Study of INBRX-105 and INBRX-105 With Pembrolizumab in Patients With Solid Tumors Including Head and Neck Cancer
- Conditions
- Head and Neck Squamous Cell CarcinomaNon-small Cell Lung CancerMelanomaGastric AdenocarcinomaMetastatic Solid TumorsRenal Cell CarcinomaNasopharyngeal CarcinomaEsophageal AdenocarcinomaOropharyngeal Carcinoma
- Interventions
- Drug: INBRX-105 - PDL1x41BB antibody
- Registration Number
- NCT03809624
- Lead Sponsor
- Inhibrx Biosciences, Inc
- Brief Summary
This is a first-in-human, open-label, nonrandomized, four-part trial to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of INBRX-105 and INBRX-105 in combination with Pembrolizumab. INBRX-105, a next generation bispecific antibody, targets the human programmed death-ligand 1 (PD-L1) receptor and the human 4-1BB receptor. INBRX-105 provides localized conditional T-cell co-stimulation through 4-1BB agonism.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 160
- Parts 1 and 3 (escalation cohorts; completed): Patients with locally advanced or metastatic non-resectable solid tumors, whose disease has progressed despite standard therapy and for whom no further standard therapy exists.
- Part 2 (expansion cohorts): Patients with non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma or solid tumors amenable to paired biopsies, with locally advanced or metastatic, non-resectable disease, which has progressed despite standard therapy or for whom no standard or clinically acceptable therapy exists.
- Part 4 relapsed or refractory to CPI cohorts: NSCLC, cutaneous melanoma, HNSCC, MSI/TMB-high or MMRd solid tumors
- Part 4 CPI naive cohorts: locally advanced or metastatic, non-resectable NSCLC or HNSCC
- Refractory or relapsed to anti-PD-1 or anti-PD-L1, and anti-CTLA4 if applicable (NOTE: For all tumor types with checkpoint inhibitor approvals) with exception of the treatment naive NSCLC cohort.
- PD-L1 positivity by immunohistochemistry (IHC): Parts 1 and 3 (escalation cohorts) PD-L1 positivity is not required. Parts 2 and 4 (expansion cohorts): Combined Positive Score (CPS) or Tumor Proportion Score (TPS) above certain thresholds as defined per protocol.
- Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
- Prior exposure to 4-1BB 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. Exceptions: Hormone replacement therapy, testosterone, or oral contraceptives. NOTE: Previous exposure to anti-PD-L1 checkpoint inhibitor requires a minimum washout period of 24 weeks prior to the first dose of study drug.
- Hematologic malignancies (e.g., ALL, AML, MDS, CLL, CML, NHL, Hodgkin 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-105.
- 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). Exceptions as defined in protocol for expansion cohorts will apply.
- History of hepatitis or cirrhosis (e.g., non-alcohol steatohepatitis, alcohol or drug-related, autoimmune, hepatitis B, or hepatitis C). 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Expansion Cohort Melanoma INBRX-105 - PDL1x41BB antibody Patients will be treated with single-agent INBRX-105 at either the MTD or RP2D. Expansion Cohort Non-small Cell Lung Cancer INBRX-105 - PDL1x41BB antibody Patients will be treated with single-agent INBRX-105 at either the MTD or RP2D. Expansion Cohort PD-L1 Positive Basket INBRX-105 - PDL1x41BB antibody Patients with gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with single-agent INBRX-105 at either the MTD or RP2D. Expansion Cohort Nasopharyngeal or Oropharyngeal Carcinoma INBRX-105 - PDL1x41BB antibody Patients with head and neck squamous cell carcinoma (NPC or OPC) will be treated with single-agent INBRX-105 at either the MTD or RP2D. Combination Expansion Cohort Melanoma INBRX-105 - PDL1x41BB antibody CPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab. Single Agent Escalation INBRX-105 - PDL1x41BB antibody INBRX-105 will be escalated in patients with locally advanced or metastatic solid tumors. INBRX-105 Escalation in Combination with Pembrolizumab INBRX-105 - PDL1x41BB antibody INBRX-105 will be escalated in combination with Pembrolizumab in pateitns with locally advanced or metastatic solid tumors. Combination Expansion Cohort Non-small Cell Lung Cancer INBRX-105 - PDL1x41BB antibody CPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab. Combination Expansion Cohort CPI Naive HNSCC INBRX-105 - PDL1x41BB antibody CPI naive patients (PD-L1 IHC \>50%) will be treated with INBRX-105 in combination with Pembrolizumab. Combination Expansion Cohort Cohort PD-L1 Positive Basket INBRX-105 - PDL1x41BB antibody CPI-relapsed/refractory patients with head and neck squamous cell carcinoma, gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-105 in combination with Pembrolizumab. Combination Expansion Cohort CPI Naive Non-small Cell Lung Cancer INBRX-105 - PDL1x41BB antibody CPI naive patients (PD-L1 IHC between 1 and 49%) will be treated with INBRX-105 in combination with Pembrolizumab. Combination Expansion Cohort Cohort PD-L1 Positive Basket Pembrolizumab CPI-relapsed/refractory patients with head and neck squamous cell carcinoma, gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-105 in combination with Pembrolizumab. INBRX-105 Escalation in Combination with Pembrolizumab Pembrolizumab INBRX-105 will be escalated in combination with Pembrolizumab in pateitns with locally advanced or metastatic solid tumors. Combination Expansion Cohort Non-small Cell Lung Cancer Pembrolizumab CPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab. Combination Expansion Cohort Melanoma Pembrolizumab CPI relapsed/refractory patients will be treated with INBRX-105 in combination with Pembrolizumab. Combination Expansion Cohort CPI Naive Non-small Cell Lung Cancer Pembrolizumab CPI naive patients (PD-L1 IHC between 1 and 49%) will be treated with INBRX-105 in combination with Pembrolizumab.
- Primary Outcome Measures
Name Time Method Frequency of adverse events of INBRX-105 Up to 2-3 years Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-105 Up to 2-3 years The MTD and/or RP2D of INBRX-105 will be determined.
Severity of adverse events of INBRX-105 Up to 2-3 years Severity of adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
- Secondary Outcome Measures
Name Time Method Time to Cmax (Tmax) of INBRX-105 Up to 2-3 years Time to Cmax (Tmax) of INBRX-105 will be determined.
Area under the serum concentration time curve (AUC) of INBRX-105 Up to 2-3 years Area under the serum concentration time curve (AUC) of INBRX-105 will be determined.
Maximum observed serum concentration (Cmax) of INBRX-105 Up to 2-3 years Maximum observed serum concentration (Cmax) of INBRX-105 will be determined.
Immunogenicity of INBRX-105 Up to 2-3 years Frequency of anti-drug antibodies (ADA) against INBRX-105 will be determined.
Trough observed serum concentration (Ctrough) of INBRX-105 Up to 2-3 years Trough observed serum concentration (Cmax) of INBRX-105 will be determined.
Trial Locations
- Locations (23)
City of Hope
🇺🇸Duarte, California, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
START Mountain Region
🇺🇸West Valley City, Utah, United States
City of Hope at Irvine Lennar
🇺🇸Duarte, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Valkyrie Clinical Trials
🇺🇸Los Angeles, California, United States
Emory University - Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
New Experimental Therapeutics of San Antonio - NEXT Oncology
🇺🇸San Antonio, Texas, United States
Northwest Medical Specialties, PLLC
🇺🇸Tacoma, Washington, United States
Goshen Center for Cancer Care
🇺🇸Goshen, Indiana, United States
Abramson Cancer Center - University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States
Abramson Cancer Center at Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
University of Colorado Denver
🇺🇸Denver, Colorado, United States
Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Norton Cancer Center
🇺🇸Louisville, Kentucky, United States
Providence Cancer Institute
🇺🇸Portland, Oregon, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Nebraska Cancer Specialists - Grand Island
🇺🇸Omaha, Nebraska, United States
HonorHealth Research Institute
🇺🇸Scottsdale, Arizona, United States
Stanford University
🇺🇸Palo Alto, California, United States