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Hoffmann-La Roche BP40234: An open-label, multicenter, phase II study to evaluate the therapeutic activity of RO6874281, an immunocytokine, consisting of interleukin-2 variant (IL-2v) targeting fibroblast activation protein-Α (FAP), in combination with atezolizumab (anti-PD-L1), administered intravenously, in participants with advanced and/or metastatic solid tumors

Description

This is a study to evaluate the therapeutic activity of RO6874281 as a combination therapy in participants with advanced and/or metastatic solid tumors. It is an open-label, multi-center, basket trial phase II study to evaluate the anti-tumor activity of RO6874281 in combination with atezolizumab in participants with advanced and/or metastatic solid tumors.

Status

Accepting new patients

Primary Study Objective(s)

The primary objective of this study is to measure the percentage of participants with objective response of complete response or partial response according to response evaluation criteria in solid tumors (RECIST).

Core eligibility

Note: This is only a partial list of eligibility criteria.

For cohorts F-J, including patients who have:

  • Progressed on at least one previous regimen of anticancer therapy (chemotherapy, mutation targeted therapy, and/or CPI therapy)
  • Measurable disease, as defined by RECIST Version 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or Karnofsky Performance Score greater than or equal to (>=) 70
  • Life expectancy of >= 12 weeks
  • Confirmed at least one tumor lesion with location accessible to safely biopsy per clinical judgment of the treating physician (not applicable to Part 1 Cohort A)
  • Consented to provide an archival tumor tissue sample (if available, applicable to all participants)
  • Willingness to undergo baseline and on-treatment tumor biopsies for pharmacodynamics (PD) biomarker analysis (not applicable to Part 1 Cohort A)
  • Adequate cardiovascular function as defined in the study protocol
  • AEs related to any previous 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
  • Adequate haematological, liver and renal functions
  • Unilateral pleural effusion (indications other than NSCLC) (these participants are eligible if they fulfill both of the following: (a) New York Heart Association (NYHA) Class 1 and (b) global initiative for obstructive lung disease test level 1 (forced expiratory volume 1 / forced vital capacity less than [<] 0.7 and forced expiratory volume >=80 percent [%] predicted) (use of bronchodilators allowed)
  • Gilbert's syndrome (eligible)

For CPI-Experienced Participants (Part III Cohort H), including patients who:

  • Have experienced documented disease progression on or after CPI therapy (investigational or approved) (required)
  • Have CPI that was administered as monotherapy or as part of a combination regimen at any time during the anti-cancer treatment before study enrollment
  • Suspected or documented disease progression within the first 12 weeks of CPI therapy (these participants may not be eligible and require discussion with the sponsor—screening tumor assessment should confirm previous progression)
  • Have no history of severe immune-related adverse effects from CPI treatment (National Cancer Institute Common Terminology Criteria for AEs [NCI CTCAE] grade 3 and 4)

Excluding patients who have:

  • Symptomatic or untreated central nervous system (CNS) metastases
  • History of treated asymptomatic CNS metastases as described in the protocol
  • Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >=2 weeks before enrollment
  • Leptomeningeal disease
  • An active second malignancy
  • Penetrating tumor infiltration
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
  • Episode of significant cardiovascular/cerebrovascular acute disease within six months before study treatment administration
  • History of significant vascular disease (for example, aortic aneurysm, aortic dissection)
  • Peripheral arterial thrombosis within six months before study treatment administration
  • Active or uncontrolled infections
  • Human immunodeficiency virus (HIV) or hepatitis B or hepatitis C virus infection
  • Known active bacterial, viral, fungal, mycobacterial, parasitic or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization within four weeks before study treatment administration
  • History of chronic liver disease or evidence of hepatic cirrhosis
  • Serious, non-healing wound, active ulcer or untreated bone fracture
  • Dementia or altered mental status that would prohibit informed consent
  • History of, active or suspicion of autoimmune disease
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.) or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Bilateral pleural effusion confirmed by X-ray
  • Any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory findings that give reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
  • Taken concurrent therapy with any other investigational drug
  • Taken immunomodulating agents as described in study protocol
  • Been on chronic use of steroids
  • Had radiotherapy within the last four weeks before start of study treatment administration, with the exception of limited field palliative radiotherapy
  • Had administration of a live, attenuated vaccine within four weeks before Cycle 1 Day 1 or at any time during the study and five months after the last dose of atezolizumab
  • Had major surgery or significant traumatic injury < 28 days before study treatment administration (excluding fine-needle biopsies) or anticipation of the need for major surgery during study treatment
  • Known hypersensitivity to any of the components of the RO6874281 drug product or atezolizumab drug product
  • Severe dyspnea at rest or requiring supplementary oxygen therapy