INBRX-106 in Combination With Pembrolizumab in First-line PD-L1 CPS≥20 HNSCC

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06295731
• Other study ID #: INBRX106-01-201
• Secondary ID: EU CT
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: May 14, 2024
• Est. completion date: May 2029

Study information

• Verified date: May 2024
• Source: Inhibrx, Inc.
• Contact: Study Director - Inhibrx
• Phone: 858-500-7833
• Email: clinicaltrials[@]inhibrx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Carcinoma (HNSCC)
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• INBRX-106
INBRX-106 by intravenous (IV) infusion, given every 3 weeks (QW3)
• Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given every 3 weeks (QW3)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Inhibrx, Inc.

Country where clinical trial is conducted

United States, 

Outcome

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