Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Phase 1
Recruiting
- Conditions
- Solid TumorRenal Cell CarcinomaHead and Neck CancerUrothelial CarcinomaMelanomaNon-Small Cell Lung CancerGastric Cancer
- Interventions
- Registration Number
- NCT04198766
- Lead Sponsor
- Inhibrx Biosciences, Inc
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 333
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 exclusion criteria per protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 4 (Cohort F7b) INBRX-106 Expansion with pembrolizumab, pemetrexed and cisplatin in NSCLC Carboplatin AUC-6 Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 500mg/m2 pemetrexed and 75mg/m2 cisplatin IV every 3 weeks Part 4 (Cohort F6) INBRX-106 Expansion with pembrolizumab in Uveal Melanoma Pemetrexed 500 mg/m2 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 Part 3 INBRX-106 Escalation in Combination with pembrolizumab (Not Recruiting) pembrolizumab 200 mg INBRX-106 will be escalated, in combination with pembrolizumab, in subjects with locally advanced or metastatic solid tumors. Part 2 (Cohorts C1/C2) INBRX-106 Escalation in Various Solid Tumor Types (Not Recruiting) pembrolizumab 200 mg 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 Part 2 (Cohort C3) INBRX-106 Escalation in NSCLC pembrolizumab 200 mg Subjects with non-small cell carcinoma relapsed or refractory to prior checkpoint inhibitor (CPI) therapy will be treated with INBRX-106 Part 4 (Cohort F3b) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC pembrolizumab 200 mg 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. This is one of the randomized cohorts. Part 4 (Cohort F4) INBRX-106 Expansion in Combination with pembrolizumab pembrolizumab 200 mg Subjects with melanoma (any type), head and neck squamous cell carcinoma (non-nasopharyngeal) OR 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. Part 4 (Cohort F5)INBRX-106 Expansion with pembrolizumab in MSI/TMB-high/MMRd tumors Not Recuriting pembrolizumab 200 mg 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 Part 4 (Cohort F6) INBRX-106 Expansion with pembrolizumab in Uveal Melanoma pembrolizumab 200 mg 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 Part 4 (Cohort F7b) INBRX-106 Expansion with pembrolizumab, pemetrexed and cisplatin in NSCLC pembrolizumab 200 mg Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 500mg/m2 pemetrexed and 75mg/m2 cisplatin IV every 3 weeks Part 4(Cohort F7c)INBRX-106 Expansion with pembrolizumab, (Nab)-paclitaxel and carboplatin in NSCLC pembrolizumab 200 mg Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 200mg/m2 paclitaxel and carboplatin AUC-6 IV every 3 weeks OR INBRX-106, 200mg pembrolizumab, 100mg/m2 nab-paclitaxel (dosed Days 1,8 and 15 every cycle) and carboplatin AUC-6 IV every 3 weeks. Treating physician to determine if paclitaxel or nab-paclitaxel will be given Part 4 (Cohort F7a) INBRX-106 Expansion with pembrolizumab, pemetrexed and carboplatin in NSCLC Pemetrexed 500 mg/m2 Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 500mg/m2 pemetrexed and carboplatin AUC-5 IV every 3 weeks Part 1 INBRX-106 Escalation (Not Recruiting) INBRX-106 - Hexavalent OX40 agonist antibody INBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors. Part 3 INBRX-106 Escalation in Combination with pembrolizumab (Not Recruiting) INBRX-106 - Hexavalent OX40 agonist antibody INBRX-106 will be escalated, in combination with pembrolizumab, in subjects with locally advanced or metastatic solid tumors. Part 2 (Cohorts C1/C2) INBRX-106 Escalation in Various Solid Tumor Types (Not Recruiting) INBRX-106 - Hexavalent OX40 agonist antibody 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 Part 4 (Cohort F3a) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC (alternating) INBRX-106 - Hexavalent OX40 agonist antibody Subjects with non-small cell lung cancer will be treated with alternating dosing of INBRX-106 0.3 mg/kg Q6W and 400 mg pembrolizumab IV Q6W. This is one of the randomized cohorts. Part 4 (Cohort F3a) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC (alternating) pembrolizumab 400 mg Subjects with non-small cell lung cancer will be treated with alternating dosing of INBRX-106 0.3 mg/kg Q6W and 400 mg pembrolizumab IV Q6W. This is one of the randomized cohorts. Part 4 (Cohort F3b) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC INBRX-106 - Hexavalent OX40 agonist antibody 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. This is one of the randomized cohorts. Part 4 (Cohort F3b) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC pembrolizumab 400 mg 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. This is one of the randomized cohorts. Part 4 (Cohort F3c) Pembrolizumab Expansion Arm (Not Recruiting) INBRX-106 - Hexavalent OX40 agonist antibody Subjects with non-small cell lung cancer will be treated with 200 mg pembrolizumab IV every 3 weeks. This is one of the randomized cohorts. Part 4 (Cohort F3d) INBRX-106 Expansion in Combination with pembrolizumab in NSCLC (concurrent) INBRX-106 - Hexavalent OX40 agonist antibody Subjects with non-small cell lung cancer will be treated concurrently every 6 weeks with INBRX-106 0.1 mg/kg and 200 mg pembrolizumab IV every 3 weeks. This is one of the randomized cohorts. Part 4 (Cohort F4) INBRX-106 Expansion in Combination with pembrolizumab INBRX-106 - Hexavalent OX40 agonist antibody Subjects with melanoma (any type), head and neck squamous cell carcinoma (non-nasopharyngeal) OR 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. Part 4 (Cohort F5)INBRX-106 Expansion with pembrolizumab in MSI/TMB-high/MMRd tumors Not Recuriting INBRX-106 - Hexavalent OX40 agonist antibody 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 Part 4 (Cohort F6) INBRX-106 Expansion with pembrolizumab in Uveal Melanoma INBRX-106 - Hexavalent OX40 agonist antibody 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 Part 4 (Cohort F7b) INBRX-106 Expansion with pembrolizumab, pemetrexed and cisplatin in NSCLC INBRX-106 - Hexavalent OX40 agonist antibody Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 500mg/m2 pemetrexed and 75mg/m2 cisplatin IV every 3 weeks Part 4 (Cohort F7b) INBRX-106 Expansion with pembrolizumab, pemetrexed and cisplatin in NSCLC Paclitaxel 200mg/m2 Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 500mg/m2 pemetrexed and 75mg/m2 cisplatin IV every 3 weeks Part 4 (Cohort F7b) INBRX-106 Expansion with pembrolizumab, pemetrexed and cisplatin in NSCLC Nab paclitaxel 100mg/m2 Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 500mg/m2 pemetrexed and 75mg/m2 cisplatin IV every 3 weeks Part 4(Cohort F7c)INBRX-106 Expansion with pembrolizumab, (Nab)-paclitaxel and carboplatin in NSCLC INBRX-106 - Hexavalent OX40 agonist antibody Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 200mg/m2 paclitaxel and carboplatin AUC-6 IV every 3 weeks OR INBRX-106, 200mg pembrolizumab, 100mg/m2 nab-paclitaxel (dosed Days 1,8 and 15 every cycle) and carboplatin AUC-6 IV every 3 weeks. Treating physician to determine if paclitaxel or nab-paclitaxel will be given Part 4 (Cohort F6) INBRX-106 Expansion with pembrolizumab in Uveal Melanoma Carboplatin AUC-5 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 Part 4 (Cohort F7a) INBRX-106 Expansion with pembrolizumab, pemetrexed and carboplatin in NSCLC INBRX-106 - Hexavalent OX40 agonist antibody Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 500mg/m2 pemetrexed and carboplatin AUC-5 IV every 3 weeks Part 4 (Cohort F7a) INBRX-106 Expansion with pembrolizumab, pemetrexed and carboplatin in NSCLC pembrolizumab 200 mg Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 500mg/m2 pemetrexed and carboplatin AUC-5 IV every 3 weeks Part 4 (Cohort F7a) INBRX-106 Expansion with pembrolizumab, pemetrexed and carboplatin in NSCLC Cisplatin 75mg/m2 Subjects with advanced/metastatic NSCLC, any PD-L1 TPS will be treated with INBRX-106 0.1mg/kg, 200mg pembrolizumab, 500mg/m2 pemetrexed and carboplatin AUC-5 IV every 3 weeks
- Primary Outcome Measures
Name Time Method 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
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
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).
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
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
- Secondary Outcome Measures
Name Time Method 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.
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.
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.
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.
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.
Trial Locations
- Locations (16)
Valkyrie Clinical Trials
🇺🇸Los Angeles, California, United States
Winship Cancer Institute - Emory University
🇺🇸Atlanta, Georgia, United States
Vanderbilt University School of Medicine
🇺🇸Nashville, Tennessee, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Froedtert Hospital and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
City of Hope
🇺🇸Duarte, California, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States
Renovatio Clinical
🇺🇸The Woodlands, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Renovatio Clinical - El Paso
🇺🇸El Paso, Texas, United States
Henry Ford Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States