China’s NMPA Grants Priority Review to Tafasitamab Plus Lenalidomide in Transplant-Ineligible R/R DLBCL

China’s National Medical Products Administration has granted priority review to the biologics license application (BLA) seeking the approval of tafasitamab in combination with lenalidomide (Revlimid) for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT).¹

“Today's BLA acceptance marks an important milestone for InnoCare [Pharma]. DLBCL is the most common type of non-Hodgkin lymphoma globally, and there is a significant unmet need for [patients with] DLBCL in China,” Jasmine Cui, PhD, co-founder, chairwoman, and chief executive officer of InnoCare Pharma, stated in a news release. “We believe that this tafasitamab regimen will bring a novel treatment therapy to [patients with] DLBCL in China.”

Previously, in July 2020, the FDA granted accelerated approval to tafasitamab-cxix (Monjuvi) plus lenalidomide for adult patients with relapsed/refractory DLBCL not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for ASCT.² In August 2021, the European Commission granted conditional marketing authorization to tafasitamab (Minjuvi) plus lenalidomide followed by single-agent tafasitamab for adult patients with relapsed/refractory DLBCL who are not candidates for ASCT.³

The prior regulatory decisions were both supported by data from the phase 2 L-MIND trial (NCT02399085), and long-term data from the study showed that the combination was well tolerated and generated durable responses.⁴

Findings from a 5-year analysis of L-MIND published in Haematologica demonstrated that evaluable patients (n = 80) experienced an objective response rate (ORR) of 57.5% (95% CI, 45.9%-68.5%), including a complete response (CR) rate of 41.3% and a partial response rate of 16.3%. The stable disease rate was 16.3%.

At a median follow-up of 32.7 months (95% CI, 24.4-53.6), patients experienced a median duration of CR that was not reached (NR), and the estimated 5-year duration of CR rate was 80.7% (95% CI, 59.1%-91.6%). At a median follow-up of 44.0 months (95% CI, 29.9-57.0), the median duration of response (DOR) was NR.

At a median follow-up of 45.6 months (95% CI, 22.9-57.6), the median progression-free survival (PFS) was 11.6 months (95% CI, 5.7-45.7), and at a median follow-up of 65.6 months, the median overall survival (OS) was 33.5 months (95% CI, 18.3-NR).

The open-label, single-arm, global, multicenter trial enrolled patients at least 18 years of age with ASCT-ineligible, relapsed/refractory DLBCL who received 1 to 3 prior lines of systemic therapy that included at least 1 CD20-directed therapy. An ECOG performance status of 0 to 2 was also required.

Notably, patients with primary refractory disease were excluded from the study; however, since the definition of primary refractory disease changed over the course of the study, some patients with primary refractory disease were eligible and included. At study launch, primary refractory disease was defined as no response to or progression or relapse within 3 months of receiving a previous anti-CD20–containing regimen. The definition was updated to within 6 months of receiving a prior anti-CD20–containing treatment, meaning patients whose disease relapsed within 3 to 6 months after completing prior therapy were initially eligible to enroll in the study.

All patients were administered tafasitamab and lenalidomide for up to 12 28-day cycles, followed by tafasitamab monotherapy once every 2 weeks in patients with stable disease or better, and treatment continued until disease progression.

Intravenous tafasitamab was given at 12 mg/kg once per week during cycles 1 to 3, then once every 2 weeks thereafter. Oral lenalidomide was administered at 25 mg per day for days 1 to 21 for up to 12 cycles.⁵

ORR served as the trial’s primary end point. Secondary end points included DOR, PFS, OS, time to progression, time to next treatment, and safety.⁴

The long-term analysis showed that safety data were consistent with prior analyses and that toxicities were manageable. The frequency of adverse effects (AEs) decreased during tafasitamab monotherapy, and no new safety concerns were identified.

The rate of serious treatment-emergent AEs was 58.0%, and the most common of these toxicities included pneumonia (8.6%), febrile neutropenia (6.2%), neoplasms (4.9%), pulmonary embolism (3.7%), COVID-19 infection (3.7%), bronchitis (2.5%), lower respiratory tract infection (2.5%), dyspnea (2.5%), atrial fibrillation (2.5%), and congestive cardiac failure (2.5%).

References

1. InnoCare announces the acceptance of biologics license application for tafasitamab in combination with lenalidomide for the treatment of relapsed or refractory diffuse large B-cell lymphoma in adult patients in China. News release. InnoCare Pharma. June 20, 2024. Accessed June 20, 2024. https://www.innocarepharma.com/en/news/activity/en020240620-InnoCare-Announces-Acceptance-of-BLA-for-Tafasitamab-in-China
2. FDA grants accelerated approval to tafasitamab-cxix for diffuse large B-cell lymphoma. FDA. July 31, 2020. Accessed June 20, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tafasitamab-cxix-diffuse-large-b-cell-lymphoma
3. MorphoSys and Incyte announce the European Commission approval of Minjuvi (tafasitamab) in combination with lenalidomide for the treatment of adults with relapsed or refractory DLBCL. News release. MorphoSys. August 26, 2021. Accessed June 20, 2024. https://www.morphosys.com/en/news/morphosys-and-incyte-announce-european-commission-approval-minjuvir-tafasitamab-combination
4. Duell J, Abrisqueta P, Andre M, et al. Tafasitamab for patients with relapsed or refractory diffuse large B-cell lymphoma: final 5-year efficacy and safety findings in the phase II L-MIND study. Haematologica. 2024;109(2):553-566. doi:10.3324/haematol.2023.283480
5. Open label study to evaluate the safety and efficacy of lenalidomide with MOR00208 in patients with R-R DLBCL (L-MIND). ClinicalTrials.gov. Updated October 23, 2023. Accessed June 20, 2024. https://clinicaltrials.gov/study/NCT02399085