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

NCT01633970 | Completed Phase 1

• 2 other identifiers: GP283282012-001422-10
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Cancer

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Atezolizumab Dose

  Days 1-21 of Cycle 1 (Cycle length = 21 days) for Arms A, C, D and E and the 28 days following the first administration of atezolizumab in Arm B

• Percentage of Participants With Adverse Events

  From Baseline up to 90 days after last dose of study drug or until initiation of another anti-cancer therapy (up to approximately 5 years)

• Percentage of Participants With Dose-Limiting Toxicities (DLTs)

  Days 1-21 of Cycle 1 (Cycle length = 21 days) for Arms A, C, D and E and the 28 days following the first administration of atezolizumab in Arm B

Secondary Outcomes (26)

• Duration of Objective Response According to RECIST v1.1

  From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years)

• Duration of Objective Response According to irRC

  From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years)

• Progression-Free Survival According to RECIST v1.1

  From treatment initiation until documented disease progression or death from any cause, whichever occurs first (up to approximately 5 years)

• Progression-Free Survival According to irRC

  From treatment initiation until documented disease progression or death from any cause, whichever occurs first (up to approximately 5 years)

• Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) of Atezolizumab

  Pre-infusion (0 hour [hr]) on Cycle 1 Day 1 (cycle length = 21 or 14 days) up to approximately 5 years (detailed timeframe is provided in outcome measure description)

Study Arms (6)

A: Atezolizumab + Bevacizumab

EXPERIMENTAL

Participants will receive atezolizumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion (or a selected dose level not to exceed the single agent MTD or MAD determined in Study PCD4989g) with bevacizumab 15 mg/kg every 3 weeks (q3w). After establishment of MTD or MAD, participants will receive bevacizumab 15 mg/kg IV infusion on Day 1 of Cycle 1 followed by atezolizumab 1200 mg IV infusion q3w after Days 5-7 and then atezolizumab 1200 mg q3w and bevacizumab 15 mg/kg q3w on Day 1 of all subsequent cycles until disease progression or unacceptable toxicity.

Drug: Atezolizumab; Drug: Bevacizumab

B: Atezolizumab + Bevacizumab + FOLFOX

EXPERIMENTAL

Participants will receive FOLFOX IV infusion (oxaliplatin \[85 milligrams per square meter {mg/m\^2}\], leucovorin \[400 mg/m\^2\], 5-FU \[400 mg/m\^2\]) on Day 1 of Cycle 1 and then atezolizumab 800 mg IV infusion every 2 weeks (q2w), bevacizumab 10 mg/kg IV infusion q3w and FOLFOX q2w on Day 1 of all subsequent cycles as per institutional guidelines until disease progression or unacceptable toxicity.

Drug: 5-FU; Drug: Atezolizumab; Drug: Bevacizumab; Drug: Leucovorin; Drug: Oxaliplatin

C: Atezolizumab + Carboplatin + Paclitaxel

EXPERIMENTAL

Participants will receive atezolizumab 1200 mg IV infusion q3w in combination with paclitaxel 200 mg/m\^2 IV infusion q3w and then carboplatin IV q3w (on Day 1 of every 3-week cycle) to achieve an initial target area under the curve (AUC) of 6 milligrams per milliliter\*minute (mg/mL\*min) until disease progression or unacceptable toxicity.

Drug: Atezolizumab; Drug: Carboplatin; Drug: Paclitaxel

D: Atezolizumab + Carboplatin + Pemetrexed

EXPERIMENTAL

Participants will receive atezolizumab 1200 mg IV infusion q3w in combination with premetrexed 500 mg/m\^2 IV infusion q3w and then carboplatin IV q3w (on Day 1 of every 3-week cycle) to achieve an initial target AUC of 6 mg/mL\*min until disease progression or unacceptable toxicity.

Drug: Atezolizumab; Drug: Carboplatin; Drug: Pemetrexed

E: Atezolizumab + Carboplatin + Nab-paclitaxel

EXPERIMENTAL

Participants will receive atezolizumab 1200 mg IV infusion q3w (on Day 1 of every 3-week cycle) in combination with nab-paclitaxel 100 mg/m\^2 IV infusion once weekly (qw) (on Days 1, 8 and 15 of every 3-week cycle) and then carboplatin IV infusion q3w (on Day 1 of every 3-week cycle) to achieve an initial target AUC of 6 mg/mL\*min until disease progression or unacceptable toxicity.

Drug: Atezolizumab; Drug: Carboplatin; Drug: Nab-paclitaxel

F: Atezolizumab + Nab-paclitaxel

EXPERIMENTAL

Participants will receive atezolizumab 800 mg IV infusion q2w (Days 1 and 15) in combination with nab-paclitaxel 125 mg/m\^2 IV infusion qw (on Days 1, 8 and 15 of every 3-week cycle) until disease progression or unacceptable toxicity.

Drug: Atezolizumab; Drug: Nab-paclitaxel

Interventions

5-FU DRUG

Participants will receive 5-FU 400 mg/m\^2 IV q2w.

B: Atezolizumab + Bevacizumab + FOLFOX

Atezolizumab DRUG

Participants will receive IV atezolizumab (800 mg q2w or 1200 mg q3w) q3w.

Also known as: MPDL3280A

A: Atezolizumab + Bevacizumab; B: Atezolizumab + Bevacizumab + FOLFOX; C: Atezolizumab + Carboplatin + Paclitaxel; D: Atezolizumab + Carboplatin + Pemetrexed; E: Atezolizumab + Carboplatin + Nab-paclitaxel; F: Atezolizumab + Nab-paclitaxel

Bevacizumab DRUG

Participants will receive bevacizumab 10 mg/kg or 15 mg/kg IV q3w.

Also known as: Avastin

A: Atezolizumab + Bevacizumab; B: Atezolizumab + Bevacizumab + FOLFOX

Carboplatin DRUG

Participants will receive carboplatin IV q3w with target AUC of 6 mg/mL.

C: Atezolizumab + Carboplatin + Paclitaxel; D: Atezolizumab + Carboplatin + Pemetrexed; E: Atezolizumab + Carboplatin + Nab-paclitaxel

Leucovorin DRUG

Participants will receive leucovorin 400 mg/m\^2 IV q2w.

B: Atezolizumab + Bevacizumab + FOLFOX

Nab-paclitaxel DRUG

Participants will receive nab-paclitaxel 100 mg/m\^2 IV qw.

E: Atezolizumab + Carboplatin + Nab-paclitaxel; F: Atezolizumab + Nab-paclitaxel

Oxaliplatin DRUG

Participants will receive oxaliplatin 85 mg/m\^2 IV q2w.

B: Atezolizumab + Bevacizumab + FOLFOX

Paclitaxel DRUG

Participants will receive paclitaxel 200 mg/m\^2 IV q3w.

C: Atezolizumab + Carboplatin + Paclitaxel

Pemetrexed DRUG

Participants will receive pemetrexed 500 mg/m\^2 IV q3w.

D: Atezolizumab + Carboplatin + Pemetrexed

Eligibility Criteria

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

You may qualify if:

• 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 (\</=) 1 prior to study entry, with the 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:

You may not qualify if:

• 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
• 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:

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (11)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

Georgetown University Medical Center Lombardi Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Uni of Chicago

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital.

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Med Ctr

Boston, Massachusetts, 02215, United States

Location

Dana Farber Can Ins

Boston, Massachusetts, 02215, United States

Location

Laura and ISAAC Perlmutter Cancer Center at NYU Langone.

New York, New York, 10016, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Carolina BioOncology Institute; Can Therapy & Res Ctr

Huntersville, North Carolina, 28078, United States

Location

Sarah Cannon Research Inst.

Nashville, Tennessee, 37203, United States

Location

Related Publications (2)

• Adams S, Diamond JR, Hamilton E, Pohlmann PR, Tolaney SM, Chang CW, Zhang W, Iizuka K, Foster PG, Molinero L, Funke R, Powderly J. Atezolizumab Plus nab-Paclitaxel in the Treatment of Metastatic Triple-Negative Breast Cancer With 2-Year Survival Follow-up: A Phase 1b Clinical Trial. JAMA Oncol. 2019 Mar 1;5(3):334-342. doi: 10.1001/jamaoncol.2018.5152.

  PMID: 30347025 DERIVED

• Liu SV, Camidge DR, Gettinger SN, Giaccone G, Heist RS, Hodi FS, Ready NE, Zhang W, Wallin J, Funke R, Waterkamp D, Foster P, Iizuka K, Powderly J. Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. Eur J Cancer. 2018 Sep;101:114-122. doi: 10.1016/j.ejca.2018.06.033. Epub 2018 Jul 24.

  PMID: 30053670 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Fluorouracil; atezolizumab; Bevacizumab; Carboplatin; Leucovorin; 130-nm albumin-bound paclitaxel; Oxaliplatin; Paclitaxel; Pemetrexed

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 22, 2012
• First Posted: July 6, 2012
• Study Start: July 11, 2012
• Primary Completion: February 26, 2020
• Study Completion: February 26, 2020
• Last Updated: October 8, 2020

Record last verified: 2020-10

Locations

US (11)