TECELRA Suspension for injection Ref.[116126] Active ingredients: Afamitresgene autoleucel

5.1 Cytokine Release Syndrome

Cytokine release syndrome (CRS), including potentially life-threatening reaction has been observed following administration of TECELRA. CRS occurred in 75% of patients, 2% of whom had Grade ≥ 3 CRS. The median time to onset was 2 days (range: 1 to 5 days) and the median time to resolution was 3 days (range: 1 to 14 days). The most common symptoms were fever (97%), tachycardia (52%), hypotension (30%), nausea/vomiting (21%) and headache (15%) [see Adverse Reactions (6)]. Management for CRS (including Grade 1) was tocilizumab (55%). Thirteen patients received one dose and five patients received more than one dose. Of the five patients who received more than one dose of tocilizumab, two patients received dexamethasone in addition to tocilizumab.

Ensure that healthcare providers administering TECELRA have immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions.

During and following TECELRA administration, closely monitor patients for signs and symptoms of CRS. Following treatment with TECELRA, monitor patients for at least 7 days at the healthcare facility for CRS. Continue to monitor patients for CRS for at least 4 weeks following treatment with TECELRA. Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care based on severity and consider further management per current practice guidelines.

5.2 Immune Effector Cell-associated Neurotoxicity Syndrome

Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) has been observed following administration of TECELRA. One patient (2%) had Grade 1 ICANS. Time to onset was two days and time to resolution was one day. Symptoms included mild mental status changes. Other symptoms may include disorientation to time and place, mild drowsiness, mild inattention. Severe symptoms may include altered level of consciousness, seizures, cerebral edema, impairment of cognitive skills, progressive aphasia, motor weakness.

Ensure that healthcare providers administering TECELRA have immediate access to medications and resuscitative equipment to manage ICANS.

During and following TECELRA administration, closely monitor patients for signs and symptoms of ICANS. Following treatment with TECELRA, monitor patients for at least 7 days at the healthcare facility for ICANS. Continue to monitor patients for ICANS for at least 4 weeks following treatment with TECELRA. Counsel patients to seek medical attention should signs or symptoms of ICANS occur. At the first sign of ICANS, immediately evaluate patients for hospitalization and institute treatment with supportive care based on severity and consider further management per current practice guidelines.

Effect on Ability to Drive and Use Machines

Due to the potential for neurologic events, including dizziness and presyncope, patients receiving TECELRA are at risk for altered or decreased coordination in the 4 weeks following infusion.

Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

5.3 Prolonged Severe Cytopenia

Patients may exhibit severe cytopenias, including neutropenia and thrombocytopenia [see Adverse Reactions (6)].

Patients exhibited anemia, neutropenia, and/or thrombocytopenia 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%). The median time to resolution was 7.3 weeks (range: 6.1 to 8.4 weeks) for anemia, 9.3 weeks (range: 6.4 to 12.3 weeks) for neutropenia and 6.3 weeks (range: 6.1 to 6.4 weeks) for thrombocytopenia.

Monitor blood counts after TECELRA infusion. Manage cytopenia with growth factor and blood product transfusion according to local institutional guidelines/clinical practice.

5.4 Infections

Infections may occur following lymphodepleting chemotherapy and TECELRA infusion. Infections (all grades) occurred in 32% of patients with synovial sarcoma. Grade 3 or higher infections occurred in 14% of patients.

Do not administer TECELRA to patients with active infections and/or inflammatory disorders.

Monitor patients for signs and symptoms of infection before and after TECELRA infusion and treat patients appropriately.

Febrile neutropenia was observed in patients after TECELRA infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated.

Viral reactivation has occurred in patients following treatment with TECELRA. Perform screening for Epstein-Barr Virus, Cytomegalovirus, Hepatitis B Virus, Hepatitis C Virus, Human Immunodeficiency Virus, and any other infectious agents if clinically indicated. Consider antiviral therapy to prevent viral reactivation per local guidelines.

5.5 Secondary Malignancies

Patients treated with TECELRA may develop secondary malignancies or recurrence of their cancer. Monitor for secondary malignancies.

In the event that a secondary malignancy occurs, contact Adaptimmune at 1-855-24MYADAP (1-855-246-9232) to obtain instructions on patient samples to collect for testing.

5.6 Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) in TECELRA. Observe patients for hypersensitivity reactions during infusion.

5.7 Potential for HIV Nucleic Acid Test False-Positive Results

The lentiviral vector used to make TECELRA has limited, short spans of genetic material which are identical to HIV. Therefore, some commercial HIV nucleic acid tests may yield false-positive results in patients who have received TECELRA.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety data described in this section reflects the exposure to TECELRA in 44 patients with advanced synovial sarcoma treated in the SPEARHEAD-1 clinical trial (Cohort 1). Patients with synovial sarcoma received TECELRA across a dose of 2.68 x 10⁹ to 10 x 10⁹ MAGE-A4 TCR positive T cells [see Clinical Studies (14)].

Serious adverse reactions occurred in 52% of patients with synovial sarcoma. The most common serious adverse reactions (occurring in ≥5%) included CRS (9%) and pleural effusion (7%).

Table 1 summarizes adverse reactions that occurred in at least 10% of patients.

Table 1. Adverse Reactions Occurring in ≥10% of Patients in SPEARHEAD-1 (Cohort 1):

^* As per American Society for Transplantation and Cellular Therapy (ASTCT) criteria^1
† Any infection includes all infection terms under the 'Infections and infestations' System Organ Class

Other clinically important adverse reactions occurring in patients receiving TECELRA include Grade 1 ICANS reported in one patient (2%).

Table 2. Laboratory Abnormalities* Worsened from Baseline in ≥10% of Patients in SPEARHEAD-1 (Cohort 1):

Grading based on NCI CTCAE version 5.0.
^* Abnormalities are laboratory values that were considered an adverse event.

None.

Risk Summary

There are no available data with TECELRA use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with TECELRA to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known if TECELRA has the potential to be transferred to the fetus and cause fetal toxicity. Therefore, TECELRA is not recommended for women who are pregnant, and pregnancy after TECELRA administration should be discussed with the treating physician. Report all pregnancies following treatment with TECELRA to Adaptimmune at 1-855-24MYADAP (1-855-246-9232).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Risk Summary

There is no information regarding the presence of TECELRA in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TECELRA and any potential adverse effects on the breastfed infant from TECELRA or from the underlying maternal condition.

Pregnancy Testing

Verify pregnancy status of females with reproductive potential prior to starting treatment with TECELRA.

Contraception

There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with TECELRA.

The safety and effectiveness of TECELRA have not been established in pediatric patients.

Of the 44 patients with synovial sarcoma in the SPEARHEAD-1 study that received TECELRA, 6.8% were 65 years of age or older. Clinical studies of TECELRA did not include sufficient numbers of patients aged 65 and over to conclude whether they respond differently from younger patients.