Clinical Trials /

A Study to Assess the Safety and Tolerability of Atezolizumab in Combination With Other Immune-Modulating Therapies in Participants With Locally Advanced or Metastatic Solid Tumors

NCT02174172

Description:

This global, multicenter, open-label study will evaluate the safety and tolerability of atezolizumab in combination with other immune-modulating therapies in the treatment of selected advanced or metastatic malignancies. The atezolizumab plus ipilimumab arm (Arm A) will focus primarily on participants with advanced or metastatic non-small cell lung cancer (NSCLC). The atezolizumab plus interferon alfa-2b arm (Arm B), plus pegylated interferon alfa-2a (PEG-interferon alfa-2a, Arm C), and atezolizumab plus PEG-interferon Alfa-2a plus bevacizumab (Arm D) will enroll participants with advanced or metastatic renal cell carcinoma (RCC), metastatic NSCLC and melanoma. The atezolizumab plus obinutuzumab) (Arm E) will enroll participants with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Atezolizumab will be administered as intravenous (IV) infusion every 3 weeks (q3w).

Related Conditions:
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Assess the Safety and Tolerability of Atezolizumab in Combination With Other Immune-Modulating Therapies in Participants With Locally Advanced or Metastatic Solid Tumors
  • Official Title: A Phase Ib Study of The Safety And Pharmacology of Atezolizumab (Anti-Pd-L1 Antibody) Administered With Ipilimumab, Interferon-Alpha, or Other Immune-Modulating Therapies in Patients With Locally Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: GO29322
  • SECONDARY ID: 2014-000812-33
  • NCT ID: NCT02174172

Conditions

  • Solid Cancers

Interventions

DrugSynonymsArms
AtezolizumabTecentriq, RO5541267, MPDL3280AArm A: Atezolizumab with Ipilimumab
BevacizumabAvastin®Arm D:Atezolizumab with PEG-interferon alfa-2a and Bevacizumab
Interferon alfa-2bArm B: Atezolizumab with Interferon alfa-2b
IpilimumabArm A: Atezolizumab with Ipilimumab
ObinutuzumabArm E: Atezolizumab with Obinutuzumab
PEG-interferon alfa-2aPegasys®Arm C: Atezolizumab with PEG- interferon alfa-2a

Purpose

This global, multicenter, open-label study will evaluate the safety and tolerability of atezolizumab in combination with other immune-modulating therapies in the treatment of selected advanced or metastatic malignancies. The atezolizumab plus ipilimumab arm (Arm A) will focus primarily on participants with advanced or metastatic non-small cell lung cancer (NSCLC). The atezolizumab plus interferon alfa-2b arm (Arm B), plus pegylated interferon alfa-2a (PEG-interferon alfa-2a, Arm C), and atezolizumab plus PEG-interferon Alfa-2a plus bevacizumab (Arm D) will enroll participants with advanced or metastatic renal cell carcinoma (RCC), metastatic NSCLC and melanoma. The atezolizumab plus obinutuzumab) (Arm E) will enroll participants with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Atezolizumab will be administered as intravenous (IV) infusion every 3 weeks (q3w).

Trial Arms

NameTypeDescriptionInterventions
Arm A: Atezolizumab with IpilimumabExperimentalParticipants will receive atezolizumab along with ipilimumab.
  • Atezolizumab
  • Ipilimumab
Arm B: Atezolizumab with Interferon alfa-2bExperimentalParticipants will receive atezolizumab along with Interferon alfa-2b.
  • Atezolizumab
  • Interferon alfa-2b
Arm C: Atezolizumab with PEG- interferon alfa-2aExperimentalParticipants will receive atezolizumab along with PEG- interferon alfa-2a.
  • Atezolizumab
  • PEG-interferon alfa-2a
Arm D:Atezolizumab with PEG-interferon alfa-2a and BevacizumabExperimentalParticipants will receive atezolizumab along with PEG- interferon alfa-2a and bevacizumab.
  • Atezolizumab
  • Bevacizumab
  • PEG-interferon alfa-2a
Arm E: Atezolizumab with ObinutuzumabExperimentalParticipants will receive atezolizumab along with obinutuzumab or atezolizumab alone.
  • Atezolizumab
  • Obinutuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically documented locally advanced or metastatic solid tumors
             meeting the following study drug-specific criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

          -  Life expectancy greater than or equal to (>/=) 12 weeks

          -  Measurable disease, as defined by RECIST v1.1

          -  Adequate hematologic and end organ function as confirmed by laboratory results within
             14 days prior to the first study treatment

        Inclusion criteria specific to Arm A: Atezolizumab+ Ipilimumab

          -  Escalation stage: NSCLC participants

          -  Mandatory biopsy cohort: NSCLC or melanoma atezolizumab

          -  Prior atezolizumab-treated cohort: participants with NSCLC or melanoma previously
             treated with atezolizumab

        Inclusion criteria specific to Arm B: Atezolizumab+ Interferon alfa-2b

          -  Escalation stage: RCC or melanoma participants

          -  Expansion stage: RCC or melanoma participants

          -  Mandatory biopsy cohort: RCC or melanoma participants

          -  Prior immunotherapy-treated cohort: participants with RCC, NSCLC, or melanoma
             previously treated with programmed death-ligand 1 (PD-L1)/ Programmed death 1 (PD-1)

        Inclusion Criteria Specific to Arm C (Atezolizumab plus PEG-Interferon Alafa-2a):

        - Cohort 1: participants with RCC

        Inclusion Criteria Specific to Arm D (Atezolizumab plus PEG-Interferon Alfa-2a
        +Bevacizumab)

          -  Cohort 1: participants with metastatic RCC with no prior line of systemic therapy for
             metastatic disease

          -  Cohorts 2-3: disease progression during or after at least one previous systemic,
             anti-cancer treatment for locally advanced or metastatic non-squamous solid tumors;
             participants with sensitizing epidermal growth factor receptor (EGFR) mutations or
             anaplastic lymphoma kinase (ALK) rearrangements must have failed or are intolerant to
             prior treatment with EGFR or ALK inhibitors; participants with melanoma with
             actionable BRAF mutations (e.g., V600) must have failed or are intolerant to prior
             treatment with BRAF inhibitors

        Inclusion Criteria Specific to Arm E (Atezolizumab +Obinutuzumab)

        - R/M HNSCC participants with at least one prior line of systemic therapy

        Inclusion Criteria Specific to prior Anti-PD-L1/PD-1 Treated Cohorts:

          -  No permanent discontinuation of atezolizumab or other immunotherapies due to a
             treatment-related adverse event

          -  Recovery from all immunotherapy-related adverse events to Grade less than or equal to
             (≤) 1 or baseline at the time of consent

        Exclusion Criteria:

        General Medical Exclusions:

          -  Pregnant and lactating women

          -  Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3
             weeks prior to initiation of study treatment, with the following exception: (1)
             hormone-replacement therapy or oral contraceptives; (2) tyrosine kinase inhibitors
             (TKIs) that have been discontinued greater than (>) 7 days prior to Cycle 1, Day 1,
             baseline scans must be obtained after discontinuation of prior TKIs

          -  Investigational therapy within 28 days prior to initiation of study treatment

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

          -  Known hypersensitivity or allergy to Chinese hamster ovary cell products or any
             component of the atezolizumab formulation

          -  History of or active autoimmune disease

          -  History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
             pneumonitis, organizing pneumonia, risk of pulmonary toxicity, or evidence of active
             pneumonitis on screening chest computed tomography (CT) scan

          -  Prior allogeneic bone marrow transplantation or prior solid organ transplantation

          -  History of human immunodeficiency virus (HIV)

          -  Participants with active hepatitis B

          -  Participants with active hepatitis C

          -  Participants with active tuberculosis

          -  Participants with a history of confirmed progressive multifocal leukoencephalopathy

          -  Any serious medical condition, physical examination finding, or abnormality in
             clinical laboratory tests that, in the investigator's judgment, precludes the
             participant's safe participation in and completion of the study

        Cancer-Specific Exclusions:

          -  Active or untreated central nervous system (CNS) metastases, as determined by CT or
             magnetic resonance imaging (MRI) evaluation during screening and prior radiographic
             assessments

          -  Spinal cord compression not definitively treated with surgery and/or radiation or
             previously diagnosed and treated spinal cord compression without evidence that disease
             has been clinically stable for >/= 2 weeks prior to screening

          -  Leptomeningeal disease

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (once monthly or more frequently); participants with indwelling
             catheters are allowed.

          -  Uncontrolled tumor-related pain

          -  Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of
             bisphosphonate therapy or denosumab

          -  History of other malignancy within 2 years prior to screening, except for
             appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma,
             Stage I uterine cancer, localized prostate cancer treated with curative intent, ductal
             carcinoma in situ treated surgically with curative intent, or other cancers with a
             similar outcome

        Exclusion Criteria Related to Medications:

          -  Prior treatment with cluster of differentiation 137 (CD137) agonists or immune
             checkpoint blockade therapies (Note: Participants enrolled in the prior
             anti-PD-L1/PD-1 treated cohorts with melanoma may have received prior anti-cytotoxic
             T-lymphocyte-associated protein 4 treatment or other immunotherapies)

          -  Treatment with systemic immunostimulatory agents within four weeks or five half-lives
             of the drug, whichever is shorter, prior to Cycle 1, Day 1

          -  Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1,
             Day 1 (the use of inhaled corticosteroids and mineralocorticoids is allowed)

        Exclusion Criteria Specific to Interferon Alpha Therapy (Arms B-D):

          -  History of depression, suicidal ideation or behavior, bipolar disorder, or psychosis

          -  Hypersensitivity to interferon alpha or any component of the product

        Exclusion Criteria Specific to Bevacizumab (Arm D)

          -  Inadequately controlled hypertension

          -  Prior history of hypertensive crisis or hypertensive encephalopathy

          -  Significant vascular disease within 6 months prior to Day 1

          -  History of hemoptysis

          -  Evidence of bleeding diathesis or significant coagulopathy (in the absence of
             therapeutic anticoagulation)

          -  History of tracheoesophageal fistula, gastrointestinal perforation, or intra-abdominal
             abscess within 6 months prior to Day 1

          -  Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine
             parenteral hydration, parenteral nutrition, or tube feeding

          -  Evidence of abdominal free air that is not explained by paracentesis or recent
             surgical procedure

          -  Proteinuria, as demonstrated by urine dipstick or > 1.0 gram of protein in a 24-hour
             urine collection

          -  Metastatic disease that involves major airways or blood vessels, or centrally located
             mediastinal tumor masses of large volume

        Exclusion Criteria Specific Obinutuzumab (Arm E)

          -  Hypersensitivity to obinutuzumab

          -  Prior treatment with obinutuzumab
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended Phase II Dose (RP2D) of Atezolizumab When Given in Combination With Ipilimumab and Interferon Alfa-2b
Time Frame:From the first atezolizumab treatment up to 21 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants with Best Overall Response, as Assessed Using Conventional Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame:Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr])
Safety Issue:
Description:
Measure:Percentage of Participants with Best Overall Response, as Assessed Using Immune Modified RECIST Criteria
Time Frame:Screening to progression or death, up to 4.5 years (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr])
Safety Issue:
Description:
Measure:Duration of Objective Response
Time Frame:Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr])
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:Baseline to death (up to 4.5 yr)
Safety Issue:
Description:
Measure:Progression-Free Survival
Time Frame:Screening to progression or death, up to 4.5 yr (assessed at baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr])
Safety Issue:
Description:
Measure:Percentage of Participants with Objective Response, as Assessed Using Conventional RECIST v1.1
Time Frame:Screening to progression or death, up to 4.5 yr (assessed at Baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr])
Safety Issue:
Description:
Measure:Percentage of Participants with Objective Response, as Assessed Using Immune Modified RECIST Criteria
Time Frame:Screening to progression or death, up to 4.5 yr (assessed at Baseline, every 6 weeks for 48 weeks and every 12 weeks thereafter up to treatment completion/early termination [up to 4.5 yr])
Safety Issue:
Description:
Measure:Serum Atezolizumab Concentration
Time Frame:Baseline up to 4.5 years (detailed timeframe is given in outcome description)
Safety Issue:
Description:Arm A: Predose (0 hour [hr]), 30 minutes (min) post end of infusion on Day 1;Day 8,Day 15 of Cycle (cy) 1;Predose (0 hr) on Day 1 of cy 2,3,4,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 years [yr]). Arm B: Predose (0 hr) on Day 1,30 min post end of infusion on Day 8,Day 15,Day 22 of cy 1;Predose (0 hr) on Day 1 of cy 2,3,4,5,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Arms C,D: Predose (0 hr), 30 min post end of infusion on Day 1 cy 1,3;Predose (0 hr) on Day 1 of cy 2,4,8, every 8 cy thereafter up to end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Arm E: Predose (0 hr), 30 min post end of infusion on Day 1 cy 1,5;Predose (0 hr) on Day 1 of cy 2,3,4,8, every 8 cy thereafter up to treatment end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Cycle length = 21 days (28 days for Arm B, cycle 1)
Measure:Serum Ipilimumab Concentration
Time Frame:Baseline up to 4.5 years (detailed timeframe is given in outcome description)
Safety Issue:
Description:Predose (0 hr), 30 min post end of infusion on Day 1 of Cy 1,3;Predose on Day 1 of Cy 4; end of treatment/ withdrawal;≥ 90 days post last dose (up to 4.5 yr) Cycle length = 21 days
Measure:Serum Bevacizumab Concentration
Time Frame:Baseline up to 4.5 years (detailed timeframe is given in outcome description)
Safety Issue:
Description:Predose (0 hr), 30 min post end of infusion on Day 1 of Cy 1,3; end of treatment/ withdrawal;≥ 90 days post last dose (up to 4.5 yr) Cycle length = 21 days
Measure:Serum Obinutuzumab Concentration
Time Frame:Baseline up to 4.5 years (detailed outcome given in outcome description)
Safety Issue:
Description:Predose (0 hr), 30 min post end of infusion on Days -13, -12 and on Day 1 Cy 5; end of treatment/withdrawal;≥90 days post last dose (up to 4.5 yr) Cycle length = 21 days
Measure:Anti-Drug Antibody to Atezolizumab
Time Frame:Baseline up to 4.5 years (detailed timeframe is given in outcome description)
Safety Issue:
Description:Detailed timeframe: Arm A: Predose (0 hr) on Day 1 of Cy 1,2,3,4,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Arm B: Predose (0 hr) on Day 1 of Cy 1,2,3,4,5,8; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Arms C, D, E: Predose (0 hr) on Day 1 of cy 1,2,3,4,8, thereafter every 8 Cy up to end of treatment/ withdrawal;≥ 90 days post last dose (up to 4.5 yr). Cycle length = 21 days (28 days for Arm B, cycle 1)
Measure:Anti-Drug Antibody to Ipilimumab
Time Frame:Baseline up to 4.5 years (detailed timeframe is given in outcome description)
Safety Issue:
Description:Pre-dose (0 hr) on Day 1 of Cy 1, 4, end of treatment/ withdrawal;≥ 90 days post last dose (up to 4.5 yr) Cycle length = 21 days
Measure:Anti-Drug Antibody to Bevacizumab
Time Frame:Baseline up to 4.5 years (detailed timeframe is given in outcome description)
Safety Issue:
Description:Predose (0 hr) on Day 1 of Cy 1, 3; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr). Cycle length = 21 days
Measure:Anti-Drug Antibody to Obinutuzumab
Time Frame:Baseline up to 4.5 years (detailed timeframe is given in outcome description)
Safety Issue:
Description:Predose (0 hr) on Days -13 and -12; end of treatment/withdrawal;≥ 90 days post last dose (up to 4.5 yr) Cycle length = 21 days

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Hoffmann-La Roche

Last Updated

May 12, 2020