Full Press Release Details
Announces Online Publication of LOTIS-2 Results in
of ZYNLONTA (loncastuximab tesirine-lpyl) was based on data from LOTIS-2
demonstrated substantial single-agent activity, durable responses and an acceptable safety profile in broad population of difficult-to-treat
patients with relapsed or refractory DLBCL
LAUSANNE, Switzerland, May 12, 2021
- ADC Therapeutics SA (NYSE: ADCT), a commercial-stage biotechnology company leading the development of novel antibody drug
conjugates (ADCs) to treat hematological malignancies and solid tumors, today announced that results of LOTIS-2, a multicenter, open-label,
single-arm Phase 2 clinical trial evaluating the safety and efficacy of single-agent ZYNLONTATM in adult patients with relapsed
or refractory diffuse large B-cell lymphoma (DLBCL) following two or more systemic treatments, have been published online in The Lancet
"Patients with relapsed or refractory
DLBCL who have been heavily pretreated and have difficult-to-treat disease represent an urgent area of medical need that newly approved
ZYNLONTA is now able to address," said Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive
Cancer Center, Case Western Reserve University and lead author of The Lancet Oncology paper. "The LOTIS-2 study
established that ZYNLONTA demonstrated substantial single-agent activity and produced durable responses with an acceptable safety profile
in this patient population."
LOTIS-2 enrolled 145 patients, including
those with high-risk characteristics for poor prognosis, such as double-/triple-hit, transformed, and primary refractory DLBCL. Key results
"We are proud to have the results
of our LOTIS-2 trial published in a prestigious peer-reviewed journal," said Jay Feingold, MD, PhD, Senior Vice President and Chief
Medical Officer at ADC Therapeutics. "On the heels of the FDA approval, this further reinforces the value of ZYNLONTA as the first
CD19-targeted ADC single-agent treatment for relapsed or refractory DLBCL and the potential for it to become the standard-of-care for
3L+ DLBCL patients in need of new treatment options."
The study can be found on The Lancet
Oncology's website at: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00139-X/fulltext.
About ADC Therapeutics
ADC Therapeutics (NYSE: ADCT) is a commercial-stage
biotechnology company improving the lives of cancer patients with its next-generation, targeted antibody drug conjugates (ADCs). The
Company is advancing its proprietary ADC technology to transform the treatment paradigm for patients with hematologic malignancies and
ADC Therapeutics' CD19-directed
ADC ZYNLONTA (loncastuximab tesirine-lpyl) is approved by the FDA for the treatment of relapsed or refractory diffuse large B-cell
lymphoma after two or more lines of systemic therapy. ZYNLONTA is also in late-stage clinical trials in combination with other agents.
Cami (camidanlumab tesirine) is being evaluated in a late-stage clinical trial for relapsed or refractory Hodgkin lymphoma and in a Phase
1b clinical trial for various advanced solid tumors. In addition to ZYNLONTA and Cami, the Company has multiple PBD-based ADCs in ongoing
clinical and preclinical development.
ADC Therapeutics is based in Lausanne
(Biop le), Switzerland and has operations in London, the San Francisco Bay Area and New Jersey. For more information, please visit
https://adctherapeutics.com/ and follow the Company on Twitter and LinkedIn.
ZYNLONTA is a trademark of ADC
About ZYNLONTA (loncastuximab
ZYNLONTATM is a CD19-directed
antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine
(PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms.
This ultimately results in cell cycle arrest and tumor cell death.
The U.S. Food and Drug Administration
(FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large
B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified
(NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. This indication is approved by the FDA under accelerated
approval based on overall response rate and continued approval for this indication may be contingent upon verification and description
of clinical benefit in a confirmatory trial.
The FDA approval was based on data from
LOTIS-2, a large (n=145) Phase 2 multinational, single-arm clinical trial of ZYNLONTA for the treatment of adult patients with r/r DLBCL
following two or more prior lines of systemic therapy. Results from the trial demonstrated an overall response rate (ORR) of 48.3% (70/145
patients), which included a complete response (CR) rate of 24.1% (35/145 patients) and a partial response (PR) rate of 24.1% (35/145
patients). Patients had a median time to response of 1.3 months and the median duration of response (mDoR) for the 70 responders was
10.3 months (inclusive of patients who were censored). In a pooled safety population the most common adverse reactions ( 20%) were
thrombocytopenia, gamma-glutamyltransferase increased, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia,
rash, edema, nausea and musculoskeletal pain. In LOTIS-2, the most common ( 10%) grade 3 treatment-emergent adverse events were
neutropenia (26.2%), thrombocytopenia (17.9%), gamma-glutamyltransferase increased (17.2%) and anemia (10.3%).
ZYNLONTA is also being evaluated as a
therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.
Important Safety Information
WARNINGS AND PRECAUTIONS
Serious effusion and edema occurred in
patients treated with ZYNLONTA. Grade 3 edema occurred in 3% (primarily peripheral edema or ascites) and Grade 3 pleural effusion occurred
in 3% and Grade 3 or 4 pericardial effusion occurred in 1%.
Monitor patients for new or worsening
edema or effusions. Withhold ZYNLONTA for Grade 2 or greater edema or effusion until the toxicity resolves. Consider diagnostic imaging
in patients who develop symptoms of pleural effusion or pericardial effusion, such as new or worsened dyspnea, chest pain, and/or ascites
such as swelling in the abdomen and bloating. Institute appropriate medical management for edema or effusions.
Treatment with ZYNLONTA can cause serious
or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Grade 3 or 4 neutropenia occurred in 32%, thrombocytopenia
in 20%, and anemia in 12% of patients. Grade 4 neutropenia occurred in 21% and thrombocytopenia in 7% of patients. Febrile neutropenia
Monitor complete blood counts throughout
treatment. Cytopenias may require interruption, dose reduction, or discontinuation of ZYNLONTA. Consider prophylactic granulocyte colony-stimulating
factor administration as applicable.
Fatal and serious infections, including
opportunistic infections, occurred in patients treated with ZYNLONTA. Grade 3 or higher infections occurred in 10% of patients, with
fatal infections occurring in 2%. The most frequent Grade 3 infections included sepsis and pneumonia.
Monitor for any new or worsening signs
or symptoms consistent with infection. For Grade 3 or 4 infection, withhold ZYNLONTA until infection has resolved.
Serious cutaneous reactions occurred
in patients treated with ZYNLONTA. Grade 3 cutaneous reactions occurred in 4% and included photosensitivity reaction, rash (including
exfoliative and maculo-papular), and erythema.
Monitor patients for new or worsening
cutaneous reactions, including photosensitivity reactions. Withhold ZYNLONTA for severe (Grade 3) cutaneous reactions until resolution.
Advise patients to minimize or avoid exposure to direct natural or artificial sunlight including exposure through glass windows. Instruct
patients to protect skin from exposure to sunlight by wearing sun-protective clothing and/or the use of sunscreen products. If a skin
reaction or rash develops, dermatologic consultation should be considered.
Embryo-Fetal Toxicity
Based on its mechanism of action, ZYNLONTA
can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (SG3199) and affects actively
Advise pregnant women of the potential
risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ZYNLONTA and for 9 months
after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment
with ZYNLONTA and for 6 months after the last dose.
In a pooled safety population of 215
patients (Phase 1 and LOTIS-2), the most common (>20%) adverse reactions, including laboratory abnormalities, were thrombocytopenia,
increased gamma-glutamyltransferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema,
nausea, and musculoskeletal pain.
In LOTIS-2, serious adverse reactions