Publication follows oral presentation at the
American Society of Hematology (ASH) Annual Meeting
Combination in r/r follicular lymphoma
shows best ORR of 97% and CR rate of 77% with 12-month PFS
of 95%
Additional IIT data also presented at ASH on
ZYNLONTA monotherapy in marginal zone lymphoma shows
ORR of 91% and 70% CR
LAUSANNE, Switzerland, Dec. 9, 2024
/PRNewswire/ -- ADC Therapeutics SA (NYSE: ADCT), a
commercial-stage global leader and pioneer in the field of antibody
drug conjugates (ADCs), today announced updated data from the
investigator-initiated Phase 2 clinical trial evaluating
ZYNLONTA® (loncastuximab tesirine-lpyl) in
combination with rituximab to treat relapsed or refractory (r/r)
follicular lymphoma (FL) were published in the December issue of
The Lancet Haematology, following an oral presentation of
the data at the recent 66th American Society of
Hematology (ASH) Annual Meeting and Exposition.
"We are excited by the publication of these results in The
Lancet Haematology demonstrating ZYNLONTA's robust clinical
activity in follicular lymphoma, particularly in patients
classified as high-risk POD24 and those with high tumor burden
where there remains significant unmet need," said Mohamed Zaki, MD, PhD, Chief Medical Officer of
ADC Therapeutics. "In addition, encouraging data from another
investigator-initiated trial of ZYNLONTA as a single agent to treat
marginal zone lymphoma were also presented at ASH. Collectively, we
believe these data underscore ZYNLONTA's promise for patients with
indolent B-cell lymphomas and add to a growing body of evidence
showing the potential of ZYNLONTA beyond diffuse large B-cell
lymphoma."
ZYNLONTA in combination with rituximab to treat r/r
follicular lymphoma (FL)
The investigator-initiated
trial conducted at the Sylvester Comprehensive Cancer Center
at the University of Miami Miller
School of Medicine evaluated the combination in patients with r/r
FL treated with ≥1 line of systemic therapy presenting high-disease
burden as defined by GELF criteria or POD24 at enrollment. The
primary endpoint of the study is complete response rate (CR) by
week 12 PET/CT based on Lugano 2014 criteria. The trial enrolled 39
patients, all of which were evaluated for safety and 35 of which
were evaluated for efficacy.
Patients were a median age of 68 years (range 47 to 89) and the
majority received one previous line of therapy (n=26; 67%). R-CHOP
was the most common first-line therapy (n=22; 56%) followed by
bendamustine with rituximab (n=10; 26%), single-agent rituximab
(n=6; 15%) and fludarabine, mitoxantrone and dexamethasone (n=1;
3%).
Highlights from the results published in The Lancet
Haematology included:
- Best overall response rate (ORR) of 97.4% (n=38) and CR rate of
76.9% (n=30)
- After a median follow-up of 15.6 months, the median
progression-free survival (PFS) was not reached, and the 12-month
PFS was 94.6%
- The most common treatment-emergent adverse events (TEAEs) were
hyperglycemia (n=17; 43.6%) followed by increased alkaline
phosphatase (n=16; 41%) and neutropenia, fatigue and increased
aspartate aminotransferase and alanine aminotransferase (n=15;
38.5%)
- The most common grade ≥3 TEAE were lymphopenia (n=8; 20.5%)
followed by neutropenia (n=5; 12.9%)
- No Grade 5 TEAEs occurred.
The publication titled, "Loncastuximab tesirine with rituximab
in patients with relapsed or refractory follicular lymphoma: a
single centre, single arm Phase 2 trial," is now available online
and will be published in the December issue of The Lancet
Haematology. The results were also presented during a
session on indolent B-cell lymphomas at ASH by Juan Pablo Alderuccio, MD, lead investigator and
Associate Professor of Medicine and Hematologist at Sylvester. More
details on the trial can be found
at https://clinicaltrials.gov/ (identifier: NCT04998669).
ZYNLONTA as a single agent to treat r/r marginal zone
lymphoma (MZL)
Data from an open-label, multi-institutional
investigator-initiated trial evaluating the safety and efficacy of
ZYNLONTA in 23 adult r/r MZL patients, previously treated with ≥1
line of systemic therapy, were also shared as a poster presentation
at ASH by lead investigator, Izidore
Lossos, MD, Professor of Medicine and Chief of the Lymphoma
Section of the Division of Hematology at the Sylvester
Comprehensive Cancer Center, University of
Miami. The median age in this study was 65 years (range
45-82). The median number of previous treatments was 2 (range 1 to
4).
As of October 15, 2024, 23
patients were evaluable for response. Highlights from the results
presented include:
- ORR of 91% (n=21); 70% CR (n=16). ZYNLONTA led to CR in 7 of 11
patients (64%) with POD24 assessed for response and one patient who
progressed after CAR-T.
- All but 1 CR are currently maintained with the longest
follow-up of 27 months from the start of treatment (median duration
of CR is 11.5 months).
- All of the 23 enrolled patients experienced expected adverse
events (AE), most commonly grade 1 or 2. Grade 3 and 4 AEs were
observed in 15 and 1 (neutropenia) patients, respectively. Local
edema was observed in 10 (43.4%) patients. Three patients needed
dose reduction and one patient discontinued treatment after cycle 4
because of cholestatic hepatitis. The patient clinically fully
recovered with normalization in liver function test
abnormalities.
More details on this ongoing Phase 2 clinical trial can be found
at https://clinicaltrials.gov/ (identifier: NCT05296070).
About ZYNLONTA® (loncastuximab
tesirine-lpyl)
ZYNLONTA® 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) and the European
Medicines Agency (EMA) have 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. The trial included a
broad spectrum of heavily pre-treated patients (median three prior
lines of therapy) with difficult-to-treat disease, including
patients who did not respond to first-line therapy, patients
refractory to all prior lines of therapy, patients with
double/triple hit genetics and patients who had stem cell
transplant and CAR-T therapy prior to their treatment with
ZYNLONTA. This indication is approved by the FDA under accelerated
approval and in the European Union under conditional 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. Please see full prescribing
information including important safety information about ZYNLONTA
at www.ZYNLONTA.com.
ZYNLONTA is also being evaluated as a therapeutic option in
combination studies in other B-cell malignancies and earlier lines
of therapy.
About ADC Therapeutics
ADC Therapeutics (NYSE: ADCT)
is a commercial-stage global leader and pioneer in the field of
antibody drug conjugates (ADCs). The Company is advancing its
proprietary ADC technology to transform the treatment paradigm for
patients with hematologic malignancies and solid tumors.
ADC Therapeutics' CD19-directed ADC ZYNLONTA (loncastuximab
tesirine-lpyl) received accelerated approval by the FDA and
conditional approval from the European Commission for the treatment
of relapsed or refractory diffuse large B-cell lymphoma after two
or more lines of systemic therapy. ZYNLONTA is also in development
in combination with other agents and in earlier lines of therapy.
In addition to ZYNLONTA, ADC Therapeutics has multiple ADCs in
ongoing clinical and preclinical development.
ADC Therapeutics is based in Lausanne (Biopôle), Switzerland, and has operations in
London and New Jersey. For more information, please visit
the Company website at adctherapeutics.com and follow us on
LinkedIn.
ZYNLONTA® is a registered trademark of ADC Therapeutics SA.
Forward-Looking Statements
This press release contains forward-looking statements within the
meaning of the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995. In some cases you can identify
forward-looking statements by terminology such as "may", "will",
"should", "would", "expect", "intend", "plan", "anticipate",
"believe", "estimate", "predict", "potential", "seem", "seek",
"future", "continue", or "appear" or the negative of these terms or
similar expressions, although not all forward-looking statements
contain these identifying words. Forward-looking statements are
subject to certain risks and uncertainties that can cause actual
results to differ materially from those described. Factors that may
cause such differences include, but are not limited to: whether the
interim results for the investigator-initiated trials led by the
University of Miami studying FL and MZL
are predictive of future results and the timing and success of the
same IIT trials, the potential regulatory and/or compendia strategy
and the future opportunity for FL and MZL; the expected cash runway
into mid-2026 the Company's ability to grow ZYNLONTA® revenue in
the United States; the ability of
our partners to commercialize ZYNLONTA® in foreign markets, the
timing and amount of future revenue and payments to us from such
partnerships and their ability to obtain regulatory approval for
ZYNLONTA® in foreign jurisdictions; the timing and results of the
Company's or its partners' research and development projects or
clinical trials including LOTIS 5 and
7, ADCT 602 as well as early research in certain solid tumors with
different targets, linkers and payloads; the timing and outcome of
regulatory submissions for the Company's products or product
candidates; actions by the FDA or foreign regulatory authorities;
projected revenue and expenses; the Company's indebtedness,
including Healthcare Royalty Management and Blue Owl and Oaktree
facilities, and the restrictions imposed on the Company's
activities by such indebtedness, the ability to comply with the
terms of the various agreements and repay such indebtedness and the
significant cash required to service such indebtedness; and the
Company's ability to obtain financial and other resources for its
research, development, clinical, and commercial activities.
Additional information concerning these and other factors that may
cause actual results to differ materially from those anticipated in
the forward-looking statements is contained in the "Risk Factors"
section of the Company's Annual Report on Form 10-K and in the
Company's other periodic and current reports and filings with the
U.S. Securities and Exchange Commission. These statements involve
known and unknown risks, uncertainties and other factors that may
cause actual results, performance, achievements or prospects to be
materially different from any future results, performance,
achievements or prospects expressed in or implied by such
forward-looking statements. The Company cautions investors not to
place undue reliance on the forward-looking statements contained in
this document.
CONTACTS:
Investors
Marcy
Graham
ADC Therapeutics
Marcy.Graham@adctherapeutics.com
+1 650-667-6450
Media
Nicole Riley
ADC Therapeutics
Nicole.Riley@adctherapeutics.com
+1 862-926-9040
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