Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab 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 22, 2021
• Sponsor: Inhibrx, Inc.
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Inhibrx, Inc.

Tracking Information

• First Submitted Date: December 11, 2019
• First Posted Date: December 13, 2019
• Last Update Posted Date: January 22, 2021
• Actual Study Start Date: December 10, 2019
• Estimated Primary Completion Date: December 2, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 11, 2019)

• 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
• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 11, 2019)

• 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.
• 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.
• 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.
• 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.
• 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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: December 11, 2019)

• 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).
• 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).

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
• Official Title: An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Phase 1 Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Solid Tumor
• Non-Small Cell Lung Cancer
• Melanoma
• Head and Neck Cancer
• Gastric Cancer
• Renal Cell Carcinoma
• 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).
• Drug: Pembrolizumab
  Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
  Other Name: Keytruda

Study Arms

• Experimental: Part 1 INBRX-106 Escalation
  INBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors.
  Intervention: Drug: INBRX-106 - Hexavalent OX40 agonist antibody
• 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.
  Intervention: Drug: INBRX-106 - Hexavalent OX40 agonist antibody
• 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.
  Interventions:

  • Drug: INBRX-106 - Hexavalent OX40 agonist antibody
  • Drug: Pembrolizumab
• 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.
  Interventions:

  • Drug: INBRX-106 - Hexavalent OX40 agonist antibody
  • Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 11, 2019): 150
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 15, 2023
• Estimated Primary Completion Date: December 2, 2022 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Terri Boyea, Director Clin Ops; 858-500-7833; clinicaltrials@inhibrx.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04198766
• Other Study ID Numbers: Ph 1 INBRX-106; MK3475 KEYNOTE A99 ( Other Identifier: Merck & Co., Inc. )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Inhibrx, Inc.
• Study Sponsor: Inhibrx, Inc.
• Collaborators: Merck Sharp & Dohme Corp.

Investigators

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

• PRS Account: Inhibrx, Inc.
• Verification Date: January 2021