Cancer
Conditions
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.
Interventions
DRUG5-FU
Participants will receive 5-FU 400 mg/m\^2 IV q2w.
DRUGAtezolizumab
Participants will receive IV atezolizumab (800 mg q2w or 1200 mg q3w) q3w.
DRUGBevacizumab
Participants will receive bevacizumab 10 mg/kg or 15 mg/kg IV q3w.
DRUGCarboplatin
Participants will receive carboplatin IV q3w with target AUC of 6 mg/mL.
DRUGLeucovorin
Participants will receive leucovorin 400 mg/m\^2 IV q2w.
DRUGNab-paclitaxel
Participants will receive nab-paclitaxel 100 mg/m\^2 IV qw.
DRUGOxaliplatin
Participants will receive oxaliplatin 85 mg/m\^2 IV q2w.
DRUGPaclitaxel
Participants will receive paclitaxel 200 mg/m\^2 IV q3w.
DRUGPemetrexed
Participants will receive pemetrexed 500 mg/m\^2 IV q3w.
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 (\</=) 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: \- 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)
Design outcomes
Primary
| Measure | 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 |
Secondary
| Measure | Time frame |
|---|---|
| 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) |
| Duration of Objective Response According to RECIST v1.1 | From Baseline until death or disease progression, whichever occurs first (up to approximately 5 years) |
| 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) |
| 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) |
| 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) |
Countries
United States
Outcome results
None listed