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

NCT05582590 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NEXI-003-HPV-101
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Oropharyngeal Cancer; Human Papilloma Virus; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Oropharyngeal Squamous Cell Carcinoma; Oropharyngeal Cancer, Metastatic; Head and Neck Cancer Metastatic; HPV-Related Squamous Cell Carcinoma; HPV-Related Mucosal Head and Neck Squamous Cell Carcinoma; Relapsed Oropharyngeal SCC; Refractory Oropharyngeal Squamous Cell Carcinoma

Keywords

relapsed or refractory HPV-related oropharyngeal cancer; human papilloma virus-related cancer; HPV-related head and neck cancer; HPV-related oropharyngeal cancer; cell therapy; adoptive cell therapy; NEXI-003; Head and neck cancer

Outcome Measures

Primary Outcomes (7)

• Adverse Events (AEs)

  Frequencies of patients with treatment-emergent AEs (TEAEs)

  12 months

• Dose-Limiting Toxicities (DLTs)

  DLTs in Cycle 1

  28 days

• Severities of AEs

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

  12 months

• Relationship of AEs

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

  12 months

• Serious Adverse Events (SAEs)

  Frequencies of patients with treatment-emergent SAEs

  12 months

• Adverse Events of Special Interest (AESIs) - Cytokine Release Syndrome (CRS)

  Frequencies of patients with treatment-emergent CRS

  12 months

• Adverse Events of Special Interest (AESIs) - Immune Effector cell-associated neurotoxicity syndrome (ICANS)

  Frequencies of patients with treatment-emergent ICANS

  12 months

Secondary Outcomes (8)

• Overall response rate (ORR)

  12 months

• Duration of response (DoR)

  12 months

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

  12 months

• Determine manufacturing feasibility by assessing the manufactured product for Cell Viability

  1 month

• Determine manufacturing feasibility by assessing the manufactured product for Cell Yield

  1 month

Study Arms (5)

Cohort 1

EXPERIMENTAL

2 x 10\^8 NEXI-003 T cells (derived from peripheral blood mononuclear cells \[PBMCs\] of the patient) administered by intravenous infusion on Day 1 of each cycle

Drug: Fludarabine; Drug: Cyclophosphamide; Biological: NEXI-003 T cells

Cohort 2

EXPERIMENTAL

2 x 10\^8 NEXI-003 T cells (derived from peripheral blood mononuclear cells \[PBMCs\] of the patient) administered by intravenous infusion on Days 1 and 8 of each cycle

Drug: Fludarabine; Drug: Cyclophosphamide; Biological: NEXI-003 T cells

Cohort 3

EXPERIMENTAL

2 x 10\^8 NEXI-003 T cells (derived from peripheral blood mononuclear cells \[PBMCs\] of the patient) administered by intravenous infusion on Days 1, 8, and 15 of each cycle

Drug: Fludarabine; Drug: Cyclophosphamide; Biological: NEXI-003 T cells

Cohort 4

EXPERIMENTAL

4 x 10\^8 NEXI-003 T cells (derived from peripheral blood mononuclear cells \[PBMCs\] of the patient) administered by intravenous infusion on Day 1, and 2 x 10\^8 NEXI-003 T cells administered by intravenous infusion on Days 8 and 15 of each cycle

Drug: Fludarabine; Drug: Cyclophosphamide; Biological: NEXI-003 T cells

Dose Expansion Stage

EXPERIMENTAL

Dose Expansion Stage to further define the safety and clinical activity, and to confirm the recommended Phase 2 dose of the NEXI- 003 T cell product at the dose established from the Dose Escalation Stage.

Drug: Fludarabine; Drug: Cyclophosphamide; Biological: NEXI-003 T cells

Interventions

Fludarabine DRUG

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

Also known as: Fludara

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Dose Expansion Stage

Cyclophosphamide DRUG

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

Also known as: Cytoxan

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Dose Expansion Stage

NEXI-003 T cells BIOLOGICAL

Adoptive Cell Therapy specified dose on specified day(s)

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Dose Expansion Stage

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Any adverse event(s) that the patient may have experienced from prior therapy must have resolved to ≤ Grade 1 according to NCI CTCAE version 5.0.
• Measurable disease per RECIST v1.1 criteria (at least 1 lesion that can be measured accurately in at least 1 dimension with the longest diameter ≥ 10 mm \[MRI or CT scan sliced thickness ≤ 5 mm\]).
• Pulse oximetry ≥ 92% on room air.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy of at least 3 months.
• Be willing to comply with the study schedule and all other protocol requirements.
• Women of childbearing potential (WOCBP), defined as a sexually mature woman who has not undergone a hysterectomy or tubal ligation or who has not been naturally postmenopausal for at least 24 consecutive months, must have 2 negative pregnancy tests prior to treatment. All sexually active WOCBP and all sexually active male patients must agree to use highly effective methods of birth control throughout the study.
• Ability of the patient to understand and willingness to sign a written informed consent form.

You may not qualify if:

• 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.
• Treatment with any investigational agent(s) at the time of informed consent.
• Left ventricular ejection fraction (LVEF) \< 45%, congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis.
• The following hematological laboratory results at Screening (these results must be independent of blood product or hematopoietic growth factor support):
• Hemoglobin \< 9.0 g/dL.
• Platelet count \< 100,000/μL.
• Absolute neutrophil count (ANC) \< 1000/ μL.
• The following chemistry laboratory results at Screening:
• Serum creatinine ≥ 1.5 mg/dL or estimated glomerular filtration rate (eGFR) ≤ 50 mL/min/1.73 m\^2.
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3x the upper limit of normal (ULN) or serum total bilirubin \> 2 mg/dL (except for patients in whom hyperbilirubinemia is attributed to Gilbert's Syndrome).
• International normalized ratio (INR) or activated partial thromboplastin time (aPTT) \> 1.5x ULN within 1 week prior to the start of lymphodepletion chemotherapy, unless on a stable dose of an anticoagulant.
• Are pregnant or breastfeeding.

Sponsors & Collaborators

• NexImmune Inc.: lead

MeSH Terms

Conditions

Oropharyngeal Neoplasms; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Neoplasm Metastasis; Recurrence

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Kristi Jones

CONTACT

650-743-4135; kjones@neximmune.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Standard 3+3 study design for the Dose Escalation Stage and a Dose Expansion Stage

Study Record Dates

• First Submitted: October 10, 2022
• First Posted: October 17, 2022
• Study Start: March 31, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 25, 2027
• Last Updated: January 16, 2024

Record last verified: 2024-01