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The ASCO Post – FDA Pipeline: Assay Approval, Breakthrough Designations for AI Technology and CLL, and More

The ASCO Post – FDA Pipeline: Assay Approval, Breakthrough Designations for AI Technology and CLL, and More

In the past week, the U.S. Food and Drug Administration (FDA) approved a companion diagnostic assay, granted Breakthrough Device and Breakthrough Therapy designations, and extended the review period of a proposed treatment. The agency also published four draft guidances and one final guidance regarding cancer trial eligibility criteria.

VENTANA PD-L1 (SP142) Assay Approved as Companion Diagnostic in Triple-Negative Breast Cancer

The FDA approved the VENTANA PD-L1 (SP142) Assay as the first companion diagnostic to aid in identifying patients with triple-negative breast cancer eligible for treatment atezolizumab plus nanoparticle albumin-bound (nab)-paclitaxel. Assessment of programmed cell death ligand 1 (PD-L1) biomarker status on tumor-infiltrating immune cells with the assay is essential for identifying patients who are most likely to benefit from the treatment.


The VENTANA PD-L1 (SP142) Assay was developed to enhance visual contrast of tumor-infiltrating immune cell staining. In triple-negative breast cancer, PD-L1 is primarily expressed on tumor-infiltrating immune cells rather than on tumor cells themselves. Launched in 2016, the VENTANA PD-L1 (SP142) Assay is the primary diagnostic assay within the atezolizumab clinical development program and was used to enroll and stratify patients in atezolizumab clinical trials.

FDA Grants Breakthrough Device Designation to Paige.AI

Paige.AI has been granted Breakthrough Device designation by the FDA. The FDA’s Breakthrough Device designation is granted for technologies that have the potential to provide for more effective diagnosis or treatment for life-threatening or irreversibly debilitating diseases where timely availability is in the best interest of patients because no approved alternative exists—or because the technology offers significant advantages over existing approved alternatives. The Breakthrough Device program was created by the 21st Century Cures Act.


Paige.AI was launched in early 2018 based on a license agreement with Memorial Sloan Kettering Cancer Center. Memorial Sloan Kettering began digitizing its pathology slides 4 years ago. Under the license agreement, Paige.AI receives deidentified images of digitized slides—more than 1 million such slides to date—and is funding the digitization of an additional 4 million archive slides, which in total will create the largest digital pathology dataset. Paige.AI is working with this deidentified dataset to develop a comprehensive portfolio of artificial intelligence products across cancer subtypes to serve the needs of pathologists around the world.

Breakthrough Therapy Designation for Venetoclax in Combination With Obinutuzumab in CLL

The FDA granted Breakthrough Therapy designation to venetoclax for use in combination with obinutuzumab as a fixed duration investigational combination for untreated adult patients with chronic lymphocytic leukemia (CLL). The agency will review the venetoclax-plus-obinutuzumab combination under its real-time oncology review pilot program, which aims to explore a more efficient review process to ensure safe and effective cancer medicines are available to patients as early as possible.


The supplemental new drug application for the venetoclax and obinutuzumab combination is based on data from the phase III CLL14 trial, which studied patients receiving the first-line combination treatment for 12 months. CLL14 is the first randomized trial in CLL to examine a chemotherapy-free, fixed-duration treatment regimen.

Extension of Review Period for Selinexor New Drug Application

The FDA has extended the Prescription Drug User Fee Act (PDUFA) action date for the new drug application (NDA) for selinexor. The previously disclosed April 6, 2019, PDUFA date has been extended by 3 months, to July 6, 2019.


The NDA, which is currently under Priority Review by the FDA, is seeking accelerated approval for selinexor in combination with dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody.


On February 26, 2019, the FDA’s Oncologic Drugs Advisory Committee (ODAC) met to discuss the selinexor NDA. The committee voted 8 to 5 recommending that the FDA wait for the results from the randomized, open-label, phase III BOSTON study before making a final decision regarding approval.


Following the ODAC meeting, at the FDA’s request, additional existing clinical information was submitted as an amendment to the NDA, which allowed the FDA to extend the PDUFA action date.

FDA Takes New Steps to Broaden Patient Participation in Cancer Clinical Trials

This week, the FDA published four draft guidances and one final guidance regarding cancer trial eligibility criteria. These guidances provide recommendations on how sponsors can safely and effectively broaden the criteria for the inclusion of certain patient populations in clinical trials. This broadening includes the inclusion of—when appropriate—pediatric patients, and patients with HIV, hepatitis B and hepatitis C, brain metastases, prior or concurrent malignancies, or organ dysfunction.


The four draft guidances were developed by the FDA with input from stakeholders (including ASCO and Friends of Cancer Research) to encourage inclusiveness in cancer trial enrollment to maximize the generalizability of trial results.


The final guidance, Considerations for the Inclusion of Adolescent Patients in Adult Oncology Clinical Trials, finalizes the draft guidance of the same name issued on June 4, 2018.


FDA Commissioner Scott Gottlieb, MD, commented:


When drug developers design a clinical trial, they identify eligibility criteria to define what types of patients qualify for participation in the trial. They base the eligibility criteria on factors such as the mechanism of action of the drug, characteristics of the disease, the expected toxicities of the investigational drug, and the ability to recruit trial participants from the patient population to meet the objectives of the clinical trial. However, in trials testing treatments for cancer, some eligibility criteria have become commonly accepted over time or used as a template across trials—without a clear scientific or clinical rationale or justification. In other cases, eligibility criteria can be deliberately restrictive, even though it is not clinically merited. As a result, [patients with cancer] are often unnecessarily restricted from participating in trials. Overly restrictive eligibility criteria may slow patient accrual, limit patients’ access to clinical trials, and lead to trial results that don’t fully represent treatment effects in the patient population that will ultimately receive the drug.


The FDA issued new recommendations for broadening cancer trial eligibility criteria that are designed to help address these challenges. A clinical trial that’s more representative of the patient population can maximize the generalizability of the trial results and the ability to understand the therapy’s benefit-risk profile across the patient population likely to receive the drug in clinical practice. For example, broadening eligibility criteria to include pediatric patients, when appropriate, may provide information on safe and effective use in children and may accelerate the development of effective therapies for pediatric patients. Another patient population that’s typically excluded from clinical trials is patients with HIV, hepatitis B, and hepatitis C. Including these patients in clinical trials can be justified in many cases, and may accelerate the development of effective therapies in patients [with cancer] that also have these chronic infections. Additionally, patients with brain metastases, organ dysfunction, and prior or concurrent malignancies are typically unnecessarily excluded from cancer clinical trials. These are all patient groups that we aim to address with the new policies being released.


These policies will help ensure that the design of clinical trials reflects the diversity of the population that receives drugs in the real world. For far too long, certain patients have been unnecessarily excluded from the chance to be a part of a clinical trial. [These new] policies will help to shift the design of oncology clinical trials to be more representative of the patients that may ultimately benefit from novel treatments.