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

NCT02323191 | Completed Phase 1

• 3 other identifiers: BP294282014-002428-29RG7155
• Study Type: interventional
• Target: 221
• Locations: 4 countries
• Sites: 12

Brief Summary

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.

Conditions

Solid Cancers

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With Dose Limiting Toxicities (DLTs)

  21 days

• Maximum Tolerated Dose (MTD) of Emactuzumab

  21 days

• Percentage of Participants With Adverse Events (AEs)

  Baseline up to 3 years

Secondary Outcomes (21)

• Maximum Observed Plasma Concentration (Cmax) of Emactuzumab

  predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description)

• Maximum Observed Plasma Concentration (Cmax) of Atezolizumab

  predose (-4 h) on D1 of C1, C2, C3, C4, C6, then every 8 cycles (Cycle Length=21 days); 0.5h post end of infusion (60 minutes infusion) on D1 of C1; 120 days post last infusion (up to approximately 3 years)

• Minimum Observed Plasma Trough Concentration (Cmin) of Emactuzumab

  predose (-4 h) on D1 of C2, C3, C4, C5, C6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years)

• Minimum Observed Plasma Trough Concentration (Cmin) of Atezolizumab

  predose (-4 h) on D1 of C1, C2, C3, C4, C6, then every 8 cycles (Cycle Length=21 days)

• Area under the Concentration-Time Curve (AUC) of Emactuzumab

  predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description)

Study Arms (2)

Part 1 (Dose-finding): Emactuzumab + Atezolizumab

EXPERIMENTAL

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

Drug: Atezolizumab; Drug: Emactuzumab

Part 2 (Expansion): Emactuzumab + Atezolizumab

EXPERIMENTAL

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

Drug: Atezolizumab; Drug: Emactuzumab

Interventions

Atezolizumab DRUG

Participants will receive atezolizumab intravenously at a fixed dose of 1200 milligram (mg) q3w.

Also known as: MPDL3280A, TECENTRIQ

Part 1 (Dose-finding): Emactuzumab + Atezolizumab; Part 2 (Expansion): Emactuzumab + Atezolizumab

Emactuzumab DRUG

Participants will receive emactuzumab intravenously in ascending dose levels with a starting dose of 500 mg.

Also known as: RO5509554

Part 1 (Dose-finding): Emactuzumab + Atezolizumab; Part 2 (Expansion): Emactuzumab + Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group performance status 0 or 1

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (12)

Yale Cancer Center; Medical Oncology

New Haven, Connecticut, 06520, United States

Location

Massachusetts General Hospital.

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber - Harvard

Boston, Massachusetts, United States

Location

Memorial Sloan-Kettering Cancer Center Breast & Imaging Center

New York, New York, 10065, United States

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

Centre Leon Berard; Departement Oncologie Medicale

Lyon, 69373, France

Location

Institut Claudius Regaud; Departement Oncologie Medicale

Toulouse, 31059, France

Location

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, 94805, France

Location

Clinica Universitaria de Navarra; Servicio de Oncologia

Pamplona, Navarre, 31008, Spain

Location

Hospital del Mar; Servicio de Oncologia

Barcelona, 08003, Spain

Location

Centro Integral Oncológico Clara Campal Ensayos Clínicos START

Madrid, 28050, Spain

Location

Related Publications (1)

• Gomez-Roca C, Cassier P, Zamarin D, Machiels JP, Perez Gracia JL, Stephen Hodi F, Taus A, Martinez Garcia M, Boni V, Eder JP, Hafez N, Sullivan R, Mcdermott D, Champiat S, Aspeslagh S, Terret C, Jegg AM, Jacob W, Cannarile MA, Ries C, Korski K, Michielin F, Christen R, Babitzki G, Watson C, Meneses-Lorente G, Weisser M, Ruttinger D, Delord JP, Marabelle A. Anti-CSF-1R emactuzumab in combination with anti-PD-L1 atezolizumab in advanced solid tumor patients naive or experienced for immune checkpoint blockade. J Immunother Cancer. 2022 May;10(5):e004076. doi: 10.1136/jitc-2021-004076.

  PMID: 35577503 DERIVED

MeSH Terms

Interventions

atezolizumab; emactuzumab

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2014
• First Posted: December 23, 2014
• Study Start: January 19, 2015
• Primary Completion: August 21, 2020
• Study Completion: August 21, 2020
• Last Updated: August 27, 2020

Record last verified: 2020-08

Locations

US (5); ES (3); BE (1); FR (3)