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

• ClinicalTrials.gov Identifier: NCT04198766
• Recruitment Status: Recruiting
• First Posted: December 13, 2019
• Last Update Posted: January 14, 2020
• Sponsor: Inhibrx, Inc.
• Information provided by (Responsible Party): Inhibrx, Inc.

Study Description

Brief Summary:

This is a first-in-human, 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).

Condition or disease	Intervention/treatment	Phase
Solid Tumor; Non-Small Cell Lung Cancer; Melanoma; Head and Neck Cancer; Gastric Cancer; Renal Cell Carcinoma; Urothelial Carcinoma	Drug: INBRX-106 - Hexavalent OX40 agonist antibody; Drug: Pembrolizumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Phase 1 Study of INBRX 106 in Subjects With Locally Advanced or Metastatic Solid Tumors
• Actual Study Start Date: December 10, 2019
• Estimated Primary Completion Date: December 2, 2022
• Estimated Study Completion Date: March 15, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1 INBRX-106 Escalation; INBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors.	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).
Experimental: Part 2 INBRX-106 Expansion; Subjects with non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-106 at the RP2D.	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).
Experimental: Part 3 INBRX-106 Escalation in Combination with Pembrolizumab; INBRX-106 will be escalated, in combination with pembrolizumab, in subjects with locally advanced or metastatic solid tumors.	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).; Drug: Pembrolizumab; Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.; Other Name: Keytruda
Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab; Subjects with non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-106 at the RP2D in combination with pembrolizumab.	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).; Drug: Pembrolizumab; Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.; Other Name: Keytruda

Outcome Measures

Primary Outcome Measures :

1. Frequency of adverse events of INBRX-106 as single agent and in combination with pembrolizumab [ Time Frame: 2-4 years ]
   Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0
2. Severity of adverse events of INBRX-106 as single agent and in combination with pembrolizumab [ Time Frame: 2-4 years ]
   Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0
3. MTD and/or RP2D of INBRX-106 as single agent and in combination with pembrolizumab [ Time Frame: 2-4 years ]
   Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-106 and INBRX-106 in combination with pembrolizumab

Secondary Outcome Measures :

1. Area under the serum concentration time curve (AUC) of INBRX-106 [ Time Frame: 2-4 years ]
   Area under the serum concentration time curve (AUC) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
2. Maximum observed serum concentration (Cmax) of INBRX-106 [ Time Frame: 2-4 years ]
   Maximum observed serum concentration (Cmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
3. Trough observed serum concentration (Ctrough) of INBRX-106 [ Time Frame: 2-4 years ]
   Trough observed serum concentration (Ctrough) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
4. Time to Cmax (Tmax) of INBRX-106 [ Time Frame: 2-4 years ]
   Time to Cmax (Tmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
5. Immunogenicity of INBRX-106 [ Time Frame: 2-4 years ]
   Frequency of anti-drug antibodies (ADA) against INBRX-106 as a single agent and in combination with pembrolizumab will be determined.

Other Outcome Measures:

1. Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab [ Time Frame: 2-4 years ]
   Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).
2. Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab [ Time Frame: 2-4 years ]
   Tumor response will be determined by immune Response Evaluation Criteria in Solid Tumors (iRECIST).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Select Inclusion Criteria:

• Males or females aged ≥18 years.
• Parts 1 and 3 (dose escalation): 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 or for whom no standard or clinically acceptable therapy exists.
• Part 4 (pembrolizumab combination expansion cohorts): Subjects with melanoma, HNSCC, G/GEA, RCC, or TCC (Cohort F1) or NSCLC (Cohorts F2 and F3), with locally advanced or metastatic, non resectable disease, which has progressed despite all standard therapies 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) ≥ 5%.
• 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)
• Sarcomas
• 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.

Contacts and Locations

Contacts

Contact: Kirsti Cook, VPClinOps; 858-500-7833; clinicaltrials@inhibrx.com

Contact: Kevin Bayer, MgrClinOps; 858-500-7833; clinicaltrials@inhibrx.com

Locations

United States, Michigan

START Midwest; Recruiting

Grand Rapids, Michigan, United States, 49546

Contact: Katie Robinson 616-389-1739 Katie.Robinson@startmidwest.com

United States, Texas

NEXT Oncoloy; Recruiting

San Antonio, Texas, United States, 78229

Contact: Sarah Gomez 210-580-9521 sgomez@nextoncology.com

Sponsors and Collaborators

Inhibrx, Inc.

Investigators

• Study Director: Klaus Wagner, MD, PhD; Inhibrx, Inc.

More Information

• Responsible Party: Inhibrx, Inc.
• ClinicalTrials.gov Identifier: NCT04198766
• Other Study ID Numbers: Ph 1 INBRX-106
• First Posted: December 13, 2019
• Last Update Posted: January 14, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Inhibrx, Inc.:

Phase 1; Phase 1 Clinical Trial; Solid Tumors; Melanoma; Head and Neck Cancer; Stomach Cancer; Gastric Cancer; Lung Cancer; Non-Small Cell Lung Cancer; Kidney Cancer; Renal Cell Carcinoma; Bladder Cancer; Urothelial Carcinoma; OX40; PD-1; Pembrolizumab; Keytruda

Additional relevant MeSH terms:

Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma; Stomach Neoplasms; Head and Neck Neoplasms; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Adenocarcinoma; Kidney Neoplasms