Loncastuximab Tesirine BLA Receives Priority Review in China for Relapsed/Refractory DLBCL

The China National Medical Products Administration (NMPA) has accepted and granted priority review to the biologics license application (BLA) seeking the approval of loncastuximab tesirine-lpyl (Zynlonta) for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) following at least 2 prior lines of systemic therapy.¹

The application was based on data from the phase 2 bridging trial, OL-ADCT-402-001, which evaluated the efficacy and safety of loncastuximab tesirine monotherapy in Chinese patients with relapsed/refractory DLBCL.

“Safer and more effective treatments are still urgently needed to address significant unmet medical needs among patients with relapsed/refractory DLBCL after two or more lines of systemic therapy in China. I hope loncastuximab tesirine will be accessible to Chinese patients with relapsed/refractory DLBCL soon,” Professor Zhu Jun, principal investigator of the OL-ADCT-402-001 study and party secretary of Beijing Cancer Hospital and director of Internal Medicine, said in a news release.

“We are pleased with the swift progress of the development program for loncastuximab tesirine in China as evidenced by the NMPA’s recent acceptance of the BLA and priority review designation,” Ameet Mallik, chief executive officer of ADC Therapeutics, said. “This is a significant step forward in our commitment to making loncastuximab tesirine available to benefit patients worldwide.”

In April 2021, and December 2022, the FDA and the European Medicines Agency granted accelerated and conditional approvals for loncastuximab tesirine, respectively, for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma.^2,3

Both approvals were based on data from the open-label, single-arm, phase 2 LOTIS-2 trial (NCT03589469), which enrolled 145 patients with relapsed or refractory DLBCL or high-grade B-cell lymphoma after at least two prior systemic treatments.2 In the study patients received loncastuximab tesirine at 0.15 mg/kg every 3 weeks for 2 cycles, then 0.075 mg/kg every 3 weeks thereafter until progressive disease or unacceptable toxicity.

The trial population was heavily pretreated, having received a median of 3 prior lines of therapy including stem cell transplant and CAR T-cell therapy. Additionally, some patients had double- or triple-hit genetics.¹

The primary end point of the study was independent review committee–assessed overall response rate (ORR) using Lugano 2014 criteria. Results showed that the ORR was 48.3% (n = 70; 95% CI, 39.9%-56.7%), with a complete response rate of 24.1% (95% CI, 17.4%-31.9%).2 After a median follow-up of 7.3 months, the median duration of response was 10.3 months (95% CI, 6.9-not evaluable); approximately one-third (36%) of responders were censored for response duration prior to 3 months.

Regarding safety, the most frequent adverse effects that occurred in at least 20% of patients including laboratory abnormalities, thrombocytopenia, increased gamma-glutamyl transferase, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea, and musculoskeletal pain.

Continued approval for this indication in the United States and European Union may depend on confirmation of clinical benefit in a confirmatory trial.1

“This is a meaningful milestone. Our partnership with ADC Therapeutics began in December 2020, and it took us only two and a half years to complete the clinical study and submit the first BLA,” Ed Zhang, co-founder and chief executive officer of Overland Pharmaceuticals, said. “We would like to extend our sincere gratitude to participating patients, clinical investigators, the health authority, and our partner ADC Therapeutics for their strong support in making this achievement possible. We look forward to our continued collaboration with all stakeholders to maximize the potential benefits of loncastuximab tesirine for patients in China.”

References

1. Overland ADCT BioPharma announces NMPA accepts biologics license application and grants priority review for ZYNLONTA for treatment of relapsed or refractory diffuse large B-cell lymphoma. News release. Overland ADCT BioPharma. July 24, 2023. Accessed July 24, 2023. https://www.overlandpharma.com/overland-adct-biopharma-announces-nmpa-accepts-biologics-license-application-and-grants-priority-review-for-zynlonta-for-treatment-of-relapsed-or-refractory-diffuse-large-b-cell-lymphoma/
2. FDA grants accelerated approval to loncastuximab tesirine-lpyl for large B-cell lymphoma. News release. FDA. April 23, 2021. Accessed July 24, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-loncastuximab-tesirine-lpyl-large-b-cell-lymphoma
3. ADC Therapeutics and Sobi announce European Commission approval of Zynlonta (loncastuximab tesirine) for the treatment of relapsed or refractory diffuse large B-cell lymphoma. News release. December 21, 2022. Accessed July 24, 2023. https://ir.adctherapeutics.com/press-releases