Encouraging results with loncastuximab tesirine plus rituximab for DLBCL patients

Data from the first part of the LOTIS-5 trial suggests clinical efficacy and safety of loncastuximab tesirine (Lonca) plus rituximab (R) as a treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma (DLBCL). These findings and data from the second part of the ongoing phase III LOTIS-5 study were recently presented at the annual ASCO meeting in 2022.

LOTIS-2 and LOTIS-5

Despite available treatment options, clinical outcomes for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma (DLBCL) are poor. This includes rituximab, which is the standard immunotherapy used as a frontline treatment and subsequent therapy. The phase II LOTIS-2 trial showed promising results with Lonca, an antibody conjugate (ADC) for DLBCL patients. Furthermore, preclinical studies have shown that combining Lonca with R prolongs tumour control. Importantly, part 1 of the LOTIS-5 study has demonstrated the clinical efficacy of Lonca-R for patients with R/R DLBCL. Currently, part 2 of the LOTIS-5 study is ongoing with the aim to evaluate the efficacy and safety of Lonca-R vs standard immunochemotherapy of R + gemcitabine + oxaliplatin (R-GemOx) in patients with R/R DLBCL.

Finding the best combination

This ongoing open-label, randomised, multicentre study includes 330 patients who will receive (1:1) Lonca-R or  R-GemOx. The main objective of this arm of LOTIS-5 is to evaluate the best combination, i.e. Lonca-R or R-GemOx. The study’s primary endpoint is progression-free survival (assessed by an independent central review), and secondary endpoints include overall survival, overall response rate, complete response rate, duration of response, frequency and severity of adverse events, changes from baseline in safety, laboratory and clinical variables, concentration and pharmacokinetic parameters of Lonca (conjugated and total antibody and unconjugated warhead), immunogenicity, and changes in patient-reported outcomes.

Conclusion

This part of LOTIS-5 commenced in January 2022, and the enrolment of participants is ongoing. The results are to be awaited, but have the potential to provide valuable data with regards to the treatment of diffuse large B-cell lymphoma.

Reference

Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 2021;22:790-800.

Hamandani M, Linhares Y, Gandhi M, et al. Phase 3 randomized study of loncastuximab tesirine in combination with rituximab (Lonca-R) versus immunochemotherapy in patients with R/R DLBCL (LOTIS-5). Presented at ASCO 2022. J Clin Oncol 2022;40:TPS7591.

Ryan MC, Palanca-Wessels MC, Schimpf B, et al. Therapeutic potential of SGN-CD19B, a PBD-based anti-CD19 drug conjugate, for treatment of B-cell malignancies. Blood 2017;130:2018-26.