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.
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.
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.
Sequential
INBRX-106 - Hexavalent OX40 agonist antibody
DrugThe active ingredient of INBRX-106 is a recombinant, humanized, hexavalent IgG antibody that targets the human OX40 receptor (TNFRSF4).
pembrolizumab 200 mg
Drugpembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
pembrolizumab 400 mg
Drugpembrolizumab 400 mg by IV infusion given on Day 1 of alternating 21-day cycles (every 6 weeks)
Carboplatin AUC-5
Drugcarboplatin 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.
Carboplatin AUC-6
Drugcarboplatin AUC-6 by intravenous (IV) infusion, given on Day 1 of each 21-day cycle of cycles 1-4
Pemetrexed 500 mg/m2
Drugpemetrexed 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
Drugcisplatin 75mg/m2 by intravenous (IV) infusion, given on Day 1 of each 21-day cycle of cycles 1-4
Paclitaxel 200mg/m2
Drugpaclitaxel 200mg/m2 by intravenous (IV) infusion, given on Day 1 of each 21-day cycle of cycles 1-4
Nab paclitaxel 100mg/m2
DrugNab 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)
DrugGemcitabine 1000 mg/m2 given by intravenous (IV) infusion on Days 1 and 8 of each 21-day cycle of cycles 1-4
15
Treatment groupsSee each treatment group below.
Frequency of adverse events of INBRX-106 as single agent and in combination with pembrolizumab
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
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
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
The evaluation of efficacy will be based on the subject's measurable disease using RECIST v1.1
Area under the serum concentration time curve (AUC) of INBRX-106
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
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
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
Time to Cmax (Tmax) of INBRX-106 as a single agent and in combination with pembrolizumab with or without chemotherapy will be determined.
Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab with or without chemotherapy
Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).
Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab with or without chemotherapy
Tumor response will be determined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Click on the lead sponsor to view all of their trials.
Inhibrx Biosciences, Inc
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
