ADC Therapeutics Reports Strong Lymphoma Responses, Plans Phase III Study

Key Points

• ZYNLONTA plus glofitamab showed promising early results in relapsed or refractory DLBCL: Among 97 evaluable patients, the overall response rate was 88.7% and the complete response rate was 75.3%. ADC Therapeutics is preparing a Phase III study, though the complete response results were investigator-assessed and central review is not complete.
• ZYNLONTA also produced high response rates in marginal zone lymphoma: A Phase II study reported a 93% overall response rate and 74.4% complete response rate, and the company plans to pursue breakthrough therapy designation. Separately, Phase III LOTIS-5 improved progression-free survival versus R-GemOx, but did not show a statistically significant overall-survival difference.
• Preliminary third-quarter ZYNLONTA sales were about $21 million ($65.6 million year to date), and estimated quarter-end cash was $189 million, or $196 million pro forma after financing. The company said its cash runway is expected to extend into 2029 following an $86.6 million investment and debt amendments.

ADC Therapeutics NYSE: ADCT outlined new lymphoma data and plans for further studies of its cancer drug ZYNLONTA, while reporting preliminary third-quarter sales of approximately $21 million and an expected cash runway into 2029.

The company said Wednesday that five oral presentations and multiple posters featuring ZYNLONTA data have been accepted for the American Society of Hematology annual meeting, scheduled for December 12–15. The presentations include results from the early-stage LOTIS-7 combination study and an investigator-initiated study in marginal zone lymphoma.

ZYNLONTA is currently approved for patients with diffuse large B-cell lymphoma, or DLBCL, who have received at least two prior lines of treatment. CEO Ameet Mallik said the company is seeking to expand its use into earlier treatment settings and other lymphomas.

LOTIS-7 Results and Phase III Plans

In the phase Ib LOTIS-7 study, ZYNLONTA combined with glofitamab produced an overall response rate of 88.7% and a complete response rate of 75.3% among 97 efficacy-evaluable patients with relapsed or refractory DLBCL, Chief Medical Officer Mohamed Zaki said. The data cutoff was June 15, 2026.

Among patients whose disease was primarily refractory, the overall response rate was 78.4% and the complete response rate was 64.7%. For patients previously treated with CAR-T therapy, those rates were 74.1% and 63%, respectively.

At a median follow-up of 10.35 months, median response duration, complete response duration and progression-free survival had not been reached. The 12-month duration of complete response rate was 79%, Zaki said.

Cytokine release syndrome occurred in 32% of treated patients, with all cases grade 1 or 2 except one grade 3 case. There were no grade 3 or higher ICANS events, a neurological complication associated with some immune therapies. Three grade 5 treatment-emergent adverse events were reported: one due to sepsis and two due to capillary leak syndrome.

Mallik said the complete response rate was investigator-assessed and that a central review had not been completed for the full study. The company expects a more comprehensive update at the meeting and plans to seek publication alongside the presentation.

ADC Therapeutics has submitted a briefing book for an upcoming Food and Drug Administration meeting and is pursuing a phase III study of the combination. Mallik said Roche contributed to the proposed study design and briefing book but would not attend the FDA meeting.

Marginal Zone Lymphoma and LOTIS-5

In a multicenter phase II study of ZYNLONTA alone in relapsed or refractory marginal zone lymphoma, the overall response rate was 93% and the complete response rate was 74.4% among 43 efficacy-evaluable patients, Zaki said. At a median follow-up of 23.2 months, the estimated two-year progression-free survival rate was 90.8%.

All 46 treated patients experienced adverse events, most commonly grade 1 or 2. Grade 3 events occurred in 23 patients and grade 4 events in five. Mallik said the company intends to seek breakthrough therapy designation and evaluate regulatory pathways for the treatment.

In the 420-patient phase III LOTIS-5 study, ZYNLONTA plus rituximab significantly improved progression-free survival compared with R-GemOx in patients with second-line or later DLBCL. Median progression-free survival was 6.14 months versus 4.73 months, respectively. There was no statistically significant difference in overall survival.

Within the study’s protocol-defined 105-day reporting window, grade 5 treatment-emergent adverse events occurred in 13.2% of patients receiving ZYNLONTA plus rituximab, compared with 4.6% receiving R-GemOx. Using a standard 30-day post-treatment window, the rates were 1.5% and 3%, respectively.

Restructuring and Preliminary Financials

CFO Pepe Carmona said an October restructuring included an $86.6 million private investment in public equity, amendments to the company’s HealthCare Royalty agreement and a reduction in outstanding senior secured loan principal to $50 million. The loan changes eliminated scheduled principal amortization in favor of a payment in August 2029.

Preliminary ZYNLONTA net sales were approximately $21 million for the third quarter and $65.6 million for the year to date, with increased sales volume driving the gains, Carmona said. Estimated quarter-end cash was $189 million, or $196 million on a pro forma basis after the financing and related transactions.

The company cautioned that the financial figures are preliminary and subject to change. It plans to file its quarterly report and issue a press release on November 9 without holding another earnings call.

About ADC Therapeutics (NYSE:ADCT)

ADC Therapeutics SA NYSE: ADCT is a biotechnology company focused on developing and commercializing antibody-drug conjugates (ADCs) for the treatment of cancer. Its ADC platform is designed to combine monoclonal antibodies that target specific tumor-associated antigens with potent cytotoxic payloads, with the goal of selectively delivering treatment to cancer cells while limiting exposure to healthy tissue.

The company's lead product is Zynlonta (loncastuximab tesirine-lpyl), an ADC directed against the CD19 antigen.

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