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Completed

NCT Number: NCT01988896

Study of Atezolizumab in Combination With Cobimetinib in Participants With Locally Advanced or Metastatic Solid Tumors

This is a Phase Ib, open-label, multicenter study designed to assess the safety, tolerability, and pharmacokinetics of coadministration of intravenous (IV) dosing of atezolizumab (an engineered anti-programmed death-ligand 1 [anti-PD-L1] antibody) and oral dosing of cobimetinib in participants with metastatic or locally advanced cancer for which no standard therapy exists.

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Key information

Conditions

Solid Tumors

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Peter MacCallum Cancer Centre-East Melbourne, Melbourne, Victoria, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Solid tumor that is metastatic, locally advanced or recurrent
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy greater than or equal to (>/=) 12 weeks
  • Measurable disease, as defined by RECIST v 1.1
  • Adequate hematologic and end organ function
  • Use of highly effective contraception
  • Histological tumor tissue specimen
  • Participants enrolling in the indication-specific expansion cohorts in Stage 2 must consent to tumor biopsies and must have one of the following types of cancer:
  • Metatastic colorectal cancer
  • Non-small cell lung cancer
  • Melanoma

Exclusion criteria

Cancer-Specific Exclusion Criteria:

  • Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment
  • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
  • Known active or untreated central nervous system (CNS) metastases
  • Leptomeningeal disease
  • Uncontrolled tumor-related pain or uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent (once monthly or more frequently) drainage procedures
  • Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab

General Medical Exclusion Criteria:

  • Pregnant and lactating women
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cell or any component of the atezolizumab formulation
  • History of autoimmune disease
  • Participants with prior allogeneic stem cell or solid organ transplantation
  • Positive test for human immunodeficiency virus (HIV)
  • Participants with active hepatitis B, hepatitis C, or tuberculosis
  • Severe infections within 4 weeks prior to Cycle 1 Day 1
  • Signs or symptoms of infection within 2 weeks prior to Cycle 1 Day 1
  • Received therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
  • Significant cardiovascular disease
  • Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1 Day 1 or anticipation of need for a major surgical procedure during the course of the study
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1

Exclusion criteria

Unique to Cobimetinib:

  • History of prior significant toxicity from another mitogen-activated protein kinase (MEK) pathway inhibitor requiring discontinuation of treatment
  • Allergy or hypersensitivity to components of the cobimetinib formulations
  • History of congenital long QT syndrome or corrected QT interval (QTc) greater than (>) 450 milliseconds at screening
  • Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower, as determined by echocardiogram or Multi Gated Acquisition Scan (MUGA) scan
  • History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
  • History of malabsorption syndrome or other condition that would interfere with enteral absorption

Exclusion criteria

Related to Medications:

  • Prior treatment with clusters of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, systemic immunostimulatory agents, or systemic immunosuppressive medications

Treatment and study plan

Atezolizumab

Drug

Atezolizumab will be administered at a fixed dose as specified via IV infusion.

Other names: MPDL3280

Cobimetinib

Drug

Cobimetinib will be administered orally at an escalating dose during Stage 1 and at RP2D during Stage 2.

Other names: GDC-0973

Primary outcomes

  1. Phase I: Percentage of Participants With Dose-Limiting Toxicities (DLTs)

    Time frame: Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase

  2. Phase I: Maximum Tolerated Dose of Cobimetinib

    Time frame: Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase

  3. Phase I: Recommended Phase II Dose of Cobimetinib when Combined with Atezolizumab

    Time frame: Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase

Secondary outcomes

  1. Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Azetolizumab

    Time frame: Pre-infusion (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, 8 (cycle length=42 days for Cycle 1; 28 days for subsequent cycles) and at treatment completion visit (up to approximately 3.5 years)

  2. Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs)

    Time frame: Baseline up to approximately 3.5 years

  3. Serum Maximum Concentration (Cmax) of Atezolizumab

    Time frame: Pre-infusion (Hour 0) on Day 1 of Cycles 2, 3, 4, 8 (cycle length=28 days) and at treatment completion visit (up to approximately 3.5 years); 30 minutes post-infusion (duration=60 minutes) on Cycle 1 Day 1 (cycle length=42 days)

  4. Serum Minimum Concentration (Cmin) of Atezolizumab

    Time frame: Pre-infusion (Hour 0) on Day 1 of Cycles 2, 3, 4, 8 (cycle length=28 days) and at treatment completion visit (up to approximately 3.5 years)

  5. Plasma Cmax of Cobimetinib

    Time frame: Pre-dose (Hour 0) and Hours 2, 4, 6 post-dose on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days)

  6. Plasma Cmin of Cobimetinib

    Time frame: Pre-dose (Hour 0) on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days)

  7. Area Under the Concentration-Time Curve (AUC) of Cobimetinib

    Time frame: Pre-dose (Hour 0) and Hours 2, 4, 6 post-dose on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days)

  8. Percentage of Participants With Best Overall Response, as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

    Time frame: Baseline up to 3.5 years (detailed time frame is provided in the description)

    Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 of Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until progressive disease [PD] or death due to any cause, whichever occurs first [up to approximately 3.5 years])

  9. Percentage of Participants With Objective Response (OR; Confirmed Complete Response or Partial Response) as Assessed by Investigator Using RECIST v1.1

    Time frame: Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years])

  10. Duration of OR, as Determined by Investigator Using RECIST v1.1

    Time frame: Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years])

  11. Progression-Free Survival (PFS), as Determined by Investigator Using RECIST v1.1

    Time frame: Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years])

  12. Overall Survival (OS)

    Time frame: Baseline up to death due to any cause (up to approximately 3.5 years)

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

A Phase Ib Study of the Safety and Pharmacology of Atezolizumab Administered With Cobimetinib in Patients With Locally Advanced or Metastatic Solid Tumors

Important dates

Study start
2013
Primary completion
2019
Study completion
2019
First posted
Nov 20, 2013
Registry last updated
Dec 17, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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