publication date: Jul. 27, 2018
Drugs & Targets
FDA approves magnetic device system for sentinel biopsies in breast cancer
FDA approved Magtrace and Sentimag Magnetic Localization System (Sentimag System), a magnetic device system for guiding lymph node biopsies in patients with breast cancer undergoing mastectomy. It uses magnetic detection during sentinel lymph node biopsy procedures to identify specific lymph nodes, known as sentinel lymph nodes, for surgical removal.
FDA granted approval of the Sentimag System to Endomagnetics Inc.
Sentinel lymph nodes are the first lymph nodes to which cancer cells are most likely to spread from a primary tumor. For patients with breast cancer, testing the sentinel lymph nodes indicates whether the cancer has spread from the breast. A sentinel lymph node biopsy is used to identify, remove and examine lymph nodes to determine whether cancer cells are present.
The Sentimag System uses magnetic materials to guide the sentinel lymph node biopsy procedure. The system is comprised of a sensitive magnetic sensing probe and base unit designed to detect small amounts of Magtrace, the magnetic tracer drug that is injected into breast tissue.
The Magtrace particles travel to lymph nodes and become physically trapped in them, facilitating magnetic detection of the lymph nodes. Following the injection of Magtrace, the Sentimag probe is applied to the patients’ skin in areas closest to the tumor site containing the lymph nodes. The sensing of the magnetic particles is indicated by changes in audio and visual alerts from the base unit, enabling the surgeon to move the hand-held probe around the area of the lymph nodes, and locate the sentinel lymph node or nodes (if there are more than one). The surgeon then makes a small incision and removes the node, which is checked by a pathologist for the presence of cancer cells.
A negative sentinel lymph node biopsy result suggests that cancer has not spread to nearby lymph nodes. A positive result may indicate that cancer is present in the sentinel lymph node and may be present in other nearby lymph nodes and, possibly, other organs. This information can help a doctor determine the stage of the cancer and develop an appropriate treatment plan.
The FDA evaluated data from a trial of 147 patients with breast cancer to compare the Sentimag System to the control method of injecting patients with blue dye and radioactive materials together and using a gamma probe to identify the sentinel lymph node.
Patients were administered both methods to compare lymph node detection rates. The lymph node detection rate for the Sentimag System was 94.3 percent while the control method detection rate was 93.5 percent. Overall, 98.0 percent of patients had the same detection rate with both the Sentimag System and the control method.
The most common adverse event reported include breast discoloration, which is reported to disappear after three months in patients who underwent mastectomy, cardiac disorder and potential allergic reaction to the magnetic materials.
The Sentimag System is contraindicated in any patient with hypersensitivity to iron oxide or dextran compounds It is also not recommended for patients with iron overload disease or with a metal implant in the axilla or in the chest.
Magtrace may travel to regions away from the injection site such as liver or spleen, if injected directly into the bloodstream. In such cases the presence of Magtrace may cause image artifacts during Magnetic Resonance Imaging. Magtrace residues have not been reported to produce artifacts affecting imaging in X-ray, positron emission tomography scans, computed tomography scans, PET/CT scans or ultrasound studies.
FDA reviewed the Sentimag System application using a coordinated, cross-agency approach. The clinical review was conducted by CDRH in consultation with the Center for Drug Evaluation and Research and with support from the Oncology Center of Excellence, while all other aspects of review and the final product approval determination was conducted by CDRH.
FDA accepts Celyad IND application for CYAD-101, a non-gene edited allogeneic CAR-T candidate
Celyad said FDA has accepted the company’s Investigational New Drug application for CYAD-101, the first non-gene edited allogeneic clinical program. FDA has indicated that the Allo-SHRINK trial, evaluating the safety and clinical activity of CYAD-101 in patients with unresectable colorectal cancer in combination with standard chemotherapy, is allowed to proceed.
CYAD-101, Celyad’s first allogeneic CAR-T cell product, encodes both the company’s autologous CYAD-01 CAR-T and a novel peptide, TCR Inhibiting Molecule, an inhibitor of TCR signaling. TCR signaling is responsible for the graft vs. host disease, and tampering or eliminating its signaling could therefore reduce or eliminate GvHD.
In CYAD101, the TIM peptide is encoded alongside the CAR construct allowing allogeneic T cell production through a single transduction step. CYAD-101 benefits from using a manufacturing process that is highly similar to Celyad’s well established process for its clinical autologous CAR-T cell products.
While autologous CAR-T therapies now have well established efficacy in B cell malignancies, the approach can be more challenging for some patients, especially those where the quality of the apheresis is poor.
Keytruda approved in China for advanced melanoma
The China National Drug Administration approved Merck’s Keytruda for the treatment of adult patients with unresectable or metastatic melanoma following failure of one prior line of therapy. This is the first approval of an anti-PD-1 therapy for advanced melanoma in China.
The approval of Keytruda in China was based on overall response rate data from the phase Ib KEYNOTE-151 study, which evaluated Keytruda monotherapy in Chinese patients with previously treated locally advanced or metastatic melanoma who received one prior line of systemic therapy.
In 2018, the CNDA granted priority review status to Keytruda, which accelerated the approval process by allowing for simultaneous clinical validation for the first time – creating an industry leading approval turnaround time for imported cancer medicine in China.
KEYNOTE-151 is an open-label, single-arm, multi-center, phase Ib trial evaluating Keytruda monotherapy in 103 Chinese patients with previously treated locally advanced or metastatic melanoma who received one prior line of systemic therapy.
Patients were enrolled to receive KEYTRUDA at a dose of 2 mg/kg every three weeks. The primary efficacy outcome measure was ORR as assessed by Blinded Independent Central Review using RECIST 1.1. Secondary efficacy outcome measures were duration of response and progression-free survival (as assessed by BICR per RECIST 1.1 and irRECIST), ORR (as assessed by BICR per irRECIST) and overall survival.
BMS, Tsinghua University to develop therapies for autoimmune diseases, cancer
Bristol-Myers Squibb Co. and Tsinghua University have entered into a collaboration to discover therapeutic agents against novel targets for autoimmune diseases and cancers.
The collaboration brings together BMS and Tsinghua University’s scientific expertise and capabilities with a focus on validating new targets and generating early drug candidates for clinical development.
Under the collaboration, The Innovation Center for Immune Therapy of Tsinghua University will conduct research on projects and BMS will have an option to exclusively license therapeutic agents discovered by Tsinghua University.
The collaboration is an expansion of an existing relationship between Bristol-Myers Squibb and Tsinghua University that began in 2012, which focused on autoimmune target discovery, structural biology research, as well as the science of mapping the 3D protein structure of biological molecular targets.