Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)

Non-Small Cell Lung Cancer Clinical Trial

Official title:

An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Multicohort, Phase 1/2 Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04198766
• Other study ID #: Ph 1 Ph 2 INBRX-106
• Secondary ID: MK3475 KEYNOTE A
• Status: Recruiting
• Phase: Phase 1
• Start date: December 10, 2019
• Est. completion date: May 15, 2026

Study information

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

Clinical Trial Summary

This is a Phase 1/2, open-label, non-randomized, 4-part Phase 1 trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of INBRX 106 administered as a single agent or in combination with the anti-PD-1 checkpoint inhibitor (CPI) pembrolizumab (Keytruda).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 333
• Est. completion date: May 15, 2026
• Est. primary completion date: February 2, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Select Inclusion Criteria:

• Males or females aged =18 years.

• Parts 1 and 3 (escalation cohorts): Subjects with locally advanced or metastatic non resectable solid tumors, whose disease has progressed despite all standard therapies or for whom no further standard or clinically acceptable therapy exists.

• Part 2 (single-agent expansion cohort): Subjects with NSCLC, melanoma, HNSCC, G/GEA, RCC, or TCC, with locally advanced or metastatic, non-resectable disease, which has progressed despite all standard therapies including CPI or for whom no standard or clinically acceptable therapy exists.

• Part 4 (expansion cohorts in combination with pembrolizumab): Subjects with melanoma (all types), HNSCC, G/GEA, RCC, TCC, NSCLC, or MSI-high, TMB-high, MMR-deficient tumors, with locally advanced or metastatic, non resectable disease, which is either CPI-naive (melanoma, HNSCC, NPC) or progressed despite all standard therapies including CPI (NSCLC, RCC, TCC, uveal melanoma, MSI-high, TMB-high, or MMR-deficient solid tumors) or for whom no standard or clinically acceptable therapy exists.

• All subjects with non-squamous NSCLC must have documentation of absence of tumor activating EGFR mutations and absence of ALK gene rearrangements.

• PD-L1 by IHC (22C3): Parts 1 and 3: IHC optional. Part 2: IHC result mandatory but any score allowed. Part 4: Combined Positive Score (CPS) = 1% (or Tumor Proportion Score =50% for NSCLC; for TMB-high tumors, any TPS% is allowed).

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

Select Exclusion Criteria:

• Prior exposure to OX40 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 with certain exceptions.

• Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin's 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-106.

• 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) infection for Parts 1 and 3. 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.

• Additional in- and exclusion criteria per protocol.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Renal Cell
• Carcinoma, Transitional Cell
• Gastric Cancer
• Head and Neck Cancer
• Head and Neck Neoplasms
• Lung Neoplasms
• Melanoma
• Non-Small Cell Lung Cancer
• Renal Cell Carcinoma
• Solid Tumor
• Stomach Neoplasms
• Urothelial Carcinoma

Intervention

Drug:
• INBRX-106 - Hexavalent OX40 agonist antibody
The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).
• Pembrolizumab 200 mg
Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
• Pembrolizumab 400 mg
Pembrolizumab 400 mg by IV infusion given on Day 1 of alternating 21-day cycles (every 6 weeks)

Locations

Country	Name	City	State
United States	Winship Cancer Institute - Emory University	Atlanta	Georgia
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	Henry Ford Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Renovatio Clinical - El Paso	El Paso	Texas
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	START Midwest	Grand Rapids	Michigan
United States	University of Iowa	Iowa City	Iowa
United States	Valkyrie Clinical Trials	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University School of Medicine	Nashville	Tennessee
United States	Nebraska Cancer Specialists	Omaha	Nebraska
United States	St. Joseph Hospital of Orange	Orange	California
United States	Providence Portland Medical Center	Portland	Oregon
United States	NEXT Oncology	San Antonio	Texas
United States	Renovatio Clinical	The Woodlands	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Inhibrx, Inc.	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab	Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).	2-4 years
Other	Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab	Tumor response will be determined by immune Response Evaluation Criteria in Solid Tumors (iRECIST).	2-4 years
Primary	Frequency of adverse events of INBRX-106 as single agent and in combination with pembrolizumab	Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0	2-4 years
Primary	Severity of adverse events of INBRX-106 as single agent and in combination with pembrolizumab	Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0	2-4 years
Primary	MTD and/or RP2D of INBRX-106 as single agent and in combination with pembrolizumab	Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-106 and INBRX-106 in combination with pembrolizumab	2-4 years
Secondary	Area under the serum concentration time curve (AUC) of INBRX-106	Area under the serum concentration time curve (AUC) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.	2-4 years
Secondary	Maximum observed serum concentration (Cmax) of INBRX-106	Maximum observed serum concentration (Cmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.	2-4 years
Secondary	Trough observed serum concentration (Ctrough) of INBRX-106	Trough observed serum concentration (Ctrough) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.	2-4 years
Secondary	Time to Cmax (Tmax) of INBRX-106	Time to Cmax (Tmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.	2-4 years
Secondary	Immunogenicity of INBRX-106	Frequency of anti-drug antibodies (ADA) against INBRX-106 as a single agent and in combination with pembrolizumab will be determined.	2-4 years