Efficacy and Safety of ABP 798: Results from the JASMINE Trial in Patients with Follicular Lymphoma in Comparison with Rituximab Reference Product

Abstract

Introduction: ABP 798 is being developed as a biosimilar to rituximab reference product (RP), a CD20-directed cytolytic antibody that is approved in the US and EU for the treatment of non-Hodgkin lymphoma (NHL).

Methods: This randomized, double-blind, comparative clinical study (JASMINE) evaluated the efficacy and safety of ABP 798 compared with rituximab RP. Adult, anti-CD20 treatment naïve patients diagnosed with grade 1, 2, or 3a follicular B-cell NHL expressing CD20 were randomized 1:1 to receive a 375 mg/m2 infusion of either ABP 798 or rituximab RP once weekly for 4 weeks and at weeks 12 and 20. Tumor assessments were performed at baseline and weeks 12 and 28. Primary endpoint was the risk difference (RD) of overall response rate (ORR) of complete response, unconfirmed complete response, or partial response by week 28 based on data from central, independent, and blinded assessments of disease.

Results: Of the 256 randomized patients, 254 were treated with ABP 798 (n = 128; 100%) or rituximab RP (n = 126; 98.4%); 96 (78.0%) patients in the ABP 798 group and 87 (70.2%) in the rituximab RP group had a best ORR by week 28. The point estimate of RD in ORR between ABP 798 and rituximab RP from the adjusted generalized linear model for stratification factors was 7.7%. Clinical equivalence was based on sequential testing of the one-sided 95% lower confidence limits and one-sided 95% upper confidence limits of RD in ORR (- 1.4% and 16.8%, respectively) which was within the prespecified non-inferiority margin (- 15%) and non-superiority margin (35.5%), respectively. Results of sensitivity analyses were consistent with the primary efficacy analysis. ABP 798 was also comparable to rituximab RP across additional secondary endpoints, further supporting the conclusion of similarity, and including: RD of ORR at week 12; trough serum concentrations; percent of patients with complete depletion of CD19+ cell count at day 8; safety; and immunogenicity.

Conclusions: These results support a conclusion of similar clinical efficacy between ABP 798 and rituximab RP in patients with follicular lymphoma.

Nct number: NCT02747043; first posted April 21, 2016.

Eudract number: 2013-005,542-11; submitted 14 October, 2014.

Conflict of interest statement

Dietger Niederwieser reports personal fees from Cellectis, Daiichi, and Novartis. David Chien, Vladimir Hanes, and Mindy Mo are employees and stockholders of Amgen Inc. Patrick Cobb, Vincent Delwail, Cecily Forsyth, Roman Hajek, Caroline Hamm, and Alessandra Tucci have nothing to disclose.

There is a plan to share data. This may include de-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request, and also related data dictionaries, study protocol, statistical analysis plan, informed consent form, and/or clinical study report. Data sharing requests relating to data in this manuscript will be considered after the publication date and (1) this product and indication (or other new use) have been granted marketing authorization in both the US and Europe or (2) clinical development discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for these data. Qualified researchers may submit a request containing the research objectives, the Amgen product(s), and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labeling. A committee of internal advisors reviews requests. If not approved, a Data Sharing Independent Review Panel may arbitrate and make the final decision. Requests that pose a potential conflict of interest or an actual or potential competitive risk may be declined at Amgen’s sole discretion and without further arbitration. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at https://www.amgen.com/datasharing.

Figures

Fig. 1

Study design in patients with NHL grade 1–3a follicular lymphoma stage II–IV CD20 +. IV intravenous, NHL non-Hodgkin lymphoma, RP reference product. ↓ indicates IV infusion. *Post-treatment tumor assessments

Fig. 2

Study disposition. RP reference product

Fig. 3

Primary efficacy endpoint of RD of ORR by week 28, based on data from the central, independent, blinded assessments of disease for the modified full analysis set. CI confidence interval, ORR overall response rate, RD risk difference. *The CI limits correspond to the one-sided 95% CI lower limit and the one-sided 95% CI upper limit

Fig. 4

Serum concentrations over time by treatment (week 4–12) in the subset of patients who agreed to the optional PK testing. Note: This graph represents PK results from the 45 patients treated with ABP 798 and the 41 patients treated with rituximab RP who agreed to the optional PK sampling. The sample sizes for each visit (ABP 798 vs rituximab) were as follows: week 4 predose (44 vs 39), week 4 post-dose (36 vs 32), week 5 (38 vs 37), and week 12 predose (44 vs 41). PK pharmacokinetic, RP reference product