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Atezolizumab and Tiragolumab in Patients With NSCLC or Advanced Solid Tumors Having Had Prior Treatment With a PD-1 Inhibitor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03977467
Recruitment Status : Recruiting
First Posted : June 6, 2019
Last Update Posted : March 4, 2022
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief Summary:
This is a Phase II, two part trial (A and B), open label study of Atezolizumab and tiragolumab, or atezolizumab combined with SOC chemotherapy in patients with NSCLC or advanced solid tumors that have had prior treatment with a PD-1 inhibitor (e.g. nivolumab or pembrolizumab).

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Solid Tumor Drug: Atezolizumab Other: Chemotherapy (Arm A Only) Drug: Tiragolumab Phase 2

Detailed Description:
Arm A consists of approximately 20 patients with advanced NSCLC who received first-line anti-PD-1 therapy, who have subsequent disease progression. Arm B consists of approximately 15 patients per disease type (renal cell carcinoma [RCC] progressing on prior anti-PD-1 therapy, triple negative breast cancer [TNBC] progressing on prior anti-PD-1 therapy, NSCLC progressing on check-point inhibitors plus chemotherapy in the first-line setting; and microsatellite instability-high [MSI-high] solid tumors [as determined by local testing for MSI/mismatch repair (MMR)] progressing on prior anti-PD-1 therapy).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Atezolizumab and Tiragolumab in Patients With NSCLC or Advanced Solid Tumors Who Have Had Prior Treatment With a PD-1 Inhibitor
Actual Study Start Date : August 30, 2019
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A (Chemo + Atezolizumab)
In Arm A, patients with NSCLC will receive chemotherapy plus atezolizumab at a flat dose of 1200 mg intravenously (IV) every 3 weeks. Standard of care chemotherapy is defined as a platinum-doublet therapy (or triplet if bevacizumab is used) of the Investigator's choice.
Drug: Atezolizumab
atezolizumab at a flat dose of 1200 mg IV every 3 weeks
Other Name: TECENTRIQ

Other: Chemotherapy (Arm A Only)
Standard of care chemotherapy is defined as a platinum-doublet therapy (or triplet if bevacizumab is used) of the Investigator's choice.

Experimental: Arm B (Atezolizumab and Tiragolumab)
In Arm B, patients with advanced solid tumors will be treated with atezolizumab at a flat dose of 1200 mg IV every 3 weeks in combination with tiragolumab at a flat dose of 600 mg IV every 3 weeks until progression or unacceptable toxicity.
Drug: Atezolizumab
atezolizumab at a flat dose of 1200 mg IV every 3 weeks
Other Name: TECENTRIQ

Drug: Tiragolumab
tiragolumab at a flat dose of 600 mg IV every 3 weeks




Primary Outcome Measures :
  1. Efficacy (overall response rate [ORR]) [ Time Frame: Up to 6 months ]

    Assess the efficacy (overall response rate [ORR]) of combining atezolizumab with standard of care chemotherapy in non-small cell lung cancer (NSCLC) and atezolizumab combined with tiragolumab in patients with advanced solid tumors who have progressed after prior exposure to anti-PD- treatment.

    Overall Response Rate (ORR) is defined as the proportion of patients with confirmed complete response (CR) or partial response (PR (i.e. 2 CRs or PRs at least 4 weeks apart) according to the immune-modified RECIST criteria.



Secondary Outcome Measures :
  1. The incidence of treatment-emergent adverse events (AEs) as a measure of safety [ Time Frame: Up to 6 months ]
    Determine the safety of atezolizmab combined with SOC chemotherapy, and atezolizumab combined with tiragolumab, in patients with NSCLC and other advanced solid tumors.

  2. The incidence of serious adverse events (AEs) as a measure of safety [ Time Frame: Up to 6 Months ]
    Determine the safety of atezolizmab in patients with NSCLC and other advanced solid tumors

  3. Determine the disease control rate (DCR) [ Time Frame: Up to 6 months ]

    Estimate the 6-month disease control rate (DCR) in patients with NSCLC and other advanced solid tumors.

    Disease Control Rate (DCR) is defined as the proportion of patients with CR, PR, or SD for at least 6 months according to the immune-modified RECIST criteria


  4. Determine the progression-free survival (PFS) [ Time Frame: Up to 6 Months ]

    Estimate the progression-free survival (PFS) in patients with NSCLC and other advanced solid tumors.

    Progression Free Survival (PFS), defined as the time from the first day of study drug administration (Day 1) to PD as defined by the immune-modified RECIST criteria, or death on study. Patients who are alive and free from disease progression will be censored at the date of last tumor assessment.


  5. Determine the overall survival (OS) [ Time Frame: Up to 6 Months ]

    Estimate the overall survival (OS) in patients with NSCLC and other advanced solid tumors.

    Overall Survival (OS), defined as the time from the first day of study drug administration (Day 1) to death on study. Patients who are alive will be censored at the date of last known date alive




Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 - 1 (Appendix A).
  2. Adequate hematologic function defined as:

    • Absolute neutrophil count (ANC) ≥1500/μL with one exception: Patients with benign ethnic neutropenia (BEN): ANC >1300/ μL
    • Lymphocyte count ≥0.5 × 109/L (500/µL)
    • Hemoglobin (Hgb) ≥9 g/dL (patients may be transfused to meet this criterion)
    • Platelets ≥100,000/µL (without transfusion, within 7 days of enrollment)
  3. Adequate liver function defined as:

    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the upper limit of normal (ULN)
    • Total bilirubin ≤1.5 x ULN (patients with known Gilbert syndrome: serum bilirubin level ≤ 3 x ULN)
  4. Adequate renal function defined as serum creatinine ≤1.5 mg/dL (133 μmol/L) or calculated creatinine clearance ≥30 mL/min as calculated by the Cockcroft Gault formula
  5. For patients not receiving therapeutic anticoagulation: INR or aPTT ≤1.5 × ULN. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen.
  6. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of <1% per year, during their participation in the study and for 5 months following last dose of study drug(s).

    • A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.
    • Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not adequate methods of contraception.
  7. Male patients with a female partner of childbearing potential or a pregnant female partner must remain abstinent (refrain from heterosexual intercourse) or use a condom must also refrain from donating sperm during the treatment period and for 5 months after the last dose of study drug. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal or post-ovulation methods) and withdrawal are not adequate methods of contraception. Men must also refrain from donating sperm during their participation in the study
  8. Age ≥18 years.
  9. Willingness to provide a new pre-treatment tumor biopsy.
  10. Willingness and ability to comply with study and follow-up procedures.
  11. Ability to understand the nature of this study and give written informed consent.
  12. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
  13. Asymptomatic patients with treated or untreated CNS lesions are eligible, provided that all of the following criteria are met:

    • Measurable disease, per RECIST v1.1, must be present outside the CNS.
    • The patient has no history of intracranial hemorrhage or spinal cord hemorrhage.
    • The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment.
    • The patient has no ongoing requirement for corticosteroids as therapy for CNS disease.
    • If the patient is receiving anti-convulsant therapy, the dose is considered stable.

    Inclusion Arm A - Non-small cell lung cancer

  14. Advanced squamous or non-squamous NSCLC
  15. Disease progression after prior documented clinical benefit, defined as having at least one scan demonstrating at least stable disease (SD), on first-line treatment with anti-PD-1 monotherapy
  16. Previously received and tolerated nivolumab or pembrolizumab monotherapy or immunotherapy doublets such as nivolumab/ipilimumab therapy (and was the last therapy prior to enrollment)

    Inclusion Arm B - Advanced solid tumors

  17. Patients with advanced RCC, progressing on anti-PD-1 therapy, Advanced TNBC, progressing on anti-PD-1 therapy, and patients with NSCLC progressing on check-point inhibitors plus chemotherapy in the first-line setting. MSI-high solid tumors as defined by local testing for MSI/MMR will also be included.
  18. Evidence of disease progression after receiving clinical benefit, defined as having at least one scan demonstrating at least SD, during most recent PD-1 inhibitor treatment.

Exclusion Criteria:

  1. History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
  2. History of any Grade 3 or 4 toxicities to a prior CPI treatment
  3. Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulations
  4. Most recent immunotherapy ≤21 days and ≥ Grade 1 immunotherapy-related side effects, with the exception of alopecia.
  5. Use of systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) ≤28 days or 5 half-lives (whichever is shorter) prior to the first dose of study drugs.
  6. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF- agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study, with the following exceptions:

    • Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.
    • Patients who received mineralocorticoids (e.g., fludrocortisone), inhaled corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
  7. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during the course of the study or within 5 months after the last dose of atezolizumab or tiragolumab
  8. Uncontrolled tumor-related pain
  9. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment.

    • Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.

  10. Requirement for use of denosumab during the study. Patients who are receiving denosumab for any reason (including hypercalcemia) must be willing and eligible to receive a bisphosphonate instead while in the study.
  11. Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy.
  12. Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
  13. Symptomatic, untreated, or actively progressing CNS metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 2 weeks prior to study entry and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy. Anticonvulsant therapy at a stable dose is permitted.
  14. Prior allogeneic stem cell or solid organ transplantation
  15. Pregnant or lactating females
  16. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan

    • History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

  17. Uncontrolled diabetes mellitus. Patients with Type II diabetes are eligible if they require only oral hypoglycemic agents and fasting blood glucose level is ≤120. Patients with Type I diabetes are eligible if HbAlc is ≤7%.
  18. Significant cardiovascular disease, such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina (see Appendix B)
  19. History of leptomeningeal disease
  20. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)

    • Patients with indwelling catheters (e.g., PleurX) are allowed.

  21. Uncontrolled or symptomatic hypercalcemia (-1.5 mmol/L ionized calcium or calcium -12 mg/dL or corrected serum calcium -ULN).
  22. Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis (see Appendix F for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions:

    • Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
    • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
    • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:

      • Rash must cover ˂ 10% of body surface area
      • Disease is well controlled at baseline and requires only low-potency topical corticosteroids
      • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months
  23. Serious active infection within 4 weeks of treatment (including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia), or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
  24. Known active Hepatitis B (HBV) or C (HCV) infection; HBV and HCV testing is not required as part of this study.
  25. Known history of human immunodeficiency virus (HIV1 or 2); HIV testing is not required as part of this study
  26. Positive Epstein-Barr virus (EBV) viral capsid antigen (VCA) immunoglobulin M (IgM) test at screening. An EBV PCR test should be performed as clinically indicated to screen for acute infection or suspected chronic active infection. Patients with a positive EBV PCR test are excluded.
  27. Active tuberculosis
  28. In the opinion of the Investigator, any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results or may render the patient at high risk from treatment complications
  29. Has a second primary malignancy that in the judgment of the investigator and sponsor may affect the interpretation of results.
  30. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
  31. Prior treatment with anti-T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT) therapeutic antibodies.
  32. Major surgical procedure within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study.

    Exclusion Arm A Non-small cell lung cancer

  33. Intervening treatment with a regimen other than CPI prior to enrollment in this study.
  34. NSCLC with an activating EGFR mutation or ALK fusion oncogene

    • For patients with non-squamous NSCLC histology: unknown EGFR and/or ALK status requires testing
    • For patients with squamous NSCLC histology: unknown EGFR and/or ALK status does not require test results at screening. However, exclusion is applied if the status of either driver oncogene is known to be positive.
    • For patients with NSCLC of mixed histology: unknown EGFR and/or ALK status requires testing at screening Note: ALK and/or EGFR status may be assessed locally or submitted for central laboratory testing. If ALK and/or EGFR status is assessed locally, testing must be performed on tissue or cytology using a validated FDA-approved test. If samples are submitted for central laboratory testing, five additional slides are required.
  35. Known c-ros oncogene 1 (ROS1) rearrangement: ROS1 testing at screening is not required for study inclusion; however, patients with known ROS1 rearrangements are excluded.

    Exclusion Arm B - Advanced Solid Tumors

  36. Prior treatment with anti-TIGIT therapeutic antibodies.
  37. Known hypersensitivity to any component of the tiragolumab formulation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03977467


Contacts
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Contact: Sarah Cannon Development Innovations 844-710-6157 CANN.InnovationsMedical@sarahcannon.com

Locations
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United States, Florida
Florida Cancer Specialists - South Recruiting
Fort Myers, Florida, United States, 33991
Principal Investigator: James A Reeves Jr., MD         
Florida Cancer Specialists - North Recruiting
Saint Petersburg, Florida, United States, 33705
Principal Investigator: Gail L Shaw Wright, MD         
Florida Cancer Specialists - Panhandle Recruiting
Tallahassee, Florida, United States, 32308
Principal Investigator: Viralkumar K Bhanderi, MD         
Florida Cancer Specialists - East Recruiting
West Palm Beach, Florida, United States, 33401
Principal Investigator: Todd A Gersten, MD         
United States, Missouri
MidAmerica Division, Inc., c/o Research Medical Center (HCA Midwest) Recruiting
Kansas City, Missouri, United States, 64132
Principal Investigator: Peter J Van Veldhuizen, MD         
United States, Tennessee
Tennessee Oncology - Chattanooga Recruiting
Chattanooga, Tennessee, United States, 37404
Principal Investigator: Davey B Daniel, MD         
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
Contact: Melissa Johnson, MD         
Principal Investigator: Melissa Johnson, MD         
Sponsors and Collaborators
SCRI Development Innovations, LLC
Genentech, Inc.
Investigators
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Study Chair: Melissa Johnson, MD SCRI Development Innovations, LLC
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Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT03977467    
Other Study ID Numbers: MULTI 29
First Posted: June 6, 2019    Key Record Dates
Last Update Posted: March 4, 2022
Last Verified: February 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by SCRI Development Innovations, LLC:
atezolizumab
NSCLC
Non-Small Cell Lung Cancer
advanced solid tumors
tiragolumab
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Atezolizumab
Antineoplastic Agents