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

Solid Cancers Clinical Trial

Official title:

Open-Label, Multicenter, Dose Escalation Phase Ib Study With Expansion Phase to Evaluate the Safety, Pharmacokinetics, and Activity of RO5509554 (Emactuzumab) and MPDL3280A (Atezolizumab) Administered in Combination in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02323191
• Other study ID #: BP29428
• Secondary ID: 2014-002428-29RG
• Status: Completed
• Phase: Phase 1
• Start date: January 19, 2015
• Est. completion date: August 21, 2020

Study information

• Verified date: August 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: August 21, 2020
• Est. primary completion date: August 21, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Solid Cancers

Intervention

Drug:
• Atezolizumab
Participants will receive atezolizumab intravenously at a fixed dose of 1200 milligram (mg) q3w.
• Emactuzumab
Participants will receive emactuzumab intravenously in ascending dose levels with a starting dose of 500 mg.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires St-Luc	Bruxelles
France	Centre Leon Berard; Departement Oncologie Medicale	Lyon
France	Institut Claudius Regaud; Departement Oncologie Medicale	Toulouse
France	Institut Gustave Roussy; Departement Oncologie Medicale	Villejuif
Spain	Hospital del Mar; Servicio de Oncologia	Barcelona
Spain	Centro Integral Oncológico Clara Campal Ensayos Clínicos START	Madrid
Spain	Clinica Universitaria de Navarra; Servicio de Oncologia	Pamplona	Navarra
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber - Harvard	Boston	Massachusetts
United States	Massachusetts General Hospital.	Boston	Massachusetts
United States	Yale Cancer Center; Medical Oncology	New Haven	Connecticut
United States	Memorial Sloan-Kettering Cancer Center Breast & Imaging Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Dose Limiting Toxicities (DLTs)		21 days
Primary	Maximum Tolerated Dose (MTD) of Emactuzumab		21 days
Primary	Percentage of Participants With Adverse Events (AEs)		Baseline up to 3 years
Secondary	Maximum Observed Plasma Concentration (Cmax) of Emactuzumab	predose (-4 hours [h]) and 0.5h post end of infusion (90 minutes infusion) on Days (D) 1 of Cycle (C) 1, 2, 3, 4, 5, 6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D15 of C1, C2, C4; D12, D19 of C1, C4; 44 and 120 days post last infusion; 28 day follow-up visit (up to approximately 3 years)	predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Area under the Concentration-Time Curve (AUC) of Emactuzumab	predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C2, C3, C4, C5, C6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D15 of C1, C2, C4; D12, D19 of C1, C4; 44 and 120 days post last infusion; 28 day follow-up visit (up to approximately 3 years)	predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description)
Secondary	Total Clearance (CL) of Emactuzumab		predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C4 (Cycle Length=21 days); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D12, D15, D19 of C1, C4
Secondary	Volume of Distribution at Steady State (Vss) of Emactuzumab		predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C4 (Cycle Length=21 days); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D12, D15, D19 of C1, C4
Secondary	Accumulation Ratio (Rac) of Emactuzumab		predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C4 (Cycle Length=21 days); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D12, D15, D19 of C1, C4
Secondary	Terminal Elimination Half-life (t1/2) of Emactuzumab		predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C4 (Cycle Length=21 days); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D12, D15, D19 of C1, C4
Secondary	Emactuzumab Concentration at the time of Tumor Progression (Cprog)	predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C2, C3, C4, C5, C6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D15 of C1, C2, C4; D12, D19 of C1, C4; 44 and 120 days post last infusion; 28 day follow-up visit (up to approximately 3 years)	predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description)
Secondary	Emactuzumab Concentration at the Time of Tumor Response (Complete Response/Partial Response)	predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C2, C3, C4, C5, C6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D15 of C1, C2, C4; D12, D19 of C1, C4; 44 and 120 days post last infusion; 28 day follow-up visit (up to approximately 3 years)	predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description)
Secondary	Emactuzumab Concentration at the Time of Infusion-related Reaction (IRR) or Hypersensitivity Reaction	predose (-4 h) and 0.5h post end of infusion (90 minutes infusion) on D1 of C1, C2, C3, C4, C5, C6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years); 5h postdose on D1 of C1; postdose on D2, D4 or D5, D8, D15 of C1, C2, C4; D12, D19 of C1, C4; 44 and 120 days post last infusion; 28 day follow-up visit (up to approximately 3 years)	predose (-4 h) on Day 1 of Cycle 1 up to approximately 3 years (detailed timeframe provided in measure description)
Secondary	Change From Baseline in Tumor-Associated Macrophages (TAMs) Levels in Paired-Tumor Biopsies at Specified Timepoints		Baseline (predose [-4 h] on D1 of C2; Cycle Length=21 days), at disease progression (up to approximately 3 years)
Secondary	Change From Baseline in Dermal Macrophages Levels in Paired Skin Biopsies at Specified Timepoints		Baseline, D15 of C1 (Cycle Length=21 days)
Secondary	Change From Baseline in Circulating Cluster of Differentiation (CD) 14DimCD16high Monocytes Levels in Peripheral Blood at Specified Timepoints	Baseline (predose [-4 h] on D1 of C1), predose [-4 h] on D1 of C2, C3, C5, then every other cycle (Cycle Length=21 days) until disease progression (up to approximately 3 years); postdose on D2, D8, D15 of C1, C2; D4 or D5 of C1; 44 days post last infusion (up to approximately 3 years)	Baseline up to approximately 3 years (detailed timeframe provided in measure description)
Secondary	Percentage of Participants With Anti-therapeutic Antibodies to Emactuzumab		predose (-4 h) on D1 of C1, C2, C3, C4, C6, all subsequent cycles (Cycle Length=21 days) until disease progression (up to approximately 3 years), 44 and 120 days post last infusion, 28 day follow-up visit (up to approximately 3 years)
Secondary	Percentage of Participants With Anti-therapeutic Antibodies to Atezolizumab		predose (-4 h) on D1 of C1, C2, C3, C4, C6, then every 8 cycles (Cycle Length=21 days; up to approximately 3 years), 120 days post last infusion (up to approximately 3 years)
Secondary	Percentage of Participants With Best Overall Response as Determined Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1		Baseline up to disease progression or death, whichever occurs first (assessed up to approximately 3 years)
Secondary	Percentage of Participants With Best Overall Response as Determined Using Modified RECIST		Baseline up to disease progression or death, whichever occurs first (assessed up to approximately 3 years)
Secondary	Percentage of Participants With Objective Response as Determined Using RECIST v1.1		Baseline up to disease progression or death, whichever occurs first (assessed up to approximately 3 years)
Secondary	Percentage of Participants With Objective Response as Determined Using Modified RECIST		Baseline up to disease progression or death, whichever occurs first (assessed up to approximately 3 years)