Head and Neck Squamous Cell Carcinoma (HNSCC), HPV Oropharyngeal Squamous Cell Carcinoma (HPV+ OPSCC)
Conditions
Keywords
OX40 receptor agonist, PD-L1 positive, Pembrolizumab, Immunotherapy, Chemotherapy-free, HNSCC, Head and Neck Cancer, Keytruda, Oropharyngeal cancer, INBRX-106, HPV positive, squamous cell carcinoma, OPSCC, ordastobart
Brief summary
This seamless phase 2/3 randomized controlled study will evaluate the efficacy and safety of the hexavalent OX40 agonist antibody ordastobart (INBRX-106) combined with the anti-PD-1 antibody pembrolizumab versus pembrolizumab (+ placebo in phase 3) as first-line treatment for patients with recurrent or metastatic (R/M) HPV-positive Oropharyngeal Squamous Cell Carcinoma (HPV+ OPSCC) expressing PD-L1.
Interventions
DRUGINBRX-106
INBRX-106 0.1 mg/kg 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 recurrent/metastatic oropharyngeal squamous cell carcinoma (OPSCC) considered incurable by local therapies. * Has tumor PD-L1 expression with a combined proportion score (CPS) ≥1 by central testing. * HPV-positive tumor status as assessed locally by p16 immunohistochemistry (IHC). * Has measurable disease per RECIST 1.1 guidelines. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion criteria
* Has primary tumor site (any histology) of any other location than oropharynx. * Has received prior systemic therapy (eg, prior chemo-, immune-, or biologic therapy) for R/M 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 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. * Active or high risk of tumor-associated bleeding. * 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 by investigator (ORRinv) | From randomization to progressive disease (PD) or death (up to 1 year) | defined as the proportion of patients with complete response (CR) or partial response (PR) on 2 consecutive occasions ≥4 weeks apart, as determined by the Investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). |
| Phase 3: Progression-Free Survival by Investigator (PFSinv) | From randomization to PD or death (up to 4 years) | defined as the time from randomization to first occurrence of PD, as determined by the Investigator according to RECIST 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) | defined as the time from randomization to death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 and 3: Objective Response Rate by Blinded Independent Review Committee (ORRbirc) | From randomization to PD or death (up to 1 year) | defined as the proportion of patients with a CR or PR on 2 consecutive occasions ≥4 weeks apart, per RECIST 1.1 |
| Phase 2 and 3: Duration of Response by Investigator and by BIRC (DORinv, DORbirc) | From the first occurrence of a documented objective response to PD or death (up to 4 years) | defined as the time from the first occurrence of a documented objective response (CR/PR) until PD, both as determined by the Investigator or BIRC, respectively, according to RECIST 1.1, or death from any cause (whichever occurs first) |
| Phase 2 and 3: Clinical Benefit Rate (CBR) by Investigator and by BIRC | From randomization to PD or death (up to 1 year) | defined as the proportion of patients with stable disease (SD) for ≥12 weeks or a CR or PR, as determined by the Investigator or BIRC respectively, according to RECIST 1.1. |
| Phase 2 and 3: Progression-free survival by BIRC (PFSbirc) | From randomization to PD or death (up to 4 years) | defined as the time from randomization to first occurrence of PD, as determined by the BIRC according to RECIST 1.1, or death from any cause (whichever occurs first). |
| Phase 2 and 3: PFSinv and PFSbirc rates at 6, 9, 12 and 24 months | From randomization to PD or death, with landmark-specific timeframes (up to 2 years) | defined as the proportion of patients who are progression-free, as determined by the Investigator or BIRC, respectively, according to RECIST 1.1, and alive 6, 9, 12 and 24 months after randomization. |
| Phase 2 and Phase 3: OS rates at 12 and 24 months | From randomization to death, with landmark-specific timeframes (up to 2 years) | defined as the proportion of patients who are alive 12 and 24 months after randomization. |
| Phase 2: PFS by Investigator (PFSinv) | From randomization to PD or death (up to 4 years) | defined as the time from randomization to first occurrence of PD, as determined by the Investigator according to RECIST 1.1, or death from any cause (whichever occurs first). |
| Phase 2: Overall Survival (OS) | From randomization to death (up to 4 years) | defined as the time from randomization to death from any cause |
| Phase 3: Objective Response Rate by investigator (ORRinv) | From randomization to progressive disease (PD) or death (up to 1 year) | defined as the proportion of patients with CR or PR on 2 consecutive occasions ≥4 weeks apart, as determined by the Investigator according to RECIST 1.1. |
| Phase 3: Time to Chemotherapy (TTCtx) | From randomization until the start of chemotherapy or death (up to 4 years) | defined as the time from randomization until the start date of chemotherapy or death from any cause (whichever occurs first). |
| Phase 2 and Phase 3: Incidence and Severity of treatment-emergent Adverse Events (AEs) | From first study treatment dose until the end of protocol-defined safety follow-up period (up to 2 years) | Incidence will be reported as the number of participants with at least one AE, with severity determined according to the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 5 (NCI CTCAE v 5.0) |
| Phase 2 and Phase 3: Evaluate the safety and tolerability of study treatment | Up to approximately 24 months | Incidence of dose interruptions and treatment discontinuation. |
| Phase 2 and Phase 3: Number of patients who experienced abnormalities in vital signs and clinical laboratory parameters | From first study treatment dose until the end of protocol-defined safety follow-up period (up to 2 years) | 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. |
| Phase 3: 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 |
| Phase 3: TTCD in physical functioning (PF) | From randomization until treatment discontinuation (up to 2 years) | defined as the time from randomization to the first documentation of a ≥10 point decrease from baseline in the EORTC QLQ-C30 linearly transformed PF scale score. |
| Phase 3: TTCD in role functioning (RF) | From randomization until treatment discontinuation (up to 2 years) | defined as the time from randomization to the first documentation of a ≥10 point decrease from baseline in the EORTC QLQ-C30 linearly transformed RF scale score. |
| Phase 3: TTCD in Global Health Status/quality of life (GHS/QoL) | From randomization until treatment discontinuation (up to 2 years) | defined as the time from randomization to the first documentation of a ≥10 point decrease from baseline in the EORTC QLQ-C30 linearly transformed GHS/QoL scale score. |
Countries
Australia, Belgium, Bulgaria, France, Italy, Malaysia, Poland, Romania, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTStudy Director - Inhibrx
STUDY_DIRECTORClinical Lead
Inhibrx Biosciences, Inc
Outcome results
None listed