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

Overview

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).

Interventions

• Drug INBRX-109
  Tetravalent DR5 Agonist Antibody
• Drug Irinotecan
  Chemotherapy
• Drug Temozolomide
  Chemotherapy
• Drug carboplatin
  chemotherapy
• Drug pemetrexed
  chemotherapy
• Drug Leucovorin
  chemotherapy
• Drug Fluorouracil
  chemotherapy
• Drug Bevacizumab
  targeted therapy
• Drug Trifluridine + Tipiracil
  chemotherapy

Primary outcome measures

• Frequency and severity of adverse events of INBRX-109 [Time frame: Up to 8 years]
• Evaluating Tumor Response for colorectal cancers and Ewing sarcoma [Time frame: Up to 8 years]

Secondary outcome measures (3)

• Immunogenicity of INBRX-109 [Time frame: Up to 8 years]
• Characterize the pharmacokinetics of INBRX-109 as a single agent, and of INBRX-109 in combination with distinct chemotherapies. [Time frame: Up to 8 years]
• Median progression-free survival for colorectal adenocarcinoma and Ewing sarcoma. [Time frame: Up to 8 years]

Eligibility criteria

Inclusion criteria

• 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.
• 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 who have failed 1 (one) prior line of systemic therapy that did not include irinotecan.
• Colorectal adenocarcinoma: Patients who have failed 2 but no more than 3 prior lines of systemic therapy and are FTD/TPI-naïve.
• Measurable disease as defined by RECISTv1.1 (or modified RECIST for mesothelioma) criteria.
• Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
• 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).
• Estimated life expectancy of at least 12 weeks.
• Availability of archival tissue or fresh cancer biopsy are mandatory.

Exclusion criteria

• Prior treatment with or exposure to DR5 agonists.
• 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.
• Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies.
• 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.
• Subject has undergone allogeneic hematopoietic stem cell or bone marrow transplantation within the last 5 years. Exceptions per protocol.
• Prior or concurrent malignancies. Exceptions per protocol.
• Hematologic malignancies.
• 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.
• 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.
• Acute viral or toxic liver disease within 12 months prior to the first dose of study drug.
• Evidence or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
• Known sensitivity or contraindications to the following drugs:

• Ewing sarcoma: irinotecan or TMZ
• colorectal adenocarcinoma: FU, leucovorin, irinotecan, bevacizumab or FTP/TPI
• Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease less than 3 months prior to enrollment.
• 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.
• Major surgery within 4 weeks prior to enrollment on this trial.
• Systemic infection requiring antibiotics within 2 weeks prior to the first dose of study drug.
• Other exclusion criteria per protocol.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 23 centers

• HonorHealth Research Institute — Scottsdale
• Precision NextGen Oncology and Research — Beverly Hills
• City of Hope — Duarte
• Valkyrie Clinical Trials — Los Angeles
• University of California, San Diego (UCSD) - Moores Cancer Center — San Diego
• University of California, San Francisco (UCSF) — San Francisco
• Sarcoma Oncology Center — Santa Monica
• University of Colorado Hospital — Aurora
• … and 15 more centers

United Kingdom · 4 centers

• Great North Children's Hospital — London
• University College London Hospital — London
• The Royal Marsden NHS Foundation Trust — London
• Royal Manchester Children's Hospital — Manchester

Spain · 3 centers

• Hospital Universitario Vall d'Hebron — Barcelona
• Hospital de la Santa Creu i Sant Pau — Barcelona
• Hospital Clinico San Carlos — Madrid

France · 2 centers

• Centre Leon Berard — Lyon
• Gustave Roussy — Villejuif

Italy · 2 centers

• La Fondazione e l'Istituto di Candiolo — Candiolo
• Fondazione IRCCS Istituto Nazionale dei Tumori — Milan

Netherlands · 2 centers

• University Medical Center Groningen — Groningen
• Academisch Ziekenhuis Leiden — Leiden

Publications

• Subbiah V, Chawla SP, Conley AP, Wilky BA, Tolcher A, Lakhani NJ, Berz D, Andrianov V, Crago W, Holcomb M, Hussain A, Veldstra C, Kalabus J, O'Neill B, Senne L, Rowell E, Heidt AB, Willis KM, Eckelman BP. Preclinical Characterization and Phase I Trial Results of INBRX-109, A Third-Generation, Recombinant, Humanized, Death Receptor 5 Agonist Antibody, in Chondrosarcoma. Clin Cancer Res. 2023 Aug 15 PMID 37265425

Identifiers

NCT: NCT03715933 · Ph1 INBRX-109

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗