This week, the U.S. Food and Drug Administration (FDA) granted Priority Review to treatments for non–small cell and small cell lung cancers, as well as for diffuse large-B cell lymphoma (DLBCL); Breakthrough Therapy designation to an antibody-drug conjugate for bladder cancer; and a double Fast Track designation to a single-fusion protein for the treatment of head and neck cancer and gastric or gastroesophageal junction carcinoma.
Priority Review for Atezolizumab Monotherapy as First-Line Treatment for Certain NSCLCs
The FDA accepted a supplemental biologics license application and granted Priority Review to atezolizumab as a first-line monotherapy for patients with advanced nonsquamous and squamous non–small cell lung cancer (NSCLC) without EGFR or ALK mutations with high programmed cell death ligand 1 (PD-L1) expression as determined by PD-L1 biomarker testing. The FDA set a Prescription Drug User Fee Act (PDUFA) target action date of June 19, 2020.
Atezolizumab is a monoclonal antibody that blocks the activity of PD-L1. The application is based on results from the phase III IMpower110 study, which showed that atezolizumab monotherapy improved overall survival by 7.1 months compared with chemotherapy (median overall survival = 20.2 vs 13.1 months; hazard ratio [HR] = 0.595, 95% confidence interval [CI] = 0.398–0.890; P = .0106) in patients with high PD-L1 expression. Safety for atezolizumab appeared to be consistent with the agent’s known safety profile, and no new safety signals were identified. Grade 3 and 4 treatment-related adverse events were reported in 12.9% of those receiving atezolizumab vs 44.1% of those receiving chemotherapy.
Priority Review for Lurbinectedin in Relapsed Small Cell Lung Cancer
The FDA accepted a new drug application seeking accelerated approval and granted Priority Review to lurbinectedin for the treatment of patients with small cell lung cancer (SCLC) who have had disease progression after prior platinum-containing therapy. The FDA set a PDUFA target action date of August 16, 2020.
Lurbinectedin is a synthetic compound currently under clinical investigation. It is a selective inhibitor of the oncogenic transcription programs on which many tumors are particularly dependent. Together with its effect on cancer cells, lurbinectedin inhibits oncogenic transcription in tumor-associated macrophages, downregulating the production of cytokines that are essential for the growth of the tumor.
The application is based on data from a phase II monotherapy basket trial, which included evaluation of lurbinectedin for the treatment of relapsed SCLC. A total of 105 patients from 39 centers were recruited in Europe and the United States. The trial met its primary endpoint of objective response rate, and its results were presented at the 2019 ASCO Annual Meeting by Paz-Ares et al (Abstract 8506).
Priority Review for Selinexor in Relapsed or Refractory Diffuse Large B-Cell Lymphoma
The FDA accepted a supplemental new drug application seeking accelerated approval for oral selinexor tablets for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (not otherwise specified) who have received at least two prior therapies. The FDA also granted Karyopharm’s request for Priority Review, and set a a PDUFA target action date of June 23, 2020.
Selinexor has received both Orphan Drug and Fast Track designations from the FDA for the treatment for patients with relapsed or refractory DLBCL. The drug is a first-in-class, oral selective inhibitor of nuclear export compound. It functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). Selinexor blocks the nuclear export of tumor-suppressor, growth-regulatory, and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anticancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion.
Breakthrough Therapy Designation for Enfortumab Vedotin-ejfv in Combination With Pembrolizumab in First-Line Advanced Bladder Cancer
The FDA granted Breakthrough Therapy designation for enfortumab vedotin-ejfv in combination with pembrolizumab for the treatment of patients with unresectable locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy in the first-line setting.
Enfortumab vedotin-ejfv is a first-in-class antibody-drug conjugate that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer. The Breakthrough Therapy designation was granted based on results from the dose-escalation cohort and expansion cohort A of the phase Ib/II EV-103 trial, which is evaluating patients with locally advanced or metastatic urothelial cancer who are unable to receive cisplatin-based chemotherapy treated in the first-line setting with enfortumab vedotin-ejfv in combination with pembrolizumab. Initial results from the trial were presented at the European Society of Medical Oncology Congress 2019, and updated findings at the 2020 Genitourinary Cancers Symposium (Abstract 441).
Two Fast Track Designations for ALX148: Head and Neck Cancer and Gastric or Gastroesophageal Junction Adenocarcinoma
The FDA granted two Fast Track designations to ALX148: one for the first-line treatment of patients with head and neck squamous cell carcinoma, and the second, for the second-line treatment of patients with HER2-positive gastric or gastroesophageal junction carcinoma. Data supporting these Fast Track designations were based on an open-label, multicenter phase I clinical trial of ALX148 in combination with pembrolizumab or trastuzumab.
The manufacturer of the agent commented, “We are encouraged by the initial data from our phase I clinical trial that showed a 40% objective response rate in checkpoint inhibitor–naive patients with [head and neck squamous cell carcinoma] whose tumors had progressed on prior platinum therapy, and a 21% objective response rate in patients with gastric or gastroesophageal junction carcinoma where all responders’ disease had progressed upon at least one prior anti-HER2–containing regimen.”
ALX148 is an intravenously administered fusion protein containing two engineered high-affinity CD47 binding domains of SIRPα linked to an inactive Fc region of human immunoglobulin.
