ADC Therapeutics Announces The Lancet Haematology Publication of Data from Investigator-Initiated Trial Evaluating ZYNLONTA® in Combination with Rituximab to Treat Relapsed/Refractory Follicular Lymphoma

Rhea-AI Summary

ADC Therapeutics announced updated data from two clinical trials evaluating ZYNLONTA®. In the first trial, ZYNLONTA combined with rituximab for relapsed/refractory follicular lymphoma showed a 97.4% overall response rate and 76.9% complete response rate, with 12-month progression-free survival of 94.6%. The study enrolled 39 patients with a median age of 68 years.

In the second trial, ZYNLONTA as monotherapy for relapsed/refractory marginal zone lymphoma demonstrated a 91% overall response rate and 70% complete response rate in 23 patients. The median duration of complete response was 11.5 months, with the longest follow-up at 27 months.

Positive

• High efficacy in follicular lymphoma with 97.4% ORR and 76.9% CR rate
• Strong 12-month progression-free survival rate of 94.6%
• Impressive results in marginal zone lymphoma with 91% ORR and 70% CR rate
• Durable responses with median CR duration of 11.5 months in MZL

Negative

• Treatment-related adverse events reported in all patients in MZL trial
• One patient discontinued treatment due to cholestatic hepatitis
• 43.6% of FL patients experienced hyperglycemia

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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 66^th 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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FAQ

What were the efficacy results for ZYNLONTA plus rituximab in follicular lymphoma?

The combination showed a 97.4% overall response rate and 76.9% complete response rate, with 12-month progression-free survival of 94.6%.

What were the main side effects of ZYNLONTA in the follicular lymphoma trial (ADCT)?

The most common side effects were hyperglycemia (43.6%), increased alkaline phosphatase (41%), and neutropenia, fatigue, and increased liver enzymes (38.5% each).

How effective was ZYNLONTA as monotherapy in marginal zone lymphoma?

ZYNLONTA showed a 91% overall response rate and 70% complete response rate in marginal zone lymphoma patients, with responses lasting up to 27 months.