ADC Therapeutics Announces Results From LOTIS-5 Phase 3 Confirmatory Clinical Trial of ZYNLONTA® in Combination with Rituximab in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Rhea-AI Summary

ADC Therapeutics (NYSE: ADCT) reported topline Phase 3 LOTIS-5 results for ZYNLONTA + rituximab in relapsed or refractory DLBCL. The combo met the primary endpoint, improving progression-free survival (HR=0.73; p=0.008) vs R-GemOx, with higher response and complete response rates and longer complete response duration.

Overall survival showed no detrimental effect (HR=0.96). Total adverse event rates were similar between arms, but serious, Grade 5 events and withdrawals were more frequent with ZYNLONTA + rituximab, especially in patients ≥75. ADC Therapeutics plans a pre-sBLA FDA meeting in August and targets an sBLA filing in Q4 2026.

Positive

• Primary endpoint met: PFS HR 0.73 (p=0.008) favoring ZYNLONTA + rituximab
• Median PFS improved to 6.1 months vs 4.7 months for R-GemOx
• Overall response rate 58.1% vs 45.2% with ZYNLONTA + rituximab
• Complete response rate 39.5% vs 26.7%; DoCR 16.8 vs 12.3 months
• 48.5% vs 16.7% of complete responders remained in CR at 24 months
• Pre-sBLA FDA meeting planned August 2026; sBLA submission targeted Q4 2026

Negative

• Serious adverse events higher with ZYNLONTA + rituximab: 49.0% vs 34.5%
• Grade 5 TEAEs 13.2% (27 patients) vs 4.6% (9 patients), mainly ≥75 years
• TEAEs leading to any drug withdrawal 25.5% vs 9.1% in control arm
• Higher rates of infection, hepatotoxicity, and edema/effusion in ZYNLONTA arm

News Market Reaction – ADCT

-57.14%

25 alerts

-57.14% Session close to close

-58.6% Trough in 12 hr 6 min

$391.75M Market Cap

0.2x Rel. Volume

In the Jun 4 session, ADCT declined 57.14%, reflecting a significant negative market reaction. Argus tracked a trough of -58.6% from its starting point during tracking. Our momentum scanner triggered 25 alerts that day, indicating elevated trading interest and price volatility.

Data tracked by StockTitan Argus on the day of publication.

Market Context

The stock dropped -57.1% in the session following this news. A negative reaction despite the positiv...

Analysis

The stock dropped -57.1% in the session following this news. A negative reaction despite the positive PFS result would fit ADCT’s history of sharp sell-offs on clinical news, such as the -14.13% move on a LOTIS-7 update. The higher incidence of serious and Grade 5 TEAEs in the ZYNLONTA combination arm, particularly in older patients, plus an effective S-3 resale registration for 9.83M warrant shares and potential $37.5M in proceeds, could have amplified concerns.

Key Figures

PFS primary endpoint: HR 0.73; p=0.008 (two-sided) Median PFS: 6.1 vs 4.7 months Overall response rate: 58.1% vs 45.2% +5 more

8 metrics

PFS primary endpoint HR 0.73; p=0.008 (two-sided) LOTIS-5 independent review committee analysis

Median PFS 6.1 vs 4.7 months ZYNLONTA+rituximab vs R-GemOx in LOTIS-5

Overall response rate 58.1% vs 45.2% ZYNLONTA+rituximab vs R-GemOx in LOTIS-5

Complete response rate 39.5% vs 26.7% ZYNLONTA+rituximab vs R-GemOx in LOTIS-5

Median DoCR 16.8 vs 12.3 months Duration of complete response in LOTIS-5

Grade 5 TEAEs 13.2% vs 4.6% ZYNLONTA+rituximab vs R-GemOx safety in LOTIS-5

Serious adverse events 49.0% vs 34.5% ZYNLONTA+rituximab vs R-GemOx in LOTIS-5

Any TEAE 98.5% vs 97.5% Overall TEAE rates in LOTIS-5

Previous Clinical trial Reports

5 past events · Latest: Dec 03 (Positive)

Same Type Pattern 5 events

Date	Event	Sentiment	24h Move	Catalyst
Dec 03	LOTIS-7 Phase 1b data	Positive	-14.1%	Updated LOTIS-7 Phase 1b data showed high ORR and CR with manageable safety.
Dec 02	LOTIS-7 update call	Neutral	-14.1%	Announcement of conference call to discuss LOTIS-7 Phase 1b trial update.
Jun 12	LOTIS-7 EHA2025 data	Positive	+4.0%	EHA2025 presentation showed 93.3% ORR and 86.7% CR with durable responses.
May 14	LOTIS-7 presentations	Positive	+37.1%	Promising LOTIS-7 Phase 1b data with 95.5% ORR and 90.9% CR highlighted.
Dec 02	LOTIS-7 update call	Neutral	-14.1%	Notice of upcoming webcast to review LOTIS-7 safety and efficacy data.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Pattern Detected

Clinical-trial news has produced mixed reactions: strong LOTIS-7 data previously saw both sharp gains and steep sell-offs, with an average move of -0.26% around such headlines.

Recent Company History

Recent clinical communication has centered on ZYNLONTA combinations in relapsed/refractory DLBCL, particularly LOTIS-7 Phase 1b data with very high response rates and manageable safety. Market reactions have varied sharply: a 37.12% rise on May 14, 2025 contrasted with a -14.13% drop on updated LOTIS-7 data in December. Today’s LOTIS-5 Phase 3 confirmatory results extend this narrative from earlier-phase combinations toward a pivotal regimen that could support regulatory expansion via a planned sBLA.

Key Terms

progression-free survival (PFS), overall survival (OS), complete response (CR), overall response rate (ORR), +4 more

8 terms

progression-free survival (PFS) medical

"achieved statistical significance on the trial's primary endpoint of progression-free survival (PFS)"

Progression-free survival (PFS) measures the length of time in a clinical trial or treatment period during which a patient’s disease does not get worse. Investors watch PFS because longer PFS in trials can signal a drug’s effectiveness, influence regulatory approval and reimbursement decisions, and affect commercial value—think of it as how long a product keeps a problem from returning, which helps estimate future sales and competitive advantage.

overall survival (OS) medical

"no detrimental effect on the key secondary efficacy endpoint of overall survival (OS)"

Overall survival (OS) is the length of time from the start of a treatment or clinical study until death from any cause, essentially measuring how long patients live after a therapy begins. Investors watch OS because it is the most direct evidence a treatment extends life; stronger OS results can drive regulatory approvals, wider use and higher revenue expectations, much like sales figures proving a product actually works.

complete response (CR) medical

"a higher complete response (CR) rate and duration of CRs (DoCR) were observed"

A complete response (CR) is when a company or individual fully satisfies a specific requirement or condition, indicating that the issue or task has been resolved completely. For investors, it signals that a problem has been fully addressed, which can influence decisions about trust, future actions, or the company's overall status. Think of it as a full "checkmark" showing everything has been successfully handled.

overall response rate (ORR) medical

"Overall response rate (ORR) was 58.1% vs. 45.2%"

Overall response rate (ORR) is the percentage of trial participants whose disease measurably improves—typically tumor shrinkage or disappearance—according to predefined medical criteria. Investors watch ORR because it provides an early, concrete signal of a therapy’s effectiveness and commercial potential, similar to seeing what share of products in a test batch actually work before deciding to back wider production.

treatment emergent adverse event (TEAE) medical

"Overall, treatment emergent adverse event (TEAE) rates were similar between arms"

A treatment emergent adverse event (TEAE) is any unwanted medical problem that either appears or gets worse after a patient starts a study drug or medical intervention. Investors care because the number, severity and timing of TEAEs shape a therapy’s safety record, influence regulator decisions and labeling, and can materially affect a drug’s market prospects — like tracking new complaints that show up once a product is rolled out.

serious adverse events (SAEs) medical

"Higher rates of SAEs were seen in the test arm (49.0% vs. 34.5%)"

Serious adverse events (SAEs) are significant negative outcomes, such as severe health issues, hospitalizations, or death, that occur during a medical study or treatment. For investors, SAEs matter because they can signal potential risks associated with a product or company, potentially affecting its reputation, regulatory approval, or financial performance. Recognizing SAEs helps gauge the safety and reliability of medical-related investments.

CAR-T medical

"patients who cannot access or who progress on a CAR-T or other complex therapies"

CAR-T is a type of cancer therapy that reprograms a patient’s own immune cells to seek and destroy specific cancer cells, like teaching guard dogs a new scent to track intruders. It matters to investors because CAR-T treatments can command high prices, drive strong revenue for successful developers, and carry regulatory and manufacturing risks that can sharply affect a company’s valuation and long-term growth prospects.

Biologics License Application (sBLA) regulatory

"prepare for the planned supplemental Biologics License Application (sBLA) filing"

A biologics license application (sBLA) is a formal request submitted to regulatory authorities seeking approval to market a biological medicine, such as vaccines or therapies made from living organisms. It is a comprehensive package of data showing that the product is safe, effective, and manufactured to high quality standards. For investors, receiving approval signals a potential product launch, which can significantly impact a company's growth and valuation.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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Company to host conference call today at 4:30 p.m. EDT

LAUSANNE, Switzerland, June 3, 2026 /PRNewswire/ -- ADC Therapeutics SA (NYSE: ADCT) today announced topline data from its Phase 3 LOTIS-5 confirmatory trial evaluating ZYNLONTA^® (loncastuximab tesirine-lpyl) in combination with rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). ZYNLONTA plus rituximab achieved statistical significance on the trial's primary endpoint of progression-free survival (PFS) and demonstrated no detrimental effect on the key secondary efficacy endpoint of overall survival (OS). In addition, a higher complete response (CR) rate and duration of CRs (DoCR) were observed with ZYNLONTA plus rituximab. Overall, treatment emergent adverse event (TEAE) rates were similar between arms. Similar rates of overall Grade ≥3 TEAEs greater than 5% were observed across both arms, with hematologic TEAEs higher in the control arm and infection, hepatotoxicity, and edema/effusion higher in the test arm. Serious adverse events (SAEs), TEAEs leading to study drug withdrawal, and Grade 5 events were higher in the test arm, with the majority of Grade 5 TEAEs in the test arm occurring in patients aged 75 years or older.

"In the context of a positive study, based on the totality of the data, we plan to discuss the benefit-risk profile of this combination with the U.S. FDA as we prepare for the planned supplemental Biologics License Application (sBLA) filing," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "We would like to extend our thanks to the patients, investigators, and clinical teams who contributed to this important trial."

The LOTIS-5 trial is a randomized, open‐label, two‐arm, multicenter study evaluating ZYNLONTA plus rituximab versus the standard immunochemotherapy rituximab gemcitabine‐oxaliplatin (R‐GemOx), for the treatment of r/r DLBCL after one or more lines of systemic therapy. The study met the primary endpoint of PFS (per independent review committee) with statistical significance (HR = 0.73; p-value = 0.008 two sided), with a median PFS of 6.1 months for ZYNLONTA plus rituximab vs 4.7 months for R-GemOx. Overall survival showed no detrimental effect with ZYNLONTA plus rituximab compared to the control arm (HR = 0.96, impacted by the earlier use and a higher rate of new anti-lymphoma treatment switching in the control arm). Overall response rate (ORR) was 58.1% vs. 45.2%, CR rate was 39.5% vs. 26.7%, median duration of response (DOR) was 9.2 months vs. 7.7 months, and median DoCR was 16.8 months vs. 12.3 months for ZYNLONTA plus rituximab compared to R-GemOx, respectively. Of patients achieving CR, 48.5% vs. 16.7% remained in CR at 24 months in favor of ZYNLONTA plus rituximab. Of note, results in North America were consistent with the overall study results.

Overall, TEAE rates were similar between arms (98.5% vs. 97.5%). Higher rates of SAEs were seen in the test arm (49.0% vs. 34.5%). Grade ≥3 TEAEs observed in > 5% of patients were hematologic (40.7% vs. 59.4%), followed by infection/infestations (24.5% vs. 15.7%), then hepatotoxicity (17.2% vs. 8.1%) and oedema/effusion (7.4% vs. 0.5%) when comparing ZYNLONTA plus rituximab to R-GemOx. A higher rate of Grade 5 TEAEs was observed in the ZYNLONTA plus rituximab arm (27 pts/13.2%) vs. R-GemOx (9 pts/4.6%). Of note, the majority of Grade 5 TEAEs in the test arm occurred in patients aged 75 years or older. Higher rates of TEAEs leading to any drug withdrawal occurred in the ZYNLONTA plus rituximab arm (25.5% vs. 9.1%). In this study, the TEAE reporting window was defined as 105 days after the last dose of study treatment or the start of new anticancer therapy, whichever is earlier. The rates of TEAEs in this study were impacted by the longer overall TEAE observation time in the test vs. control arm. This difference is primarily driven by a higher rate of and earlier switching to subsequent therapies in the control arm.

"LOTIS-5 was designed to address a clear unmet need in r/r DLBCL in patients who cannot access or who progress on a CAR-T or other complex therapies," said Mehdi Hamadani, MD, Professor of Medicine, Associate Director of Clinical Research, Section Chief of Hematologic Malignancies at Medical College of Wisconsin and principal investigator for the trial. "Based on these results, I believe this combination may provide an additional option in treating relapsed or refractory DLBCL."

"Based on these topline results from LOTIS-5, we look forward to discussing next steps for this combination of ZYNLONTA plus rituximab with the U.S. FDA," said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. "We intend to conduct a pre-sBLA meeting in August and are preparing for a planned sBLA submission in the fourth quarter of 2026."

In addition, the Company will continue to evaluate a broad range of value maximizing alternatives, including but not limited to near-term cost reduction initiatives.

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

Conference Call Details
ADC Therapeutics management will host a conference call and live audio webcast to discuss the LOTIS-5 results today at 4:30 p.m. EDT. To access the conference call, please register here. Registrants will receive the dial-in number and unique PIN. 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 & 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 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).

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.

Headquartered in Lausanne (Biopôle), Switzerland, with operations in 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.

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 adequacy of the LOTIS-5 clinical trial data to support full regulatory approval and our ability to maintain accelerated approval in the United States and foreign jurisdictions for our product; the timing, content and outcome of meetings with and feedback or other communications provided by regulatory authorities including U.S. FDA; the timing, submission and acceptance of an sBLA submission related to LOTIS-5 and potential approval; the actual and perceived benefit-risk profile for ZYNLONTA as studied in the LOTIS-5 trial; the assessment of the data from LOTIS-5 study, including additional analyses of outcomes observed for safety, efficacy and within key geographic regions and across certain patient sub-populations; the path for full regulatory approval for ZYNLONTA in the United States and foreign jurisdictions; our ability to identify and execute value-maximizing options and the cost and impact of such options; our expected cash runway into at least 2028; our ability to comply with the terms of our indebtedness; changes in our regulatory and commercial strategy; the Company's ability to sustain or 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, results and publication of the Company's clinical trials including LOTIS-7; the timing, publication 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, trade barriers and most favored nation drug pricing and the 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.

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

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SOURCE ADC Therapeutics SA

FAQ

What were the key results of ADC Therapeutics (NYSE: ADCT) LOTIS-5 Phase 3 trial for ZYNLONTA plus rituximab in r/r DLBCL?

LOTIS-5 met its primary endpoint, with ZYNLONTA plus rituximab improving progression-free survival versus R-GemOx. According to ADC Therapeutics, the regimen also showed higher overall and complete response rates, longer response durations, and no detrimental effect on overall survival in relapsed or refractory diffuse large B-cell lymphoma.

How did progression-free survival compare between ZYNLONTA plus rituximab and R-GemOx in the LOTIS-5 trial for ADCT?

ZYNLONTA plus rituximab significantly improved progression-free survival versus R-GemOx in LOTIS-5. According to ADC Therapeutics, the hazard ratio was 0.73 (p=0.008), with median PFS of 6.1 months for ZYNLONTA plus rituximab versus 4.7 months for R-GemOx in r/r DLBCL.

What response rates and durability were seen with ZYNLONTA plus rituximab in ADC Therapeutics LOTIS-5 study?

ZYNLONTA plus rituximab showed higher response rates and longer durability than R-GemOx. According to ADC Therapeutics, overall response was 58.1% vs 45.2%, complete response 39.5% vs 26.7%, median duration of response 9.2 vs 7.7 months, and median duration of complete response 16.8 vs 12.3 months.

What safety profile was observed for ZYNLONTA plus rituximab in the LOTIS-5 Phase 3 trial of ADCT?

Overall adverse event rates were similar between treatment arms, but some serious events were more frequent with ZYNLONTA plus rituximab. According to ADC Therapeutics, serious adverse events, Grade 5 events, and treatment-emergent events leading to drug withdrawal occurred more often, especially in patients aged 75 years or older.

What are ADC Therapeutics regulatory plans for ZYNLONTA after the LOTIS-5 trial results?

ADC Therapeutics plans to advance ZYNLONTA plus rituximab toward a supplemental Biologics License Application. According to ADC Therapeutics, the company intends to hold a pre-sBLA meeting with the U.S. FDA in August 2026 and targets an sBLA submission in the fourth quarter of 2026.

How did overall survival compare between ZYNLONTA plus rituximab and R-GemOx in LOTIS-5 for ADCT?

Overall survival showed no detrimental effect for ZYNLONTA plus rituximab compared with R-GemOx. According to ADC Therapeutics, the overall survival hazard ratio was 0.96, with results influenced by earlier use and higher switching to new anti-lymphoma therapies in the control arm.

Why is ADC Therapeutics LOTIS-5 trial important for patients with relapsed or refractory DLBCL who are not candidates for CAR-T?

LOTIS-5 evaluated an antibody-drug conjugate-based regimen for patients lacking access to CAR-T or progressing after complex therapies. According to ADC Therapeutics, ZYNLONTA plus rituximab improved progression-free survival and response metrics, potentially offering an additional treatment option for these relapsed or refractory DLBCL patients.