Head and Neck Squamous Cell Carcinoma (HNSCC)
Conditions
Keywords
OX40 receptor agonist, PD-L1 positive, Pembrolizumab, Immunotherapy, Chemotherapy-free, HNSCC, Head and Neck Cancer, Keytruda, Oropharyngeal cancer, Hypopharyngeal cancer, Laryngeal cancer, Oral cancer, INBRX-106
Brief summary
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.
Interventions
DRUGINBRX-106
INBRX-106 by intravenous (IV) infusion, given every 3 weeks (QW3)
DRUGPembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given every 3 weeks (QW3)
Sponsors
Inhibrx Biosciences, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Phase 2: open label; Phase 3: double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Objective Response Rate (ORR) | up to 6 months | 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) |
| Phase 3: Progression-Free Survival (PFS) | From randomization to first occurrence of progressive disease (PD) or death (up to 4 years) | 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). |
| Phase 3: Overall Survival (OS) | From randomization until death from any cause (up to 4 years) | OS is the time from randomization to death due to any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 3: Objective Response Rate (ORR) | From randomization until treatment discontinuation (up to 2 years) | 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) |
| Duration of Response (DOR) | From the first occurrence of a documented objective response to PD or death (up to 4 years) | 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) |
| Clinical Benefit Rate (CBR) | From randomization until treatment discontinuation (up to 2 years) | 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. |
| Phase 3: Time to Chemotherapy (TTCtx) | From randomization until the start of chemotherapy or death (up to 4 years) | TTCtx is defined as the time from randomization until the start date of chemotherapy or death from any cause (whichever occurs first). |
| Time to Confirmed Deterioration (TTCD) in Pain Presence and Interference | From randomization until treatment discontinuation (up to 2 years) | 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 |
| TTCD in physical functioning (PF) | From randomization until treatment discontinuation (up to 2 years) | 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. |
| TTCD in role functioning (RF) | From randomization until treatment discontinuation (up to 2 years) | 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. |
| TTCD in Global Health Status/quality of life (GHS/QoL) | From randomization until treatment discontinuation (up to 2 years) | 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. |
| Incidence and severity of Adverse Events (AEs) | Up to approximately 24 months | 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) |
| Number of patients who experienced abnormalities in vital signs and clinical laboratory parameters | Up to approximately 24 months | 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. |
Countries
Australia, Belgium, Bulgaria, France, Italy, Malaysia, Poland, Romania, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Lead
Inhibrx Biosciences, Inc
Outcome results
None listed