A Study of Intravenous (IV) Cergutuzumab Amunaleukin and Atezolizumab in Combination in Participants With Locally Advanced and/or Metastatic Solid Tumors



Status:Recruiting
Conditions:Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:3/15/2019
Start Date:June 29, 2015
End Date:May 28, 2019
Contact:Reference Study ID Number: BP29435 www.roche.com/about_roche/roche_worldwide.htm
Email:global-roche-genentech-trials@gene.com
Phone:888-662-6728 (U.S. and Canada)

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A Phase 1b, Open-Label, Multi-Center, Dose Escalation Study of the Safety, Pharmacokinetics, and Therapeutic Activity of Cergutuzumab Amunaleukin, an Immunocytokine, Which Consists of a Variant of Interleukin 2 (IL 2v), That Targets Carcinoembryonic Antigen (CEA), and Atezolizumab, an Antibody That Targets Programmed Death-Ligand 1 (PD-L1), Administered Intravenously, in Patients With Locally Advanced and/or Metastatic Solid Tumors

This is an open-label, multi-center, Phase Ib clinical study of cergutuzumab amunaleukin, in
combination with atezolizumab, to investigate the safety, pharmacokinetics, and therapeutic
activity in participants with locally advanced and/or metastatic carcinoembryonic antigen
(CEA)-positive solid tumors, whose disease has progressed on or who are intolerant to the
standard of care therapy. Enrolled participants who continue treatment will be treated until
loss of clinical benefit, unacceptable toxicities, or withdrawal of consent. The study will
include 2 parts: a dose-escalation Part I and a dose expansion Part II. The anticipated
treatment period is 24 months for both cergutuzumab amunaleukin and atezolizumab and may be
modified if emerging data suggest a benefit.


Inclusion Criteria:

- Confirmed locally advanced and/or metastatic solid tumor, with at least one tumor
lesion of non-critical location accessible to biopsy (with exception of non-small cell
lung cancer [NSCLC] participants), and with confirmed progression at baseline that has
progressed on, or participant is intolerant to, the standard of care therapy

- Radiologically measurable and clinically evaluable disease as per RECIST v1.1

- Life expectancy, in the opinion of the investigator, greater than or equal to (>=) 12
weeks

- Eastern Cooperative Oncology Group Performance Status 0-1

- 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

- Adequate cardiac, hematological, liver and renal function

- Negative serum pregnancy test within 7 days prior to study treatment in premenopausal
women and women <= 2 years 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% per year during
the treatment period and for at least five months after the last dose of atezolizumab
and at least four months after the last dose of cergutuzumab amunaleukin, whichever is
the longest

- For men: agreement to remain abstinent or use contraceptive measures and agreement to
refrain from donating sperm

- Locally or centrally confirmed CEA expression in archival tumor tissue

- Participants with unilateral pleural effusion will be eligible for inclusion if they
fulfill the Global Initiative for Obstructive Lung Disease classification of 0-1 level
for pulmonary function and New York Heart Association (NYHA) classification class 1
for cardiac function

Exclusion Criteria:

- Active or untreated central nervous system (CNS) metastases as determined by computed
tomography (CT) or magnetic resonance imaging evaluation during screening and prior
radiographic assessments; participants with a history of treated asymptomatic CNS
metastases are eligible

- 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 prior to randomization

- Leptomeningeal disease

- Participants with an active second malignancy (other than non-melanoma skin cancer or
cervical carcinoma in situ). Participants who have a history of malignancy are not
considered to have an active malignancy if they have completed therapy and are
considered by their treating physician to be at <= 30 percent (%) risk for relapse

- Evidence of significant, uncontrolled concomitant diseases which could affect
compliance with the protocol or interpretation of results, including diabetes
mellitus, history of relevant pulmonary disorders, and known autoimmune diseases

- Participants with bilateral pleural effusion and NSCLC participants with uni- or
bilateral effusion confirmed at screening by X-ray are not eligible

- Uncontrolled hypertension, unstable angina, congestive heart failure of any NYHA
classification stage greater than (>) 2, serious cardiac arrhythmia requiring
treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia),
history of myocardial infarction within 6 months of enrollment

- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or
anticipation that such a live attenuated vaccine will be required during the study.
Influenza vaccination should be given during influenza season only. Participants must
not receive live, attenuated influenza vaccine within 4 weeks prior to Cycle 1, Day 1,
at any time during the study or 5 months after the last dose of atezolizumab

- Known Human Immunodeficiency Virus (HIV)

- Active hepatitis B (HBV) or hepatitis C (HCV) infection

- Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to
hospitalization for complications of infection, bacteremia, or severe pneumonia

- Received oral or intravenous (IV) antibiotics within 2 weeks prior to Cycle 1, Day 1.
Participants receiving prophylactic antibiotics (for prevention of a urinary tract
infection chronic obstructive pulmonary disease) are eligible

- Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that would
contraindicate the use of an investigational drug

- Major surgery or significant traumatic injury less than (<) 28 days prior to the first
cergutuzumab amunaleukin infusion (excluding biopsies) or anticipation of the need for
major surgery during study treatment

- Dementia or altered mental status that would prohibit informed consent

- History or risk of autoimmune disease, including but not limited to systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's
syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or
glomerulonephritis

- Participants with a history of autoimmune hypothyroidism on a stable dose of thyroid
replacement hormone or participants with controlled Type 1 diabetes mellitus on a
stable insulin regimen may be eligible for this study with approval by the medical
monitor

- Inclusion of participants with confirmed positive serology of at least one
auto-antibody panel (anti-nuclear antibody, anti-double stranded DNA, cytoplasmic
anti-neutrophil cytoplasmic antibody, and perinuclear anti-neutrophil cytoplasmic
antibody) at screening should be discussed between Sponsor and investigators, and if
judged clinically relevant could be referred to a specialist (Rheumatologist) to
exclude an underlying auto-immune disease

- History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia), or
evidence of active pneumonitis on screening chest CT scan. History of radiation
pneumonitis in the radiation field (fibrosis) is permitted

- Baseline QTc interval > 470 milliseconds (ms), baseline resting bradycardia <45 beats
per minute (bpm), or baseline resting tachycardia >100 bpm

- Pregnant or breast-feeding women

- Known hypersensitivity to any of the components of cergutuzumab amunaleukin and
atezolizumab; hypersensitivity to Chinese hamster ovary cell products or other
recombinant human antibodies

- Investigational therapy within 28 days prior to initiation of study treatment

- Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3
weeks prior to initiation of study treatment, with the exceptions stated in the
protocol

- Prior corticosteroids as anti-cancer therapy within a minimum of 14 days of first
receipt of study drug

- Last dose with any of the following agents including but not limited to: etanercept,
infliximab, tacrolimus, cyclosporine, mycophenolic acid, alefacept, or efalizumab <28
days prior to first dose of study drug

- Last dose of prior immunotherapies including but not limited to: interferon alpha,
interferon-beta, interleukin (IL)-2, conjugated IL-2, cergutuzumab amunaleukin
(CEA-IL2v) , cytokines, anti-cytotoxic T lymphocyte antigen-4, anti-PD-L1, or
anti-PD-1 <28 days prior to first cergutuzumab amunaleukin infusion

- History of severe immune-related adverse effects from CEA-IL2v or anti-PD-1
(nivolumab, pembrolizumab) or anti-PD-L1 (atezolizumab) therapies (Common Terminology
Criteria for Adverse Events Grade 3 and 4)

- Regular immunosuppressive therapy

- Treatment with systemic immunosuppressive medications including, but not limited to:
prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor
necrosis factor agents within 2 weeks prior to Cycle 1, Day 1. Participants who have
received acute and/or low-dose systemic immunosuppressant medications may be enrolled
in the study after discussion with and approval by the Medical Monitor. The use of
inhaled corticosteroids and mineralocorticoids for participants with orthostatic
hypotension or adrenocortical insufficiency is allowed

- Radiotherapy within the last 4 weeks before start of study drug treatment with the
exception of limited field palliative radiotherapy for bone pain relief
We found this trial at
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333 Cedar Street
New Haven, Connecticut 06520
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Nashville, Tennessee 37203
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1275 York Ave
New York, New York 10021
(212) 639-2000
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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630 W 168th St
New York, New York
212-305-2862
Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
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