Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Purpose
This is a Phase 1/2, 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).
Conditions
- Solid Tumor
- Non-Small Cell Lung Cancer
- Melanoma
- Head and Neck Cancer
- Gastric Cancer
- Renal Cell Carcinoma
- Urothelial Carcinoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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. 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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
- Masking Description
- Part 4 NSCLC cohort is randomized 1;1:1, open-label
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Part 1 INBRX-106 Escalation |
INBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors. |
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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. |
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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. |
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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 |
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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 |
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|
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 |
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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 |
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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 |
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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 |
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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 |
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Recruiting Locations
Vanderbilt University School of Medicine
Nashville, Tennessee 37204
Nashville, Tennessee 37204
More Details
- Status
- Recruiting
- Sponsor
- Inhibrx, Inc.