Adaptimmune Therapeutics plc (Nasdaq:ADAP) announced on 8/14/18 a favorable review of safety data from the second dose cohort of patients who received one billion transduced SPEAR T‑cells targeting MAGE-A4 in the ongoing basket study in nine solid tumor indications. Based on these data, the Safety Review Committee (SRC) has endorsed dose escalation to the third dose cohort of 1.2 to 6 billion cells.
To date, three patients have received 100 million transduced MAGE‑A4 SPEAR T-cells in the first dose cohort, and three patients received one billion cells in the second cohort. No evidence of toxicity related to off-target binding or alloreactivity has been reported. Most adverse events were consistent with those typically experienced by cancer patients undergoing cytotoxic chemotherapy or other cancer immunotherapies.
“In Cohorts 1 and 2, we have observed cell expansion consistent with the doses administered. We are initiating dosing with 1.2 to 6 billion cells in the MAGE-A10 and MAGE-A4 studies. We have a number of patients whose cell products have been manufactured and these cells can be used when patients are ready for therapy. We remain on track to deliver initial data on response assessments from these cohorts during the second half of 2018,” said Rafael Amado, Adaptimmune’s President of Research & Development.
MAGE-A4 SPEAR T-cell therapy is directed to a member of the MAGE-A family of cancer testis antigens expressed in a number of solid tumor cell types. The MAGE-A4 antigen is among the most commonly expressed cancer testis antigens.
Overview of Study Design MAGE-A4 Pilot Study
- This is a first-in-human, open-label study utilizing a modified 3+3 design in up to 36 patients with escalating doses of 100 million (Cohort 1), 1 billion (Cohort 2), and 1.2‑6 billion (Cohort 3) transduced SPEAR T-cells to evaluate safety, including dose limiting toxicities (DLTs) followed by a possible expansion phase with doses of up to 10 billion SPEAR T-cells
- This active trial is being evaluated across nine solid tumor indications including urothelial, melanoma, head and neck, ovarian, NSCLC, esophageal, and gastric cancers; as well as synovial sarcoma and myxoid/round cell liposarcoma (MRCLS)
- Patients are screened under a separate protocol (Screening Protocol: NCT02636855) to identify those who have the relevant HLA-A*02 alleles and MAGE-A4 tumor expression
- There was a 21-day stagger between patients in Cohort 1, with this stagger dropping to 7 days in Cohorts 2, and 3. There is no pre-determined stagger in the potential expansion phase
- Cohorts 1-3 were intended to enroll 3 patients each with an expansion to 6 patients if DLTs were observed
- The expansion phase can enroll up to 30 patients
- The lymphodepletion regimen are:
- Cohorts 1 and 2 - fludarabine (flu) (30mg/m2/day) and cyclophosphamide (cy) (600 mg/m2/day) for 3 days
- Cohorts 3 and expansion phase - flu (30mg/m2/day) for 4 days and cy (600 mg/m2/day) for 3 days
- Efficacy is assessed by overall response rate, time to response, duration of response, progression-free survival, and overall survival at weeks 4, 8, and 12, month 6, and then every 3 months until confirmation of disease progression
In addition to MAGE-A4, Adaptimmune has four additional candidates in development. The candidates are in Ph II trials.