study is the ORR in patients treated with ADCT-402, as confirmed by the central review. Secondary endpoints are duration of response, complete response rate, relapse-free survival, progression-free survival, and overall survival, as well as safety, pharmacokinetics, and health-related quality of life. Approx. 140 patients with relapsed or refractory DGBZL in several centers in the USA and Europe are expected to participate in the study.

“We are pleased that we have dosed the first patient in our clinical phase II study to evaluate ADCT-402 in DGBZL patients with recurrent and refractory disease after two or more treatments with multi-active ingredients. Our Phase I clinical trial of ADCT-402 for the treatment of non-Hodgkin lymphoma showed a significant effect in DGBZL patients and an acceptable safety profile, ”said Jay Feingold, MD, PhD, chief medical officer and senior vice president of clinical Development at ADC Therapeutics. “Unfortunately, there is no effective treatment for patients with multiple relapsed and refractory DGBZL, so we are excited about the opportunity to improve outcomes for these patients with ADCT-402 in a one-arm study. We are expected to publish the results of the Phase II study in the third quarter of 2019 and hope that the data will support our BLA filing with the FDA. "

Alex Spira, MD, PhD, FACP, director of the Virginia Cancer Specialists Research Institute and Clinical Assistant Professor of Oncology at the Johns Hopkins School of Medicine, added, “DGBZL patients who have relapsed or refractory to second-line chemotherapy have one very bad prognosis. There is a significant unmet need for new, effective treatment options for this patient population, and we believe that ADCT-402 has the potential to improve patient outcomes for this disease. For more information on the Phase II clinical trial, please visit www.clinicaltrials.gov (Identifier NCT03589469).

ADC Therapeutics is also planning several combination studies in the fourth quarter of 2018.

Diffuse large B-cell lymphoma (DGBZL)

Non-Hodgkin lymphoma is the seventh most common cancer in the United States. In 2017, it accounted for an estimated 4.3 percent of new cancers.1 Almost a third of NHL diseases (32.5 percent) are diffuse large B-cell lymphomas (DGBZL) .2 The most common initial treatment for DGBZL patients is chemo immunotherapy. The patients respond very well to the initial treatment, but more than half of them do not get the disease under long-term control.3 The current standard of treatment for recurrent DGBZL is further chemotherapy, possibly followed by a stem cell transplant (SCT). The prognosis for relapse patients is poor, especially for those with chemotherapy-refractory disease and a short interval between remission and relapse and those with relapse after high-dose therapy and SCT. There is a significant unmet need for effective treatments for patients with relapsed or refractory DGBZL.

ADCT-402

ADCT-402 is an antibody-drug conjugate (ADC) consisting of a humanized monoclonal antibody that binds to a human CD19 that is linked to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD19-expressing cell, ADCT-402 is internalized into the cell, where enzymes release the PBD-based “warhead”. CD19 is a clinically validated target for the treatment of B-cell malignancies. The PBD-based “warhead” is able to form highly cytotoxic cross-connections between DNA strands, block cell division and cause cell death. Preliminary data from a Phase I clinical trial in patients with relapsed or refractory B-cell non-Hodgkin lymphoma show a significant effect of ADCT-402 in patients with diffuse large B-cell lymphoma (DGBZL). ADCT-402 is also being evaluated in an ongoing Phase I clinical trial in patients with relapsed or refractory acute B-lymphoblastic leukemia (B-ALL). The U.S. The Food and Drug Administration has granted ADCT-402 orphan drug status for the treatment of DGBZL and mantle cell lymphoma.

ADC Therapeutics

ADC Therapeutics SA (ADCT) is an oncological drug discovery and development company specializing in the development of proprietary antibody-drug conjugates (ADCs for the treatment of major hematological and solid tumors. The company's ADCs are) highly targeted biopharmaceutical drugs that chemically combine surface antigen-specific monoclonal antibodies present on certain tumor cells with a novel class of potent pyrrolobenzodiazepine (PBD) -based “warheads.” The company has several PBD-based ADCs in ongoing clinical trials in the US and Europe and an extensive pipeline of additional preclinical ADCs under development. ADCT has world-class partners such as AstraZeneca and its arm in the global research and development of biological MedImmune. The company is headquartered in Lausanne (B iopôle), Switzerland, and operations in London, San Francisco and New Jersey. For more information, see www.adctherapeutics.com.

1 Siegel et al., 2017
2 Al-Hamadani et al., 2015
3 Gisselbrecht et al., 2010