ADC Therapeutics Announces Updated Data from LOTIS-7 Clinical Trial Presented at the European Hematology Association 2025 Congress

Rhea-AI Summary

ADC Therapeutics announced updated data from the LOTIS-7 Phase 1b trial evaluating ZYNLONTA in combination with glofitamab for relapsed/refractory DLBCL patients. The combination demonstrated remarkable efficacy with a 93.3% overall response rate and 86.7% complete response rate among 30 evaluable patients. Notably, 25 of 26 patients achieving complete response maintained it at data cutoff. The treatment showed a manageable safety profile across 41 safety-evaluable patients, with main grade 3+ adverse events including neutropenia (24.4%) and anemia (9.8%). Based on these promising results, the company is expanding the trial enrollment to 100 patients at the 150 µg/kg dose level.

Positive

• High efficacy with 93.3% overall response rate and 86.7% complete response rate in r/r DLBCL patients
• Strong durability of response with 25 of 26 complete responders maintaining their response
• Effective even in CAR-T treated patients with 5 of 6 achieving complete response
• Manageable safety profile with no Grade 5 adverse events
• Trial expansion to 100 patients indicates confidence in treatment potential

Negative

• Treatment-related adverse events led to discontinuation in 6 patients
• Notable occurrence of cytokine release syndrome in both dosing groups
• Presence of Grade 3 or higher adverse events including neutropenia (24.4%) and anemia (9.8%)

Insights

Clinical Oncology Expert

ADC's ZYNLONTA + glofitamab combo shows remarkable 93.3% response rate in difficult-to-treat lymphoma with manageable safety profile.

The updated LOTIS-7 trial data for ZYNLONTA in combination with glofitamab presents exceptionally strong efficacy signals in relapsed/refractory DLBCL patients. The 93.3% overall response rate and 86.7% complete response rate across 30 evaluable patients are truly remarkable metrics for this difficult-to-treat population. Most impressive is the durability shown, with 25 of 26 complete responders maintaining their response at data cutoff.

The efficacy in post-CAR-T patients (5 of 6 achieving complete response) is particularly noteworthy, as these represent some of the most challenging cases with few remaining options. This suggests the combination could potentially address a significant unmet need in treatment-resistant lymphoma.

The safety profile appears manageable with primarily hematologic adverse events, which is expected with these therapies. The reported cytokine release syndrome was predominantly low-grade, though higher frequency at the 120 µg/kg dose versus the 150 µg/kg dose is interesting and somewhat counterintuitive. This warrants monitoring in the expanded cohort.

The company's decision to expand enrollment to 100 patients at the 150 µg/kg dose indicates confidence in both the efficacy and tolerability at this dose level. The faster median time to complete response at the higher dose (42 days vs. 80 days) further supports this decision and suggests potential for improved patient outcomes.

The conversion of 12 patients from stable disease or partial response to complete response over time highlights the profound activity of this combination and suggests that early response assessments may underestimate the full benefit of this treatment approach in DLBCL.

ZYNLONTA^® in combination with glofitamab (COLUMVI^®) in patients with r/r DLBCL demonstrated clinically meaningful benefit with overall response rate (ORR) of 93.3% and a complete response (CR) rate of 86.7% across 30 efficacy evaluable patients

25 of 26 patients achieving CR remained in CR as of the data cut-off

Initial data show the combination is generally well tolerated with a manageable safety profile

Company expanding enrollment for LOTIS-7 to 100 patients at 150 µg/kg dose

Company to host conference call today at 8:00 a.m. ET/2:00 p.m. CEST

LAUSANNE, Switzerland, June 12, 2025 /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 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) to be presented at the European Hematology Association 2025 Congress (EHA2025) in Milan, Italy. The Company will host a conference call and webcast featuring LOTIS-7 trial principal investigator and EHA presenting author, Juan Alderuccio, MD, Clinical Site Disease Group Leader, Lymphoma Section, at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine today at 8:00 a.m. ET to discuss the results. To access the conference call, please register here.

"The data seen in this study with the combination of ZYNLONTA and glofitamab has shown a manageable safety profile along with strong efficacy data from patients with relapsed or refractory DLBCL, with complete responses observed regardless of prior therapy, including CAR-T," said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. "The combination of these two anti-cancer agents holds significant promise for advancing the treatment landscape and addressing unmet need in patients with these hard-to-treat lymphomas."

The presentation highlights updated data as of April 14, 2025, in which r/r LBCL patients received dose levels of 120 µg/kg or 150 µg/kg of ZYNLONTA plus the bispecific antibody glofitamab, with 41 patients evaluable for safety and 30 patients evaluable for efficacy.

Key highlights of the LOTIS-7 data presentation are as follows:

• Best overall response data among the 30 efficacy evaluable patients shows overall response rate (ORR) of 93.3% (28/30 pts) as assessed by Lugano Criteria
• Complete response (CR) rate of 86.7% (26/30 pts)
  • Of these, 25/26 patients achieving CR remain in CR as of the data cut-off
    • Median time to CR in 120 µg/kg = 80 days
    • Median time to CR in 150 µg/kg = 42 days

• 12 patients converted from stable disease (SD) or partial response (PR) to CR over time (1 and 11 pts respectively)
• Of the 6 patients previously treated with CAR-T and undergoing response assessment, 5 achieved a CR
• Among the 41 safety evaluable patients, the combination was generally well tolerated with a manageable safety profile and no DLTs across dose levels
  • Grade 3 or higher treatment emergent adverse events (TEAEs) observed in > 5% of patients included neutropenia (24.4%), anemia (9.8%), AST increased (7.3%), GGT increased (7.3%), and thrombocytopenia (7.3%)
  • In the 150 µg/kg dose, cytokine release syndrome (CRS) (23.8%), all of which were Grade 1, and immune effector cell-associated neurotoxicity syndrome (ICANS) (4.8%), with one case of Grade 2, were observed
  • In the 120 µg/kg dose, CRS all grades (55%), all of which were Grade 1/2 except one case of Grade 3, and ICANS (10%), with one case of Grade 1 and one case of Grade 2, were observed
  • TEAEs leading to discontinuation included 3 each for ZYNLONTA and glofitamab
  • There were no Grade 5 TEAEs observed

"We believe these new data are differentiating and further reinforce the potential of ZYNLONTA plus the bispecific glofitamab to improve outcomes for DLBCL patients who need it most," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "This early safety and efficacy data support the ongoing expansion of this study to 100 patients at the 150 µg/kg dose of ZYNLONTA plus glofitamab. We look forward to discussing the results with Dr. Alderuccio during our conference call today in addition to the presentation of the data set across two key conferences."

This data will be shared at EHA2025 during a poster presentation on June 14 at 6:30 p.m. CEST and also as an oral encore presentation at the 18th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland on Friday, June 20 at 9:00 a.m. ET. The Company plans to share additional data before the end of 2025.

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 ZYNLONTA^®
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 biotechnology company helping to improve the lives of those affected by cancer with its next-generation, targeted 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.

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, including statements regarding the potential of ZYNLONTA^® in combination with the bispecific antibody glofitamab, including the reproducibility and durability of any favorable results initially seen in patients dosed to date, and the Company's research, development and regulatory plans, including the timing and results of clinical trials and the timing and outcome of regulatory submissions. 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 future LOTIS-7 clinical trial results will be consistent with or different from the LOTIS-7 data presented at EHA and ICML and future compendia and regulatory strategy and opportunity; 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, as well as early research in certain solid tumors with different targets, linkers and payloads; the timing and results of investigator-initiated trials including those studying FL and MZL and the potential regulatory and/or compendia strategy and the future opportunity; 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:
Investor Relations
Marcy Graham
ADC Therapeutics
Marcy.Graham@adctherapeutics.com
+1 650-667-6450

Media Relations
Nicole Riley
ADC Therapeutics
Nicole.Riley@adctherapeutics.com
+1 862-926-9040

View original content to download multimedia:https://www.prnewswire.com/news-releases/adc-therapeutics-announces-updated-data-from-lotis-7-clinical-trial-presented-at-the-european-hematology-association-2025-congress-302479844.html

SOURCE ADC Therapeutics SA

FAQ

What are the response rates for ADCT's ZYNLONTA and glofitamab combination in DLBCL?

The combination showed a 93.3% overall response rate and 86.7% complete response rate in 30 efficacy evaluable patients with r/r DLBCL.

How effective is ADCT's treatment in CAR-T failure patients?

Among 6 patients previously treated with CAR-T therapy, 5 achieved a complete response, showing strong efficacy in this difficult-to-treat population.

What are the main side effects of ADCT's ZYNLONTA-glofitamab combination?

Main Grade 3+ adverse events included neutropenia (24.4%), anemia (9.8%), and cytokine release syndrome was observed in both dosing groups, though generally manageable.

How many patients is ADCT expanding the LOTIS-7 trial to include?

ADC Therapeutics is expanding the trial enrollment to 100 patients at the 150 µg/kg dose level.

How durable are the responses to ADCT's combination therapy?

The responses showed strong durability with 25 out of 26 patients who achieved complete response maintaining their response as of the data cutoff.