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A Phase 1b Study of MPDL3280A (an Engineered Anti-PDL1 Antibody) in Combination With Avastin (Bevacizumab) and/or With Chemotherapy in Patients With Locally Advanced or Metastatic Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01633970
First received: June 22, 2012
Last updated: November 19, 2014
Last verified: November 2014

June 22, 2012
November 19, 2014
July 2012
February 2016   (final data collection date for primary outcome measure)
  • Safety: Incidence of adverse events [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Dose-limiting toxicities/maximum tolerated dose [ Time Frame: 21 days for Arms A, C, D and E and the 28 days following the first administration of MPDL3280A in Arm B ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01633970 on ClinicalTrials.gov Archive Site
  • Pharmacokinetics: Area under the concentration-time curve [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Best overall response (tumor assessments according to RECIST criteria) [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Objective response rate (complete response + partial response) [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Duration of objective response [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Phase 1b Study of MPDL3280A (an Engineered Anti-PDL1 Antibody) in Combination With Avastin (Bevacizumab) and/or With Chemotherapy in Patients With Locally Advanced or Metastatic Solid Tumors
A Phase Ib Study of the Safety and Pharmacology of MPDL3280A Administered With Bevacizumab and/or With Chemotherapy in Patients With Advanced Solid Tumors

The primary aim of the study is to assess the safety, pharmacology and prelimina ry efficacy of MPDL3280A (an engineered anti-PDL1 antibody) administered with be vacizumab (Arm A) and with bevacizumab plus FOLFOX (Arm B), with carboplatin and paclitaxel (Arm C), with carboplatin and pemetrexed (Arm D), with carboplatin a nd nab-paclitaxel (Arm E), and with nab-paclitaxel (Arm F) in patients with adva nced solid tumors.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Neoplasms
  • Drug: FOLFOX
    q2w
  • Drug: MPDL3280A
    1200 mg Q3W
  • Drug: MPDL3280A
    800 mg Q2W
  • Drug: bevacizumab [Avastin]
    15 mg/kg iv q3w
  • Drug: bevacizumab [Avastin]
    10 mg/kg q2w
  • Drug: carboplatin
    IV q3w with target AUC of 6 mg/mL
  • Drug: nab-paclitaxel
    100 mg/m2 IV q1w
  • Drug: paclitaxel
    200 mg/m2 IV q3w
  • Drug: pemetrexed
    500 mg/m2 IV q3w
  • Experimental: A: MPDL3280A + bevacizumab
    Interventions:
    • Drug: MPDL3280A
    • Drug: bevacizumab [Avastin]
  • Experimental: B: MPDL3280A + bevacizumab + FOLFOX
    Interventions:
    • Drug: FOLFOX
    • Drug: MPDL3280A
    • Drug: bevacizumab [Avastin]
  • Experimental: C: MPDL3280A + carboplatin + paclitaxel
    Interventions:
    • Drug: MPDL3280A
    • Drug: carboplatin
    • Drug: paclitaxel
  • Experimental: D: MPDL3280A + carboplatin + pemetrexed
    Interventions:
    • Drug: MPDL3280A
    • Drug: carboplatin
    • Drug: pemetrexed
  • Experimental: E: MPDL3280A + carboplatin + nab-paclitaxel
    Interventions:
    • Drug: MPDL3280A
    • Drug: carboplatin
    • Drug: nab-paclitaxel
  • Experimental: F: MPDL3280A + nab-paclitaxel
    Interventions:
    • Drug: MPDL3280A
    • Drug: nab-paclitaxel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
180
May 2017
February 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • 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 </=1 prior to study entry, with the exception of alopecia

Eligible Tumor Types:

Arm A Escalation Cohorts/Arm A Biopsy Cohort/Arm 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 patient is eligible

Arm A Safety Expansion Cohort/Arm B Escalation Cohorts/Arm B Safety Expansion Cohort/Arm B Biopsy Cohort (Liver Lesions)

  • Histologically or cytologically confirmed metastatic CRC. Patients in the Arm A Safety Expansion Cohort must have mCRC for which established therapies have proved ineffective or intolerable. Patients with malignancies other than CRC 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 Safety Expansion Cohort: Up to 10 patients with CRC and high microsatellite instability (MSI-H) tumors will be enrolled.

Arm A RCC Cohort:

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

Arms C, D, and E Cohorts:

  • Histologically or cytologically documented Stage IIIB (not eligible for definitive chemoradiotherapy), Stage IV, or recurrent NSCLC.

Arm F Cohort:

  • Histologically confirmed ER-, PR-, and HER-negative (triple-negative) adenocarcinoma of the breast (TNBC) that has been treated with systemic cytotoxic therapy. Locally recurrent disease must not be amenable to resection with curative intent. Patients with tumors amenable to excisional, punch, or core needle biopsy are eligible for a separate biopsy expansion cohort.

Exclusion Criteria:

  • 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 > 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 other recombinant human antibodies
  • History of autoimmune disease
  • History of idiopathic pulmonary fibrosis
  • History of HIV or hepatitis C infection; history of hepatitis B is allowed if infection has resolved (absence of HBsAg)
  • Severe infections within 4 weeks prior to Day 1, or signs or symptoms of significant infection within 2 weeks prior to Day 1
  • Initiation of oral antibiotics < 14 days prior to Day 1
  • History of myocardial infarction, unstable angina or stroke with 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
  • Any bevacizumab-specific exclusion criteria

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.

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 patient for 5-FU toxicity.

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

  • Prior chemotherapy for locally advanced or metastatic NSCLC.
  • For patients 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.
  • Patients with a known EGFR sensitizing mutation must have experienced disease progression during or after treatment with an approved EGFR tyrosine kinase inhibitor.
  • Patients with a known 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 TNBC
  • Treatment with a taxane-containing regimen within 6 months before enrollment
Both
18 Years and older
No
Contact: Reference Study ID Number: GP28328 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com
United States
 
NCT01633970
GP28328, 2012-001422-10
Not Provided
Genentech, Inc.
Genentech, Inc.
Not Provided
Study Director: Clinical Trials Genentech, Inc.
Genentech, Inc.
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP