Avapritinib Approved for Advanced Systemic Mastocytosis
The FDA approved avapritinib for adult patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia.
Efficacy was evaluated in EXPLORER (NCT02561988) and PATHFINDER (NCT03580655), two multi-center, single-arm, open-label clinical trials enrolling patients with AdvSM. The main efficacy outcome measure was overall response rate (ORR) per modified IWG-MRT-ECNM response criteria, as adjudicated by a central committee. Additional efficacy measures were duration of response, time to response, and changes in individual measures of mast cell burden. Fifty-three patients received daily doses of avapritinib, up to 200 mg.
The ORR in all evaluable patients in both trials combined was 57 percent (95% CI: 42, 70) (n=53), with 28 percent complete remissions and 28 percent partial remissions. The median duration of response was 38.3 months (95% CI: 19, not estimable) and the median time to response was 2.1 months. The most common adverse reactions (incidence >= 20%) in patients with AdvSM were edema, diarrhea, nausea, and fatigue/asthenia.
Avapritinib is not recommended for the treatment of patients with AdvSM with platelet counts of less than 50 x 109/L. The recommended avapritinib dose is 200 mg orally once daily for patients with AdvSM.
Orphan Drug Designation for Devimistat for Treatment of Biliary Cancer
The FDA granted orphan drug designation to devimistat for the treatment of biliary cancer, which includes gallbladder cancer and bile duct cancer. Biliary cancer is classified as a rare disease, affecting just 12,000 people in the U.S. each year, respectively.
"Biliary cancer is often identified as an advanced stage cancer and considered aggressive with only modest response to existing treatment options for patients," said Vaibhav Sahai, MBBS, MS, Associate Professor of Medical Oncology at The University of Michigan Medicine and principal investigator on the Phase Ib/II clinical trial of devimistat in combination with gemcitabine and cisplatin for patients with biliary cancer. "The orphan drug designation for devimistat showcases the importance of discovering these new treatment options."
Devimistat is a first-in-class clinical lead compound of Rafael, which targets enzymes that are involved in cancer cell energy metabolism and are located in the mitochondria of cancer cells. Devimistat is designed to target the mitochondrial tricarboxylic acid cycle, a process essential to tumor cell multiplication and survival, selectively in cancer cells. Devimistat substantially increases the sensitivity of cancer cells to a diverse range of chemotherapeutic agents. This synergy allows for potential combinations of the compound with lower doses of these generally toxic drugs to be more effective and lower a patient's side effects. Combination with devimistat represents a diverse range of opportunities to substantially improve patient's benefit in many different cancers.
Implant Loosening in Orthopaedic Oncology & Complex Revision Surgery
The FDA granted 510(k) clearance for a modular collar portfolio featuring BioGrip 3D-printed implant technology. The patented design, now available as part of the ELEOS Limb Salvage System, was created to help address the clinical challenge of aseptic loosening (also known as implant loosening) in musculoskeletal oncology and complex orthopaedic limb salvage surgery.
With its new 3D-printed porous structure and novel nano-HA treatment, the modular collar is designed to help provide bone ingrowth at the bone-implant interface, which may help address aseptic loosening. The treatment helps to accelerate and enhance osseointegration.
The 3D-printed, nano-HA treated design is one of two interchangeable collar designs added to address these complex clinical challenges. The clearance also includes an oval-shaped collar design to provide greater contact in distal femoral replacements, where subsidence is a common challenge among complex revision and trauma applications.
"Research has shown that designs treated with hydroxyapatite provide greater surface area for bone ingrowth and may result in lower rates of implant loosening," said Shervin Oskouei, MD, Division Director of Orthopedic Oncology at Emory University and Chief of Orthopedic Surgery at Emory University Hospital Midtown. "Having this technology available at the bone-implant junction is critical to supporting a reconstruction that may lead to improved implant longevity for these complex procedures."
CLN-619, a Novel MICA/B-Targeted Antibody for Treating of Solid Tumors
The FDA cleared an IND application for CLN-619. It is a first-in-class monoclonal antibody designed to promote an antitumor response by engaging both natural killer (NK) and T cells through the MICA/B-NKG2D axis, with therapeutic potential for both solid and liquid tumor indications.
CLN-619 is a humanized IgG1 monoclonal antibody that binds to MICA and MICB expressed on a wide variety of cancer cells. MICA/B are stress-induced ligands recognized by both cytotoxic innate and adaptive immune cells via their NKG2D receptor. To evade lysis by these immune cells, tumor cells shed MICA/B from their cell surface. CLN-619 promotes an antitumor response through multiple mechanisms of action, including prevention of the proteolytic release of MICA/B from cancer cells, antibody-dependent cell-mediated cytotoxicity, enhancement of MICA/B binding to NKG2D, and reduction of the inhibitory effect of shed MICA/B.
In preclinical studies, animals treated with CLN-619 as a monotherapy demonstrated significant inhibition of tumor growth and a dramatic reduction of serum levels of soluble MICA. Multiple studies evaluating serum samples from cancer patients have demonstrated that high serum levels of shed MICA correlate with a poor prognosis.
New Companion Diagnostic to Identify ALK-Positive Metastatic Non-Small Cell Lung Cancer
FoundationOneCDx received FDA approval as a companion diagnostic for brigatinib, which is currently FDA-approved for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. This tissue-based comprehensive genomic profiling test is now able to detect ALK+ mNSCLC and identify patients who may be appropriate for treatment with brigatinib, which is approved as a first-line or later-line therapy.
NSCLC is the most common form of lung cancer, accounting for 85 percent of the estimated 1.8 million new cases of lung cancer diagnosed globally each year. Approximately 3-5 percent of patients with NSCLC have a rearrangement in the ALK gene.
FoundationOne CDx, which now has 28 companion diagnostic claims, is the first and only FDA-approved tissue-based broad companion diagnostic that is clinically and analytically validated for solid tumors. This latest approval reinforces the test's ability to detect ALK rearrangements, which can be missed with alternate testing methods (Clin Cancer Res 2013;19(15):4273-81).
Brigatinib is a potent and selective next-generation tyrosine kinase inhibitor (TKI) that was designed to target ALK molecular alterations. It is approved in the U.S., European Union (EU), and Japan as a first-line treatment for patients with ALK+ mNSCLC previously not treated with an ALK inhibitor. The TKI is also approved in more than 40 countries, including the U.S., Canada and the EU, for the treatment of people living with ALK+ mNSCLC who have taken crizotinib, but their NSCLC has worsened or they cannot tolerate this treatment.