FDA advisory panel backs polatuzumab vedotin-piiq benefit-risk profile in first-line DLBCL
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Key takeaways:
- The Oncologic Drugs Advisory Committee voted 11-2 that polatuzumab vedotin-piiq has a favorable benefit-risk profile for patients with previously untreated LBCL.
- The FDA is expected to make a final decision on a supplemental biologics license application for the indication by April 2.
Polatuzumab vedotin-piiq exhibited a favorable risk-benefit profile as first-line treatment for patients with large B-cell lymphoma, according to an 11-2 vote of the FDA’s Oncologic Drugs Advisory Committee.
The vote occurred as FDA considers a supplemental biologics license application for polatuzumab vedotin-piiq (Polivy, Genentech) in combination with rituximab (Rituxan; Genentech, Biogen) cyclophosphamide, doxorubicin and prednisone (R-CHP) for patients with previously untreated diffuse large B-cell lymphoma.
A final decision on the application is expected by April 2, according to a Genentech press release. The agency is not required to follow advisory committee recommendations but often does so.
“[This] committee decision to recognize the potential of this Polivy combination as a first-line treatment option is important, since four in 10 people with diffuse large B-cell lymphoma relapse or do not respond to initial treatment,” Levi Garraway, MD, PhD, chief medical officer and head of global product development for Genentech, said in the press release.
Polatuzumab vedotin-piiq — an antibody-drug conjugate — targets CD79b on the surface of malignant B cells. The FDA granted the agent accelerated approval in June 2019 for use in combination with bendamustine and rituximab as treatment for relapsed or refractory DLBCL after at least two previous therapies.
The advisory committee based its decision on results of the randomized phase 3 POLARIX trial, which evaluated the agent plus R-CHP vs. the standard-of-care R-CHOP regimen (R-CHP plus vincristine).
The trial included 879 patients (mean age, 63.1 years; 53.8% male) with previously untreated large B-cell lymphoma.
Researchers assigned 440 patients to polatuzumab vedotin-piiq (Polivy, Genentech), which is composed of a potent microtubule inhibitor conjugated through a protease-cleavable peptide linker to a CD79b monoclonal antibody, plus R-CHP. The other 439 patients received R-CHOP.
Investigator-assessed PFS served as the primary endpoint. EFS for efficacy reasons, complete response rate assessed by PET/CT at end of treatment and OS served as key secondary endpoints.
The polatuzumab vedotin-piiq regimen conferred a 27% reduction in relative risk for disease progression, relapse or death compared with R-CHOP (HR = 0.73; 95% CI, 0.57-0.95), which met the primary endpoint. The regimens exhibited similar overall safety profiles.
FDA documents referred to the PFS benefit in POLARIX as modest and highlighted the lack of a significant difference in OS between groups (HR = 0.94; 95% CI, 0.67-1.33). However, most advisory committee members agreed that the PFS benefit had clinical relevance for this patient population.
“If there are going to be improvements in the care of [patients with large B-cell lymphoma], it may need to start with seemingly small, incremental but clinically meaningful and statistically significant steps such as this,” committee member Ravi A. Madan, MD, clinical director of the genitourinary malignancies branch at NCI, said prior to the vote.
Committee member Mikkael A. Sekeres, MD, professor of medicine and chief of the division of hematology in the leukemia section at University of Miami Sylvester Comprehensive Cancer Center, took issue not with use of PFS as a primary endpoint but rather the lack of central confirmation of diagnosis and progression.
“I’m not sure I trust who progressed and who didn’t and what their base disease was,” said Sekeres, who voted against the question.
Sekeres and other committee members acknowledged that identifying a survival advantage could take several more years of follow-up.
“As front-line therapy, if we can cure more patients, that’s a win,” Anthony D. Sung, MD, associate professor of medicine at Duke University School of Medicine, said prior to the vote. “It would be great to have more quality of life and [patient-reported outcomes] data but, if we can say to our patients, ‘Hey, you have a greater chance of being cured with this regimen,’ I think many patients would take it, and I think as a provider I would prescribe it.”
References:
- Genentech. FDA advisory committee votes in favor of the clinical benefit of Genentech's Polivy combination for people with previously untreated diffuse large B-cell lymphoma (press release). Available at: www.gene.com/media/press-releases/14984/2023-03-09/fda-advisory-committee-votes-in-favor-of. Published March 9, 2023. Accessed March 9, 2023.
- March 9, 2023 meeting of the Oncologic Drugs Advisory Committee (ODAC). Available at: https://www.youtube.com/watch?v=zCf87ABhqpU. Accessed March 9, 2023.
- Polatuzumab Vedotin-piiq for first-line treatment of diffuse large B-cell lymphoma. FDA introductory comments. Available at: www.fda.gov/media/166090/download. Accessed March 9, 2023.
- Polatuzumab vedotin (POLIVY). Presentation to the Oncologic Drugs Advisory Committee BLA 761121/S-008. Genentech, Inc. Available at: www.fda.gov/media/166091/download. Accessed March 9, 2023.
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