Head and Neck Cancer, HPV-Positive Oropharyngeal Squamous Cell Carcinoma, Oropharyngeal Squamous Cell Carcinoma
Conditions
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
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.
Detailed description
This is a two-part study to evaluate the safety, tolerability, and efficacy of neoadjuvant and adjuvant therapy in participants with locally advanced HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). In part 1 (phase 2a), the first 10 eligible participants will be enrolled into a single-arm safety cohort and receive the experimental treatment regimen. This lead-in will assess safety, tolerability, and early biomarker response to the neoadjuvant combination. All 10 participants in part 1 (phase 2a) receive the investigational therapy (NAI, IBRX-042, Nab-paclitaxel) followed by standard of care (SOC) radiation with concomitant cisplatin, and NAI and IBRX-042 post radiation. The key primary objective in safety lead-in includes evaluating and confirming there are no unexpected severe adverse interactions between the combination agents. Early efficacy signals such as clearance of circulating tumor HPV DNA (using the NavDx® assay) will also be assessed to gauge biomarker response. Upon successful completion of the safety lead-in (defined by acceptable safety profile and tolerability of the experimental regimen in the first 10 patients), part 2 (phase 2) will expand into an exploratory randomized trial, which will be a randomized 1:1 comparison between two arms, the experimental arm (arm A) and a SOC control arm (arm B). Randomization will be stratified by tumor stage and smoking history to ensure balance between arms of important risk factors. This part of the study will evaluate comparative efficacy and safety outcomes between the de-intensified experimental approach and the standard chemoradiotherapy approach.
Interventions
NAI 1.2 mg administered subcutaneously as part of the experimental treatment regimen.
BIOLOGICALhAd5-HPV Vaccine (IBRX-042)
IBRX-042 administered subcutaneously as part of the experimental treatment regimen.
DRUGNab-Paclitaxel
Nab-paclitaxel 100 mg/m² administered intravenously during neoadjuvant treatment cycles.
DRUGCisplatin
Cisplatin 40 mg/m² administered intravenously concurrently with radiation therapy.
RADIATIONDe-Intensified IMRT
IMRT 40 Gy, delivered once daily, 5 days/week, over 4 weeks (20 total fractions)
RADIATIONStandard of Care IMRT
SOC IMRT 70 Gy, delivered once daily, 5 days/week, over 7 weeks (35 total fractions)
Sponsors
ImmunityBio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years old. 2. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4. 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. 5. 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. 6. 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. 7. Participants should be suitable for organ-preserving therapy (i.e., radiation) with no immediate need for surgical resection (the trial is non-surgical upfront). 8. Must be willing to accept the randomized treatment assignment after the safety lead-in. During the initial safety phase, all participants receive experimental therapy; once randomization begins, patients and investigators will not choose the arm - it will be assigned by the randomization schedule. Enrolled patients should have no clear contraindication to either arm's therapy (for instance, a patient who absolutely cannot receive cisplatin due to allergy or comorbidity might not be suitable, since cisplatin is required in both arms). The inclusion/
Exclusion criteria
are structured to ensure a homogeneous population suitable for both the experimental approach and SOC chemoradiation. 9. Ability to attend required study visits and return for adequate follow-up, as required by this protocol. 10. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to approximately 2 years after completion of treatment | 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). |
Outcome results
None listed