There are no available data with afamitresgene autoleucel use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with afamitresgene autoleucel to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known if afamitresgene autoleucel has the potential to be transferred to the fetus and cause fetal toxicity. Therefore, afamitresgene autoleucel is not recommended for women who are pregnant, and pregnancy after afamitresgene autoleucel administration should be discussed with the treating physician.
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.
There is no information regarding the presence of afamitresgene autoleucel 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 afamitresgene autoleucel and any potential adverse effects on the breastfed infant from afamitresgene autoleucel or from the underlying maternal condition.
No carcinogenicity or genotoxicity studies have been conducted with afamitresgene autoleucel.
A genomic insertion site analysis was performed on afamitresgene autoleucel products from five patients. There was no evidence for preferential integration near genes of concern. No studies have been conducted to evaluate the effects of afamitresgene autoleucel on fertility.
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 afamitresgene autoleucel in 44 patients with advanced synovial sarcoma treated in the SPEARHEAD-1 clinical trial (Cohort 1). Patients with synovial sarcoma received afamitresgene autoleucel across a dose of 2.68 x 109 to 10 x 109 MAGE-A4 TCR positive T cells.
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):
| SOC Grouped Term | (N=44) | |
|---|---|---|
| All Grades n (%) | Grade ≥ 3 n (%) | |
| Investigations | ||
| Weight decreased | 5 (11) | 1 (2) |
| Gastrointestinal disorders | ||
| Nausea | 29 (66) | 1 (2) |
| Vomiting | 16 (36) | 0 (0) |
| Constipation | 14 (32) | 0 (0) |
| Abdominal pain | 11 (25) | 2 (5) |
| Diarrhea | 9 (21) | 0 (0) |
| General disorders and administration site conditions | ||
| Fatigue | 15 (34) | 0 (0) |
| Pyrexia | 14 (32) | 1 (5) |
| Non-cardiac chest pain | 10 (23) | 1 (2) |
| Chills | 7 (16) | 0 (0) |
| Edema | 9 (21) | 0 (0) |
| Asthenia | 7 (17) | 1 (2) |
| Chest pain | 6 (14) | 0 (0) |
| Immune system disorders | ||
| Cytokine Release Syndrome* | 33 (75) | 1 (2) |
| Infections and infestations | ||
| Any infection† | 14 (32) | 6 (14) |
| Nervous system disorders | ||
| Headache | 8 (18) | 1 (2) |
| Dizziness | 5 (11) | 0 (0) |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 10 (23) | 1 (2) |
| Musculoskeletal and connective tissue disorders | ||
| Back pain | 9 (21) | 2 (5) |
| Pain in extremity | 6 (14) | 0 (0) |
| Respiratory, thoracic, and mediastinal disorders | ||
| Dyspnea | 11 (25) | 2 (5) |
| Cough | 8 (18) | 0 (0) |
| Vascular disorders | ||
| Hypotension | 9 (21) | 0 (0) |
| Hypertension | 7 (16) | 1 (2) |
| Cardiac disorders | ||
| Sinus Tachycardia/ Tachycardia | 9 (21) | 0 (0) |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 6 (14) | 0 (0) |
* As per American Society for Transplantation and Cellular Therapy (ASTCT) criteria1
† Any infection includes all infection terms under the 'Infections and infestations' System Organ Class
Other clinically important adverse reactions occurring in patients receiving afamitresgene autoleucel 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):
| Laboratory Abnormalities | (N=44) | |
|---|---|---|
| All Grades n (%) | Grade 3 or 4 n (%) | |
| Lymphocyte count decreased | 43 (98) | 43 (98) |
| Neutrophil count decreased | 42 (96) | 40 (91) |
| White blood cell decreased | 42 (96) | 38 (86) |
| Red blood cell decreased | 42 (96) | 14 (32) |
| Platelet count decreased | 36 (82) | 9 (21) |
| Alanine aminotransferase increased | 20 (46) | 2 (5) |
Grading based on NCI CTCAE version 5.0.
* Abnormalities are laboratory values that were considered an adverse event.
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