A Study of Emactuzumab and Atezolizumab Administered in Combination in Participants With Advanced Solid Tumors

Roche

Status and phase: Completed; Phase 1

Conditions: Solid Cancers

Treatments: Drug: Atezolizumab; Drug: Emactuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02323191

2014-002428-29 (EudraCT Number)

RG7155 (Other Identifier)

BP29428

Details and patient eligibility

About

This Phase 1, open-label, multicenter, global study will evaluate the safety, pharmacokinetics, and activity of emactuzumab and atezolizumab administered in combination in participants with selected locally advanced or metastatic solid tumors that are not amenable to standard treatment.

Participants who receive emactuzumab and atezolizumab will continue to receive study drug as long as they experience clinical benefit in the opinion of the investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data, biopsy results (if available), and clinical status, or withdrawal of consent.

Enrollment: 221 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Eastern Cooperative Oncology Group performance status 0 or 1
• Participants must have histologically confirmed diagnosis of locally advanced and/or metastatic triple negative breast cancer, ovarian cancer, bladder cancer, gastric cancer, or soft tissue sarcoma, with exceptions defined in the exclusion criteria
• Measurable disease at baseline as per RECIST version 1.1
• Life expectancy of greater than or equal to (>=) 16 weeks
• Adequate bone marrow, liver, cardiac, and renal function
• Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women less than or equal to (<=) 12 months post-menopause. Postmenopausal state is defined as amenorrhea for greater than (>) 12 months.

Exclusion criteria

• Allergy or hypersensitivity to components of the emactuzumab formulation or to components of the atezolizumab formulation
• Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening (within 28 days before C1D1) and prior radiographic assessments. Participants with radiographically stable, asymptomatic previously irradiated lesions are eligible provided participant is >= 4 weeks beyond completion of cranial irradiation and >= 3 weeks off of corticosteroid therapy. Participants with metastases to the brain stem, midbrain, pons, medulla, or within 10 millimeter (mm) of the optic apparatus (optic nerves and chiasm) are completely excluded
• Leptomeningeal disease
• History of or active autoimmune disease
• Evidence of significant, uncontrolled concomitant diseases, which could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of symptomatic bronchospasm)
• Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment, with the exceptions provided in the protocol
• Prior corticosteroids as anti-cancer therapy within a minimum of 14 days of first receipt of study drug
• Prior toxicities from chemotherapy, radiotherapy, and other anti-cancer therapies, including immunotherapy that have not regressed to Grade <=1 severity (Common Terminology Criteria for Adverse Events [CTCAE] v4.03, or later versions)
• History of human immunodeficiency virus (HIV)
• Participants with active hepatitis B, active hepatitis C, or active tuberculosis
• Participant has had pulmonary embolism or any other thrombo-embolic event within 6 months prior to study entry
• Participants has a history of hematological malignancy within the last 5 years prior to study entry
• Treatment with systemic immunosuppressive medications - Pregnant or lactating women

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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221 participants in 2 patient groups

Part 1 (Dose-finding): Emactuzumab + Atezolizumab

Experimental group

Description:

Participants will receive escalating doses of emactuzumab along with atezolizumab every 3 weeks (q3w).

Treatment:

Drug: Emactuzumab

Drug: Atezolizumab

Part 2 (Expansion): Emactuzumab + Atezolizumab

Experimental group

Description:

Participants will receive emactuzumab at or below the MTDs for the combination treatments that are determined during Part 1 along with atezolizumab.

Treatment:

Drug: Emactuzumab

Drug: Atezolizumab