Brief Title
Study of INBRX-105 and INBRX-105 With Pembrolizumab in Patients With Solid Tumors
Official Title
An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Phase 1 - 2 Study of INBRX-105 and INBRX-105 in Combination With Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
Brief Summary
This is a first-in-human, open-label, nonrandomized, four-part Phase 1/2 trial to determine
the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2
dose (RP2D) of INBRX-105 and INBRX-105 in combination with Pembrolizumab. INBRX-105, a next
generation bispecific antibody, targets the human programmed death-ligand 1 (PD-L1) receptor
and the human 4-1BB receptor. INBRX-105 provides localized conditional T-cell co-stimulation
through 4-1BB agonism.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Frequency of adverse events of INBRX-105
Secondary Outcome
Area under the serum concentration time curve (AUC) of INBRX-105
Condition
Metastatic Solid Tumors
Intervention
INBRX-105 - PDL1x41BB antibody
Study Arms / Comparison Groups
Single Agent Escalation
Description: INBRX-105 will be escalated in patients 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
300
Start Date
January 30, 2019
Completion Date
December 2025
Primary Completion Date
August 2025
Eligibility Criteria
Inclusion Criteria:
- Parts 1 and 3 (escalation cohorts): Patients with locally advanced or metastatic
non-resectable solid tumors, whose disease has progressed despite standard therapy and
for whom no further standard therapy exists.
- Part 2 (expansion cohorts): Patients with non-small cell lung cancer, cutaneous
melanoma, head and neck squamous cell carcinoma or solid tumors amenable to paired
biopsies, with locally advanced or metastatic, non-resectable disease, which has
progressed despite standard therapy or for whom no standard or clinically acceptable
therapy exists.
- Part 4 relapsed or refractory to CPI cohorts: NSCLC, cutaneous melanoma, HNSCC,
MSI/TMB-high or MMRd solid tumors
- Part 4 CPI naive cohorts: locally advanced or metastatic, non-resectable NSCLC or
HNSCC
- Refractory or relapsed to anti-PD-1 or anti-PD-L1, and anti-CTLA4 if applicable (NOTE:
For all tumor types with checkpoint inhibitor approvals) with exception of the
treatment naive NSCLC cohort.
- PD-L1 positivity by immunohistochemistry (IHC): Parts 1 and 3 (escalation cohorts)
PD-L1 positivity is not required. Parts 2 and 4 (expansion cohorts): Combined Positive
Score (CPS) or Tumor Proportion Score (TPS) above certain thresholds as defined per
protocol.
- Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
Exclusion Criteria:
- Prior exposure to 4-1BB 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.
Exceptions: Hormone replacement therapy, testosterone, or oral contraceptives. NOTE:
Previous exposure to anti-PD-L1 checkpoint inhibitor requires a minimum washout period
of 24 weeks prior to the first dose of study drug.
- Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin 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-105.
- 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). Exceptions
as defined in protocol for expansion cohorts will apply.
- History of hepatitis or cirrhosis (e.g., non-alcohol steatohepatitis, alcohol or
drug-related, autoimmune, hepatitis B, or hepatitis C). 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.
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
Administrative Informations
NCT ID
NCT03809624
Organization ID
Ph 1 Ph 2 INBRX-105
Responsible Party
Sponsor
Study Sponsor
Inhibrx, Inc.
Study Sponsor
Vasily Andrianov, MD, Study Director, Inhibrx, Inc.
Verification Date
January 2023