Top news of the week in oncology drug development.
Sacituzumab Govitecan Granted Breakthrough Status
The investigational antibody-drug conjugate sacituzumab govitecan (IMMU-132) received an FDA breakthrough therapy designation for the treatment of patients with triple-negative breast cancer following at least 2 prior treatments. The designation, which will expedite the development and review of sacituzumab govitecan in TNBC, is based on a phase II trial in which the therapy induced a response rate of 31% in heavily pretreated patients with metastatic TNBC.
In those treated with a median of 5 prior therapies, there were 2 complete responses and 16 partial responses. The clinical benefit ratio was 53% at ≥4 months and 45% at ≥6 months. The median progression-free survival was 6.0 months and the overall survival data were not yet mature, with 83% of patients still alive. Sacituzumab govitecan is a humanized IgG antibody targeted against Trop-2 conjugated to SN-38, which is an active metabolite of the chemotherapy irinotecan. Trop-2 is expressed in more than 90% of TNBC. A phase III study to explore the ADC in TNBC is still being planned.
See more at: http://www.onclive.com/web-exclusives/fda-grants-antibody-drug-conjugate-breakthrough-designation-in-tnbc
ASCO Names Immunotherapy as Advance of the Year
ASCO has named immunotherapy, specifically agents targeted against the PD-1/PD-L1 immune checkpoints, as its “Cancer Advance of the Year.” In melanoma, 2015 already began with three approvals of checkpoint inhibitors: ipilimumab (Yervoy), nivolumab (Opdivo), and pembrolizumab (Keytruda). By the end of the year, FDA had expanded the approval for single-agent nivolumab to include the frontline treatment of patients with BRAF wild-type advanced melanoma.
Most recently, in January 2016, the FDA expanded its frontline approval of nivolumab again, this time as a single agent and in combination with ipilimumab to include BRAF V600 patients. In the field of squamous non—small cell lung cancer, the FDA approved nivolumab for patients whose disease progresses after platinum-based doublet chemotherapy in March 2015. By October that year, the approval was expanded to include patients with nonsquamous NSCLC or EGFR- or ALK-targeted agents in patients harboring those mutations. In September 2015, pembrolizumab was given accelerated approval as a treatment for patients with advanced, PD-L1 positive NSCLC who had received prior therapies.
The treatment paradigm for metastatic renal cell carcinoma also saw an FDA approval of nivolumab in November 2015. Nivolumab is now indicated for patients with advanced RCC who have had prior anti-angiogenic therapy. In addition to approvals, atezolizumab was granted breakthrough therapy designations, chimeric antigen receptor T-cell therapies continued to advance, and promising data were submitted for rindopepimut in glioblastoma.
See more at: http://www.onclive.com/web-exclusives/asco-selects-immunotherapy-as-cancer-advance-of-the-year
Blinatumomab Improves Survival in Phase III ALL Study
The phase III TOWER study has been halted after an independent panel determined that blinatumomab improved overall survival versus standard chemotherapy in patients with Philadelphia chromosome—negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia. TOWER is the confirmatory study for the accelerated approval of blinatumomab, which the FDA granted in December 2014, based on phase II data demonstrating strong clinical activity with the agent in ALL.
In the preceding phase II study, the complete response rate was 32.4%, the CR with partial hematological recovery rate was 9.2%. The combined CR/CRh rate was 41.6%. Overall, 80% of patients who achieved a CR also responded by MRD testing. Approximately 39% of patients who achieved a CR/CRh went on to receive a stem cell transplant. At this point, Amgen has not yet released data from the TOWER trial. Findings from the phase III study are being prepared for presentation at an upcoming scientific meeting, Amgen reported.
See more at: http://www.onclive.com/web-exclusives/blinatumomab-improves-survival-in-acute-lymphoblastic-leukemia
FDA Rejects MCNA for Bladder Cancer
On Wednesday, the FDA issued a complete response letter to Telesta Therapeutics informing the company that its biologics license application for MCNA in bladder cancer would not be approved and that an additional phase III clinical trial was needed to adequately evaluate the immunotherapy. In August 2015, the FDA assigned a priority review designation to MCNA as a treatment for patients with high-risk non-muscle invasive bladder cancer following first-line bacillus Calmette-Guérin therapy, with an action date scheduled for February 27, 2016.
However, the regulatory agency subsequently called for the BLA for MCNA to be discussed at a joint committee meeting of 2 of its advisory panels: ODAC and the Cellular, Tissue and Gene Therapies Advisory Committee. At the advisory hearing, panel members voted 18-6 against recommending approval of MCNA. The BLA the panel considered was primarily based on findings from the open-label phase III trial EN3348-301 (Study 301), in which 25% of patients treated with MCNA remained disease-free at 1-year, and at 2-years, the disease-free survival rate was 19%. However, the primary endpoint of the study was a 1-year DFS rate of ≥40%.
See more at: http://www.onclive.com/web-exclusives/fda-issues-complete-response-letter-for-immunotherapy-mcna-in-bladder-cancer
FDA Approves Single-Dose Fosaprepitant for CINV
The FDA approved single-dose fosaprepitant dimeglumine in combination with other antiemetic agents for the prevention of delayed chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. In the delayed phase, patients in the fosaprepitant arm had a 78.9% CR rate compared with 68.5% in the control arm (P <.001). The CR rate was also significantly improved in the overall phase (77.1% vs 66.9%; P <.001).
However, in the acute phase, there was not a significant CR rate improvement at 93.2% versus 91.0%, respectively (P = .184). In the overall phase, the rate of individuals with no vomiting was 82.7% in the fosaprepitant arm versus 72.9% in the control arm (P <.001). The rate of patients without significant nausea was also improved with fosaprepitant at 83.2% versus 77.9% with ondansetron and dexamethasone alone (P = .030).
See more at: http://www.onclive.com/web-exclusives/fda-approves-single-dose-fosaprepitant-for-cinv
Osimertinib Approved for NSCLC in Europe
The European Commission has granted a conditional marketing authorization to osimertinib (Tagrisso, AZD9291) for patients with locally advanced or metastatic EGFR T790M mutation-positive non—small cell lung cancer, regardless of prior treatment with EGFR TKI. The EC noted in its approval that the EGFR T790M alteration could be detected using either tumor or blood testing. The approval was based on data from two phase II studies and one phase I expansion study, which together investigated osimertinib in 474 patients with NSCLC.
In the phase II AURA and AURA2 trials, the objective response rate with osimertinib was 66% and median progression-free survival was 9.7 months. In the phase I expansion arm, the ORR with osimertinib was 62%, median PFS was 11 months, and the duration of response was 9.7 months. The EC decision followed a positive opinion by the Committee for Medicinal Products for Human Use of the European Medicines Agency in December 2015. In the Unite States, the FDA approved osimertinib in November 2015.
See more at: http://www.onclive.com/web-exclusives/osimertinib-approved-in-europe-for-egfr-t790m-mutant-nsclc