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 Information
Recruitment Status
Drug
Estimated Enrollment
150
Start Date
December 10, 2019
Completion Date
March 15, 2023
Primary Completion Date
December 2, 2022
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
Klaus Wagner, MD, PhD, 858-500-7833, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
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 Corp.
Study Sponsor
Klaus Wagner, MD, PhD, Study Director, Inhibrx, Inc.
Verification Date
July 2021