Loncastuximab Tesirine Continues to Improve ORR in Relapsed or Refractory DLBCL

Jay Feingold, MD

Jay Feingold, MD

An update to the phase II study of loncastuximab tesirine (ADCT-402) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) showed promising overall response rate (ORR), according to a press release from ADC Therapeutics SA.¹

The ORR with loncastuximab tesirine was 45.5%, with responses observed in 66 out of 145 patients. Twenty percent of the responses were complete responses (CRs), and 25.5% were partial responses (PRs).¹These data follow another promising study update presented at the 2019 American Society for Hematology (ASH) Annual Meeting.²

The ORR observed in 24 of the 52 study participants as of October 4, 2019, was 46.2%, which included CRs in 19.2% of patients and PRs in 26.9% of patients. At the time, the median duration of response (DOR) in complete responders was not reached. However, the median DOR among partial responders was 5.7 months. Additionally, 19.2% of the patients had stable disease.²

The toxicity profile of loncastuximab tesirine reported at ASH was manageable in the relapsed/refractory DLBCL patient population. Most of the adverse events (AEs) were grade 3 or lower and occurred in only 5% of the study participants. The most common AEs were neutrophil count decreased (32.7%), gamma-glutamyl transferase increased (25%), platelet count decreased (21.2%), and anemia (11.5%), and hypokalemia (5.8%).²

The latest phase II data also showed a significant improvement in ORR compared with results seen in the phase I study of loncastuximab tesirine in patients with relapsed/refractory DLBCL. The phase I ORR was 41.4% in 29 out of 70 patients, which included CRs in 21.4% of patients and PRs in 20% of patients.¹

“These data exceeded our primary end point target and reinforce the significant single-agent antitumor activity and manageable toxicity profile of loncastuximab tesirine in patients with relapsed or refractory DLBCL who have failed established therapies. Loncastuximab tesirine has demonstrated its potential to fill a critical unmet need for a new therapy and become a key part of the treatment paradigm for all heavily pretreated patients with DLBCL. We plan to present final data from the pivotal phase II clinical trial at a future scientific meeting,” Jay Feingold, MD, PhD, senior vice president and chief medical officer of ADC Therapeutics, said in a press release.

The single-arm, multi-center, open-label phase II clinical trial is ongoing, evaluating the safety, efficacy, and pharmacokinetics of loncastuximab tesirine, an antibody-drug conjugate, in patients with relapsed/refractory DLBCL. Patients in the trial are given intravenous infusions of loncastuximab tesirine for 30 minutes once every 3 weeks. For the first 2 cycles, the dosage is 150 μg/kg followed by 75 μg/kg for subsequent cycles. Treatment with loncastuximab tesirine is continued for up to 1 year or until the time of disease progression, unacceptable toxicity, or other discontinuation criteria.¹

Based on these data, ADC Therapeutics plans to submit a Biologic License Application to the FDA for accelerated approval of loncastuximab tesirine as a single-agent treatment for relapsed/refractory DLBCL in the United States. The company is also preparing to launch the drug in the second quarter of 2021.¹

References

1. ADC Therapeutics Announces Positive Results from Pivotal Phase 2 Clinical Trial of Single Agents Loncastuximab Tesirine (ADCT-402) In Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma [news release]. Lausanne, Switzerland: ADC Therapeutics SA; January 9, 2020. https://bit.ly/2NauM90. Accessed January 9, 2020.
2. ADC Therapeutics Announces Oral Presentation of Interim Efficacy Data from Pivotal Phase 2 Clinical Trial of ADCT-402 (Loncastuximab Tesirine) in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma at 61st ASH Annual Meeting [news release]. Lausanne, Switzerland: ADC Therapeutics SA; December 9, 2020. https://bit.ly/36yPUgF. Accessed January 9, 2020.