Head and Neck Squamous Cell Carcinoma (HNSCC) Clinical Trial
Official title:
Phase 2/3, Randomized Study of OX40 Agonist INBRX-106 With Pembrolizumab vs Pembrolizumab as First Line Treatment for Patients With Locally Advanced or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Expressing PD-L1(CPS ≥20)
This seamless phase 2/3 randomized controlled study will evaluate the efficacy and safety of the hexavalent OX40 agonist antibody INBRX-106 combined with the anti-PD-1 antibody pembrolizumab versus pembrolizumab (+ placebo in phase 3) as first-line treatment for patients with locally advanced recurrent or metastatic head and neck squamous cell carcinoma (R/M HSNSCC) incurable by local therapies, expressing PD-L1 with a combined proportion score (CPS) ≥20.
Status | Recruiting |
Enrollment | 410 |
Est. completion date | May 2029 |
Est. primary completion date | May 2029 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Has histologically or cytologically confirmed diagnosis of metastatic, recurrent head and neck squamous cell carcinoma (HNSCC) that is considered incurable by local therapies. - Has tumor PD-L1 expression of CPS =20. Tumor tissue must be provided for PD-L1 biomarker analysis. - Has human papilloma virus (HPV) testing results for oropharyngeal cancer by p16 immunohistochemistry (IHC) testing. - Has measurable disease per RECIST 1.1 guidelines. - Has the primary tumor location of the oral cavity, oropharynx, hypopharynx, or larynx. - Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. - Female patients of childbearing potential must have a negative highly sensitive pregnancy test within 72 hours prior to randomization and must not be breastfeeding. - Male and female patients of childbearing potential must be willing to completely abstain from heterosexual sex or agree to use a highly effective method of contraception. Exclusion Criteria: - Has primary tumor site (any histology) of nasopharynx or salivary glands or occult primary site. - Has received prior systemic therapy (eg, prior chemo-, immune-, or biologic therapy) for locally advanced unresectable or metastatic HNSCC. - Prior systemic therapy completed >6 months prior to signing informed consent is allowed if given as part of multimodal treatment for locoregionally advanced disease with curative intent, and no PD/recurrence occurred within 6 months of its completion. Prior systemic immunotherapy in the locoregionally advanced disease with curative intent, including but not limited to anti-PD-(L)1 agents, is allowed if PD/recurrence occurred =12 months after its completion. - Has clinically active central nervous system metastases and/or carcinomatous meningitis. - Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. - Rapidly progressing disease or with features that may confer a high risk of tumor-associated hemorrhage or uncontrolled tumor pain. - Current or history of immune-related disease that required systemic treatment in past 2 years, except for replacement therapy. |
Country | Name | City | State |
---|---|---|---|
United States | City of Hope Medical Center | Duarte | California |
United States | Mid Florida Hematology and Oncology Center | Orange City | Florida |
United States | Christus St. Vincent Regional Cancer Center | Santa Fe | New Mexico |
Lead Sponsor | Collaborator |
---|---|
Inhibrx, Inc. |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Phase 2: Objective Response Rate (ORR) | ORR is defined as the proportion of patients with a complete response (CR) or partial response (PR) on 2 consecutive occasions =4 weeks apart, per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | up to 6 months | |
Primary | Phase 3: Progression-Free Survival (PFS) | PFS is defined as the time from randomization to first occurrence of PD, as determined by the Investigator according to RECIST v 1.1, or death from any cause (whichever occurs first). | From randomization to first occurrence of progressive disease (PD) or death (up to 4 years) | |
Primary | Phase 3: Overall Survival (OS) | OS is the time from randomization to death due to any cause | From randomization until death from any cause (up to 4 years) | |
Secondary | Phase 3: Objective Response Rate (ORR) | ORR is defined as the proportion of patients with a CR or PR on 2 consecutive occasions =4 weeks apart, per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | From randomization until treatment discontinuation (up to 2 years) | |
Secondary | Duration of Response (DOR) | DOR is defined as the time from the first occurrence of a documented objective response to PD, as determined by the Investigator according to RECIST v1.1, or death from any cause (whichever occurs first) | From the first occurrence of a documented objective response to PD or death (up to 4 years) | |
Secondary | Clinical Benefit Rate (CBR) | CBR is defined as the proportion of patients with stable disease (SD) for =12 weeks or a CR or PR, as determined by the Investigator according to RECIST v1.1. | From randomization until treatment discontinuation (up to 2 years) | |
Secondary | Phase 3: Time to Chemotherapy (TTCtx) | TTCtx is defined as the time from randomization until the start date of chemotherapy or death from any cause (whichever occurs first). | From randomization until the start of chemotherapy or death (up to 4 years) | |
Secondary | Time to Confirmed Deterioration (TTCD) in Pain Presence and Interference | TTCD in pain presence and interference is defined as the time from randomization to the first documentation of =10-point increase in pain score, as determined using the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 (EORTC QLQ-C30) questionnaire | From randomization until treatment discontinuation (up to 2 years) | |
Secondary | TTCD in physical functioning (PF) | TTCD in PF is defined as the time from randomization to the first documentation of a =10 point decrease from baseline in the Quality of Life-Core 30 (EORTC QLQ-C30) linearly transformed PF scale score. | From randomization until treatment discontinuation (up to 2 years) | |
Secondary | TTCD in role functioning (RF) | TTCD in RF is defined as the time from randomization to the first documentation of a =10 point decrease from baseline in the Quality of Life-Core 30 (EORTC QLQ-C30) linearly transformed RF scale score. | From randomization until treatment discontinuation (up to 2 years) | |
Secondary | TTCD in Global Health Status/quality of life (GHS/QoL) | TTCD in GHS/QoL is defined as the time from randomization to the first documentation of a =10 point decrease from baseline in the Quality of Life-Core 30 (EORTC QLQ-C30) linearly transformed GHS/QoL scale score. | From randomization until treatment discontinuation (up to 2 years) | |
Secondary | Incidence and severity of Adverse Events (AEs) | Incidence will be reported as the number of participants with at least one adverse event, with severity determined according to the National Cancer Institute Criteria for Adverse Events, version 5 (NCI CTCAE v 5.0) | Up to approximately 24 months | |
Secondary | Number of patients who experienced abnormalities in vital signs and clinical laboratory parameters | Vital signs include respiratory rate, pulse rate, systolic and diastolic blood pressure, and temperature. Clinical laboratory parameter include hematology and biochemistry tests over the course of the study. | Up to approximately 24 months |
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