Combination demonstrated clinically meaningful benefit in r/r FL patients with 96% overall response rate and 85% complete response rate
LAUSANNE, Switzerland, Dec. 12, 2023 (GLOBE NEWSWIRE) -- ADC Therapeutics SA (NYSE: ADCT) today announced initial results from an investigator-initiated Phase 2 clinical trial evaluating ZYNLONTA® (loncastuximab tesirine-lpyl) in combination with rituximab demonstrated a high response rate in patients with relapsed or refractory (r/r) follicular lymphoma (FL). The data from the single-institution study conducted at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine were reported during an oral presentation yesterday at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition by the study’s lead investigator, Juan Pablo Alderuccio, MD, associate professor of medicine and hematologist at Sylvester.
“In this first-ever study evaluating the combination of ZYNLONTA and rituximab in patients with relapsed or refractory follicular lymphoma, the overall response rate was 96% and complete response rate was 85%, with a significant number of patients achieving an early response,” said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. “We believe the high early response rates highlight the exciting potential of ZYNLONTA to be used in combination with an established therapy to improve the treatment paradigm for patients with high-risk follicular lymphoma, including those with POD24, high disease burden and/or advanced disease, whose disease progresses after first-line therapy.”
The trial is designed to evaluate the combination in patients with r/r FL treated with ≥1 line of systemic therapy presenting GELF criteria or POD24 at enrollment. The primary endpoint of the study is complete response (CR) by week 12 PET/CT based on Lugano 2014 criteria. As of the data cutoff date of November 26, 2023, 33 patients were enrolled out of a targeted 39 patients.
Patients were a median age of 68 years (range 47 to 89) and median lines of prior therapy were 1 (range 1-6). R-CHOP was the most common first-line therapy (n=18; 54.5%) followed by bendamustine with rituximab (n=8; 24.2%) and single-agent rituximab (n=6; 18.2%).
The initial results are based on an analysis of 27 patients evaluable for efficacy and 32 patients evaluable for toxicity. Highlights of the data presented at ASH include:
- Best overall response rate of 96.3% and CR rate of 85.2%
- After a median follow-up of 9.7 months, the median progression-free survival (PFS) was not reached, and the 12-month PFS was 92.3%
- Majority of adverse events (AEs) were grade 1. Grade 3 AEs included neutropenia (n=2; 6.2%), and one case each (3.1%) of hyperglycemia, increased ALT, fatigue, dyspnea and skin infection. Neutropenia was the only grade 4 AE (n=1; 3.1%).
“The relapsed or refractory follicular lymphoma patients enrolled in this trial represent a high-risk population in need of a safe and durable treatment option that improves outcomes,” said Dr. Alderuccio. “We are very encouraged by the high response rate produced by ZYNLONTA combined with rituximab in patients with a high disease burden and look forward to expanding the trial.”
Based on the initial results, the investigators are planning a multicenter clinical trial aiming to expand the current cohort and decrease the length of therapy to six cycles. The trial is expected to be launched in the first quarter of 2024.
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, the San Francisco Bay Area and New Jersey. For more information, please visit https://adctherapeutics.com/ and follow the Company 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: uncertainties related to the impact of IIT data in r/r follicular lymphoma presented at the 65th ASH Annual Meeting and future clinical trials and results in the same patient population, the success of the Company’s updated corporate strategy including operating efficiencies, capital deployment and portfolio prioritization; the Company’s ability to achieve the decrease in total operating expenses for 2023 and 2024, the expected cash runway into the middle of 2025, the effectiveness of the new commercial go-to-market strategy, competition from new technologies, the Company’s ability to continue to commercialize ZYNLONTA® in the United States and future revenue from the same; Swedish Orphan Biovitrum AB (Sobi®) ability to successfully commercialize ZYNLONTA® in the European Economic Area and market acceptance, adequate reimbursement coverage, and future revenue from the same; approval by the NMPA of the BLA for ZYNLONTA in China submitted by Overland ADCT BioPharma and future revenue from the same, our strategic partners’, including Mitsubishi Tanabe Pharma Corporation, ability to obtain regulatory approval for ZYNLONTA® in foreign jurisdictions, and the timing and amount of future revenue and payments to us from such partnerships; the Company’s ability to market its products in compliance with applicable laws and regulations; the Company’s expectations regarding the impact of the Infrastructure Investment and Jobs Act; the timing and results of the Company’s or its partners’ research projects or clinical trials including LOTIS 5 and 7, ADCT 901, 601 and 602, the impact, if any, from discontinuation of the LOTIS-9 study, actions by the FDA or foreign regulatory authorities with respect to the Company’s products or product candidates, the timing and outcome of regulatory submissions for the Company’s products or product candidates; the ability to complete clinical trials on expected timelines, if at all; 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 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 20-F and in the Company's other periodic reports and filings with the 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. The Company undertakes no obligation to revise or update these forward-looking statements to reflect events or circumstances after the date of this press release, except as required by law.
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