Solid Tumor, Non-Small Cell Lung Cancer, Head and Neck Cancer, Melanoma, Gastric Cancer, Renal Cell Carcinoma, Urothelial Carcinoma, Resectable Non-Small-Cell Lung Cancer
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, Neoadjuvant, Adjuvant
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. Cohort F8, carboplatin AUC-5 by intravenous (IV) infusion, given on Day 1 of each 21-day cycle of cycle 2-4.
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. In Cohort F8, pemetrexed 500 mg/m2 by IV infusion given on Day 1 of each 21-Day cycle of cycles 1-4.
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
Gemcitabine 1000 mg/m2 given by intravenous (IV) infusion on Days 1 and 8 of each 21-day cycle of cycles 1-4
Sponsors
Inhibrx Biosciences, Inc
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Part 4 NSCLC Cohort F3 was 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. * For Cohort F8, subjects must have previously untreated, histologically confirmed Stage II, IIIA or IIIB (T3-4N2) NSCLC. Lymph node disease requires histologic confirmation, while T3 disease requires only radiographic documentation. Subjects need to be able to undergo planned surgery. * 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). For Cohort F8, any TPS (including 0%) is acceptable. * Adequate hematologic, coagulation, hepatic and renal function and ECOG score as defined per protocol. Select
Exclusion criteria
* Prior exposure to OX40 agonists. Exposure to anti-PD-1 and/or anti PD-L2 CPIs or an agent targeting other co-stimulatory T-cell receptor pathways. * 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. * 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, viral myocarditis, cerebrovascular accident, or other acute uncontrolled heart disease \< 3 months prior to enrollment on this trial; 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 12 weeks 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 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 | The evaluation of efficacy will be based on the subject's measurable disease using RECIST v1.1 |
| Frequency and severity of adverse events of INBRX-106 in combination with pembrolizumab and chemotherapy in adults with locally advanced or metastatic NSCLC or resectable Stage II, IIIA or IIIB (T3-4N2) NSCLC | ~2 years | Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0 |
| To assess the antitumor activity of INBRX-106 in combination with pembrolizumab and platinum doublet chemotherapy as neoadjuvant/adjuvant therapy in adult subjects with NSCLC. (Cohort F8) | ~2 years | Major pathological response (mPR) and pathological complete response (cPR) criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
Singapore, South Korea, Taiwan, United States
Contacts
CONTACTStudy Director - Inhibrx Biosciences, Inc
STUDY_DIRECTORClinical Lead
Inhibrx Biosciences, Inc
Outcome results
None listed