Clinical trial NCT03809624: Study of INBRX-105 and INBRX-105 With Pembrolizumab in Patients With Solid Tumors Including Head and Neck Cancer
Official title: An Open-Label, Multicenter, First-in-Human, Dose-Escalation, Phase 1 / 2 Study of INBRX-105 and INBRX-105 in Combination With Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Metastatic Solid Tumors
Non-small Cell Lung Cancer
Melanoma
Head and Neck Squamous Cell Carcinoma
Gastric Adenocarcinoma
Renal Cell Carcinoma
Esophageal Adenocarcinoma
Nasopharyngeal Carcinoma
Oropharyngeal Carcinoma
Keywords: Solid Tumors
Lung Cancer
Melanoma
Head and Neck Cancer
Stomach Cancer
Gastric Cancer
Kidney Cancer
Renal cell carcinoma
Renal Cancer
Urothelial Carcinoma
PDL1
41BB
PD-L1
4-1BB
Pembrolizumab
Keytruda
Nasopharyngeal carcinoma
Oropharyngeal carcinoma
Lead sponsor: Inhibrx Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2019-01-18
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Frequency of adverse events of INBRX-105
timeFrame: Up to 2-3 years
measure: Severity of adverse events of INBRX-105
timeFrame: Up to 2-3 years
measure: Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of INBRX-105
timeFrame: Up to 2-3 years
Secondary outcomes:
measure: Area under the serum concentration time curve (AUC) of INBRX-105
timeFrame: Up to 2-3 years
measure: Maximum observed serum concentration (Cmax) of INBRX-105
timeFrame: Up to 2-3 years
measure: Trough observed serum concentration (Ctrough) of INBRX-105
timeFrame: Up to 2-3 years
measure: Time to Cmax (Tmax) of INBRX-105
timeFrame: Up to 2-3 years
measure: Immunogenicity of INBRX-105
timeFrame: Up to 2-3 years
Other outcomes:
measure: Anti-tumor activity of INBRX-105
timeFrame: Up to 2-3 years
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Duarte
country: United States
facility: City of Hope at Irvine Lennar
state: California
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: Valkyrie Clinical Trials
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: University of Colorado Denver
state: Colorado
city: Atlanta
country: United States
facility: Emory University - Winship Cancer Institute
state: Georgia
city: Goshen
country: United States
facility: Goshen Center for Cancer Care
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Center
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists - Grand Island
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Portland
country: United States
facility: Providence Cancer Institute
state: Oregon
city: Philadelphia
country: United States
facility: Abramson Cancer Center - University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center at Pennsylvania Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: New Experimental Therapeutics of San Antonio - NEXT Oncology
state: Texas
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
Study officials:
affiliation: Inhibrx Biosciences, Inc
name: Clinical Lead
role: STUDY_DIRECTOR
References: