Randomized Phase 2/3 Study of INBRX-106 and Pembrolizumab Versus Pembrolizumab in PD-L1 CPS ≥20 Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
- Trial ID
- 2024-515538-34-00
- Protocol
- INBRX106-01-201
- Sponsor
- Inhibrx Biosciences Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the **efficacy** of INBRX-106 combined with pembrolizumab versus pembrolizumab alone as a first-line treatment for patients with recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) expressing PD-L1 (CPS ≥20). This comparison is clinically relevant as it aims to determine whether the addition of INBRX-106 can enhance the therapeutic outcomes of pembrolizumab, potentially offering a more effective treatment option for this patient population.
Secondary objectives include:
- Evaluating efficacy based on supportive endpoints and iRECIST-assessed endpoints.
- Assessing safety and tolerability.
- Investigating the impact on pain, function, and health-related quality of life (HRQoL).
- Analyzing pharmacokinetics (PK) and immunogenicity.
- Exploring potential biomarkers.
Participants
The clinical trial involves a total of **235 participants** diagnosed with **Head and Neck Squamous Cell Carcinoma**. The study population includes both male and female subjects, aged 18 years and older, who are not considered part of a vulnerable population. Participants were selected based on their ability to provide informed consent, a life expectancy of more than three months, and adequate organ function as determined by specific laboratory criteria. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include histological or cytological documentation of recurrent or metastatic carcinoma considered incurable by local therapies, a primary tumor located in the oral cavity, oropharynx, hypopharynx, or larynx, and measurable disease per RECIST v1.1 guidelines. Participants must also have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-1. The trial aims to compare the efficacy of INBRX-106 combined with pembrolizumab versus pembrolizumab alone.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of **INBRX-106** combined with **pembrolizumab** versus pembrolizumab alone in patients with recurrent or metastatic **Head and Neck Squamous Cell Carcinoma** (HNSCC) expressing PD-L1. The trial is structured in two phases, Phase 2 and Phase 3, and aims to assess the primary endpoints of overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The study is expected to commence recruitment on January 1, 2025, and conclude by May 31, 2029, with a maximum treatment period of 105 weeks for participants.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as adequate organ function, confirmed PD-L1 expression, and measurable disease per RECIST v1.1 guidelines. Following randomization, participants will receive either the investigational combination therapy or pembrolizumab alone, administered intravenously. Regular follow-up visits will be conducted to monitor treatment efficacy, safety, and any adverse events, with assessments including laboratory tests, imaging studies, and quality of life evaluations. The end-of-study visit will occur after the completion of the treatment period or upon early termination.
The expected length of participant involvement is up to 105 weeks, contingent upon individual response and tolerance to the treatment. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, withdrawal of consent, or any other reason deemed appropriate by the investigator. The trial will adhere to rigorous ethical standards, ensuring that all procedures are conducted in compliance with regulatory requirements and guidelines.
Treatment
The clinical trial involves the administration of **KEYTRUDA** (pembrolizumab), a **concentrate for solution for infusion**. This experimental medication is provided in a concentration of 25 mg/mL and is administered intravenously. The maximum daily and total dose is 200 mg, with a treatment period extending up to 105 days. Pembrolizumab is a humanized monoclonal antibody, specifically targeting the programmed death receptor-1 (PD-1) pathway, and is produced by Merck Sharp & Dohme B.V. The administration schedule and participant compliance are monitored to ensure adherence to the dosing regimen.
In addition to pembrolizumab, the trial includes the use of **INBRX-106**, a solution for injection. This investigational drug is a human IgG1 hexavalent antibody against TNFRSF4, developed by Inhibrx Biosciences Inc. It is administered intravenously at a dose of 0.1 mg/kg, with the same maximum treatment period of 105 days. The administration of INBRX-106 is carefully monitored to ensure compliance with the dosing schedule.
A commercially available 0.9% sterile saline solution is utilized as the **placebo** in this study. This solution, which has marketing authorization, serves as a control to evaluate the efficacy of the experimental treatments. The placebo is administered in a manner consistent with the experimental drugs to maintain the integrity of the study design.
Efficacy
The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints include **Objective Response Rate (ORR)**, **Progression-Free Survival (PFS)**, and **Overall Survival (OS)**. ORR is defined as the proportion of patients achieving a complete response (CR) or partial response (PR) on two consecutive occasions at least four weeks apart, as determined by the Investigator according to RECIST v1.1. PFS is defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause, whichever occurs first. OS is defined as the time from randomization to death from any cause.
Secondary endpoints include **Duration of Response (DOR)**, **Clinical Benefit Rate (CBR)**, and PFS rate at six months. DOR is the time from the first occurrence of a documented objective response to PD or death from any cause. CBR is defined as the proportion of patients with stable disease (SD) for at least 12 weeks or a CR or PR. Additional secondary endpoints involve the incidence and severity of treatment-emergent adverse events (TEAEs), incidence of dose interruptions and treatment discontinuation, and changes from baseline in select vital signs and clinical laboratory parameters. Patient-reported outcomes will be assessed using tools such as the EORTC QLQ-C30 and QLQ-H&N35 scales at specified timepoints.
The trial will also evaluate the pharmacokinetics (PK) of INBRX-106, including parameters such as Cmax, Ctrough, AUC, Vd, CL, and t1/2. The incidence of anti-drug antibodies (ADAs) and neutralizing antibodies against INBRX-106 will be monitored. The relationship between biomarkers in blood, plasma, serum, PBMCs, and/or tumor tissue with efficacy, safety, PK, disease biology, or other biomarker endpoints will also be explored. These assessments will be conducted at prespecified timepoints throughout the trial duration.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Able to understand and provide written informed consent.
- Age ≥18 years at the time of signing informed consent (minimum age requirement per local regulatory requirements).
- Histological or cytological documentation of HNSCC diagnosed as R/M and considered incurable by local therapies.
- Primary tumor location of the oral cavity, oropharynx, hypopharynx, or larynx.
- Consent to provide the most recently collected and representative tumor tissue specimen suitable for biomarker testing.
- Confirmed PD-L1 CPS ≥20, as assessed centrally using the PD-L1 IHC 22C3 pharmDx assay on the most recent tumor tissue specimen.
- Confirmed HPV tumor status for oropharyngeal cancer, as assessed centrally by p16 IHC testing on the most recent tumor tissue specimen. • Oral cavity, hypopharynx, and larynx cancer are not required to undergo HPV testing.
- Measurable disease per RECIST v1.1 guidelines. • Tumor lesion(s) previously irradiated or subjected to other locoregional therapy will be considered measurable only if PD is clearly documented at the lesion(s) after completion of therapy.
- ECOG PS score of 0-1.
- Life expectancy of >3 months.
- Adequate organ function, based on screening laboratory tests performed within 3 days of randomization, as defined by the following criteria: a. Hematological (without transfusion or growth factor support) Absolute neutrophil count (ANC) ≥1.5x 109/L (1500/µL). Platelet count ≥100x109/L (100,000/µL). Hemoglobin ≥90 g/L (9 g/dL) or ≥5.6 mmol/L. b. Renal Creatinine (Cr) ≤1.5 x upper limit of normal (ULN) OR Creatinine clearance (CrCl) ≥30 mL/min estimated per institutional standard for patients with creatinine levels >1.5 x ULN (estimated glomerular filtration rate may be used instead of Cr or CrCl). c. Hepatic Albumin ≥2.5 g/dL. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN; for patients with liver metastases, ≤5 x ULN. Serum bilirubin ≤1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). d. Coagulation International normalized ratio (INR) (or prothrombin time [PT]) <1.5 x ULN, unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants. PTT (or activated PTT [aPTT]) <1.5 x ULN, except for patients receiving anticoagulants.
- Female patients of childbearing potential must have a negative highly sensitive pregnancy test within 72 hours prior to randomization and must not be breastfeeding.
- Fertile male patients and female patients of childbearing potential must be willing to completely abstain from heterosexual sex or agree to use acceptable contraception methods from the time of signing informed consent and for the duration of study treatment through 120 days following the last dose. See Appendix C of full protocol for detailed information on fertility, childbearing potential, and acceptable contraception.
- Ability, in the Investigator’s judgment, and willingness to adhere to the study visit schedule and comply with all study specific procedures.
Exclusion Criteria
- Disease amenable for local therapy administered with curative intent.
- Primary tumor site (any histology) of nasopharynx or salivary glands or occult primary site.
- Progressive disease within 6 months of completion of curatively intended treatment for locoregionally advanced HNSCC.
- Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease. • Patients with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
- Prior systemic therapy (eg, prior chemo-, immune-, or biologic therapy) for recurrent 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 for 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.
- Treatment with any investigational systemic therapy within 28 days prior to randomization, or within 5 half-lives of the investigational drug(s), whichever is longer.
- Radiotherapy or any locoregional anticancer therapy within 14 days prior to randomization.
- Major surgical procedure or significant traumatic injury within 28 days prior to randomization. Patients must have also fully recovered from any surgery (major or minor) and/or its complications before randomization.
- Live vaccine administered within 30 days prior to randomization.
- Receiving systemic steroids (>10 mg oral prednisone per day or equivalent) or other immunosuppressive agents within 7 days prior to randomization or has a diagnosis of immunodeficiency.
- History of toxicity ≥Grade 3 related to prior immunotherapy leading to treatment discontinuation, or toxicity related to any prior treatment that has not resolved to ≤Grade 1 (except alopecia, hearing loss, endocrinopathy managed with replacement therapy, and Grade ≤2 peripheral neuropathy or other toxicities not considered a safety risk per Investigator’s judgment).
- Life expectancy <3 months.
- Active tumor bleeding.
- Rapidly progressing disease or with features that may confer a high risk of tumor associated hemorrhage (including, but not limited to, tumors encasing or infiltrating a major vessel such as carotid, jugular, and bronchial artery, and/or other high-risk features such as an arteriovenous fistula), or uncontrolled tumor pain. The Sponsor’s Medical Monitor is available for consultation.
- Known allergy or hypersensitivity to INBRX-106, pembrolizumab, or any component of their respective formulations. History of severe hypersensitivity to protein-based therapies, in particular CHO-cell derived antibodies or other mAbs.
- Current or history of immune-related disease (refer to Appendix B) that required systemic treatment in past 2 years, except for replacement therapy (eg, physiological doses of corticosteroids for treatment of endocrinopathies).
- History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
- History of organ allograft transplantations or allogeneic peripheral blood stem cell transplantation/bone marrow transplantations.
- History of other invasive malignancy within 5 years prior to screening, except for cancers with very low risk of recurrence including, but not limited to, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, papillary thyroid cancer treated with surgery, or Stage I endometrial cancer. The Sponsor’s Medical Monitor is available for consultation.
- Serious infection requiring oral or intravenous (IV) antibiotics, or other clinically significant infection within 14 days prior to randomization. • Patients who fully recovered from serious or clinically significant infections at least 14 days prior to randomization are eligible.
- Known HIV infection, or positive test for active infection with HBV (eg, hepatitis B surface antigen [HBsAg] and/or total hepatitis B core antibody [HBcAb]) or HCV (eg, RNA). • Patients cured of HCV infection (undetectable viral load, sustained virologic response for 3 months after completing treatment), or positive for HCV antibody and negative for HCV RNA are eligible. Patients who are HCV carriers and test positive for HCV RNA are not eligible. • For patients who have been successfully treated for viral hepatitis, the possibility of re-activation of the virus or reinfection with viral hepatitis should be considered by the Investigator and the overall potential benefits associated with study treatment for the patient should be deemed to exceed the overall risks.
- History or current evidence of any condition, therapy, or laboratory abnormality that in the Investigator’s opinion precludes the individual’s safe participation in and completion of the study.
- Personal or financial relationship with the Sponsor, a contractual relationship with the Investigator or the study site, or in custody or sanctioned by an official or court order.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 01 Jan 2025 | 18 |
 Bulgaria | Not Recruiting | 01 Jan 2025 | 24 |
 France | Not Recruiting | 01 Jan 2025 | 28 |
 Italy | Not Recruiting | 01 Jan 2025 | 19 |
 Poland | Not Recruiting | 01 Jan 2025 | 14 |
 Romania | Not Recruiting | 01 Jan 2025 | 24 |
 Spain | Not Recruiting | 01 Jan 2025 | 48 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
INBRX-106 | Test | SOLUTION FOR INJECTION | INTRAVENOUS | 0.1 | 105 | PRD11525793 |
INBRX-106 | Test | LYOPHILIZED POWDER FOR SOLUTION FOR INJECTION | INTRAVENOUS | 0.1 | 105 | PRD12465596 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 200 | 105 | PRD4323105 |
Commercially available 0,9 % sterile saline solution with marketing authorization will be utilized as the placebo. | Placebo | N/A | — | — | — | N/A |