LOTIS-5 Trial of Lonca-R Completes Enrollment in R/R DLBCL
Enrollment in the LOTIS-5 trial of loncastuximab tesirine-lpyl with rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma has been completed.
Microscopic, photorealistic image of lymphoma cells - Generated with Adobe Firefly
The phase 3, confirmatory LOTIS-5 trial (NCT04384484) evaluating the combination of loncastuximabtesirine-lpyl (Zynlonta) and rituximab (Rituxan; Lonca-R) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) has completed patient enrollment.1
In 2021, the FDA granted accelerated approval to loncastuximabtesirine for the treatment of patients with R/R DLBCL after 2 or more lines of systemic therapy.
Now, this randomized, open‐label, 2-part, 2‐arm, multicenter study plans to confirm the agent’s accelerated approval. It also has the potential to support its label expansion into second-lineand in combination with rituximab.
"This milestone for LOTIS-5 brings us a step closer to providing a potential combination treatment in the [after 2 or more prior lines of therapy] DLBCL setting that we believe will offer competitive efficacy with favorable safety and a convenient dosing schedule, well-suited for use in patients across care settings," said Mohamed Zaki, MD, PhD, chief medical officer of ADC Therapeutics, in a press release. "We anticipate sharing topline results of the primary endpoint analysis by the end of 2025 once the pre-specified number of events is reached and potentially submitting our supplemental BLA to the US FDA in the first quarter of 2026."
The primary end point analysis of the study is expected to deliver topline results by the end of 2025, once the predetermined number of specified events has been achieved. Regulatory submission to the FDA is planned for the first quarter of 2026, with potential approval expected by late 2026.
About the Phase 3 LOTIS-5 Trial
A total of 20 patients were enrolled in part 1 of a non-randomized safety run‐in. Those included in this portion of the trial will receive Lonca-R on day 1 of each cycle for up to 8 cycles, where 1 cycle is 3 weeks. Lonca-R is being given via an intravenous infusion of loncastuximabtesirine 150 µg/kg with rituximab 375 mg/m2 every 3 weeks for 2 cycles, then loncastuximabtesirine 75 µg/kg plus rituximab 375 mg/m2 every 3 weeks for up to 6 additional cycles.2
Enrollment was open to patients aged 18 years or older with a pathologic diagnosis of DLBCL, or high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements. Patients were required to have R/R disease following at least 1 multi-agent systemic treatment regimen, must have not been considered by the investigator to be a candidate for stem cell transplantation, and have measurable disease as defined by the 2014 Lugano Classification as assessed by PET- CT or by CT or MRI if tumor is not fluorodeoxyglucose-avid on screening PET-CT. Patients also must have had formalin-fixed paraffin-embedded tumor tissue block available, an ECOG performance status of 0 to 2, and adequate organ function.
As previously reported, results from this part of the study led to an overall response rate (ORR) by central review of 80%, as observed in 16 of the 20 patients. The complete response (CR) rate was 50% (n = 10) and no new safety signals were identified.1
In part 2 of the trial, patients with DLBCL who have received 2 or more prior lines of therapy are being randomly assigned in a 1:1 fashion to receive fixed-dose loncastuximab with rituximab or rituximab plus gemcitabine and oxaliplatin (R‐GemOx).
The primary end point of the trial is progression-free survival. Secondary end points include overall survival, ORR, CR rate,duration of response,and frequency and severity of adverse events.
REFERENCES:
ADC Therapeutics announces completion of enrollment of phase 3 confirmatory clinical trial of ZYNLONTA® in combination with rituximab in 2L+ diffuse large B-cell lymphoma. News release. ADC Therapeutics SA. December 30, 2024. Accessed January 7, 2025. https://tinyurl.com/yu48edjy
Study to evaluate loncastuximabtesirine with rituximab versus immunochemotherapy in participants with relapsed or refractory diffuse large B-cell lymphoma (LOTIS 5). ClinicalTrials.gov. Updated October 23, 2024. Accessed January 2, 2025. https://clinicaltrials.gov/study/NCT04384484?tab=table
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