The primary objective is to assess the safety of NEXI-003 in patients with relapsed or refractory HPV-related oropharyngeal cancers. The study will consist of two stages: a Dose-Escalation (Stage 1) and a Dose Expansion (Stage 2).~The first stage of the trial is the Dose-Escalation (Stage 1). A standard dose-escalation 3+3 design will be utilized to identify a safe maximum tolerated dose (MTD) of NEXI-003 in patients with relapsed or refractory HPV-related oropharyngeal cancers. The MTD of NEXI-003 T cells will be identified during the first 28-day cycle (Cycle 1) of the Dose-Escalation Stage, which is defined as the DLT period. A total of 4 dosing cohorts are planned in the Dose Escalation Stage.~Initially 3 patients are enrolled into a dosing cohort. After all 3 patients in a cohort have been followed for 28 days of Cycle 1 (the DLT Period), the safety information will be assessed by the Data Review Committee (DRC). If no DLT is reported in the first 3 patients enrolled during the 28-day initial cycle of treatment (the DLT Period), enrollment into the next higher dose cohort may begin, after safety information is assessed by the DRC. If 1 of the first 3 patients has a DLT, then 3 more patients will be enrolled into that cohort. If a DLT occurs in ≥ 2 patients, then the MTD will be judged to have been exceeded and the next lower cohort dose will be considered the MTD. If a DLT occurs in ≤ 1 of 6 patients, then patients may be enrolled in the next highest dose level. The DRC will review eligibility criteria, doses of all study treatments and safety data and make recommendations as to the further conduct of the study. If ≥ 2 patients in Cohort 1 experience a DLT, then Cohort -1 (1 x 10^8 NEXI-003 T cells on Day 1 of Cycle 1; stepdown dose, if needed) will be evaluated using the 3+3 design.~After identification of the MTD, or the finding that the last dosing cohort is tolerated well (i.e., the maximum practical dose [MPD]), 12 patients will be enrolled to receive NEXI-003 treatment at the MTD/MPD level in the Dose Expansion Stage to gain additional safety, clinical activity, and pharmacokinetic data (i.e., persistence and expansion) of the NEXI-003 antigen specific CD8+ T cell product. Safety, clinical activity, and pharmacokinetic data from the Dose Escalation and Dose Expansion stages will be assessed to determine the recommended Phase 2 dose (RP2D).~Patients in both the Dose Escalation and Dose Expansion Stages may receive additional cycles of NEXI-003 per investigator discretion and if protocol-specified criteria are met.~Each of the two stages of the study will consist of the following three consecutive study periods for each patient: Pretreatment Period (consisting of Screening, Leukapheresis/Manufacturing, and Baseline Re-evaluation), Treatment Period (consisting of lymphodepletion [LD] chemotherapy and NEXI-003 treatment), and Post-Treatment Period (consisting of Post-treatment Follow-up and Survival Follow-up). The Pretreatment Period will be approximately 4 to 6 weeks. The Treatment Period will consist of at least 28-day cycle (i.e., 4 weeks), and per investigator discretion if the patient meets protocol-specified criteria, the patient may receive additional 4-week cycles. The Post-Treatment Follow-up Period will consist of up to 9 months of post-treatment assessments, and up to 9 months of survival follow-up.
This is a multicenter, open-label, Phase I, first-in-human trial to characterize the safety and clinical activity of an antigen-specific CD8+ T-cell product in patients with relapsed or refractory locally advanced or metastatic HPV-related oropharyngeal cancers. Patients must have received at least one prior standard treatment regimen consisting of systemic immunotherapy and/or chemotherapy. The investigative agent is an autologous adoptive T-cell product derived from the patient's endogenous cytolytic T cells that are directed toward HPV-16 E6/E7, HPV-18 E6/E7 antigens, and a tumor-associated antigen (Survivin) by ex vivo exposure to an artificial antigen presenting cell to which HLA-A2 antigen-peptides have been fit within the pocket of an MHC class 1 molecule. Patients must express HLA-A*0201.