Autologous T Cells Targeting HPV16 HPV18 & Survivin in Patients With R/R HPV-related Oropharyngeal Cancers

Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNexImmune Inc.

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

The patient will be typed for HLA-A*0201 expression as determined by high resolution sequence-based typing method. If documented HLA results are available from a previous test, the patient can be enrolled using these results after review and approval by the sponsor.

Patients with cytologically or histologically confirmed locally advanced or metastatic HPV related oropharyngeal cancers with confirmed detection of HPV-16 and/or HPV-18.

Patients with HPV-related oropharyngeal cancers who have received at least 1 prior line of standard-of-care (SOC) treatment (for example, per the current NCCN Guidelines for Patients with Oropharyngeal Cancer) consisting of systemic immunotherapy and/or chemotherapeutic treatment.

The last dose of cytotoxic chemotherapy and/or steroids must be administered at least 28 days prior to the leukapheresis procedure.

Disqualifiers

A diagnosis of other malignancies if the malignancy has required therapy within the last 3 years or is not in complete remission. Exceptions are non-metastatic basal cell or squamous cell carcinomas of the skin or prostate cancer that does not require treatment. Patients taking adjuvant hormonal therapy for definitively treated cancers (e.g., breast cancer, prostate cancer) are eligible.

Major surgery within 28 days prior to the first study drug administration (minimally invasive procedures, such as diagnostic biopsies, are permitted).

Known central nervous system involvement.

Treatment with an allogeneic hematopoietic stem cell transplantation.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Fludarabine

    Drug

    Lymphodepletion Chemotherapy on Days -5, -4, and -3 before Cycle 1 ONLY

  • Cyclophosphamide

    Drug

    Lymphodepletion Chemotherapy administered on Days -5, -4, and -3 before Cycle 1 ONLY

  • NEXI-003 T cells

    Biological/Vaccine

    Adoptive Cell Therapy specified dose on specified day(s)

Treatment groups

36 Participants
are divided into 5 treatment groups
Group A: Cohort 1Experimental treatment 3 interventions
Group B: Cohort 2Experimental treatment 3 interventions
Group C: Cohort 3Experimental treatment 3 interventions
Group D: Cohort 4Experimental treatment 3 interventions
Group E: Dose Expansion StageExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Adverse Events (AEs)

Frequencies of patients with treatment-emergent AEs (TEAEs)

Time frame
12 months
2

Dose-Limiting Toxicities (DLTs)

DLTs in Cycle 1

Time frame
28 days
3

Severities of AEs

Frequencies of patients with treatment-emergent AEs (TEAEs) by severity

Time frame
12 months
4

Relationship of AEs

Frequencies of patients with treatment-emergent AEs (TEAEs) by relationship to NEXI-003 T cells

Time frame
12 months

Secondary outcomes

1

Overall response rate (ORR)

ORR as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1

Time frame
12 months
2

Duration of response (DoR)

Response as measured by RECIST v1.1 over time

Time frame
12 months
3

Determine the persistence of NEXI-003 T cells in peripheral blood

Determine NEXI-003 at pre-dose and different times post-dose by multimer-based staining of antigen-specific NEXI-003 T cells.

Time frame
12 months
4

Determine manufacturing feasibility by assessing the manufactured product for Cell Viability

Percent NEXI-003 T cell viability in each manufactured product

Time frame
1 month

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

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