This is a first-in-human, open-label, nonrandomized, four-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-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.
- 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.
- Parts 2 and 4 (expansion cohorts): Patients with non-small cell lung cancer, melanoma,
head and neck squamous cell carcinoma, gastric or gastro-esophageal junction
adenocarcinoma, renal cell carcinoma, or urothelial (transitional) cell carcinoma,
with locally advanced or metastatic, non-resectable disease, which has progressed
despite standard therapy or for whom no standard or clinically acceptable therapy
- Part 4 treatment naive NSCLC cohort: Locally advanced or metastatic, non-resectable
NSCLC, who have not received prior systemic treatment, including CPI, for advanced or
metastatic disease. PD-L1 IHC Tumor Proportion Score (TPS) ≥ 1% and < 50%. In Part 4,
all patients with non-squamous NSCLC must have documentation of absence of tumor
activating EGFR mutations and absence of ALK gene rearrangements.
- 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
- Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
- 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
- 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) infection
for Part 1. 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) for Part 1. 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
- 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.