RecruitingRecruiting
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
NCT04198766 · Inhibrx Biosciences, Inc
In plain English
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Official title
An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Multicohort, Phase 1/2 Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab in Subjects With Locally Advanced or Metastatic Solid Tumors
About this study
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.
Eligibility 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 exclusion criteria per protocol.
Study design
Enrollment target: 340 participants
Allocation: randomized
Masking: single
Age groups: adult, older_adult
Timeline
Starts: 2019-12-10
Estimated completion: 2033-07
Last updated: 2026-07-29
Interventions
Drug: INBRX-106 - Hexavalent OX40 agonist antibodyDrug: pembrolizumab 200 mgDrug: pembrolizumab 400 mgDrug: Carboplatin AUC-5Drug: Carboplatin AUC-6Drug: Pemetrexed 500 mg/m2Drug: Cisplatin 75mg/m2Drug: Paclitaxel 200mg/m2Drug: Nab paclitaxel 100mg/m2Drug: Gemcitabine (1000 mg/m2)
Primary outcomes
- • Frequency of adverse events of INBRX-106 as single agent and in combination with pembrolizumab (~2 years)
- • Severity of adverse events of INBRX-106 as single agent and in combination with pembrolizumab (~2 years)
- • MTD and/or RP2D of INBRX-106 as single agent and in combination with pembrolizumab (~2 years)
Sponsor
Inhibrx Biosciences, Inc · industry
With: Merck Sharp & Dohme LLC
Contacts & investigators
ContactStudy Director - Inhibrx Biosciences, Inc · contact · clinicaltrials@inhibrx.com · 858-500-7833
InvestigatorClinical Lead · study_director, Inhibrx Biosciences, Inc
All locations (42)
City of HopeRecruiting
Duarte, California, United States
Los Angeles Cancer NetworkRecruiting
Glendale, California, United States
California Research InstituteRecruiting
Los Angeles, California, United States
Valkyrie Clinical TrialsRecruiting
Los Angeles, California, United States
Valkyrie Clinical TrialsRecruiting
Murrieta, California, United States
Providence Medical FoundationRecruiting
Santa Rosa, California, United States
Clermont Oncology CenterRecruiting
Clermont, Florida, United States
Mid Florida Hematology and Oncology CenterRecruiting
Orange City, Florida, United States
Winship Cancer Institute - Emory UniversityRecruiting
Atlanta, Georgia, United States
The University of Chicago Medical CenterActive Not Recruiting
Chicago, Illinois, United States
University of IowaActive Not Recruiting
Iowa City, Iowa, United States
Norton Cancer InstituteRecruiting
Louisville, Kentucky, United States
Barbara Ann Karmanos Cancer InstituteCompleted
Detroit, Michigan, United States
Henry Ford Cancer InstituteRecruiting
Detroit, Michigan, United States
START MidwestActive Not Recruiting
Grand Rapids, Michigan, United States
HealthPartners Cancer Research CenterActive Not Recruiting
Saint Louis Park, Minnesota, United States
HealthPartners Cancer Research Center (Regions Hospital)Completed
Saint Paul, Minnesota, United States
Intermountain Health Cancer Centers of MontanaCompleted
Billings, Montana, United States
Nebraska Cancer SpecialistsRecruiting
Omaha, Nebraska, United States
Montefiore Medical CenterActive Not Recruiting
The Bronx, New York, United States
Cleveland ClinicActive Not Recruiting
Cleveland, Ohio, United States
Providence Portland Medical CenterActive Not Recruiting
Portland, Oregon, United States
Vanderbilt University School of MedicineActive Not Recruiting
Nashville, Tennessee, United States
Sarah Cannon Research Institute at Mary CrowleyCompleted
Dallas, Texas, United States
Renovatio Clinical - El PasoCompleted
El Paso, Texas, United States
NEXT OncologyCompleted
San Antonio, Texas, United States
Renovatio ClinicalCompleted
The Woodlands, Texas, United States
The University of Texas Health Science Center at TylerRecruiting
Tyler, Texas, United States
Virginia Cancer SpecialistsCompleted
Fairfax, Virginia, United States
Froedtert Hospital and the Medical College of WisconsinActive Not Recruiting
Milwaukee, Wisconsin, United States
Curie OncologyCompleted
Singapore, Singapore
Icon Cancer Centre Farrer ParkCompleted
Singapore, Singapore
Icon Cancer Centre Mount AlverniaCompleted
Singapore, Singapore
The Catholic University of Korea, St. Vincent's HospitalActive Not Recruiting
Gyeonggi-do, South Korea
Asan Medical CenterActive Not Recruiting
Seoul, South Korea
Severance Hospital, Yonsei University Health SystemActive Not Recruiting
Seoul, South Korea
The Catholic University of Korea Seoul St. Mary's Hospital,Active Not Recruiting
Seoul, South Korea
Changhua Christian Hospital (CCH)Active Not Recruiting
Changhua, Taiwan
E-Da Cancer HospitalActive Not Recruiting
Kaohsiung City, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)Active Not Recruiting
Kaohsiung City, Taiwan
National Cheng Kung University HospitalActive Not Recruiting
Tainan, Taiwan
Taipei Veterans General HospitalCompleted
Taipei, Taiwan