Study of ATL001 Plus ICI Therapy Now Enrolling Patients with Metastatic Melanoma

The phase 1/2 THETIS clinical trial is actively recruiting patients with metastatic melanoma to be treated with the investigation combination of ATL001 and an immune checkpoint inhibitor.

Enrollment of patients with metastatic malignant melanoma has begun in cohort B of the THETIS clinical trial, which is evaluating the use of personalized clonal neoantigen-reactive T cells (cNET) with the novel agent ATL001 administered in combination with PD-1 checkpoint inhibition, according to a press release by Achilles Therapeutics.1

Administration of the cNET agent in the study is approached with the VELOS Process 2. VELOS is a unique process designed to make manufacturing closed and automated. It utilizes dendritic cells to provide a personalized, and definite T-cell-based therapy that can selectively target more than one clonal neoantigen with better T cell fitness and less need for high-dose interleukin-2 (IL-2) compared with other processes.

“… Initiating enrollment in THETIS Cohort B, which will evaluate cNeT in combination with a PD-1 inhibitor, are major milestones for Achilles. Our personalized cell therapy has been developed to address the hardest to treat cancers, including NSCLC and melanoma, which often become resistant to other treatments,” said Iraj Ali, PhD chief executive officer of Achilles Therapeutics, in a press release. “Our VELOS Process 2 has been shown to deliver increased cNeT doses while retaining T cell fitness. We are excited by the therapeutic potential of our higher-dose cNeT monotherapy and cNeT combination treatments and look forward to reporting clinical data in the second half of 2022.”

THETIS is a first-in-human, open-label, multicenter study (NCT03997474), which aims to initially enroll 40 patients with metastatic melanoma. The study will investigate the safety and efficacy of ATL001 across 3 cohorts. In cohort A, patients will be infused with ATL001 following lymphodepletion and then given a low dose of IL-2 therapy. In cohort B, patients will first undergo lymphodepletion followed by ATL001 infusion plus checkpoint inhibition, then a low dose IL-2 regimen. Finally, in cohort C, patients will undergo lymphodepletion followed by ATL001 infusion and a high dose IL-2 regimen.2

The primary end point of the study is the safety and tolerability determined by treatment-emergent adverse events. The secondary end points of the study include the clinical activity of ATL001 in patient with metastatic melanoma, overall response rate, time to response, duration of response, disease control rate, progression-free survival, and overall survival.

To be eligible for inclusion in the study, patients must be at least 18 years of age at the time of screening with histologically confirmed melanoma. All patients must have received a PD-1/PD-L1 inhibitor to be eligible to receive ATL001, and those with a BRAF V600 mutation must have received BRAF targeted therapy before ATL001 can be infused. Patients are also required to have an ECOG performance status of 0-1, adequate organ function, adequate laboratory values at baseline, measurable disease, and a life expectancy of at least 6 months.

“Melanoma is the fifth most common cancer among men and women, with a survival rate of 30% when it has spread to other, distant parts of the body. Since both are common indications with poor prognosis at advanced stages, we look forward to evaluating how our higher-dose cNeT therapy and combination with a PD-1 inhibitor may help improve treatment responses and change the paradigm for these patients, said Karl Peggs, MD, chief medical officer, Achilles Therapeutics, in a statement.1


1. Achilles Therapeutics doses first patient with higher-dose cNeT in Phase I/IIa CHIRON trial in advanced NSCLC and initiates enrollment in cohort b of the THETIS Trial (cNeT + PD-1 checkpoint inhibitor) in metastatic malignant melanoma. News release. May 09, 2022. Accessed May 9, 2022.

2. ATL001 in patients with metastatic or recurrent melanoma. Updated July 29, 2021. Accessed May 9, 2022.