A Study of Atezolizumab Administered in Combination With Bevacizumab and/or With Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors



Status:Active, not recruiting
Conditions:Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:3/15/2019
Start Date:July 11, 2012
End Date:August 16, 2019

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A Phase Ib Study of the Safety and Pharmacology of Atezolizumab (Anti-PD-L1 Antibody) Administered With Bevacizumab and/or Chemotherapy in Patients With Advanced Solid Tumors

This open-label, Phase Ib study that has six treatment arms is designed to assess the safety,
pharmacology and preliminary efficacy of atezolizumab (MPDL3280A; an engineered
anti-programmed death-ligand 1 [PDL1] antibody) administered with bevacizumab (Arm A) and
with bevacizumab plus oxaliplatin, leucovorin, and 5-fluorouracil (5-FU) (FOLFOX) (Arm B),
with carboplatin and paclitaxel (Arm C), with carboplatin and pemetrexed (Arm D), with
carboplatin and nab-paclitaxel (Arm E), and with nab-paclitaxel (Arm F) in participants with
locally advanced or metastatic solid tumors. The study includes dose escalation cohort for
establishing the maximum tolerated dose (MTD) or maximum administered dose (MAD) and then
expansion cohort will be initiated based on a selected dose level at or below the MTD or MAD.


Inclusion Criteria:

General Inclusion Criteria:

- Histologically or cytologically documented advanced solid tumors

- Adequate hematologic and end organ function

- Measurable disease by RECIST v1.1

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

- Resolution of any acute, clinically significant treatment-related toxicity from prior
therapy to Grade less than or equal to ( exception of alopecia

Eligible Tumor Types:

Arm A Escalation Cohorts and Arms A and B Biopsy Cohort (Cutaneous/Subcutaneous Lesions)

- Histologically or cytologically documented, incurable or metastatic solid malignancy
that has failed all available or acceptable standard therapy for which the participant
is eligible Arm A and B Safety Expansion Cohorts, Arm B Escalation Cohorts, and Arm B
Biopsy Cohort (Liver Lesions)

- Histologically or cytologically confirmed metastatic colorectal cancer (mCRC).
Participants in the Arm A Safety Expansion Cohort must have mCRC for which established
therapies have proved ineffective or intolerable. Participants with malignancies other
than mCRC within 5 years prior to Day 1 (except for those with a negligible risk of
metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal
or squamous cell skin cancer, localized prostate cancer treated surgically with
curative intent, or ductal carcinoma in situ treated surgically with curative intent)
are not eligible.

Arm A renal cell carcinoma (RCC) Cohort:

- Histologically or cytologically confirmed advanced or metastatic RCC with a clear cell
component.

Arm A Tumor Type-Specific Cohort:

Gastric Cancer:

- Histologically or cytologically confirmed locally advanced or metastatic adenocarcinoma
of the stomach or gastroesophageal junction for which established therapies have proved
ineffective or intolerable. The decision may be made to restrict enrollment to participants
with a specified tumor PD-L1 status (e.g., immunohistochemistry [IHC] status 0/1 or 2/3)

Ovarian Cancer:

- Measurable/assessable ovarian cancer (defined as epithelial ovarian, fallopian tube, or
primary peritoneal cancer) that has progressed less than (<) 6 months after completing
platinum-based therapy. The following histological types are eligible: Adenocarcinoma NOS,
clear cell adenocarcinoma, endometriod adenocarcinoma, malignant Brenner's tumour, mixed
epithelial carcinoma, mucinous adenocarcinoma, serous adenocarcinoma, transitional cell
carcinoma, undifferentiated carcinoma

Bladder Cancer:

- Histologically or cytologically documented locally advanced (T4b, any N; or any T, N
2-3) or metastatic (M1, Stage IV) transitional cell carcinoma of the urothelium
(including renal pelvis, ureters, urinary bladder, urethra)

- Participants with mixed histologies are required to have a dominant transitional cell
pattern

- Locally advanced bladder cancer must be inoperable based on involvement of pelvic
sidewall or adjacent viscera (clinical stage T4b) or bulky nodal metastasis (N2-N3)

- Disease progression during or following treatment with at least one
platinum-containing regimen (e.g., GC, MVAC, CarboGem, etc.) for inoperable locally
advanced or metastatic urothelial carcinoma or disease recurrence

Cervical Cancer:

- Persistent or recurrent squamous cell carcinoma of the cervix (including adenosquamous
tumors)

Arms C, D, and E Cohorts:

- Histologically or cytologically documented Stage IIIB (not eligible for definitive
chemoradiotherapy), Stage IV, or recurrent non-small cell lung cancer (NSCLC)

Arm F Cohort:

- Histologically confirmed estrogen receptor (ER)-, progesterone receptor (PR)-, and
human epidermal growth factor receptor (HER)-negative (triple-negative) adenocarcinoma
of the breast that has been treated with systemic cytotoxic therapy. Locally recurrent
disease must not be amenable to resection with curative intent

- Participants with tumors amenable to excisional, punch, or core needle biopsy are
eligible for a separate biopsy expansion cohort

Tumor molecular status:

Arm A safety expansion cohort

- Up to 10 participants with CRC and high microsatellite instability (MSI-H) may be
enrolled

Exclusion Criteria:

General Exclusions

- Any approved anti-cancer therapy, including chemotherapy, hormonal therapy,
radiotherapy, or herbal therapy intended as anti-cancer therapy, within 3 weeks prior
to initiation of study treatment; the following are allowed: hormonal therapy with
gonadotropin-releasing hormone agonists or antagonists for prostate cancer,
hormone-replacement therapy, and palliative radiotherapy for bone metastases greater
than (>) 2 weeks prior to Day 1

- Bisphosphonate therapy for symptomatic hypercalcemia

- Known clinically significant liver disease

- Known primary central nervous (CNS) malignancy or active CNS metastases (progressing
or requiring anticonvulsants or corticosteroids for symptomatic control)

- Pregnant or lactating women

- Known hypersensitivity to Chinese hamster ovary cell products or any component of the
atezolizumab formulation

- History of autoimmune disease, idiopathic pulmonary fibrosis, human immunodeficiency
virus (HIV), hepatitis B or C infection; history of hepatitis B is allowed if
infection has resolved (absence of hepatitis B surface antigen [HBsAg])

- Severe infections within 4 weeks prior to Day 1, or signs or symptoms of significant
infection within 2 weeks prior to Day 1

- Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1

- History of myocardial infarction, unstable angina stroke or transient ischemic attack
within 6 months prior to Day 1

- Administration of a live, attenuated vaccine within 4 weeks before Day 1 or
anticipation that such a live attenuated vaccine will be required during the study
Bevacizumab-Specific Exclusions (Arms A and B) Exclusion Criteria Unique to Arm A RCC
Cohort

- Any prior systemic treatment (including tyrosine kinase inhibitors, antibody therapy,
immunotherapy, chemotherapy, hormonal therapy, or investigational therapy) for RCC.
All treatments, neo-adjuvant, adjuvant, or for locally advanced or metastatic RCC are
not permitted

Arm A Tumor Type-Specific Cohort:

Gastric Cancer:

- Prior approved or experimental anti-vascular endothelial growth factor or its receptor
(VEGF/VEGFR) therapy (including, for example, bevacizumab or nintedanib). The decision may
be made to allocate a specified number of slots to participants who have received prior
anti-VEGF/VEGFR therapy

Ovarian Cancer:

- Refractory disease

- History of bowel obstruction

- >2 prior anticancer regimens

- Prior approved or experimental anti-VEGF/VEGFR therapy (including, for example,
bevacizumab or nintedanib)

Cervical Cancer:

- > 2 prior cytotoxic regimens, not including prior cisplatin-based chemotherapy
concomitantly administered with primary pelvic radiation

Exclusion Criteria Unique to Arm B:

- Prior treatment with an oxaliplatin-containing regimen. Oxaliplatin >12 months prior
to the diagnosis of metastatic disease is permitted.

- Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene
polymorphism predisposing the participant for 5-FU toxicity

Exclusion Criteria Unique to Arms C, D, and E:

- Prior chemotherapy for locally advanced or metastatic NSCLC

- For participants who received prior adjuvant/neo-adjuvant chemotherapy or
chemoradiation for NSCLC, a treatment-free interval >6 months between the last
treatment administration and the date of recurrence in required

- Participants with a known epidermal growth factor receptor (EGFR) sensitizing mutation
must have experienced disease progression during or after treatment with an approved
EGFR tyrosine kinase inhibitor

- Participants with a known anaplastic lymphoma kinase (ALK) fusion oncogene must have
experienced disease progression during or after treatment with crizotinib

- For Arm D (carboplatin + pemetrexed), squamous cell histology or evidence of mixed
NSCLC histology with a predominance of the squamous cell type

- For Arm D (carboplatin + pemetrexed), inability to discontinue treatment with
non-steroidal anti-inflammatory drugs (NSAIDs) for 5 days

Exclusion Criteria Unique to Arm F:

- Prior therapy with more than two cytotoxic regimens for metastatic or locally advanced
triple-negative breast cancer (TNBC)

- Treatment with a taxane-containing regimen within 6 months before enrollment
We found this trial at
11
sites
2301 Erwin Rd
Durham, North Carolina 27710
919-684-8111
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
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185 Cambridge Street
Boston, Massachusetts 02114
617-724-5200
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330 Brookline Ave
Boston, Massachusetts 02215
617-667-7000
Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center (BIDMC) is one of the...
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Aurora, Colorado 80045
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450 Brookline Avenue
Boston, Massachusetts 02215
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5801 South Ellis Avenue
Chicago, Illinois 60637
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9801 Kincey Avenue
Huntersville, North Carolina 28078
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Nashville, Tennessee 37203
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New Haven, Connecticut 6520
(203) 432-4771
Yale University Yale's roots can be traced back to the 1640s, when colonial clergymen led...
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Washington, District of Columbia 20057
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