Study of INBRX-105 and INBRX-105 With Pembrolizumab in Patients With Solid Tumors Including Head and Neck Cancer

Non-small Cell Lung Cancer Clinical Trial

— PDL1x41BB  

Official title:

An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Phase 1 / 2 Study of INBRX-105 and INBRX-105 in Combination With Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03809624
• Other study ID #: Ph 1 Ph 2 INBRX-105
• Status: Recruiting
• Phase: Phase 2
• Start date: January 30, 2019
• Est. completion date: December 2025

Study information

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

Clinical Trial Summary

This is a first-in-human, open-label, nonrandomized, four-part trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of INBRX-105 and INBRX-105 in combination with Pembrolizumab. INBRX-105, a next generation bispecific antibody, targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor. INBRX-105 provides localized conditional T-cell co-stimulation through 4-1BB agonism.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Parts 1 and 3 (escalation cohorts; completed): Patients with locally advanced or metastatic non-resectable solid tumors, whose disease has progressed despite standard therapy and for whom no further standard therapy exists.

• Part 2 (expansion cohorts): Patients with non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma or solid tumors amenable to paired biopsies, with locally advanced or metastatic, non-resectable disease, which has progressed despite standard therapy or for whom no standard or clinically acceptable therapy exists.

• Part 4 relapsed or refractory to CPI cohorts: NSCLC, cutaneous melanoma, HNSCC, MSI/TMB-high or MMRd solid tumors

• Part 4 CPI naive cohorts: locally advanced or metastatic, non-resectable NSCLC or HNSCC

• Refractory or relapsed to anti-PD-1 or anti-PD-L1, and anti-CTLA4 if applicable (NOTE:

For all tumor types with checkpoint inhibitor approvals) with exception of the treatment naive NSCLC cohort.

• PD-L1 positivity by immunohistochemistry (IHC): Parts 1 and 3 (escalation cohorts) PD-L1 positivity is not required. Parts 2 and 4 (expansion cohorts): Combined Positive Score (CPS) or Tumor Proportion Score (TPS) above certain thresholds as defined per protocol.

• Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.

• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.

Exclusion Criteria:

• Prior exposure to 4-1BB agonists.

• Receipt of any investigational product or any approved anticancer drug(s) or biological product(s) within 4 weeks prior to the first dose of study drug. Exceptions: Hormone replacement therapy, testosterone, or oral contraceptives. NOTE: Previous exposure to anti-PD-L1 checkpoint inhibitor requires a minimum washout period of 24 weeks prior to the first dose of study drug.

• Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin lymphoma and multiple myeloma).

• Prior or concurrent malignancies. Exception: Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessments of INBRX-105.

• Known or active primary central nervous system (CNS) tumors, leptomeningeal disease and CNS metastases. Exception: Subjects with previously treated, asymptomatic, and clinically stable CNS metastases may be allowed study entry if certain criteria apply.

• Grade = 3 immune-related adverse events (irAEs) or irAE that lead to discontinuation of prior immunotherapy. Some exceptions as defined per protocol apply.

• Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications. Certain exceptions as defined in protocol apply.

• Treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug. Certain exceptions as defined in protocol apply.

• History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). Exceptions as defined in protocol for expansion cohorts will apply.

• History of hepatitis or cirrhosis (e.g., non-alcohol steatohepatitis, alcohol or drug-related, autoimmune, hepatitis B, or hepatitis C). Exceptions as defined in protocol for expansion cohorts will apply.

• Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or other immunosuppressive medications.

• Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease < 3 months; left ventricular ejection fraction (LVEF) < 50%; New York Heart Association (NYHA) Class III or IV congestive heart failure; or uncontrolled hypertension.

• Active, hemodynamically significant pulmonary embolism within 3 months prior to enrollment on this trial.

• Major surgery within 4 weeks prior to enrollment on this trial.

• Anti-infectious drug treatments (i.e., antibiotics) within 4 weeks prior to the first dose of study drug.

• Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC) or bone marrow (BM) transplantation.

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Renal Cell
• Esophageal Adenocarcinoma
• Gastric Adenocarcinoma
• Head and Neck Squamous Cell Carcinoma
• Melanoma
• Metastatic Solid Tumors
• Nasopharyngeal Carcinoma
• Non-small Cell Lung Cancer
• Oropharyngeal Carcinoma
• Renal Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• INBRX-105 - PDL1x41BB antibody
The active ingredient of INBRX-105 is a recombinant, humanized, bispecific IgG antibody that targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor.
• Pembrolizumab
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
United States	Emory University - Winship Cancer Institute	Atlanta	Georgia
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Colorado Denver	Denver	Colorado
United States	City of Hope	Duarte	California
United States	City of Hope at Irvine Lennar	Duarte	California
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	START Midwest	Grand Rapids	Michigan
United States	MD Anderson Cancer Center	Houston	Texas
United States	Valkyrie Clinical Trials	Los Angeles	California
United States	Norton Cancer Center	Louisville	Kentucky
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	Nebraska Cancer Specialists - Grand Island	Omaha	Nebraska
United States	Stanford University	Palo Alto	California
United States	Abramson Cancer Center - University of Pennsylvania	Philadelphia	Pennsylvania
United States	Abramson Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Providence Cancer Institute	Portland	Oregon
United States	Washington University	Saint Louis	Missouri
United States	New Experimental Therapeutics of San Antonio - NEXT Oncology	San Antonio	Texas
United States	HonorHealth Research Institute	Scottsdale	Arizona
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	START Mountain Region	West Valley City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Inhibrx, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Anti-tumor activity of INBRX-105	Tumor response will be determined by immune Response Evaluation Criteria in Solid Tumors (iRECIST).	Up to 2-3 years
Primary	Frequency of adverse events of INBRX-105	Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.	Up to 2-3 years
Primary	Severity of adverse events of INBRX-105	Severity of adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.	Up to 2-3 years
Primary	Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-105	The MTD and/or RP2D of INBRX-105 will be determined.	Up to 2-3 years
Secondary	Area under the serum concentration time curve (AUC) of INBRX-105	Area under the serum concentration time curve (AUC) of INBRX-105 will be determined.	Up to 2-3 years
Secondary	Maximum observed serum concentration (Cmax) of INBRX-105	Maximum observed serum concentration (Cmax) of INBRX-105 will be determined.	Up to 2-3 years
Secondary	Trough observed serum concentration (Ctrough) of INBRX-105	Trough observed serum concentration (Cmax) of INBRX-105 will be determined.	Up to 2-3 years
Secondary	Time to Cmax (Tmax) of INBRX-105	Time to Cmax (Tmax) of INBRX-105 will be determined.	Up to 2-3 years
Secondary	Immunogenicity of INBRX-105	Frequency of anti-drug antibodies (ADA) against INBRX-105 will be determined.	Up to 2-3 years