On January 7, 2019 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported that the Safety Review Committee (SRC) has endorsed dose escalation in the ongoing ADP-A2AFP (AFP) study in patients with hepatocellular carcinoma (liver cancer) to the second dose cohort (Press release, Adaptimmune, JAN 7, 2019, View Source;p=RssLanding&cat=news&id=2382311 [SID1234532522]). The SRC has also endorsed moving to the expansion phase of the ADP-A2M10 (MAGE-A10) lung cancer study.

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Across both studies, most adverse events have been consistent with those typically experienced by cancer patients undergoing cytotoxic chemotherapy or other cancer immunotherapies with no evidence of alloreactivity or toxicity related to off-target binding.

In the ADP-A2AFP study, two patients have received 100 million transduced SPEAR T-cells targeting AFP in the first dose cohort, and there was no evidence of hepatotoxicity. The SRC endorsed dose escalation after evaluating the first two patients and taking into consideration the benefit:risk profile observed across programs in Cohort 1.

In the ADP-A2M10 lung cancer study, ten patients have been treated in the first three cohorts (up to six billion transduced cells), and the expansion phase will allow for doses of up to ten billion transduced cells (range 1.2 to 10 billion).

"We are pleased that the SRC has endorsed moving to the expansion phase of the ADP-A2M10 lung cancer study. Additionally, our ADP-A2AFP study has progressed to the next dose level of 1 billion transduced cells. Importantly, we did not observe liver toxicity in the two patients treated at a dose of 100 million transduced cells. In our other studies, we continue to enroll in the expansion phases and, as we previously have said, we are on track to report our next clinical data by May this year," said Rafael Amado, Adaptimmune’s President of Research & Development.

Overview of ADP-A2AFP (AFP) Study Design

This is a first-in-human, open-label study utilizing a modified 3+3 design in up to 36 patients with escalating target 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 an expansion phase with doses of up to 10 billion SPEAR T-cells
This trial is being conducted in patients with hepatocellular carcinoma
There was a 21-day stagger between patients in Cohort 1, with this stagger dropping to 7 days in Cohorts 2, and 3 in the absence of DLTs. There is no pre-determined stagger in the 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 is fludarabine (flu) (20mg/m2/day) and cyclophosphamide (cy) (500 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 16, month 6, and then every 3 months until confirmation of disease progression
Overview of ADP-A2M10 (MAGE-A10) Lung Cancer Study Design

This is a first-in-human, open-label study utilizing a modified 3+3 design in up to 28 patients with escalating target 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 DLTs followed by an expansion phase with doses of up to 10 billion SPEAR T-cells
This trial is being conducted in patients with non-small cell lung cancer (NSCLC)
There was a 21-day stagger between patients in Cohort 1, with this stagger dropping to 7 days in Cohorts 2, and 3 in the absence of DLTs. There is no pre-determined stagger in the 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 10 patients
The lymphodepletion regimen is cyclophosphamide (1800 mg/m2/day) for 2 days in Cohort 1, fludarabine (flu) (30mg/m2/day) and cyclophosphamide (cy) (600 mg/m2/day) for 3 days in Cohort 2, and Cy (600 mg/m2/d) x 3 days + Flu (30 mg/m2/d) X 4 days in Cohort 3
Efficacy is assessed by response rate, duration of response, progression-free survival, and overall survival at weeks 4, 8, and 12, month 6, and then every 3 months (for 2 years) and then every 6 months until confirmation of disease progression