Open-Label, Single-Arm Phase 2 Study Of Nogapendekin Alfa Inbakicept, PD-L1 T-HaNK, And Bevacizumab And Randomized Phase 2B Study Of Nogapendekin Alfa Inbakicept, Bevacizumab, And Tumor Treatment Fields With Or Without PD-L1 T-HaNK In Participants With Recurrent Or Progressive Glioblastoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 70
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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).
- •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/
排除标准
- •are structured to ensure a homogeneous population suitable for both the experimental approach and SOC chemoradiation.
- •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.
- •Exclusion Criteria:
- •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.
- •Severe infections at the time of enrollment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
- •History of human immunodeficiency virus (HIV) with current CD4+ T-cell count < 350 cells/μL and/or a detectable HIV viral load.
- •Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk for treatment complications.
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
- •Participation in an investigational drug study or history of receiving any investigational treatment within 30 days prior to the start of treatment on this study.
- •Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
- •Pregnant and nursing women.