Clinical trial NCT04198766: Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Non-Small Cell Lung Cancer
Head and Neck Cancer
Melanoma
Gastric Cancer
Renal Cell Carcinoma
Urothelial Carcinoma
Keywords: Phase 1 and Phase 2
Phase 1 and Phase 2 Clinical Trial
Solid Tumors
Head and Neck Cancer
Lung Cancer
Non-Small Cell Lung Cancer
OX40 receptor agonist
PD-L1 positive
Pembrolizumab
Keytruda
Chemotherapy
Immunotherapy
HNSCC
Oropharyngeal cancer
Hypopharyngeal cancer
Oral cancer
INBRX-106
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Carcinoma
Carcinoma, Squamous Cell
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Antineoplastic Agents
Squamous Cell Carcinoma of Head and Neck
NSCLC
Lead sponsor: Inhibrx Biosciences, Inc
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2019-12-13
Enrollment: 333
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.
* 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.

Primary outcomes:
measure: Frequency of adverse events of INBRX-106 as single agent and in combination with pembrolizumab
timeFrame: ~2 years
measure: Severity of adverse events of INBRX-106 as single agent and in combination with pembrolizumab
timeFrame: ~2 years
measure: MTD and/or RP2D of INBRX-106 as single agent and in combination with pembrolizumab
timeFrame: ~2 years
measure: Antitumor activity of INBRX-106 in combination with pembrolizumab in expansion cohorts
timeFrame: ~2 years
measure: Frequency and severity of adverse events of INBRX-106 in combination with pembrolizumab and chemotherapy in adults with locally advanced or metastatic NSCLC
timeFrame: ~2 years
Secondary outcomes:
measure: Area under the serum concentration time curve (AUC) of INBRX-106
timeFrame: ~2 years
measure: Maximum observed serum concentration (Cmax) of INBRX-106
timeFrame: ~2 years
measure: Trough observed serum concentration (Ctrough) of INBRX-106
timeFrame: ~2 years
measure: Time to Cmax (Tmax) of INBRX-106
timeFrame: ~2 years
measure: Immunogenicity of INBRX-106
timeFrame: ~2 years
Other outcomes:
measure: Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab with or without chemotherapy
timeFrame: ~2 years
measure: Anti-tumor activity of INBRX-106 as single agent and in combination with pembrolizumab with or without chemotherapy
timeFrame: ~2 years
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: Valkyrie Clinical Trials
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute - Emory University
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt University School of Medicine
state: Tennessee
city: El Paso
country: United States
facility: Renovatio Clinical - El Paso
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Milwaukee
country: United States
facility: Froedtert Hospital and the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Inhibrx Biosciences, Inc
name: Clinical Lead
role: STUDY_DIRECTOR
References: