Full Press Release Details
Announces FDA Approval of ZYNLONTA (loncastuximab tesirine-lpyl) in Relapsed or Refractory Diffuse Large B-Cell Lymphoma
CD19-targeted antibody drug conjugate (ADC) as a single-agent treatment for adult patients with relapsed or refractory (r/r) diffuse
large B-cell lymphoma (DLBCL)
an unmet need across a broad population of third-line (3L)+ r/r patients, including patients with DLBCL not otherwise specified, DLBCL
arising from low grade lymphoma and high-grade B-cell lymphoma
ZYNLONTA demonstrated
48.3% overall response rate, 24.1% complete response rate and durable responses in heavily pretreated patients in pivotal LOTIS-2 trial
call and webcast to be held Friday, April 23rd at 4 p.m. ET
LAUSANNE, Switzerland, April 23, 2021
- ADC Therapeutics SA (NYSE: ADCT) today announced that 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 high-grade B-cell lymphoma.1 ZYNLONTA, a CD19-targeted antibody drug conjugate (ADC), has been granted
accelerated approval by the FDA based on overall response rate. Continued approval for this indication may be contingent upon verification
and description of clinical benefit in a confirmatory trial.
"There is a significant unmet need
for treatment options for patients with r/r DLBCL, including those who have been heavily pretreated and have difficult-to-treat disease,"
said Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University.
"Single-agent ZYNLONTA demonstrated clinically important outcomes in the pivotal LOTIS-2 study across several disease subtypes.
Notably, this included transplant eligible and ineligible patients and patients who previously received stem cell transplant or CAR-T
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%).
"The FDA approval of ZYNLONTA is
an exciting advancement for patients with r/r DLBCL and a transformational event for ADC Therapeutics," said Chris Martin, Chief
Executive Officer of ADC
Therapeutics. "We extend our deepest
gratitude to the patients who participated in our LOTIS-1 and LOTIS-2 clinical trials, their families, the study investigators and our
employees, as their commitment made this important milestone possible."
DLBCL, the most common type of non-Hodgkin
lymphoma in the United States, is a rapidly progressing, aggressive disease that is heterogeneous with multiple subtypes.2
More than 40% of first-line DLBCL treatments fail.3 For patients who fail first-line therapy, prognoses are poor, worsening
with each line of therapy as the chance for cure or long-term disease-free survival diminishes.4,5
ZYNLONTA will be commercially available
in the United States shortly. ADC Therapeutics has launched the Advancing Patient Support Program, a comprehensive patient support program
offering financial assistance, ongoing education and other resources to eligible patients who are prescribed ZYNLONTA.
Please see full Prescribing Information
at www.adctherapeutics.com for ZYNLONTA.
Conference Call Details
ADC Therapeutics management will host
a conference call and live audio webcast on Friday, April 23, 2021 at 4 p.m. ET. To access the live call, please dial (833) 303-1198
(domestic) or +1 914 987 7415 (international) and provide conference ID 6867157. The live webcast will be available under "Events
& Presentations" in the Investors section of the ADC Therapeutics website at ir.adctherapeutics.com.
The archived webcast will be available for 30 days following the call.
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
occurred in 28% of patients receiving ZYNLONTA. The most common serious adverse reactions that occurred in 2% receiving ZYNLONTA
were febrile neutropenia, pneumonia, edema, pleural effusion, and sepsis. Fatal adverse reactions occurred in 1%, due to infection.
Permanent treatment discontinuation due
to an adverse reaction of ZYNLONTA occurred in 19% of patients. Adverse reactions resulting in permanent discontinuation of ZYNLONTA
in 2% were gamma-glutamyltransferase increased, edema, and effusion.
Dose reductions due to an adverse reaction
of ZYNLONTA occurred in 8% of patients. Adverse reactions resulting in dose reduction of ZYNLONTA in 4% was gamma-glutamyltransferase
Dosage interruptions due to an adverse
reaction occurred in 49% of patients receiving ZYNLONTA. Adverse reactions leading to interruption of ZYNLONTA in 5% were gamma-glutamyltransferase
increased, neutropenia, thrombocytopenia, and edema.