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 July 2014 by Genentech
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT01633970
First received: June 22, 2012
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

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), and with carboplat in and nab-paclitaxel (Arm E) in patients with advanced solid tumors.


Condition Intervention Phase
Neoplasms
Drug: MPDL3280A
Drug: bevacizumab [Avastin]
Drug: FOLFOX
Drug: carboplatin
Drug: paclitaxel
Drug: pemetrexed
Drug: nab-paclitaxel
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib Study of the Safety and Pharmacology of MPDL3280A Administered With Bevacizumab and/or With Chemotherapy in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 154
Study Start Date: July 2012
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: MPDL3280A + bevacizumab Drug: MPDL3280A
multiple escalating doses IV q3w
Drug: bevacizumab [Avastin]
15 mg/kg iv q3w
Experimental: B: MPDL3280A + bevacizumab + FOLFOX Drug: FOLFOX
q2w
Drug: MPDL3280A
multiple escalating doses IV q2w
Drug: bevacizumab [Avastin]
10 mg/kg q2w
Experimental: C: MPDL3280A + carboplatin + paclitaxel Drug: carboplatin
IV q3w with target AUC of 6 mg/mL
Drug: paclitaxel
200 mg/m2 IV q3w
Experimental: D: MPDL3280A + carboplatin + pemetrexed Drug: carboplatin
IV q3w with target AUC of 6 mg/mL
Drug: pemetrexed
500 mg/m2 IV q3w
Experimental: E: MPDL3280A + carboplatin + nab-paclitaxel Drug: carboplatin
IV q3w with target AUC of 6 mg/mL
Drug: nab-paclitaxel
100 mg/m2 IV q1w

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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.

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
  • Biphosphonate 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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01633970

Contacts
Contact: Reference Study ID Number: GP28328 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
United States, Colorado
Recruiting
Aurora, Colorado, United States, 80045
United States, Connecticut
Recruiting
New Haven, Connecticut, United States, 06520-8063
United States, District of Columbia
Recruiting
Washington, District of Columbia, United States, 20057
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States, 02215
Recruiting
Boston, Massachusetts, United States, 02114
United States, North Carolina
Recruiting
Durham, North Carolina, United States, 27705
Recruiting
Huntersville, North Carolina, United States, 28078
United States, Tennessee
Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Genentech
Investigators
Study Director: Clinical Trials Genentech
  More Information

No publications provided

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT01633970     History of Changes
Other Study ID Numbers: GP28328, 2012-001422-10
Study First Received: June 22, 2012
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech:
PD-L1
PD-1
PDL1
antiPD-L1
MPDL3280A
Solid tumor
MPDL320A
Colorectal
CRC

Additional relevant MeSH terms:
Neoplasms
Pemetrexed
Bevacizumab
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014