공시 • Aug 02
Adaptimmune Therapeutics plc Receives U.S. FDA Accelerated Approval of TECELRA®
Adaptimmune Therapeutics plc announced U.S. Food and Drug Administration (FDA) accelerated approval of TECELRA® (afamitresgene autoleucel) for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A 02:01P, -A 02:02P, -A 02:03P, or -A 02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. TECELRA is the first engineered cell therapy for a solid tumor cancer approved in the U.S., and the first new therapy option in more than a decade for synovial sarcoma, a rare, soft tissue cancer that most commonly impacts young adults. The approval of TECELRA was based on results of the SPEARHEAD-1 (Cohort 1) trial, which included 44 patients. The major efficacy outcome was overall response rate (ORR) determined by independent review and supported by duration of response. TECELRA treatment resulted in an ORR of 43% with a complete response rate of 4.5%. The median duration of response was 6 months (95% CI: 4.6, not reached). Among patients who were responsive to the treatment, 39% had a duration of response of 12 months or longer. With this approval, Adaptimmune is positioned to make a significant impact on the synovial sarcoma community. HCPs can begin testing patients, Adaptimmune systems are ready to take TECELRA orders, and an integrated support program, AdaptimmuneAssist, is available to enable a seamless and personalized experience through the treatment journey. Adaptimmune plans to have at least six to ten authorized treatment centers (ATCs) up and running this year and to onboard approximately 30 treatment centers within the first two years. These ATCs are recognized leaders in sarcoma research and treatment. TECELRA is contraindicated in adults who are heterozygous or homozygous for HLA-A 02:05P. TECELRA can cause serious side effects, including cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), prolonged severe cytopenia, infections, secondary malignancies, and hypersensitivity reactions. Most common adverse reactions (incidence =20%) were CRS, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia, back pain, hypotension, diarrhea, edema, low white blood cells, low red blood cells and low platelets. Biomarker tests for human leukocyte antigens (HLA) type and melanoma-associated antigen A4 (MAGE-A4) tumor expression are required prior to treatment with TECELRA. Adaptimmune has partnered with Agilent Technologies for the development, manufacturing, and supply of a companion diagnostic for the MAGE-A4 biomarker, MAGE-A4 IHC 1F9 pharmDx, which also received approval from the U.S. FDA and is now available. Additionally, the company partnered with Thermo Fisher Scientific to expand the labeling of Thermo Fisher’s companion diagnostic product SeCoreTM CDx HLA-A Locus Sequencing System to include TECELRA and to aid in the identification of HLA-A 02:01, A 02:02, A 02:03, and A 02:06-positive patients with synovial sarcoma. TECELRA® (afamitresgene autoleucel) is a melanoma-associated antigen A4 (MAGE-A4)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A 02:01P, -A 02:02P, -A 02:03P, or -A 02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices. Important Safety Information: Cytokine release syndrome (CRS), which may be severe or life-threatening, occurred in patients receiving TECELRA. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care. Ensure that healthcare providers administering TECELRA have immediate access to medications and resuscitative equipment to manage CRS. CRS occurred in 75% of patients (2% Grade =3) with a median onset of 2 days (range: 1 to 5 days) and median resolution of 3 days (range: 1 to 14 days). CRS (including Grade 1) was managed with tocilizumab in 55% of patients who experienced CRS. In patients who experienced CRS, the most common symptoms included fever, tachycardia, hypotension, nausea/vomiting, and headache. Immune Effector Cell–associated Neurotoxicity Syndrome (ICANS): ICANS has been observed following administration of TECELRA.Monitoring for CRS and ICANS During and Following TECELRA Infusion: Ensure that healthcare providers administering TECELRA have immediate access to medications and resuscitative equipment to manage CRS and ICANS. Ensure patients are euvolemic prior to initiating TECELRA. During and following TECELRA administration, closely monitor patients for signs and symptoms of CRS and ICANS. Following treatment with TECELRA, monitor patients for at least 7 days at the healthcare facility. Continue to monitor patients for at least 4 weeks following treatment with TECELRA. Counsel patients to seek medical attention should signs or symptoms of CRS or ICANS occur. Prolonged Severe Cytopenia: Anemia, neutropenia, and/or thrombocytopenia can occur for several weeks following lymphodepleting chemotherapy and TECELRA infusion. Patients with Grade =3 cytopenia not resolved by week 4 included anemia (9%), neutropenia (11%), and thrombocytopenia (5%). Infections: Infections may occur following lymphodepleting chemotherapy and TECELRA infusion and occurred in 32% of patients (14% Grade 3). Secondary Malignancies: Patients treated with TECELRA may develop secondary malignancies or recurrence of their cancer. Monitor for secondary malignancies. Potential for HIV Nucleic Acid Test False-Positive Results: The lentiviral vector used to make TECELRA has limited, short spans of genetic material that are identical to HIV. Therefore, some commercial HIV nucleic acid tests may yield false-positive results in patients who have received TECELRA. Adverse Reactions: Most common adverse reactions (incidence =20%) are CRS, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia, back pain, hypotension, diarrhea, and edema. Most common Grade 3 or 4 laboratory abnormalities (incidence =20%) were lymphocyte count decreased, neutrophil count decreased, white cell blood count decreased, red blood cell decreased, and platelet count decreased. Most common serious adverse reactions (=5%) were CRS and pleural effusion.
