This week, the U.S. Food and Drug Administration (FDA) granted Priority Review to treatments for ovarian, prostate, and lung cancer; granted Orphan Drug designation to therapies for chemotherapy-induced thrombocytopenia and multiple myeloma; and granted Breakthrough Device designation to platforms for colorectal cancer screening and early-stage cancer treatment monitoring and recurrence surveillance.
Olaparib Granted Priority Review as First-Line Maintenance Treatment in Combination With Bevacizumab in Advanced Ovarian Cancer
A supplemental new drug application for olaparib in combination with bevacizumab has been accepted and granted Priority Review for the maintenance treatment of patients with advanced ovarian cancer who are in complete or partial response to first-line platinum-based chemotherapy with bevacizumab. A Prescription Drug User Fee Act (PDUFA) date is set for the second quarter of 2020.
The Priority Review was based on results from the phase III PAOLA-1 trial, which were published by Ray-Coquard et al in The New England Journal of Medicine. The trial compared olaparib when added to the standard of care, bevacizumab, vs bevacizumab alone in patients with advanced ovarian cancer in the first-line maintenance setting, regardless of their genetic biomarker status or outcome from previous surgery.
The investigator-assessed results showed olaparib added to bevacizumab reduced the risk of disease progression or death by 41% based on a hazard ratio of 0.59 (95% confidence interval = 0.49–0.72, P < .001) and improved progression-free survival, with a median of 22.1 months vs 16.6 months for patients treated with bevacizumab alone. The safety and tolerability profiles of olaparib and bevacizumab were consistent with previous trials for each medicine
The most common adverse events ≥ 20% for patients treated with olaparib plus bevacizumab compared to bevacizumab alone were fatigue (53% vs 32%), nausea (53% vs 22%), hypertension (46% v 60%), anemia (41% vs 10%), lymphopenia (24% vs 9%), vomiting (22% vs 11%) and arthralgia (22% vs 24%). Overall grade ≥ 3 events were reported in 57% of patients treated with olaparib plus bevacizumab and 51% for bevacizumab alone.
Adverse events led to dose interruption in 54% of patients on olaparib plus bevacizumab vs 24% on bevacizumab alone, and 41% of patients on olaparib plus bevacizumab had a dose reduction vs 7% on bevacizumab alone. Discontinuation of treatment occurred in 20% of patients on olaparib plus bevacizumab vs 6% on bevacizumab alone.
Rucaparib Granted Priority Review for Advanced Prostate Cancer
The FDA accepted a supplemental new drug application for rucaparib and granted Priority Review status to the application, with a PDUFA date of May 15, 2020. The submission was for rucaparib as a monotherapy for adult patients with BRCA1/2-mutant, recurrent, metastatic castrate-resistant prostate cancer.
The application is based on findings from the ongoing, international, multicenter, open-label phase II TRITON2 trial, which is investigating how patients with metastatic castration-resistant prostate cancer and evidence of a homologous recombination gene deficiency respond to treatment with rucaparib.
Rucaparib is an oral, small-molecule inhibitor of PARP1, PARP2, and PARP3 being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anticancer agents. Exploratory studies in other tumor types are also underway.
Priority Review for Nivolumab/Ipilimumab in NSCLC With No EGFR or ALK Mutations
The FDA accepted a supplemental biologics license application and granted it Priority Review for nivolumab in combination with ipilimumab for the first-line treatment of patients with metastatic or recurrent non–small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations. The PDUFA date is set for May 15, 2020.
The application is based on results from part 1 of the phase III CheckMate 227 study. In the two-part, open-label clinical trial, the combination of nivolumab and ipilimumab vs platinum-doublet chemotherapy was evaluated in patients with previously untreated advanced NSCLC across nonsquamous and squamous tumor histologies. The dual immunotherapy combination demonstrated significant improvement in overall survival over chemotherapy alone. The safety profile of these two agents was consistent with previously reported studies, and no new safety signals were observed.
Part 1 met both its co-primary endpoints of progression-free survival with nivolumab/ipilimumab vs chemotherapy in patients whose tumors have a high (≥ 10 mutations/megabase) tumor mutation burden, regardless of programmed cell death ligand 1 (PD-L1) expression and overall survival, demonstrating a benefit with nivolumab plus low-dose ipilimumab vs chemotherapy in the first-line treatment of patients with NSCLC whose tumors express PD-L1 ≥ 1%.
Orphan Drug Designation for Avatrombopag for the Treatment of Chemotherapy-Induced Thrombocytopenia
The FDA granted Orphan Drug designation to avatrombopag for the potential treatment of chemotherapy-induced thrombocytopenia. Enrollment remains ongoing for the phase III clinical study of avatrombopag for the treatment of patients with chemotherapy-induced thrombocytopenia.
Chemotherapy-induced thrombocytopenia results in low platelet levels and can lead to chemotherapy dose reductions, chemotherapy dose delays, or changes to chemotherapy regimens. For patients receiving chemotherapy with curative intent, alterations in their chemotherapy regimen due to low platelets may compromise their long-term outcomes. Approximately 10% of patients with cancer in the United States per year experience chemotherapy-induced thrombocytopenia. Currently, there are no treatments available for chemotherapy-induced thrombocytopenia in the United States.
Avatrombopag is an oral thrombopoietin receptor agonist administered with food, and it is approved by both the FDA and European Medicines Agency for treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. In June 2019, avatrombopag was approved by the FDA for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment.
Investigational New Drug, Orphan Drug Designation for PBCAR269A in Multiple Myeloma
The FDA accepted an investigational new drug application for PBCAR269A, an allogeneic chimeric antigen receptor (CAR) T-cell therapy candidate. The FDA has also granted Orphan Drug designation to PBCAR269A for the treatment of multiple myeloma.
PBCAR269A targets the B-cell maturation antigen and is in development for the treatment of relapsed or refractory multiple myeloma.
PBCAR269A will be evaluated in a phase I multicenter, open-label, dose-escalation and dose-expansion clinical trial in adult patients with relapsed or refractory multiple myeloma.
Preventive Screening Test for Colorectal Cancer and Precancerous Adenomas Earns Breakthrough Device Designation
A preventive screening test for colorectal cancer and precancerous adenomas has earned FDA Breakthrough Device designation. Preliminary data indicate that the screening test could provide a more effective method for early detection of advanced adenomas, thereby facilitating the removal of precancerous lesions that have the highest propensity for malignant transformation. The device could significantly reduce morbidity by detecting advanced adenomas at a higher rate than existing screening tests and preventing the development of colorectal cancer.
“Reduction in morbidity is the best way to reduce mortality associated with colorectal cancer,” said Erica Barnell, Chief Scientific Officer of Geneoscopy. “We are excited that the FDA has recognized the potential for [our] test to improve the health of the more than 100 million Americans recommended for colorectal cancer screening.”
ArcherDX Personalized Cancer Monitoring Technology Designated by as Breakthrough Device
ArcherDX, Inc, announced it has received Breakthrough Device designation from FDA for its Personalized Cancer Monitoring technology, a bespoke, minimally invasive, and highly sensitive product intended for early-stage cancer treatment monitoring and recurrence surveillance. ArcherDX's technology enables health-care providers across community and academic care settings to access genomic information in their laboratory, saving critical time and allowing care locally.
The program will provide ArcherDX with enhanced communication with the FDA regarding technology validation and clinical trial protocols and could expedite the review process.
As part of an ongoing collaboration, TRACERx investigators are utilizing ArcherDX's technology to detect low-volume minimal residual disease at high levels of sensitivity to help achieve TRACERx's goal of a more personalized approach to developing cancer treatments.
