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

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).
    

Study Phase

Phase 1

Study Type

Interventional

Primary Outcome

Frequency of adverse events of INBRX-106 as single agent and in combination with pembrolizumab

Secondary Outcome

 Area under the serum concentration time curve (AUC) of INBRX-106

Condition

Solid Tumor

Intervention

INBRX-106 - Hexavalent OX40 agonist antibody

Study Arms / Comparison Groups

 Part 1 INBRX-106 Escalation

Description:  INBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

200

Start Date

December 10, 2019

Completion Date

March 15, 2024

Primary Completion Date

December 2, 2023

Eligibility Criteria

        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 or for whom no standard or clinically
             acceptable therapy exists.

          -  Part 4 (expansion cohorts in combination with pembrolizumab): Subjects with melanoma,
             HNSCC, G/GEA, RCC, or TCC, or NSCLC, 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) ≥ 1% (or Tumor Proportion Score
             ≥1% for NSCLC).

          -  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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Vasily Andrianov, MD, 858-500-7833, [email protected]

Location Countries

United States

Location Countries

United States

NCT ID

NCT04198766

Organization ID

Ph 1 INBRX-106

Secondary IDs

MK3475 KEYNOTE A99

Responsible Party

Sponsor

Study Sponsor

Inhibrx, Inc.

Collaborators

 Merck Sharp & Dohme LLC

Study Sponsor

Vasily Andrianov, MD, Study Director, Inhibrx, Inc.

Verification Date

February 2022