ADC Therapeutics Announces Completion of Enrollment of Phase 3 Confirmatory Clinical Trial of ZYNLONTA® in Combination with Rituximab in 2L+ Diffuse Large B-Cell Lymphoma

Rhea-AI Summary

ADC Therapeutics (NYSE: ADCT) announced completion of enrollment in LOTIS-5, a Phase 3 confirmatory trial evaluating ZYNLONTA combined with rituximab for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). The study aims to confirm ZYNLONTA's 2021 accelerated FDA approval and potentially expand its label for 2L+ treatment with rituximab.

Part 1 of the trial showed promising results with an 80% overall response rate and 50% complete response rate. Part 2 randomizes patients 1:1 to receive ZYNLONTA with rituximab versus rituximab-gemcitabine-oxaliplatin. Topline results are expected by end of 2025, with potential FDA submission in Q1 2026 and approval targeted for late 2026.

Positive

• Phase 3 trial enrollment completed on schedule
• Strong Part 1 results with 80% overall response rate and 50% complete response rate
• No new safety signals identified in the trial
• Clear regulatory timeline with potential approval in late 2026

Negative

• Results and potential FDA approval still 2+ years away
• Success not guaranteed as trial results pending

LAUSANNE, Switzerland, Dec. 30, 2024 /PRNewswire/ -- ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), today announced the completion of enrollment in LOTIS-5, the Phase 3 confirmatory trial evaluating ZYNLONTA^® (loncastuximab tesirine-lpyl) in combination with rituximab (Lonca-R) in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). ZYNLONTA previously received accelerated approval for the treatment of r/r DLBCL after two or more lines of systemic therapy from the FDA in 2021.

"This milestone for LOTIS-5 brings us a step closer to providing a potential combination treatment in the 2L+ DLBCL setting that we believe will offer competitive efficacy with favorable safety and a convenient dosing schedule, well-suited for use in patients across care settings," said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. "We anticipate sharing topline results of the primary endpoint analysis by the end of 2025 once the pre-specified number of events is reached and potentially submitting our supplemental BLA to the U.S. Food and Drug Administration (FDA) in the first quarter of 2026."

The randomized, open‐label, two‐part, two‐arm, multicenter study is designed to confirm accelerated approval and may support potential label expansion into 2L+ in combination with rituximab. Twenty patients were enrolled in part 1 of a non-randomized safety run‐in. As previously reported, the results showed an overall response rate (ORR) by central review of 80% (16/20) with a complete response (CR) rate of 50% (10/20) and no new safety signals.

In part 2, patients with 2L+ DLBCL are randomized 1:1 to receive fixed-dose ZYNLONTA with rituximab or rituximab‐gemcitabine‐oxaliplatin (R‐GemOx). The primary endpoint of LOTIS-5 is progression-free survival with secondary endpoints of overall survival, ORR, CR rate and duration of response as well as frequency and severity of adverse events. Topline results of the primary endpoint analysis are anticipated by the end of 2025 once the required number of pre-specified events is reached followed by regulatory submission to the FDA in Q1 2026 and potential approval in late 2026.

For more information about LOTIS-5, please visit https://clinicaltrials.gov/ (identifier NCT04384484).

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 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 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: the timing of the achievement of the number of pre-specified events for LOTIS-5 and disclosure of full data read-out, the results of the LOTIS-5 study, the timing for regulatory submission of the supplemental BLA for ZYNLONTA, the timing and FDA approval of the same, future market acceptance and revenue for ZYNLONTA; 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 key results from LOTIS-5 Part 1 trial for ADCT's ZYNLONTA?

Part 1 of the LOTIS-5 trial showed an 80% overall response rate and 50% complete response rate, with no new safety signals identified.

When will ADCT release LOTIS-5 Phase 3 topline results for ZYNLONTA?

ADC Therapeutics expects to release topline results for the LOTIS-5 Phase 3 trial by the end of 2025.

What is the timeline for ADCT's FDA submission for ZYNLONTA's expanded indication?

ADC Therapeutics plans to submit a supplemental BLA to the FDA in Q1 2026, with potential approval expected in late 2026.

What is the primary endpoint of ADCT's LOTIS-5 Phase 3 trial?

The primary endpoint of the LOTIS-5 Phase 3 trial is progression-free survival.

How is ADCT's LOTIS-5 Phase 3 trial structured?

The trial is a randomized, open-label, two-part study where patients receive either ZYNLONTA with rituximab or rituximab-gemcitabine-oxaliplatin in a 1:1 ratio.