Clinical Trial Finder

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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 including CPI or for whom no standard or clinically acceptable therapy exists.

• - Part 4 (expansion cohorts in combination with pembrolizumab): Subjects with melanoma (all types), HNSCC, G/GEA, RCC, TCC, NSCLC, or MSI-high, TMB-high, MMR-deficient tumors, with locally advanced or metastatic, non resectable disease, which is either CPI-naive (melanoma, HNSCC, NPC) or progressed despite all standard therapies including CPI (NSCLC, RCC, TCC, uveal melanoma, MSI-high, TMB-high, or MMR-deficient solid tumors) 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 ≥50% for NSCLC; for TMB-high tumors, any TPS% is allowed).

• - Adequate hematologic, coagulation, hepatic and renal function and ECOG score as defined per protocol.

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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.

Arms

Experimental: Part 1 INBRX-106 Escalation

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

Experimental: Part 3 INBRX-106 Escalation in Combination with Pembrolizumab

INBRX-106 will be escalated, in combination with pembrolizumab, in subjects with locally advanced or metastatic solid tumors.

Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab

Subjects with melanoma (any type), head and neck squamous cell carcinoma (non-nasopharyngeal), nasopharyngeal carcinoma, MSI-high, TMB-high or MMR-deficient tumors, will be treated with INBRX-106 in combination with 200mg pembrolizumab IV every 3 weeks.

Active Comparator: Part 4 Pembrolizumab Expansion Arm, Randomized

Subjects with non-small cell lung cancer will be treated with 200 mg pembrolizumab IV every 3 weeks

Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab in NSCLC, Randomized

Subjects with non-small cell lung cancer will be treated with alternating every 6 weeks dosing of INBRX-106 0.3 mg/kg Q6W and 400 mg pembrolizumab IV

Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab in NSCLC; Randomized

Subjects with non-small cell lung cancer will be given a 0.3 mg/kg priming dose of INBRX-106 in cycle 1, followed by 0.1 mg/kg INBRX-106 and 200 mg pembrolizumab IV every 3 weeks in subsequent cycles

Experimental: Part 2 INBRX-106 Escalation in NSCLC

Subjects with non-small cell carcinoma relapsed or refractory to prior checkpoint inhibitor (CPI) therapy will be treated with INBRX-106

Experimental: Part 2 INBRX-106 Escalation in Various Solid Tumor Types

Subjects with melanoma (any type), head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma or MSI/TMB-high tumors that are relapsed or refractory to prior checkpoint inhibitor (CPI) therapy will be treated with INBRX-106

Experimental: Part 4 INBRX-106 Expansion with Pembrolizumab in Uveal Melanoma

Subjects with ocular (uveal) melanoma who are relapsed or refractory to checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 and 200 mg pembrolizumab IV every 3 weeks

Experimental: Part 4 INBRX-106 Expansion with Pembrolizumab in MSI-high, TMB-high or MMR-deficient tumors

Subjects with solid tumors that have confirmed MSI-high, TMB-high or MMR-deficient states who are relapsed or refractory to checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 and 200 mg pembrolizumab IV every 3 weeks

Interventions

Drug: - INBRX-106 - Hexavalent OX40 agonist antibody

The active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).

Drug: - Pembrolizumab 200 mg

Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.

Drug: - Pembrolizumab 400 mg

Pembrolizumab 400 mg by IV infusion given on Day 1 of alternating 21-day cycles (every 6 weeks)