Top news of the week in oncology and cancer drug development.
FDA Halts Multiple Vadastuximab Talirine Trials
The FDA has placed clinical holds on several phase I trials of vadastuximab talirine in acute myeloid leukemia. The clinical holds followed the deaths of 4 patients who were treated with vadastuximab talirine along with allogeneic stem cell transplant either prior to or following treatment.
Specifically, the FDA wants to assess the risk of hepatotoxicity, as the 4 patients who died had veno-occlusive disease. Two other patients also had hepatotoxicity. A full clinical hold has been placed on a phase I/II study of single-agent vadastuximab talirine in patients with AML, both pre- and post-ASCT.
Two other phase I trials received partial clinical holds, meaning further enrollment is halted but enrolled patients who consent can continue therapy. Enrollment continues in other ongoing trials, including the phase III CASCADE study in older patients with AML and a phase I/II trial of patients with myelodysplastic syndrome.
FDA Issues Complete Response Letter for Lutathera in NETs
The FDA has issued a complete response letter to Advanced Accelerator Applications informing the company that its new drug application for Lutathera (177Lutetium DOTA-octreotate) was not approved as a treatment for patients with gastroenteropancreatic neuroendocrine tumors, and would need to be resubmitted. The CRL, which follows a discipline review letter issued in November, requests new subgroup data, a safety update, and that revisions be made to the previously submitted data.
The letter did not request the initiation of additional studies of Lutathera; however, the FDA did note that changes were required to the manufacturing process for Lutathera and that it would not approve the application until these updates were completed. AAA did not provide an update on its progress toward meeting these demands but did note that it had started the revision process in November, when it received the DRL.
FDA Grants Priority Review to New Palbociclib Application in Breast Cancer
The FDA has granted a priority review to a supplemental new drug application supporting the conversation of the accelerated approval of palbociclib to a full approval for use in combination with letrozole as a frontline treatment for postmenopausal women with ER-positive, HER2-negative metastatic breast cancer. The sNDA for the CDK 4/6 inhibitor is based on the phase III PALOMA-2 trial, in which adding palbociclib to letrozole reduced the risk of disease progression by 42% compared with letrozole alone.
The median progression-free survival was improved by more than 10 months with the addition of palbociclib. Under the priority designation, the FDA will review the sNDA within 6 months from the acceptance of the filing, compared with the standard 10 months. The FDA is scheduled to make its final decision by April 2017.
FDA Grants Niraparib Priority Review in Ovarian Cancer
The FDA has granted a priority review to a new drug application for niraparib for use as a maintenance therapy in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who have responded to platinum-based chemotherapy. The NDA is based on data from the phase III ENGOT-OV16/NOVA trial, in which maintenance niraparib reduced the risk of progression or death by 73% compared with placebo for patients with germline BRCA-positive platinum-sensitive, recurrent ovarian cancer.
After a median follow-up of 16.9 months, the median progression-free survival with maintenance niraparib was 21.0 months compared with 5.5 months for placebo in patients with germline BRCA mutations (HR, 0.27; 95% CI, 0.17-0.41; P <.0001). These findings remained consistent across subgroups of patients, including those without BRCA mutations. Under the Prescription Drug User Fee Act, the FDA is scheduled to make its final approval decision on or before June 30, 2017.
FDA Approves New Tissue Expander for Breast Reconstruction
The FDA has approved AeroForm, a balloon-like wireless tissue expander, for patients who choose to have reconstructive surgery following a mastectomy or for those with underdeveloped breasts and soft tissue deformities. The FDA approved the AeroForm system under the de novo premarket review pathway, which is intended for novel, low- to moderate-risk devices for patients who do not have other approved options.
The approval was based on results from a clinical trial known as XPAND, which included 99 patients using the AeroForm expander and 52 patients using a saline expander. The results showed that 96.1% of the patients using AeroForm expanders and 98.8% of the patients using saline expanders could have their breast tissue expanded and exchanged to a breast implant. Moreover, the overall time needed for tissue expansion was lower with AeroForm. Tissue expansion occurred at an average of 21 days in the AeroForm group versus 46 days for saline group.
FDA Grants JCAR017 Breakthrough Designation for NHL
JCAR017 has received an FDA breakthrough therapy designation for the treatment of patients with relapsed/refractory, aggressive large B-cell non-Hodgkin lymphoma. The designation is specifically for patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, grade 3B follicular lymphoma, or not otherwise specified disease (de novo or transformed from indolent lymphoma).
JCAR017 demonstrated a 60% complete response rate in patients with relapsed or refractory CD19-positive NHL in findings from the multicenter, phase I TRANSCEND study. The study administered JCAR017 at various doses to patients with DLBCL, grade 3b follicular lymphoma, and mantle cell lymphoma. The overall response rate with the lowest dose of the therapy was 80%. CRs were seen in patients with double- and triple-hit lymphoma and for 1 patient with CNS disease.
After 3 months of follow-up, 42% of assessable patients remained in response. In addition to the FDA, the European Medicines Agency’s Committee for Medicinal Products for Human Use and Committee for Advanced Therapies has also granted JCAR017 access to the Priority Medicines scheme for relapsed/refractory DLBCL.
MM-302 Falls Short in Phase II HER2+ Breast Cancer Trial
The phase II HERMIONE trial was halted after the antibody-drug conjugate MM-302 combined with trastuzumab failed to improve progression-free survival versus chemotherapy plus trastuzumab in patients with HER2-positive metastatic breast cancer who had previously received trastuzumab, pertuzumab, and ado-trastuzumab emtansine.
The trial was stopped after a recommendation from an independent monitoring panel was confirmed through a futility analysis showing the primary endpoint of PFS improvement would not be met, according to the company developing MM-302, Merrimack Pharmaceuticals. There were no new safety signals with the treatment, and enrolled patients have the option to continue their assigned therapy. Merrimack plans to provide additional details about the antibody-drug conjugate later this month.