Phase 2 Study of NAI, HPV Vaccine, and Nab-Paclitaxel in HPV-Positive Oropharyngeal Cancer Followed by De-Intensified Radiation Compared With Standard Chemoradiation

NCT07628062 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: ResQ1190-HPV
• Study Type: interventional
• Target: 70
• Locations: 0 countries
• Sites: N/A

Brief Summary

This Phase 2a/2 study evaluates the safety, tolerability, and efficacy of neoadjuvant and adjuvant NAI, hAd5-HPV vaccine (IBRX-042), and nab-paclitaxel in participants with locally advanced HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). The study includes a Phase 2a safety lead-in followed by a randomized Phase 2 comparison of a de-intensified experimental chemoradiation approach versus standard-of-care chemoradiation.

Conditions

HPV-Positive Oropharyngeal Squamous Cell Carcinoma; Oropharyngeal Squamous Cell Carcinoma; Head and Neck Cancer

Keywords

Locally Advanced HPV-Positive OPSCC; Human Papillomavirus-Associated Oropharyngeal Cancer; HPV-16; Squamous Cell Carcinoma of the Oropharynx; Chemoradiation; Cisplatin; Intensity-Modulated Radiation Therapy; De-Intensification Strategy; Neoadjuvant Therapy; Adjuvant Immunotherapy; hAd5 HPV Vaccine; ANKTIVA; Phase 2; NavDx; Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression-free survival (PFS) as assessed by RECIST 1.1 criteria comparing the experimental treatment arm with the standard-of-care control arm in participants with locally advanced HPV-positive oropharyngeal squamous cell carcinoma (OPSCC).

  Up to approximately 2 years after completion of treatment

Study Arms (3)

Phase 2a, Single Arm (Safety Lead-In)

EXPERIMENTAL

Participants will receive neoadjuvant nogapendekin alfa inbakicept (NAI), hAd5-HPV vaccine (IBRX-042), and nab-paclitaxel followed by de-intensified intensity-modulated radiation therapy (IMRT) with concurrent cisplatin, and post-radiation NAI and IBRX-042 during the Phase 2a safety lead-in portion of the study.

Drug: Nogapendekin Alfa Inbakicept (NAI); Biological: hAd5-HPV Vaccine (IBRX-042); Drug: Nab-Paclitaxel; Radiation: De-Intensified IMRT

Arm A

EXPERIMENTAL

Participants will receive neoadjuvant nogapendekin alfa inbakicept (NAI), hAd5-HPV vaccine (IBRX-042), and nab-paclitaxel followed by de-intensified intensity-modulated radiation therapy (IMRT) with concurrent cisplatin, and post-radiation NAI and IBRX-042.

Drug: Nogapendekin Alfa Inbakicept (NAI); Biological: hAd5-HPV Vaccine (IBRX-042); Drug: Nab-Paclitaxel; Drug: Cisplatin; Radiation: De-Intensified IMRT

Arm B

ACTIVE COMPARATOR

Participants will receive standard-of-care intensity-modulated radiation therapy (IMRT) with concurrent cisplatin for locally advanced HPV-positive oropharyngeal squamous cell carcinoma (OPSCC).

Drug: Cisplatin; Radiation: De-Intensified IMRT; Radiation: Standard of Care IMRT

Interventions

Nogapendekin Alfa Inbakicept (NAI) DRUG

NAI 1.2 mg administered subcutaneously as part of the experimental treatment regimen.

Arm A; Phase 2a, Single Arm (Safety Lead-In)

hAd5-HPV Vaccine (IBRX-042) BIOLOGICAL

IBRX-042 administered subcutaneously as part of the experimental treatment regimen.

Arm A; Phase 2a, Single Arm (Safety Lead-In)

Nab-Paclitaxel DRUG

Nab-paclitaxel 100 mg/m² administered intravenously during neoadjuvant treatment cycles.

Arm A; Phase 2a, Single Arm (Safety Lead-In)

Cisplatin DRUG

Cisplatin 40 mg/m² administered intravenously concurrently with radiation therapy.

Arm A; Arm B

De-Intensified IMRT RADIATION

IMRT 40 Gy, delivered once daily, 5 days/week, over 4 weeks (20 total fractions)

Arm A; Arm B; Phase 2a, Single Arm (Safety Lead-In)

Standard of Care IMRT RADIATION

SOC IMRT 70 Gy, delivered once daily, 5 days/week, over 7 weeks (35 total fractions)

Arm B

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old.
• Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed squamous cell carcinoma of the oropharynx that is HPV-positive (p16 immunohistochemistry positive and/or HPV DNA positive). Patients with cervical lymph node metastases from an unknown primary can be included if p16-positive and likely OPSCC origin.
• Locally advanced, stage III/IV HPV-associated OPSCC that is a candidate for definitive chemoradiation. Specifically, tumors classified as T3 or T4 and/or node-positive disease (N2 or N3), without distant metastases (M0). Patients with very low-risk disease (e.g. T1-T2 N0-1) are excluded, as these might be handled with less intensive standard therapy or surgery rather than this trial approach.
• No prior definitive treatment for the current OPSCC. Patients must be treatment-naïve with respect to chemotherapy, radiation, or investigational therapy for this cancer. Prior diagnostic biopsy is allowed, but no prior curative surgery or radiation to the head and neck.
• Participants should be suitable for organ-preserving therapy (i.e., radiation) with no immediate need for surgical resection (the trial is non-surgical upfront).

You may not qualify if:

• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• Agreement to practice effective contraception for female participants of child-bearing potential and non-sterile males. Per cisplatin prescribing information, female participants of child-bearing potential must agree to use effective contraception for up to 14 months and non-sterile male participants must agree to use a condom for up to 11 months after last dose of cisplatin. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), orals, injectables, 2 forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), and hormonal therapy.
• HPV-negative or Non-OPSCC: Tumors that are p16-negative or not in the oropharynx are excluded.
• Any evidence of distant metastases (M1 disease) excludes the patient, since the trial is for curative-intent local/regional therapy.
• Previous radiation in the head/neck region or prior chemotherapy/immunotherapy for this cancer disqualifies the patient. We require a clean baseline to assess our regimen.
• Active autoimmune disease or immunosuppression. The experimental arm includes immunotherapy (IL-15 receptor agonist and IBRX-042 vaccine), patients with active serious autoimmune disorders or those requiring immunosuppressive medications (e.g. chronic steroids \>10 mg prednisone daily) are excluded to avoid severe immune-related complications. Well-controlled or mild autoimmune conditions may be considered on a case-by-case basis if risk is low.
• Inadequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to baseline:
• Absolute neutrophil count (ANC) \< 1,500 cells/μL without granulocyte colony-stimulating factor support
• Platelet count \< 100,000/μL without transfusion
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) \> 2.5 × ULN, with the following exception:
• Participants with documented liver metastases: AST and/or ALT \> 5 × ULN
• Serum bilirubin ≤ 3 × ULN
• Creatinine clearance ≤ 50 mL/min (calculated using the Cockcroft-Gault formula).
• Serum albumin \< 3.0 g/dL.
• Significant cardiovascular disease (such as New York Heart Association cardiac disease class II or greater), myocardial infarction within 3 months prior to baseline, unstable arrhythmias, or unstable angina.

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a two-part Phase 2a/2 study consisting of an initial single-arm safety lead-in cohort followed by a randomized parallel-group comparison between an experimental de-intensified chemoradiation regimen and standard-of-care chemoradiation in participants with locally advanced HPV-positive OPSCC.

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: June 4, 2026
• Study Start (Estimated): July 22, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): June 27, 2031
• Last Updated: June 4, 2026

Record last verified: 2026-05