Updated Clinical Trial Results Demonstrate Durable Response to Loncastuximab Tesirine-lpyl
Results from the LOTIS-2 and LOTIS-3 trials show durable responses and a manageable toxicity profile among patients with both diffuse large B-cell lymphoma and mantle cell lymphoma treated with loncastuximab tesirine-lpyl (Zynlonta).
Updated results from the LOTIS-2 trial show durable responses to loncastuximab tesirine-lpyl (Zynlonta) among patients with hematological malignancies and solid tumors, according to a press release from ADC Therapeutics.
LOTIS-2 is a single-arm, open-label, phase 2 clinical trial with 145 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have failed 2 or more established therapies. The updated results were presented at the 16th Annual International Conference on Malignant Lymphoma (ICML).
“The updated results from our pivotal LOTIS-2 clinical trial presented at ICML continue to reinforce the efficacy across difficult-to-treat subgroups and sustained duration of response of commercially-available Zynlonta as a single agent for patients with relapsed or refractory diffuse large B-cell lymphoma,” said Jay Feingold, MD, PhD, senior vice president and chief medical officer of ADC Therapeutics, in a press release.
According to the study, the follow-up analysis demonstrated continued substantial antitumor activity and an acceptable safety profile. The overall response rate (ORR) was 48.3% and the complete response rate (CRR) was 24.8%, with a median duration of response of 13.4 months for the 70 responding patients. The median duration of response was not reached for patients with a complete response and the median overall survival was 9.5 months.
No new safety concerns were identified, and researchers observed no increase in toxicity among patients 65 years of age and older compared to patients younger than 65 years of age. The most common grade 3 or worse treatment-emergent adverse events (TEAEs) were neutropenia (26.2%), thrombocytopenia (17.9%), increased gamma-glutamyltransferase (17.2%), and anemia (10.3%).
Updated phase 1 results from the LOTIS-3 trial also suggested potential for loncastuximab tesirine-lpyl in combination with ibrutinib among patients with relapsed or refractory DLBCL and mantle cell lymphoma. LOTIS-3 is a phase 1/2, open-label, single-arm clinical trial, which included 30 patients with DLBCL and 7 patients with mantle cell lymphoma as of the cut-off date in March 2021.
According to the press release, key data from the phase 1 results showed an ORR of 62.2% among all patients and a CRR of 35.1%. Specifically, among patients with non-germinal center B-cell DLBCL (non-GCB DLBCL), the ORR was 66.7%, and among patients with GCB DLBCL the ORR was 16.7%. Among patients with mantle cell lymphoma, the ORR was 85.7%.
In combination with ibrutinib, loncastuximab tesirine-lpyl had a manageable toxicity profile, with the most common grade 3 or worse TEAEs included anemia (10.8%), neutropenia (10.8%), thrombocytopenia (5.4%), and fatigue (5.4%). The pharmacokinetic profiles demonstrated sustained exposure and modest accumulation by the second treatment cycle.
“We’re also pleased that the updated data from the LOTIS-3 clinical trial demonstrate the encouraging antitumor activity and manageable toxicity profile of Zynlonta in combination with ibrutinib in patients with relapsed or refractory DLBCL or mantle cell lymphoma,” Feingold said in the press release. “We look forward to continued progress in all of our LOTIS trials, including the ongoing LOTIS-5 trial of Zynlonta in combination with rituximab and LOTIS-6 trial in patients with relapsed or refractory follicular lymphoma.”
ADC Therapeutics Presents Updated Zynlonta (loncastuximab tesirine-lpyl) Clinical Data at 16th Annual International Conference on Malignant Lymphoma. News release. ADC Therapeutics. June 18, 2021. Accessed June 23, 2021. https://ir.adctherapeutics.com/press-releases/press-release-details/2021/ADC-Therapeutics-Presents-Updated-ZYNLONTA-loncastuximab-tesirine-lpyl-Clinical-Data-at-16th-Annual-International-Conference-on-Malignant-Lymphoma/default.aspx