ECHELON-3 Trial Results Show Clinically Meaningful Overall Survival Improvements With Adcetris in DLBCL

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Results from an ongoing Phase III trial showed Adcetris (brentuximab vedotin) combined with lenalidomide and rituximab produced statistically significant and clinically meaningful improvements to overall survival (OS) vs. lenalidomide and rituximab plus placebo in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).¹ The antibody-drug conjugate (ADC) was acquired by Pfizer when it completed its $43 billion deal for Seagen Inc. in December 2023.²

Adcetris also achieved key secondary endpoints in the ECHELON-3 trial, with positive outcomes in progression free survival and overall response rate.

“This is the third Phase III study in a type of lymphoma to demonstrate an overall survival benefit for an Adcetris combination. Based on the strong results from ECHELON-3, we’re excited that Adcetris could address an area of high unmet need in patients with relapsed or refractory DLBCL irrespective of CD30 expression,” Roger Dansey, MD, chief development officer, Oncology, Pfizer, said in a press release. “The results are particularly encouraging because the study evaluated heavily pre-treated patients, including some who received prior [chimeric antigen receptor (CAR) T-cell therapy].”¹

Adcetris is comprised of an anti-CD30 monoclonal antibody that is attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE). The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing cells.³

DLBCL is the most common form of lymphoma, comprising approximately 25% to 30% of all non-Hodgkin lymphomas.⁴ The disease typically manifests as a rapidly growing mass or presents as enlarging lymph nodes in a nodal or extranodal site. Although DLBCL is a fast-growing and aggressive disease, patients typically respond well to six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.⁴

However, approximately 40% of patients with the disease do not respond to frontline treatment or experience a relapse following initial treatment.¹ Adcetris is a standard of care for certain types of lymphomas, with approved indications across seven disease states in the United States.

Other approved indications for Adcetris include adults with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL) combined with doxorubicin, vinblastine, and dacarbazine; in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide for patients 2 years of age and older with previously untreated high risk cHL; for adults with cHL and a high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation; for adults with cHL following failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not candidates for auto-HSCT; for adults with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas in combination with cyclophosphamide, doxorubicin, and prednisone; for adults with sALCL following the failure of at least one prior multi-agent chemotherapy regimen; and adults with primary cutaneous anaplastic large cell lymphoma or CD30-expressing mycosis fungoides following administration of prior systemic therapy.

The ongoing, randomized, double-blind, multicenter ECHELON-3 trial is comparing Adcetris with lenalidomide and rituximab vs. lenalidomide and rituximab plus placebo in 230 adults with relapsed or refractory DLBCL, regardless of CD30 expression, who were previously administered two or more lines of therapy and who are ineligible for HSCT or CAR T-cell therapy.

In terms of safety, there were no new alerts and tolerability of Adcetris was consistent with prior findings in patients with relapsed/refractory DLBCL. Full data from the trial will be submitted for presentation at an upcoming medical meeting, according to Pfizer.¹

References

1. Pfizer Announces Positive Overall Survival in Phase 3 Trial of ADCETRIS® Regimen in Patients with Relapsed/​Refractory Diffuse Large B-cell Lymphoma (DLBCL). Pfizer. News release. March 12, 2024. Accessed March 12, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-overall-survival-phase-3-trial

2. Pfizer Receives All Required Regulatory Approvals to Complete the Acquisition of Seagen. Pfizer Inc. News release. December 12, 2023. Accessed March 12, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-receives-all-required-regulatory-approvals-complete

3. Seagen Announces U.S. FDA Approval of New Indication for ADCETRIS® (brentuximab vedotin) for Children with Previously Untreated High Risk Hodgkin Lymphoma. Seagen. News release. November 10, 2022. Accessed March 12, 2024. https://finance.yahoo.com/news/seagen-announces-u-fda-approval-181200850.html

4. Padala SA, Kallam A. Diffuse Large B-Cell Lymphoma. Updated April 24, 2023. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557796/. Accessed March 12, 2024.