Summary

for people ages 18 years and up (full criteria)
at La Jolla, California and other locations
study started
estimated completion:

Description

Summary

This first-in-human, open-label, multicenter, Phase Ia/Ib, adaptive, multiple ascending-dose study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of RO6874281 as a single agent (Part A) or in combination with trastuzumab or cetuximab (Part B or C).

Official Title

An Open-Label, Multicenter, Dose-Escalation, Phase Ia/Ib Study to Evaluate Safety, Pharmacokinetics, and Therapeutic Activity of RO6874281, an Immunocytokine Consisting of Interleukin 2 Variant (IL-2v) Targeting Fibroblast Activation Protein-α (FAP), as a Single Agent (Part A) or in Combination With Trastuzumab or Cetuximab (Part B or C)

Keywords

Solid Tumor Breast Cancer Cancer of Head and Neck Head and Neck Neoplasms Trastuzumab Cetuximab RO6874281

Eligibility

You can join if…

Open to people ages 18 years and up

  • Radiologically measurable and clinically evaluable disease
  • Life expectancy of greater than or equal to (>=12) weeks
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
  • Participants with unilateral pleural effusion (other than non-small cell lung cancer[NSCLC] indication) should fulfill the following criteria for pulmonary and cardiac functions: Global Initiative for Chronic Obstructive Lung Disease (GOLD)classification 0 − 1 level and New York Heart Association (NYHA) classification class 1
  • Adequate cardiovascular, hematological, liver and renal function
  • All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to grade less than or equal to (<=) 1, except alopecia (any grade)and Grade 2 peripheral neuropathy
  • Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women less than (<) 12 months after menopause
  • For women who are not postmenopausal and have not undergone surgical sterilization:agreement to remain abstinent or use two adequate non-hormonal methods of contraception, including at least one method with a failure rate of <1 percent (%) per year, during the treatment period and for a period of time after the last dose of study drug(s) as defined in the protocol
  • For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm during the treatment period and for at least for at least 2 months after the last dose of study treatment
  • For Part A exclusively (RO6874281 monotherapy), confirmed advanced and/or metastatic solid tumor, with at least one tumor lesion of location accessible to biopsy per clinical judgment of the treating physician, and confirmed progression at baseline;for whom no standard therapy that would confer clinical benefit to the participant exists
  • For Part B exclusively (RO6874281 in combination with trastuzumab), participants with metastatic or recurrent or locally advanced human epidermal growth factor receptor 2(HER2)-positive breast cancer, as defined by the College of American Pathologists HER2 testing guidelines, who have progressed on at least two lines of HER2-directed therapies in the metastatic setting and the last therapy prior to going on study has to contain a HER2-directed antibody; baseline left ventricular ejection fraction(LVEF) of >=50% (measured by echocardiography) predose on Cycle 1 Day 1
  • For Part C exclusively (RO6874281 in combination with cetuximab), participants with metastatic or recurrent or locally advanced squamous cell carcinoma of head and neck who have progressed on cetuximab maintenance therapy after cetuximab-containing chemotherapy or radiation therapy
  • Participants with Gilbert's syndrome will be eligible for the study

You CAN'T join if...

  • History or clinical evidence of central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases, unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days prior to screening
  • Participants with an active second malignancy
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, and known autoimmune diseases or other disease with ongoing fibrosis
  • Participants (all indications) with confirmed bilateral pleural effusion and NSCLC participants with confirmed uni- or bilateral pleural effusion by X-ray are not eligible
  • Significant cardiovascular/cerebrovascular disease within 6 months prior to Day 1 of study drug administration
  • Active or uncontrolled infections
  • Known human immunodeficiency virus (HIV) or known active hepatitis B virus or hepatitis C virus infection
  • History of chronic liver disease or evidence of hepatic cirrhosis
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that give reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
  • Major surgery or significant traumatic injury <28 days prior to the first RO6874281 infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
  • Dementia or altered mental status that would prohibit informed consent
  • Pregnant or breastfeeding women
  • Known hypersensitivity to any of the components of RO6874281
  • Concurrent therapy with any other investigational drug
  • Immunomodulating agents <28 days prior to first dose of study drug
  • Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy
  • For Part B exclusively, known hypersensitivity to any of the components of trastuzumab
  • For Part C exclusively, known hypersensitivity to any of the components of cetuximab
  • For Parts A, B, and C, eligibility of participants who require blood transfusion before and after the start of the study treatment should be discussed by the Sponsor and investigator

Locations

  • UCSD - Moores Cancer Center accepting new patients
    La Jolla California 92037 United States
  • University of Arizona Cancer Center accepting new patients
    Tucson Arizona 85719 United States
  • University of Colorado Hospital - Anschutz Cancer Pavilion accepting new patients
    Aurora Colorado 80045 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Hoffmann-La Roche
ID
NCT02627274
Phase
Phase 1
Study Type
Interventional
Last Updated
April 30, 2018