ADC Therapeutics Advances in DLBCL Treatment with LOTIS-5 Phase 3 Trial
ADC Therapeutics (NYSE:ADCT) has reached a significant milestone by completing enrollment for its LOTIS-5 Phase 3 trial. This trial is crucial for evaluating the efficacy of ZYNLONTA in combination with rituximab for treating relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). ZYNLONTA, which received accelerated approval from the FDA in 2021, is under investigation in a randomized multicenter trial aimed at confirming its accelerated approval and potentially expanding its therapeutic label.
Trial Design and Objectives
The LOTIS-5 trial is structured in two parts. The first part involved twenty patients and reported promising results, with an overall response rate (ORR) of 80% and a complete response (CR) rate of 50%, without new safety concerns. The second part of the trial is more extensive, involving patients with 2L+ DLBCL who are randomized to receive either ZYNLONTA with rituximab or a combination of rituximab, gemcitabine, and oxaliplatin. The primary goal of this phase is to measure progression-free survival, with additional endpoints including overall survival, ORR, CR rate, and duration of response, alongside the frequency and severity of adverse events.
Anticipated Outcomes and Regulatory Pathway
Topline results for the primary endpoint are expected by the end of 2025, with a subsequent regulatory submission to the FDA planned for the first quarter of 2026. If the trial outcomes are favorable, approval could be granted by late 2026, marking a significant advancement in the treatment of r/r DLBCL.
Financial and Clinical Outlook
Despite the promising clinical developments, ADC Therapeutics faces financial challenges, including a negative gross profit margin and a rapid cash burn rate. However, the completion of the LOTIS-5 trial enrollment has reinforced H.C. Wainwright's positive stance on ADC Therapeutics' stock, maintaining a Buy rating with a price target of $8.00. This endorsement reflects confidence in the company's clinical advancements and the potential market impact of ZYNLONTA.
Recent Developments and Future Directions
In addition to the LOTIS-5 trial, ADC Therapeutics has reported positive preliminary results from a clinical trial assessing ZYNLONTA in combination with glofitamab for r/r DLBCL, showing a best overall response rate of 94% and a complete response rate of 72%. The company also reported an increase in net product revenues during its Third Quarter 2024 Earnings Conference Call, with Q3 2024 net product revenues of $18 million, totaling $52.9 million year-to-date. However, a net loss of $44 million for Q3 2024 underscores the financial hurdles the company faces.
ADC Therapeutics is focused on expanding the use of ZYNLONTA in hematology and developing its exatecan-based platform for solid tumors. The company anticipates that ZYNLONTA's peak sales potential could exceed $80 million, highlighting the significant market opportunity for this innovative treatment.
As ADC Therapeutics continues to navigate the complexities of clinical development and financial management, the completion of the LOTIS-5 trial enrollment represents a pivotal step forward in the fight against r/r DLBCL, offering hope to patients and stakeholders alike.
