FDA adcomm votes 11-2 to expand Roche's Polivy label in DLBCL
An FDA committee of outside cancer experts voted 11-2 Thursday that the FDA should expand Roche’s Polivy label to include it as a treatment in combo with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for the treatment of adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL).
The positive Oncologic Drugs Advisory Committee (ODAC) vote for the antibody-drug conjugate followed a four hour-plus meeting where the adcomm hashed out concerns highlighted in briefing documents released by FDA. Those concerns included issues like a modest benefit in progression-free survival, overall survival rates, and limitations in efficacy endpoints.
A representative for the FDA highlighted the overall survival hazard ratio in the DLBCL NOS subgroup, which was 1.02, with an upper bound of 1.49.
“The applicant seeks a frontline indication on the basis of a single large randomized trial. However, these findings create uncertainty about the benefit risk profile of Polivy plus R-CHOP in patients with previously untreated large B cell lymphoma, a setting where again, treatment is delivered with curative intent,” FDA Office of Oncologic Diseases clinical team leader Yvette Kasamon said before the committee.
The drug was first approved back in 2019 under the accelerated approval pathway for patients with relapsed or refractory DLBCL, not otherwise specified (NOS), after at least two prior therapies.
Committee member Mikkael Sekeres from the University of Florida voted against approval and said, “I’m not sure I trust who progressed, and who didn’t, and what their base disease was,” adding that from his view, the trial did not meet “the basics of a large clinical trial in hematologic malignancies.”
Mark Conaway of the University of Virginia was the other no vote, saying, “Even though I agree that Polivy did show benefits in this trial, for me at present here was too much uncertainty about the magnitude and the robustness of the treatment effects.”
Anthony Sung out of Duke University School of Medicine voted yes.
“This is a randomized clinical trial that met its primary endpoint of improvement in progression free survival,” Sung said, saying that he thought PFS is a “clinically significant endpoint, and I feel that the difference, even though it is small, is statistically significant and clinically significant as well.”
Committee chair Jorge Garcia, also chief of the solid tumor oncology division at Case Western Reserve University, voted yes too.
“I think that the trial met primary endpoint… And although I continue to wrestle with that lack of difference in complete responses and the existing survival data, it appears to be impractical for us to wait for that final OS — it may never arrive based upon the inability to get there,” Garcia added.
The FDA is expected to make a decision on approval sometime in early April.
