ADC Therapeutics Announces Positive Initial Data from LOTIS-7 Clinical Trial Evaluating ZYNLONTA® in Combination with Bispecific Antibody in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma

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ADC Therapeutics (NYSE: ADCT) announced positive initial data from the LOTIS-7 Phase 1b trial evaluating ZYNLONTA® in combination with glofitamab for relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The combination demonstrated a 94% best overall response rate and 72% complete response rate in evaluable patients.

The study included 29 B-NHL patients, with 18 evaluable 2L+ DLBCL patients receiving doses of 120 µg/kg or 150 µg/kg. At the 150µg/kg dose level, the combination achieved a 100% overall response rate and 78% complete response rate. Safety data showed no dose-limiting toxicities, with manageable Grade 3+ adverse events including neutropenia (24%), lymphopenia (7%), and hypokalemia (7%).

Positive

• 94% best overall response rate (ORR) in evaluable patients
• 72% complete response rate (CR) across all dose levels
• 100% ORR and 78% CR at 150µg/kg dose level
• 12 out of 13 complete responders maintain CR status
• No dose-limiting toxicities observed across all dose levels

Negative

• 24% of patients experienced Grade 3+ neutropenia
• 34.5% of patients showed Grade 1 or 2 Cytokine Release Syndrome

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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, Dec. 11, 2024 /PRNewswire/ -- 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:

• Best overall response rate (ORR) was 94% (17/18) as assessed by Lugano criteria
• Complete response (CR) was achieved in 72% (13/18) and partial response (PR) was achieved in 22% (4/18) of patients. Of those achieving CR, 12 out of 13 remain in CR as of the cutoff date.
• Among patients treated with ZYNLONTA at the 150µg/kg dose (the initial dose approved for ZYNLONTA as a monotherapy in 3L+ DLBCL patients), best ORR was 100% (9/9) and CR was achieved in 78% (7/9) of patients

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:

• Treatment emergent adverse events (TEAEs) of Grade 3 or higher occurring in ≥ 5% of patients included neutropenia (24%), lymphopenia (7%) and hypokalemia (7%)
• Cytokine Release Syndrome (CRS) of Grade 1 or 2 according to ASTCT grading was observed in 34.5% of patients and resolved with standard treatment. Low-grade Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) (Grade 2 according to ASTCT grading) was observed in two patients and both had complete resolution of symptoms. No Grade 3 or higher CRS or ICANS were observed.
• There were no Grade 5 TEAEs observed

"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.

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: plans and timelines for the clinical development for LOTIS-7, including the therapeutic potential, clinical benefits and safety thereof; uncertainty whether future data will be consistent with the initial data; expectations regarding timing, success and future data announcements for LOTIS-7; 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 and ADCT 602 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:

Investors
Marcy Graham
ADC Therapeutics
Marcy.Graham@adctherapeutics.com
+1 650-667-6450

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

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SOURCE ADC Therapeutics SA

FAQ

What are the initial results of ADCT's LOTIS-7 trial for ZYNLONTA combination therapy?

The LOTIS-7 trial showed a 94% best overall response rate and 72% complete response rate in DLBCL patients, with 100% ORR at the 150µg/kg dose level.

How many patients were evaluated in ADCT's LOTIS-7 trial as of November 2024?

As of November 20, 2024, 29 B-NHL patients were evaluated for safety, with 18 evaluable 2L+ DLBCL patients receiving specific dose levels.

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

The main Grade 3+ side effects included neutropenia (24%), lymphopenia (7%), and hypokalemia (7%), with no high-grade CRS or ICANS observed.

What is the durability of response in ADCT's LOTIS-7 trial?

Of the 13 patients achieving complete response, 12 maintained their complete response status as of the data cutoff date.