Solid Tumor, Non-Small Cell Lung Cancer, Head and Neck Cancer, Melanoma, Gastric Cancer, Renal Cell Carcinoma, Urothelial Carcinoma
Conditions
Keywords
Phase 1 and Phase 2, Phase 1 and Phase 2 Clinical Trial, Solid Tumors, Head and Neck Cancer, Lung Cancer, Non-Small Cell Lung Cancer, OX40 receptor agonist, PD-L1 positive, Pembrolizumab, Keytruda, Chemotherapy, Immunotherapy, HNSCC, Oropharyngeal cancer, Hypopharyngeal cancer, Oral cancer, INBRX-106, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Squamous Cell, Head and Neck Neoplasms, Neoplasms by Site, Carcinoma, Carcinoma, Squamous Cell, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Immunological, Antineoplastic Agents, Squamous Cell Carcinoma of Head and Neck, NSCLC
Brief summary
This is a Phase 1/2, open-label, non-randomized, 4-part 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®). KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Interventions
DRUGINBRX-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).
pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
pembrolizumab 400 mg by IV infusion given on Day 1 of alternating 21-day cycles (every 6 weeks)
DRUGCarboplatin AUC-5
carboplatin AUC-5 by intravenous (IV) infusion, given on Day 1 of each 21-day cycle of cycles 1-4
DRUGCarboplatin AUC-6
carboplatin AUC-6 by intravenous (IV) infusion, given on Day 1 of each 21-day cycle of cycles 1-4
pemetrexed 500 mg/m2 by IV infusion given on Day 1 of each 21-Day cycle for up to 35 cycles
cisplatin 75mg/m2 by intravenous (IV) infusion, given on Day 1 of each 21-day cycle of cycles 1-4
paclitaxel 200mg/m2 by intravenous (IV) infusion, given on Day 1 of each 21-day cycle of cycles 1-4
DRUGNab paclitaxel 100mg/m2
Nab paclitaxel 100mg/m2 by intravenous (IV) infusion, given on Days 1, 8 and 15 of each 21-day cycle of cycles 1-4
Sponsors
Merck Sharp & Dohme LLC
Inhibrx Biosciences, Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Part 4 NSCLC cohort is randomized 1;1:1, open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Select 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 histologically confirmed, 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, with or without chemotherapy): Subjects with melanoma (all types), HNSCC, G/GEA, RCC, TCC, NSCLC, or MSI-high, TMB-high, MMR-deficient tumors, with histologically confirmed, 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. * For Cohort F3 (NSCLC), subjects may have progressed on no more than 2 lines of standard therapy that must include at least one PD-1/L1 regimen. * For Cohort F4 (HNSCC and NPC), subjects may be previously treated with no more than 1 prior chemotherapy regimen in metastatic setting. Prior PD-1/L1 in curative (neo-adjuvant/adjuvant) setting is allowed only if completed \>/= 6 months prior to progression to local recurrence or metastatic disease. * 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. Combined Positive Score (CPS) ≥ 1% (or Tumor Proportion Score ≥50% for NSCLC; for TMB-high tumors, any TPS% is 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 active central nervous system (CNS) metastases and/or carcinomatous meningitis. Exception: Subjects who are previously treated and are radiologically and clinically stable without the requirement for steroid treatment for at least 14 days prior to first dose of study treatment 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. * Diagnosis of immunodeficiency or treatment with systemic immunosuppressive medications within 7 days 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. Exceptions as defined in protocol 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; or oxygen saturation \<92% on room air. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and severity of adverse events of INBRX-106 in combination with pembrolizumab and chemotherapy in adults with locally advanced or metastatic NSCLC | ~2 years | Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0 |
| Frequency of adverse events of INBRX-106 as single agent and in combination with pembrolizumab | ~2 years | Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0 |
| Severity of adverse events of INBRX-106 as single agent and in combination with pembrolizumab | ~2 years | Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0 |
| MTD and/or RP2D of INBRX-106 as single agent and in combination with pembrolizumab | ~2 years | Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-106 and INBRX-106 in combination with pembrolizumab |
| Antitumor activity of INBRX-106 in combination with pembrolizumab in expansion cohorts | ~2 years | Tumor response will be determined by immune Response Evaluation Criteria in Solid Tumors (iRECIST). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity of INBRX-106 | ~2 years | Frequency of anti-drug antibodies (ADA) against INBRX-106 as a single agent and in combination with pembrolizumab with or without chemotherapy will be determined. |
| Area under the serum concentration time curve (AUC) of INBRX-106 | ~2 years | Area under the serum concentration time curve (AUC) of INBRX-106 as a single agent and in combination with pembrolizumab with or without chemotherapy will be determined. |
| Maximum observed serum concentration (Cmax) of INBRX-106 | ~2 years | Maximum observed serum concentration (Cmax) of INBRX-106 as a single agent and in combination with pembrolizumab with or without chemotherapy will be determined. |
| Trough observed serum concentration (Ctrough) of INBRX-106 | ~2 years | Trough observed serum concentration (Ctrough) of INBRX-106 as a single agent and in combination with pembrolizumab with or without chemotherapy will be determined. |
| Time to Cmax (Tmax) of INBRX-106 | ~2 years | Time to Cmax (Tmax) of INBRX-106 as a single agent and in combination with pembrolizumab with or without chemotherapy will be determined. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab with or without chemotherapy | ~2 years | Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1). |
Countries
Singapore, South Korea, Taiwan, United States
Outcome results
None listed