Dose escalation in Phase 1b trial completed with no dose-limiting toxicities, no or low-grade cytokine release syndrome and no immune effector cell-associated neurotoxicity syndrome across all patients and early signs of anti-tumor activity
Enrollment in Part 2 dose expansion has been initiated
LAUSANNE, Switzerland, April 04, 2024 (GLOBE NEWSWIRE) -- ADC Therapeutics SA (NYSE: ADCT) today announced the completion of dose escalation in LOTIS-7, a Phase 1b open-label clinical trial evaluating ZYNLONTA® (loncastuximab tesirine-lpyl) in combination with bispecific antibodies glofitamab or mosunetuzumab in heavily pre-treated patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL).
In the dose escalation portion (Part 1) of LOTIS-7, no dose-limiting toxicities (DLTs), no or low-grade cytokine release syndrome (CRS) and no immune effector cell-associated neurotoxicity syndrome (ICANS) were observed across all patients when ZYNLONTA was administered in combination with glofitamab or mosunetuzumab. Additionally, after the first investigator assessment, evidence of anti-tumor activity was observed among the majority of patients, with mixed histologies including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and marginal zone lymphoma (MZL). Based on the data from Part 1, all three dose levels (90, 120 and 150 µg/kg) have now been cleared and enrollment in Part 2 dose expansion has been initiated with ZYNLONTA administered in combination with glofitamab at the 120 µg/kg and 150 µg/kg dose levels in 2L+ DLBCL.
“The early data from Part 1 of our LOTIS-7 trial highlight the potential combinability of ZYNLONTA with bispecifics in lymphoma patients,” said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. “We look forward to the continued progression of this trial in 2L+ DLBCL patients.”
“CRS is a common toxicity associated with the CAR-T and bispecific therapies currently used to treat lymphoma,” said Juan Pablo Alderuccio, MD, lead investigator of the LOTIS-7 trial and Associate Professor in the Division of Hematology at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine. “The potential for ZYNLONTA in combination with bispecifics to treat 2L+ relapsed or refractory B-NHL with the favorable toxicity profile observed thus far is encouraging given the unmet medical need in this area.”
“With no or low grades of CRS and no ICANS observed among patients in Part 1 of the study, we believe LOTIS-7 demonstrates the potential for ZYNLONTA plus bispecifics to enable broader accessibility in community settings,” said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. “Based upon the current data and coupled with the potential for additive or even synergistic efficacy with this combination, we continue to be excited about the opportunity to expand the use of ZYNLONTA in DLBCL in the future where there remains high unmet need.”
LOTIS-7 is a Phase 1b global multicenter, multi-arm study in patients with relapsed or refractory B-cell non-Hodgkin lymphoma 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. The dose-limiting toxicity period has now been cleared across all three dose levels.
For more information about the LOTIS-7 trial, visit clinicaltrials.gov (NCT04970901).
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 high-grade B-cell lymphoma. The LOTIS-2 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: the timing and results of the LOTIS-7 study including Part 2, does expansion, the effectiveness of the new commercial go-to-market strategy, competition from new technologies, and the Company’s ability to grow ZYNLONTA® revenue in the United States; 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 timing and future results from the University of Miami’s IITs in FL and MZL lymphomas; the timing and results of the Company’s or its partners’ clinical trials including LOTIS 5 and 7, ADCT 601 and 602 as well as the Company’s early-stage pipeline research projects, actions by the FDA or foreign regulatory authorities with respect to the Company’s products or product candidates; projected revenue and expenses; the Company’s indebtedness, including Healthcare Royalty Management and Oaktree and Blue Owl 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 10-K 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.
CONTACT:
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Nicole Riley
ADC Therapeutics
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