Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04198766 |
|
Recruitment Status :
Recruiting
First Posted : December 13, 2019
Last Update Posted : December 13, 2021
|
Sponsor:
Inhibrx, Inc.
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Inhibrx, Inc.
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Brief Summary:
This is a first-in-human, open-label, non-randomized, 4-part Phase 1 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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Solid Tumor Non-Small Cell Lung Cancer Melanoma Head and Neck Cancer Gastric Cancer Renal Cell Carcinoma Urothelial Carcinoma | Drug: INBRX-106 - Hexavalent OX40 agonist antibody Drug: Pembrolizumab | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 150 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Phase 1 Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors |
| Actual Study Start Date : | December 10, 2019 |
| Estimated Primary Completion Date : | December 2, 2022 |
| Estimated Study Completion Date : | March 15, 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Melanoma
Drug Information available for:
Pembrolizumab
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Part 1 INBRX-106 Escalation
INBRX-106 will be escalated in subjects with locally advanced or metastatic solid tumors.
|
Drug: INBRX-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). |
|
Experimental: Part 2 INBRX-106 Expansion
Subjects with non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-106 at the RP2D.
|
Drug: INBRX-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). |
|
Experimental: Part 3 INBRX-106 Escalation in Combination with Pembrolizumab
INBRX-106 will be escalated, in combination with pembrolizumab, in subjects with locally advanced or metastatic solid tumors.
|
Drug: INBRX-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). Drug: Pembrolizumab Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Name: Keytruda |
|
Experimental: Part 4 INBRX-106 Expansion in Combination with Pembrolizumab
Subjects with non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, gastric or gastro-esophageal junction adenocarcinoma, renal cell carcinoma, and urothelial (transitional) cell carcinoma will be treated with INBRX-106 at the RP2D in combination with pembrolizumab.
|
Drug: INBRX-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). Drug: Pembrolizumab Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
Other Name: Keytruda |
Primary Outcome Measures :
- Frequency of adverse events of INBRX-106 as single agent and in combination with pembrolizumab [ Time Frame: 2-4 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 [ Time Frame: 2-4 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 [ Time Frame: 2-4 years ]Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-106 and INBRX-106 in combination with pembrolizumab
Secondary Outcome Measures :
- Area under the serum concentration time curve (AUC) of INBRX-106 [ Time Frame: 2-4 years ]Area under the serum concentration time curve (AUC) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
- Maximum observed serum concentration (Cmax) of INBRX-106 [ Time Frame: 2-4 years ]Maximum observed serum concentration (Cmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
- Trough observed serum concentration (Ctrough) of INBRX-106 [ Time Frame: 2-4 years ]Trough observed serum concentration (Ctrough) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
- Time to Cmax (Tmax) of INBRX-106 [ Time Frame: 2-4 years ]Time to Cmax (Tmax) of INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
- Immunogenicity of INBRX-106 [ Time Frame: 2-4 years ]Frequency of anti-drug antibodies (ADA) against INBRX-106 as a single agent and in combination with pembrolizumab will be determined.
Other Outcome Measures:
- Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab [ Time Frame: 2-4 years ]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 [ Time Frame: 2-4 years ]Tumor response will be determined by immune Response Evaluation Criteria in Solid Tumors (iRECIST).
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 locally advanced or metastatic, non-resectable disease, which has progressed despite all standard therapies or for whom no standard or clinically acceptable therapy exists.
- Part 4 (expansion cohorts in combination with pembrolizumab): Subjects with melanoma, HNSCC, G/GEA, RCC, or TCC, or NSCLC, with locally advanced or metastatic, non resectable disease, which has progressed despite all standard therapies or for whom no standard or clinically acceptable therapy exists.
- 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. Part 4: Combined Positive Score (CPS) ≥ 1% (or Tumor Proportion Score ≥1% for NSCLC).
- 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 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) infection for Parts 1 and 3. 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.
- Additional in- and exclusion criteria per protocol.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04198766
Contacts
| Contact: Ryan Handy, Trial Manager | 858-500-7833 | clinicaltrials@inhibrx.com | |
| Contact: Terri Boyea, Clinical Director | clinicaltrials@inhibrx.com |
Locations
| United States, California | |
| City of Hope | Recruiting |
| Duarte, California, United States, 91010 | |
| Contact: New Patient Services 800-826-4673 sthiagarajan@coh.org | |
| United States, Georgia | |
| Winship Cancer Institute - Emory University | Recruiting |
| Atlanta, Georgia, United States, 30322 | |
| Contact: Suzanne Scott 404-778-4083 suzanne.e.scott@emrory.edu | |
| United States, Illinois | |
| The University of Chicago Medical Center | Recruiting |
| Chicago, Illinois, United States, 60637 | |
| Contact: Jeffery Chin 773-834-5004 jchin18@medicine.bsd.uchicago.edu | |
| United States, Iowa | |
| University of Iowa | Recruiting |
| Iowa City, Iowa, United States, 52242 | |
| Contact: Jordan Harrelson 319-467-5831 Jordan-harrelson@uiowa.edu | |
| United States, Michigan | |
| START Midwest | Recruiting |
| Grand Rapids, Michigan, United States, 49546 | |
| Contact: Katie Robinson 616-389-1739 Katie.Robinson@startmidwest.com | |
| United States, Nebraska | |
| Nebraska Cancer Specialists | Recruiting |
| Omaha, Nebraska, United States, 68130 | |
| Contact: Gladys Pierce 402-691-6972 gpierce@nebraskacancer.com | |
| United States, Oregon | |
| Providence Cancer Institute | Recruiting |
| Portland, Oregon, United States, 97213 | |
| Contact: Tara Foote 503-215-7192 ORCanClinRsrch@providence.org | |
| United States, Texas | |
| NEXT Oncology | Recruiting |
| San Antonio, Texas, United States, 78229 | |
| Contact: Kayla Dotson 210-595-5670 kdotson@nextoncology.com | |
Sponsors and Collaborators
Inhibrx, Inc.
Merck Sharp & Dohme Corp.
Investigators
| Study Director: | Klaus Wagner, MD, PhD | Inhibrx, Inc. |
| Responsible Party: | Inhibrx, Inc. |
| ClinicalTrials.gov Identifier: | NCT04198766 |
| Other Study ID Numbers: |
Ph 1 INBRX-106 MK3475 KEYNOTE A99 ( Other Identifier: Merck & Co., Inc. ) |
| First Posted: | December 13, 2019 Key Record Dates |
| Last Update Posted: | December 13, 2021 |
| Last Verified: | December 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Inhibrx, Inc.:
|
Phase 1 Phase 1 Clinical Trial Solid Tumors Melanoma Head and Neck Cancer Stomach Cancer Gastric Cancer Lung Cancer Non-Small Cell Lung Cancer |
Kidney Cancer Renal Cell Carcinoma Bladder Cancer Urothelial Carcinoma OX40 PD-1 Pembrolizumab Keytruda |
Additional relevant MeSH terms:
|
Carcinoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung Melanoma Stomach Neoplasms Head and Neck Neoplasms Carcinoma, Renal Cell Carcinoma, Transitional Cell Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Lung Diseases |
Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Nevi and Melanomas Gastrointestinal Neoplasms Digestive System Neoplasms Digestive System Diseases Gastrointestinal Diseases Stomach Diseases Adenocarcinoma Kidney Neoplasms |