FDA Raises Issues on 4 Cancer Drugs at Panel
FDA has released briefing documents outlining issues to be discussed during a two-day (5/20-21) Oncologic Drugs Advisory Committee meeting that is reviewing four cancer drug submissions.
During the morning session on 5/20, panel members will discuss a supplemental BLA for Genentech’s Columvi (glofitamab) injection and its use in combination with gemcitabine and oxaliplatin for treating adult patients with relapsed or refractory diffuse large B-cell lymphoma who are not candidates for autologous stem cell transplant. The drug was approved 6/2023 as monotherapy for treating adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Data to be reviewed are from STARGLO (Study GO41944), which was designated as the confirmatory trial to verify the anticipated clinical benefit of glofitamab-gxbm and to support approval in combination with gemcitabine and oxaliplatin
The agency’s briefing document says the “results from the intended confirmatory study, STARGLO, require careful consideration to assess the robustness of the efficacy and safety data in light of the inconsistent treatment effects across multiple endpoints observed between regions and the applicability of the overall results to a U.S. patient population with R/R DLBCL following at least one line of systemic therapy, who are considered ineligible for autologous stem cell transplantation.”
In the afternoon on 5/20, the panel is reviewing a Janssen Biotech supplemental BLA for Darzalex Faspro (daratumumab and hyaluronidase) injection and its use as monotherapy for treating adult patients with high-risk smoldering multiple myeloma (SMM). The briefing document notes that a core issue to be discussed is the data from the pivotal Phase 3 AQUILA trial. FDA says the study’s endpoints are of “uncertain clinical meaningfulness in SMM. While the trial met its primary PFS [progression-free survival] endpoint, there is uncertainty in the benefit of delaying progression to MM in the absence of a significant improvement in OS [overall survival]… FDA has concerns with generalizing the results observed in the AQUILA trial to a high-risk SMM patient population, as the majority of participants enrolled would be classified as intermediate and low-risk based on the current risk-stratification definitions.”
On 5/21, the morning session will discuss a UroGen Pharma NDA for mitomycin intravesical solution for treating adult patients with low-grade intermediate-risk non-muscle invasive bladder cancer. The afternoon session will discuss a Pfizer supplemental NDA for Talzenna (talazoparib) capsules and its use in combination with enzalutamide for treating adult patients with metastatic castration-resistant prostate cancer.
Regarding UroGen’s submission, the briefing document says the panel will be tasked to discuss whether a durable complete response assessed in a single-arm trial can establish efficacy in the patient population, and whether the overall benefit-risk of the investigational treatment is favorable.
And regarding Pfizer’s submission for Talzenna (talazoparib), FDA’s briefing document notes that because of issues with the design of the primary study (TALAPRO-2), “particularly the lack of a pre-specified plan for statistical testing of efficacy in patients with negative HRR [homologous recombination repair gene mutations] status, as well as the results of other studies … that showed reduced or no benefit of PARPi [PARP inhibitors] in patients without tumor HRR, there is uncertainty regarding the benefit/risk evaluation of talazoparib with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) …”
The agency further says the concerns and uncertainties could have been addressed by a dedicated trial that was adequately designed to assess patients with non-HRR mCRPC. The panel will be asked to discuss whether FDA should require new trial design proposals to “include adequate statistical power to assess the efficacy of a drug in the biomarker-negative group when the biomarker is predictive of response and the biomarker-negative group represents the largest population in the trial,” according to the briefing document. They will also be asked if TALAPRO-2’s results are sufficient to conclude a favorable benefit-risk profile for adding talazoparib to enzalutamide in patients with mCRPC.