ADC Therapeutics Announces Updated Data from LOTIS-7 Phase 1b Clinical Trial of ZYNLONTA® in Combination with Bispecific Antibody Supporting Potential Best-in-Class Regimen in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma

Rhea-AI Summary

ADC Therapeutics (NYSE: ADCT) reported updated LOTIS-7 Phase 1b data for ZYNLONTA plus glofitamab in r/r DLBCL showing an investigator-assessed ORR 89.8% and CR 77.6% in 49 efficacy-evaluable patients with ≥6 months follow-up.

The combination was described as generally well tolerated with notable safety findings including Grade ≥3 neutropenia in 32.7%, overall CRS 36.7% and two Grade 5 AEs (4.1%) with one deemed treatment-related. Enrollment to ~100 patients at the 150 µg/kg dose is on track for completion in 1H 2026, with full results and a manuscript planned by end of 2026.

Positive

• ORR 89.8% in 49 efficacy-evaluable patients
• CR 77.6% (38/49 patients)
• Relapsed subgroup ORR 100%, CR 91.7%
• 33/38 patients remained in CR at cutoff
• Enrollment to ~100 patients expected 1H 2026

Negative

• Grade ≥3 neutropenia in 32.7% of patients
• Overall CRS rate 36.7%
• Higher CRS at 120 µg/kg: 52.4%
• Grade 5 AEs occurred in 4.1% (2 patients), one treatment-related

Insights

Clinical Trial Strategist

ZYNLONTA plus glofitamab shows high response rates with an acceptable safety profile; full enrollment and data readouts scheduled in 1H 2026 and by end of 2026.

What the regimen does: The combination produced a best overall response rate of 89.8% and a complete response rate of 77.6% in 49 efficacy‑evaluable patients with ≥6 months follow‑up, including a 100% ORR in relapsed patients and durable CRs in 33 of 38 responders as of the cutoff. Responses extended to prior CAR‑T patients (6 of 8 achieved CR), showing activity across high‑need subgroups.

Dependencies and risks: Safety signals include Grade ≥3 neutropenia in 32.7%, other hematologic and hepatic events, cytokine release syndrome across dose levels (36.7%) and two Grade 5 AEs (4.1%), one deemed treatment‑related. These facts require careful assessment in the full ~100‑patient dataset to confirm tolerability at the selected 150 µg/kg dose.

Concrete items to watch and timing: Completion of enrollment (~100 patients) expected in 1H 2026, top‑line LOTIS‑5 results in 1H 2026, and full LOTIS‑7 data plus publication planned by end of 2026. Key monitorables are durability of CRs on longer follow‑up, incidence and grade of CRS/ICANS in the larger cohort, and the adjudication of the Grade 5 events.

ZYNLONTA® in combination with glofitamab (COLUMVI®) demonstrated an 89.8% ORR and 77.6% CR across the 49 efficacy-evaluable patients with a minimum of 6 months of follow-up

Combination continues to be generally well-tolerated with a manageable safety profile

LOTIS-7 trial is on track for complete patient enrollment in 1H 2026; plan to share full data at a medical meeting and submit for publication by end of 2026

Company to host conference call today at 8:00 a.m. EST

LAUSANNE, Switzerland, Dec. 3, 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). The updated data is based on investigator assessment and reflects the 49 efficacy-evaluable patients with a minimum of 6 months of follow-up from treatment initiation.

"We're excited that these data continue to demonstrate a manageable safety profile and strong efficacy including deep and durable responses in 2L+ r/r DLBCL patients treated with ZYNLONTA plus glofitamab," said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. "We are well on the way to completing enrollment of approximately 100 patients at the selected dose and plan to share full results at a medical congress and through a publication by the end of next year."

As of the November 17, 2025 cutoff date, a total of 49 patients were efficacy evaluable with a minimum of 6 months of follow-up from treatment initiation. Key highlights of the data are as follows:

• Best overall response rate (ORR) was 89.8% (44/49 patients) as assessed by Lugano criteria
• Complete response (CR) rate was 77.6% (38/49 patients)  
  • Of these, 33/38 patients achieving CR remain in CR as of the data cutoff; the 5 patients who did not remain in CR included 2 patients with progressive disease, 2 patients with Grade 5 AEs which occurred during CR, and one censored patient
• Strong efficacy in both the relapsed and primary refractory populations across both dose levels
  • In the 24 relapsed patients ORR was 100% and CR rate was 91.7%
  • In the 25 primary refractory patients ORR was 80% and CR rate was 64%
• 14 patients converted from stable disease (SD) or partial response (PR) to CR over time (1 and 13 patients respectively)
• Of the 8 patients previously treated with CAR-T, 6 achieved a CR
• The combination was generally well tolerated with a manageable safety profile
  • Grade 3 or higher treatment emergent adverse events (TEAEs) observed in > 5% of patients included neutropenia (32.7%), GGT increased (16.3%), anemia (10.2%), WBC decreased (8.2%), generalized oedema (8.2%), ALT increased (8.2%), AST increased (6.1%), and thrombocytopenia (6.1%)
  • Grade 5 AEs occurred in 2 (4.1%) patients; one was treatment-related per the investigator
  • Cytokine release syndrome (CRS) of all grades across dose levels was 36.7%
    • CRS all grades was 25.0% at the selected 150 µg/kg dose and 52.4% at the 120 µg/kg dose, with all but one low Grade
  • Immune effector cell-associated neurotoxicity syndrome (ICANS) was 4.1% across dose levels, with only Grade 1/2

"We believe these updated data further strengthen the evidence supporting the differentiated profile of the combination of ZYNLONTA and glofitamab, which has the potential to be the best-in-class bispecific antibody-based combination in 2L+ DLBCL," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "Taken together with the LOTIS-5 trial, for which top-line results are anticipated in the first half of 2026, we believe ZYNLONTA-based combinations offer complementary approaches with the potential to improve outcomes for 2L+ DLBCL patients."

Enrollment in the LOTIS-7 clinical trial is ongoing, with complete enrollment of approximately 100 patients at the selected 150 µg/kg dose expected during the first half of 2026. The Company plans to share full data at a medical meeting and submit for publication by the end of 2026. In addition, the Company plans to assess regulatory and compendia strategies.

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 global leader and pioneer in the field of antibody drug conjugates (ADCs), transforming treatment for patients through our focused portfolio with ZYNLONTA (loncastuximab tesirine-lpyl) and an early-stage PSMA-targeting ADC.

ADC Therapeutics' CD19-directed ADC ZYNLONTA 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 is leveraging its expertise to advance IND-enabling activities for a next-generation PSMA-targeting ADC which utilizes a differentiated exatecan-based payload with a novel hydrophilic linker.

Headquartered in Lausanne (Biopôle), Switzerland, with operations in London and New Jersey, ADC Therapeutics is focused on driving innovation in ADC development with specialized capabilities from clinical to manufacturing and commercialization. Learn more 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 future LOTIS-7 clinical trial results will be consistent with or different from the LOTIS-7 data presented today, the timing and outcome of the full LOTIS-7 trial, potential best-in-class results, future publication, compendia and regulatory strategy and the commercial opportunity; the success of the Company's strategic restructuring plan; changes in estimated costs associated with the restructuring plan including the workforce reduction and planned closure of the UK facility; the strengthened balance sheet and expected cash runway into at least 2028 which assumes use of minimum liquidity amount required to be maintained under its loan agreement covenants;; the timing of the PFS events and topline data release for LOTIS-5 and the results of the trial and full FDA approval; the Company's ability to grow ZYNLONTA® revenue in the United States and potential peak revenue; 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 pre-clinical research for our exatecan-based ADC targeting PSMA; 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; and the uncertainties of international trade policies, including tariffs, sanctions and trade barriers and potential impact they may have on our business, financial condition, and results of operations. 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.

CONTACT:

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

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FAQ

What were the LOTIS-7 results ADC Therapeutics (ADCT) announced on December 3, 2025?

ADC reported investigator-assessed ORR 89.8% and CR 77.6% in 49 efficacy-evaluable patients with ≥6 months follow-up.

How safe was the ZYNLONTA plus glofitamab combination in the ADCT LOTIS-7 update?

The company described a manageable safety profile with Grade ≥3 neutropenia in 32.7%, overall CRS 36.7%, and two Grade 5 AEs (4.1%), one treatment-related.

What efficacy was seen in relapsed versus primary refractory patients in ADCT LOTIS-7?

Relapsed patients showed ORR 100% and CR 91.7%; primary refractory patients showed ORR 80% and CR 64%.

When will ADC Therapeutics (ADCT) complete LOTIS-7 enrollment and release full data?

Enrollment to ~100 patients at 150 µg/kg is expected in 1H 2026; full data and a publication are planned by end of 2026.

How did cytokine release syndrome (CRS) rates differ by dose in the ADCT LOTIS-7 update?

CRS all grades was 25.0% at 150 µg/kg (selected dose) and 52.4% at 120 µg/kg, mostly low grade.