Clinical trial NCT03715933: Phase 1 Study of INBRX-109 in Subjects with Locally Advanced or Metastatic Solid Tumors Including Sarcomas
Official title: An Open-Label, Multicenter, First-in-Human, Phase 1 Dose-Escalation and Multicohort Expansion Study of INBRX-109 in Subjects with Locally Advanced or Metastatic Solid Tumors Including Sarcomas
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Colorectal Adenocarcinoma
Ewing Sarcoma
Keywords: Phase 1
Phase 1 Clinical Trial
Solid Tumors
Sarcoma
Colorectal Cancer
Colon Cancer
Rectal Cancer
DR5
Colorectal Adenocarcinoma
Ewing Sarcoma
Lead sponsor: Inhibrx Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2018-10-23
Enrollment: 321
Sex: ALL
Minimum age (years): 12
Maximum age (years): 85
Standard ages: CHILD
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, non-randomized, three-part phase 1 trial of INBRX-109, which is a recombinant humanized tetravalent antibody targeting the human death receptor 5 (DR5).


Eligibility criteria: Inclusion Criteria:

1. Males or females aged ≥12 to less than 85 years for Ewing sarcoma and 18 to less than 85 years of age for other tumors.
2. Part 3 combination therapy expansion tumor types:

   * Histologically confirmed Ewing sarcoma with a classical fusion: Patients with locally advanced or metastatic, unresectable, relapsed, or refractory disease who have received at least 1 but no more than 2 prior lines of systemic treatment with a preferred first line chemotherapy regimens.
   * Colorectal adenocarcinoma: Patients with locally advanced or metastatic, unresectable disease, who have received at least 2 but no more than 3 prior lines of systemic therapy.
3. Measurable disease as defined by RECISTv1.1 (or modified RECIST for mesothelioma) criteria.
4. Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1, or Karnofsky Performance Status score of ≥60, or Lansky Play-Performance Scale for Children score ≥60 (for patients less than 16 years).
6. Estimated life expectancy of at least 12 weeks.
7. Availability of archival tissue or fresh cancer biopsy are mandatory.

Exclusion Criteria:

1. Prior treatment with or exposure to DR5 agonists.
2. Receipt of any anticancer therapy (including investigational agents) within 4 weeks or within 5 half-lives prior to the first dose of study treatment. Exceptions per protocol.
3. Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies.
4. Receipt of radiotherapy within 4 weeks prior to the first dose of study treatment, and liver-directed within 12 months prior to the first dose of study drug.
5. Subject has undergone allogeneic hematopoietic stem cell or bone marrow transplantation within the last 5 years. Exceptions per protocol.
6. Prior or concurrent malignancies. Exceptions per protocol.
7. Hematologic malignancies.
8. Symptomatic active primary CNS tumors, leptomeningeal disease, and CNS metastases. Exceptions per protocol. Patients with any evidence or history of multiple sclerosis (MS) or other demyelinating disorders are excluded.
9. Chronic liver diseases including fatty liver. Exception: Patients \< 45 years old with fatty liver disease may be accepted as long as adequate hepatic function as defined in the inclusion/exclusion criteria is confirmed.
10. Acute viral or toxic liver disease within 12 months prior to the first dose of study drug.
11. Evidence or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
12. Known sensitivity or contraindications to the following drugs:

    * Ewing sarcoma: irinotecan or TMZ
    * colorectal adenocarcinoma: FU, leucovorin, or irinotecan
13. Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease less than 3 months prior to enrollment.
14. Acute, hemodynamically significant deep vein thrombosis or clinically significant pulmonary embolism not resolved or stable for at least 3 months prior to the start of study treatment.
15. Major surgery within 4 weeks prior to enrollment on this trial.
16. Systemic infection requiring antibiotics within 2 weeks prior to the first dose of study drug.
17. Other exclusion criteria per protocol.

Primary outcomes:
measure: Frequency and severity of adverse events of INBRX-109
timeFrame: Up to 8 years
measure: Evaluating Tumor Response for colorectal cancers and Ewing sarcoma
timeFrame: Up to 8 years
Secondary outcomes:
measure: Immunogenicity of INBRX-109
timeFrame: Up to 8 years
measure: Characterize the pharmacokinetics of INBRX-109 as a single agent, and of INBRX-109 in combination with distinct chemotherapies.
timeFrame: Up to 8 years
measure: Median progression-free survival for colorectal adenocarcinoma and Ewing sarcoma.
timeFrame: Up to 8 years
Other outcomes:
measure: Anti-tumor activity of INBRX-109
timeFrame: Up to 8 years
measure: Potential predictive response biomarkers
timeFrame: Up to 8 years
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Beverly Hills
country: United States
facility: Precision NextGen Oncology and Research
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: San Diego
country: United States
facility: University of California, San Diego (UCSD) - Moores Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco (UCSF)
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Atlanta
country: United States
facility: Emory University - Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Bethesda
country: United States
facility: Center for Cancer Research at NCI
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: START Midwest Michigan, PC
state: Michigan
city: New York
country: United States
facility: David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia- Center for Childhood Cancer Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University School of Medicine
state: Tennessee
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Fairfax
country: United States
facility: NEXT Oncology - Virginia
state: Virginia
city: Lyon
country: France
facility: Centre Leon Berard
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Candiolo
country: Italy
facility: La Fondazione e l'Istituto di Candiolo
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: London
country: United Kingdom
facility: Great North Children's Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
Study officials:
affiliation: Inhibrx Biosciences, Inc
name: Clinical Lead
role: STUDY_DIRECTOR
References: