Loncastuximab tesirine

ZYNLONTA in combination with glofitamab demonstrated clinically meaningful benefit with 94% best ORR and 72% CR rate Safety data show no dose-limiting toxicities (DLTs), no high-grade cytokine release syndrome (CRS) or high-grade immune effector cell-associated neurotoxicity syndrome (ICANS) across all patients Company to host conference call today at 8:30 a.m. EST LAUSANNE, Switzerland I December 11, 2024 I ADC Therapeutics SA (NYSE: ADCT ), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), today announced positive initial data from the LOTIS-7 Phase 1b open-label clinical trial evaluating the safety and efficacy of ZYNLONTA ® in combination with the bispecific antibody glofitamab (COLUMVI ™ ) in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). “We are excited by the strong initial results observed with ZYNLONTA plus glofitamab in second line plus patients with relapsed or refractory DLBCL,” said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. “We believe these data support our hypothesis that combining these two potent, approved, single-agent-drugs with complementary mechanisms of action will yield additive or synergistic efficacy, and a manageable safety profile given no overlapping non-hematologic toxicities, enabling administration across care settings. We are encouraged by the initial promising safety and efficacy data at both doses tested in the expansion arm.” Initial Clinical Data from Phase 1b LOTIS-7 Trial LOTIS-7 is an ongoing Phase 1b global multicenter, multi-arm study in patients with relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) including Part 1 (dose escalation) and Part 2 (dose expansion). As of the November 20, 2024 cutoff date, a total of 29 B-NHL patients from Part 1 and Part 2 across all dose levels were treated and evaluated for safety. An initial efficacy analysis was conducted on all 18 evaluable 2L+ DLBCL patients who received dose levels of 120 µg/kg (n=9) or 150 µg/kg (n=9) of ZYNLONTA plus the bispecific antibody glofitamab: Encouraging efficacy data was observed across patients with different numbers of lines and types of prior treatments and across different histologies. Initial safety data on all 29 patients suggest that ZYNLONTA plus glofitamab is generally well tolerated with no DLTs across all dose levels: “These compelling initial results support the potential of ZYNLONTA plus the bispecific glofitamab to be a best-in-class combination in a highly competitive market,” said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. “We look forward to completing enrollment of dose expansion in the first half of 2025 and plan to engage with regulatory authorities on the path forward as data including additional patients with longer follow-up become available.” Conference Call Information To access the conference call, please register here . The participant toll-free dial-in number is 1-800-836-8184 for North America and Canada. It is recommended that you join 10 minutes before the event, though you may pre-register at any time. A live webcast of the call will be available under “Events and 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. About LOTIS-7 LOTIS-7 is a Phase 1b global multicenter, multi-arm study in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) including Part 1 (dose escalation) and Part 2 (dose expansion). The three dosing arms include ZYNLONTA plus polatuzumab vedotin, ZYNLONTA plus glofitamab, and ZYNLONTA plus mosunetuzumab T-cell-engaging bispecific monoclonal antibodies (BsAbs). Enrollment in LOTIS-7 includes Part 1 of the study with a 3+3 dose escalation in 3L/3L+ heavily pre-treated patients with ZYNLONTA doses starting at 90 µg/kg and then proceeding to 120 µg/kg and 150 µg/kg. Part 2 includes dose expansion in 2L/2L+ large B-cell lymphoma in the ZYNLONTA plus glofitamab arm at dose levels determined from Part 1 (120 µg/kg and 150 µg/kg of ZYNLONTA plus the approved dosing of glofitamab). Primary endpoints of the study include safety and tolerability. Secondary efficacy endpoints include ORR, DOR, CRR, PFS, RFS, and OS as well as pharmacokinetics and immunogenicity. For more information about the LOTIS-7 trial, visit clinicaltrials.gov (NCT04970901). 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 https://adctherapeutics.com/ and follow the Company on LinkedIn . ZYNLONTA ® is a registered trademark of ADC Therapeutics SA. SOURCE: ADC Therapeutics

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 (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 (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 . 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 [email protected] +1 650-667-6450 Media Nicole Riley ADC Therapeutics [email protected] +1 862-926-9040 SOURCE ADC Therapeutics SA WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED