ADC Therapeutics SA: July 2023 Form 6-K Summary
Business context and reporting period
ADC Therapeutics SA, a biotechnology company developing antibody drug conjugates, furnished this Form 6-K for July 2023. The filing reports a voluntary pause in enrollment of new patients in the Phase 2 LOTIS-9 trial evaluating ZYNLONTA (loncastuximab tesirine-lpyl) plus rituximab in previously untreated, unfit or frail patients with diffuse large B-cell lymphoma.
Clinical and other key metrics
- As of the latest review, 40 patients had enrolled. Preliminary efficacy data were based on 30 patients enrolled by the May 10, 2023 data cutoff.
- Among 17 efficacy-evaluable patients, the investigator-assessed overall response rate was 94.1%: 10 complete responses and six partial responses. The 95% confidence interval for ORR was 71.3% to 99.9%.
- In Cohort A, the ORR was 100% among 10 evaluable patients; in Cohort B, the ORR was 85.7% among seven evaluable patients.
- Among the 30 patients in the safety population at the cutoff, six had fatal treatment-emergent adverse events, including five respiratory, thoracic or mediastinal events. One additional Grade 5 event occurred after the cutoff, bringing the total to seven.
- Five patients had Grade 3 or 4 respiratory-related events at the time of the enrollment pause. The filing also identifies additional post-cutoff Grade 3 or 4 cardiac, infection-related and respiratory events.
- Of the 12 reported Grade 3-5 respiratory-related events, 11 were assessed by investigators as unlikely or unrelated to study drug. Four of five Grade 3 or 4 events had resolved, and the affected patients completed treatment per protocol.
- The filing does not provide company revenue, profit, cash flow, margins, debt, liquidity or other corporate financial metrics.
Material changes versus the prior comparable period
- The company voluntarily paused enrollment in LOTIS-9 after reviewing aggregate safety data and consulting the Data Monitoring Committee.
- Since the May 10, 2023 cutoff, enrollment increased from 30 to 40 patients, and fatal respiratory-related events increased from six to seven.
- The company does not expect to report additional LOTIS-9 data by year-end 2023.
Guidance, outlook, risks and unusual items
- The pause is intended to allow further evaluation of the respiratory-related treatment-emergent adverse events and determination of next steps.
- The company notified study investigators, the U.S. Food and Drug Administration and the European Medicines Agency.
- All patients with fatal events had significant active respiratory and/or cardiac comorbidities, were at least 80 years old, and had a mean age of 82.7 years. Reported conditions included severe COPD, pulmonary edema, chronic bronchiectasis, idiopathic pulmonary fibrosis and recent COVID-19 infection.
- The mean time from the last dose to death was 51 days, with a range of 19 to 86 days; two of seven patients died within 30 days of the last dose.
- The company stated that all 12 patients with Grade 3-5 respiratory-related events would have been excluded from the LOTIS-5 trial, highlighting differences in the LOTIS-9 population.
- The cause of the respiratory-related events remained under investigation. The enrollment pause, potential changes to the trial, delayed data reporting and safety findings could adversely affect the development of ZYNLONTA in this setting.
Important facts for investors to verify
- Whether the FDA, EMA or other regulators impose additional requirements, clinical holds or trial modifications.
- The final attribution and underlying causes of the seven fatal events and other serious respiratory-related events.
- Whether LOTIS-9 enrollment resumes, is redesigned or is discontinued, and the resulting development and financial impact.
- Whether the preliminary efficacy results remain consistent as the full 40-patient dataset and subsequent follow-up mature.
- The company’s current cash runway, liquidity position and potential financing needs, which are not disclosed in this Form 6-K.