976TiP - SPEARHEAD-2 trial design: A phase II pilot trial of ADP-A2M4 in combination with pembrolizumab in patients with recurrent or metastatic head and neck cancer

Background

ADP-A2M4 SPEAR T-cells are genetically engineered to target MAGE-A4⁺ tumors in HLA-A*02 positive patients (pts). Safety and efficacy for ADP-A2M4 cells have been demonstrated in a phase I trial (NCT03132922). MAGE-A4 is frequently expressed in recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC). Pembrolizumab (pembro), an anti-PD-1 checkpoint inhibitor, monotherapy is approved as 1^st-line treatment of r/m HNSCC that expresses PD-L1. The combination of ADP-A2M4 and pembro may result in a synergistic effect due to the inhibition of PD-1 on ADP-A2M4 cells potentially leading to deeper and more durable anti-tumor responses.

Trial design

This single-arm trial will enroll up to 10 pts to evaluate efficacy, safety, and tolerability of ADP-A2M4 with pembro. Checkpoint inhibitor naïve r/m HNSCC pts who are HLA-A*02, MAGE-A4⁺, and PD-L1 positive (≥1%) will be eligible. Part A is a run-in-phase with pembro as standard-of-care monotherapy followed by Part B, an interventional phase, during which ADP-A2M4 will be administered with pembro post-ADP-A2M4 infusion in patients without response or following progressive disease (PD) with pembro in Part A. Part A: Pts will undergo leukapheresis, and collected T-cells will be transduced with a Lentiviral vector expressing a high affinity MAGE-A4 specific T-cell receptor. Pts will receive pembro monotherapy (200 mg IV) every 3 weeks for a minimum of 3 cycles. Disease status will be assessed at Wk 7. Pts without a response by Wk 7 will proceed to Part B. Pts who respond to pembro after 3 cycles will continue treatment in Part A until PD when they will become eligible for ADP-A2M4 treatment in Part B. Part B: Pts will undergo lymphodepleting chemotherapy w/ fludarabine and cyclophosphamide prior to receiving ADP-A2M4 at a dose range of 1x10⁹ to 10x10⁹ transduced T-cells. Pembro infusions every 3 weeks will re-start after ADP-A2M4 infusion and will continue until PD. A Safety Review Committee will review safety and benefit:risk during Part B. Disease will be assessed by investigators per RECIST v1.1 using CT/MRI scans post T-cell infusion.

Clinical trial identification

NCT03132922.

Editorial acknowledgement

Legal entity responsible for the study

Adaptimmune.

Funding

Adaptimmune.

Disclosure

E.E. Cohen: Advisory/Consultancy: ALX Oncology; Advisory/Consultancy: Ascendis; Advisory/Consultancy: Bayer; Advisory/Consultancy: Bioline Rx; Advisory/Consultancy: BMS; Advisory/Consultancy: Debio; Advisory/Consultancy: Dynavax; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck; Advisory/Consultancy: Regeneron. R. Leidner: Advisory/Consultancy: Merck; Advisory/Consultancy: Oncolys; Advisory/Consultancy: Sanofi; Research grant/Funding (institution): Bristol-Myers Squibb. N. Hyland, T. Trivedi, M. Dudley, S. Biswas, D. Williams, E. Norry: Shareholder/Stockholder/Stock options, Full/Part-time employment: Adaptimmune. All other authors have declared no conflicts of interest.