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).
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
- Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin's 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-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.