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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-001422-10 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
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| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 5-FU | Drug | Participants will receive 5-FU 400 mg/m^2 IV q2w. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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Inclusion Criteria:
General Inclusion Criteria:
Eligible Tumor Types:
Arm A Escalation Cohorts and Arms A and B Biopsy Cohort (Cutaneous/Subcutaneous Lesions)
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:
Cervical Cancer:
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:
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
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:
Cervical Cancer:
- > 2 prior cytotoxic regimens, not including prior cisplatin-based chemotherapy concomitantly administered with primary pelvic radiation
Exclusion Criteria Unique to Arm B:
Exclusion Criteria Unique to Arms C, D, and E:
Exclusion Criteria Unique to Arm F:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Genentech, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Cancer Center | Aurora | Colorado | 80045 | United States | ||
| Yale University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30347025 | Derived | 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. | |
| 30053670 |
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| 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. |
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| 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. |
|
| 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. |
|
| Atezolizumab |
| Drug |
Participants will receive IV atezolizumab (800 mg q2w or 1200 mg q3w) q3w. |
|
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| Bevacizumab | Drug | Participants will receive bevacizumab 10 mg/kg or 15 mg/kg IV q3w. |
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| Carboplatin | Drug | Participants will receive carboplatin IV q3w with target AUC of 6 mg/mL. |
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| Leucovorin | Drug | Participants will receive leucovorin 400 mg/m^2 IV q2w. |
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| Nab-paclitaxel | Drug | Participants will receive nab-paclitaxel 100 mg/m^2 IV qw. |
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| Oxaliplatin | Drug | Participants will receive oxaliplatin 85 mg/m^2 IV q2w. |
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| Paclitaxel | Drug | Participants will receive paclitaxel 200 mg/m^2 IV q3w. |
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| Pemetrexed | Drug | Participants will receive pemetrexed 500 mg/m^2 IV q3w. |
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| 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) |
| Pharmacokinetics: Maximum Serum Concentration (Cmax) of Atezolizumab | Pre-infusion (0 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) |
| Minimum Serum Concentration (Cmin) of Atezolizumab | Pre-infusion (0 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) |
| Percentage of Participants With Best Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years) |
| Percentage of Participants With Best Overall Response According to Immune-Related Response Criteria (irRC) | From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years) |
| Percentage of Participants With Objective Response (Complete Response + Partial Response) According to RECIST v1.1 | From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years) |
| Percentage of Participants With Objective Response (Complete Response + Partial Response) According to irRC | From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years) |
| Pharmacokinetics: Clearance of Atezolizumab | Pre-infusion (0 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) |
| Pharmacokinetics: Volume of Distribution of Atezolizumab | Pre-infusion (0 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) |
| Pharmacokinetics: Accumulation Ratio of Atezolizumab | Pre-infusion (0 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) |
| Pharmacokinetics: Half-Life of Atezolizumab | Pre-infusion (0 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) |
| Pharmacokinetics: Cmax of Bevacizumab | Pre-infusion (0 hr), 0.5 hrs after EOI (infusion duration=90 min) on Day 1 Cycles 1 & 3 (each cycle = 21 days); EOT; every 30 days (for up to 120 days) after EOT until death or withdrawal or study closure (up to approximately 5 years) |
| Pharmacokinetics: Cmin of Bevacizumab | Pre-infusion (0 hr), 0.5 hrs after EOI (infusion duration=90 min) on Day 1 Cycles 1 & 3 (each cycle = 21 days); EOT; every 30 days (for up to 120 days) after EOT until death or withdrawal or study closure (up to approximately 5 years) |
| Maximum Plasma Concentration of 5-FU | Pre- infusion (0 hr) on Day 1 Cycle 1; end of 5-FU bolus and 2 and 12-24 hrs after end of 5-FU bolus (infusion duration = 46 hrs) on Day 1 of Cycles 1 and 3 (each cycle=14 days) |
| Pharmacokinetics: Maximum Plasma Concentration of Oxaliplatin | Pre-infusion (0 hr) on Day 1 Cycle 1; 5-10 min before end of oxaliplatin infusion (infusion duration = 120 min) and 2 and 12-24 hrs after end of 5-FU bolus (infusion duration = 46 hrs) on Day 1 of Cycles 1 and 3 (each cycle=14 days) |
| Pharmacokinetics: Maximum Plasma Concentration of Carboplatin | Pre-infusion (0 hr), 5-10 min before and 1 hr after carboplatin EOI (infusion duration=15-30 min),24 hr after atezolizumab EOI (infusion duration=90 min)on Day 1 Cycle 1; 5-10 min before and 1 hr after carboplatin EOI Day 1 Cycle 3 (each cycle=21 days) |
| Maximum Plasma Concentration of Paclitaxel | Pre-infusion (0 hr), 5-10 min before and 1 hr after paclitaxel EOI (infusion duration=180 min), 24 hr after atezolizumab EOI (infusion duration=90 min) on Day 1 Cycle 1; 5-10 min before and 1 hr after paclitaxel EOI on Day 1 Cycle 3 (each cycle=21 days) |
| Pharmacokinetics: Maximum Plasma Concentration of Pemetrexed | Pre-infusion (0 hr), 5-10 min before and 1 hr after pemetrexed EOI (infusion duration=10 min), 24 hr after atezolizumab EOI (infusion duration=90 min) on Day 1 Cycle 1; 5-10 min before and 1 hr after pemetrexed EOI on Day 1 Cycle 3 (each cycle = 21 days) |
| Maximum Plasma Concentration of Nab-Paclitaxel (Total Paclitaxel) | Pre-infusion (0 hr), 5-10 min before and 1 hr after nab-paclitaxel EOI (infusion duration=30 min) on Day 1 of Cycles 1 and 3; 24 hr after atezolizumab EOI (infusion duration=90 min) on Day 1 Cycle 1 (each cycle=7 days) |
| Number of Cycles of Each Component of Treatment Administer | From Baseline up to approximately 5 years |
| Dose Intensity of Each Component of Treatment Administer | From Baseline up to approximately 5 years |
| Overall Survival (OS) | From first dose of study treatment until death from any cause (up to approximately 5 years) |
| New Haven |
| Connecticut |
| 06511 |
| United States |
| Georgetown University Medical Center Lombardi Cancer Center | Washington D.C. | District of Columbia | 20007 | United States |
| Uni of Chicago | Chicago | Illinois | 60637 | United States |
| Massachusetts General Hospital. | Boston | Massachusetts | 02114 | United States |
| Beth Israel Deaconess Med Ctr | Boston | Massachusetts | 02215 | United States |
| Dana Farber Can Ins | Boston | Massachusetts | 02215 | United States |
| Laura and ISAAC Perlmutter Cancer Center at NYU Langone. | New York | New York | 10016 | United States |
| Duke University Medical Center | Durham | North Carolina | 27705 | United States |
| Carolina BioOncology Institute; Can Therapy & Res Ctr | Huntersville | North Carolina | 28078 | United States |
| Sarah Cannon Research Inst. | Nashville | Tennessee | 37203 | United States |
| 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. |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D005472 | Fluorouracil |
| C000594389 | atezolizumab |
| D000068258 | Bevacizumab |
| D016190 | Carboplatin |
| D002955 | Leucovorin |
| C520255 | 130-nm albumin-bound paclitaxel |
| D000077150 | Oxaliplatin |
| D017239 | Paclitaxel |
| D000068437 | Pemetrexed |
| ID | Term |
|---|---|
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000600 | Amino Acids, Dicarboxylic |
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