LOTIS-5: Updated safety run-in results from Phase 3 trial demonstrate 80% ORR, 50% CR rate and median DoR of 8 months with no new safety signals
LOTIS-7: Study design of trial evaluating ZYNLONTA® in patients with r/r non-Hodgkin lymphoma to be highlighted in poster; actively enrolling patients in bispecific combination arms
LAUSANNE, Switzerland, Aug. 30, 2023 (GLOBE NEWSWIRE) -- ADC Therapeutics SA (NYSE: ADCT) today announced that two ZYNLONTA® (loncastuximab tesirine-lpyl) abstracts have been accepted for presentation at the Eleventh Annual Meeting of the Society of Hematologic Oncology (SOHO 2023), which will be held in Houston, Texas from September 6-9, 2023.
“We are very pleased with the progress of our ongoing ZYNLONTA development programs. For LOTIS-5, the Phase 3 study evaluating the combination of ZYNLONTA with rituximab, we are encouraged by the updated safety run-in results being presented at SOHO 2023. The data show signs of durable responses in patients with relapsed or refractory diffuse large B-cell lymphoma and, importantly, no new safety signals,” said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. “As for the LOTIS-7 Phase 1b clinical trial that is evaluating ZYNLONTA in combination with other anticancer agents, the bispecific arms are actively enrolling patients, and we will be sharing more details about the study at SOHO 2023.”
Michal Kwiatek, MD, PhD, Medical Director, Centrum Medyczne Pratia Poznan, Skorzewo, Poland and lead author of the LOTIS-5 abstract, said, “Although still early, the updated data from the safety run-in of the LOTIS-5 study look promising. The combination of ZYNLONTA and rituximab is a systemic chemo-free regimen with a fixed treatment duration, making it an appealing alternative to continuous therapies.”
LOTIS-5 Safety Run-In Results:
LOTIS-5 is a Phase 3, randomized, open‐label, two‐part, two‐arm, multicenter study of loncastuximab tesirine in combination with rituximab (Lonca-R) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). It is the confirmatory trial for accelerated approval for 3L+ and would also support potential label expansion into 2L+ in combination with rituximab. Twenty patients were enrolled in part 1 of a non-randomized safety run‐in. In part 2, approximately 330 patients will be randomized 1:1 to receive fixed-dose Lonca‐R or rituximab‐gemcitabine‐oxaliplatin (R‐GemOx).
The 20 patients in the safety run‐in were a median age of 74.5 years and had previously received a median of five cycles of Lonca-R and one previous therapy. As of the April 10, 2023, data cutoff:
- Seven patients completed treatment and five continue in follow-up.
- The overall response rate by central review was 16/20 (80%). A total of 10/20 (50%) and 6/20 (30%) patients attained complete and partial response, respectively.
- The median duration of response was 8.0 months and the median progression-free survival was 8.3 months.
- A total of 11 (55%) patients had grade ≥3 treatment-emergent adverse events (TEAEs). The most common grade ≥3 TEAEs were increased gamma-glutamyltransferase (5 patients [25%]) and neutropenia (3 patients [15%]).
These data will be presented in the following poster:
Updated Results of the Safety Run-in of the Phase 3 LOTIS-5 Trial: Novel Combination of Loncastuximab Tesirine With Rituximab (Lonca-R) Versus Immunochemotherapy in Patients With R/R DLBCL
Date and Time: Wednesday, September 6, 2023, 6:00-7:00PM CT
Location: George R. Brown Convention Center, Level 3, Grand Ballroom
Poster Number: ABCL-515
LOTIS-7:
Details of ADC Therapeutics’ poster highlighting the LOTIS-7 trial design are as follows:
Phase Ib Open-Label Study of Loncastuximab Tesirine in Combination With Other Anticancer Agents in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)
Date and Time: Wednesday, September 6, 2023, 6:00-7:00PM CT
Location: George R. Brown Convention Center, Level 3, Grand Ballroom
Poster Number: ABCL-134
LOTIS-7 is a multicenter and multi-arm study that will enroll approximately 200 patients with relapsed or refractory B-cell non-Hodgkin lymphoma in part 1 (dose escalation in approximately 60 patients) and part 2 (dose expansion in approximately 120 patients). Dosing arms include ZYNLONTA (loncastuximab tesirine-lpyl) plus polatuzumab vedotin, as well as ZYNLONTA (loncastuximab tesirine-lpyl) plus glofitamab and mosunetuzumab, t-cell-engaging bispecific monoclonal antibodies (BsAbs).
The bispecific combination arms of the LOTIS-7 trial are now actively enrolling patients with DLBCL, including transformed follicular lymphoma (FL), high-grade B-cell lymphoma (HGBCL), follicular lymphoma (FL) and marginal zone lymphoma (MZL). Combining these agents with different mechanisms of action has the potential to have increased activity compared to either agent alone.
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. For complete prescribing information including important safety information, please see https://www.adctherapeutics.com/wp-content/uploads/2022/10/ZYLONTA-PI_October-2022_LOCKED.pdf.
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 biotechnology company improving the lives of those affected by cancer with its next-generation, targeted antibody drug conjugates (ADCs). The Company is advancing its proprietary PBD-based ADC technology to transform the treatment paradigm for patients with hematologic malignancies and solid tumors.
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 development in combination with other agents. 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: future timing, results and outcomes of the LOTIS 5 and 7 studies; the success of the Company’s updated corporate strategy including operating efficiencies, capital deployment and portfolio prioritization; the Company’s ability to achieve the 2023 net product sales guidance for ZYNLONTA® and 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’s (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.
CONTACTS:
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Eugenia Litz
ADC Therapeutics
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ADC Therapeutics
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