- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04958811
Tiragolumab With Atezolizumab Plus Bevacizumab in Previously-Treated Advanced Non-squamous NSCLC
A Phase II Open-label Multi-cohort Study Evaluating the Efficacy of Tiragolumab With Atezolizumab Plus Bevacizumab in Previously-Treated Advanced Non-squamous NSCLC
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Jenny Crawford
- Phone Number: 202-687-0893
- Email: crawfojg@georgetown.edu
Study Locations
-
-
District of Columbia
-
Washington, District of Columbia, United States, 20007
- Recruiting
- MedStar Georgetown University Hospital
-
Contact:
- Jenny Crawford
- Phone Number: 202-687-0893
- Email: crawfojg@georgetown.edu
-
-
New Jersey
-
Hackensack, New Jersey, United States, 07601
- Recruiting
- John Theurer Cancer Center at Hackensack University Medical Center
-
Contact:
- Kristina Rioux
- Phone Number: 551-996-2369
- Email: Kristina.Rioux@hmhn.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Signed Informed Consent Form (ICF)
- Age ≥ 18 years at time of signing ICF
- Ability to comply with the study protocol, in the investigator's judgment
- Histologically or cytologically confirmed advanced non-squamous NSCLC that is not amenable to definitive therapy
- Tumor PD-L1 expression (TPS ≥ 1%) (cohort A only)
- EGFR, ALK, ROS1 wild-type (cohort A only)
- Confirmed activating alteration in EGFR (cohort B only)
- Disease progression during or following treatment with anti-PD(L)1 containing therapy (cohort A only)
- Disease progression during or following treatment with appropriate EGFR targeted therapy (cohort B only)
- Measurable disease per RECIST v1.1
- Biopsy post-progression on anti-PD(L)1 (cohort A) or EGFR targeted therapy (cohort B) confirming non-squamous histology prior to study treatment initiation
- ECOG Performance Status of 0-2
Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:
- ANC ≥ 1.0 x 10^9/L without granulocyte colony-stimulating factor support
- Lymphocyte count ≥ 0.5 x 10^9/L
- Platelet count ≥ 100 x 10^9/L without transfusion
- Hemoglobin ≥ 80 g/L (8 g/dL) - patients may be transfused to meet this criterion.
- AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN), with the following exceptions: Patients with documented liver metastases: AST and ALT ≤ 5 x ULN; Patients with documented liver or bone metastases: ALP ≤ 5 x ULN
- Serum bilirubin ≤ 1.5 x ULN with the following exception: Patients with known Gilbert disease: serum bilirubin ≤ 3 x ULN
- Creatinine clearance ≥ 30 mL/min (calculated using the Cockcroft-Gault formula)
- For patients not receiving therapeutic anticoagulation: INR and aPTT ≤ 1.5 x ULN
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen defined as clinical stability on unchanged dose of therapeutic anticoagulation for ≥14 days
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
- Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 6 months after the final dose of study treatment. Women must refrain from donating eggs during this same period.
- 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.
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
- With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 6 months after the final dose of bevacizumab and 90 days after the final dose of tiragolumab. Men must refrain from donating sperm during this this same period.
- With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 6 months after the final dose of bevacizumab and 90 days after the final dose of tiragolumab to avoid potential exposure to the embryo.
- 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.
Exclusion Criteria:
- Prior treatment with anti-TIGIT antibody therapy
- Prior treatment with anti-PD(L)1 therapeutic antibodies for advanced NSCLC (cohort B only)
- Untreated or symptomatic CNS metastases
- History of leptomeningeal disease
Active or history of clinically significant autoimmune disease that, in the opinion of the investigator, could compromise the health and safety of the patient if treated with investigational therapy. Notable exceptions include:
- Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone.
- Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen.
- Active or history of adrenal insufficiency on stable steroid regimen.
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible for the study provided all of following conditions are met: 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 oral corticosteroids within the previous 12 months
- 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.
- Known active tuberculosis
- Current treatment with anti-viral therapy for HBV
- Positive EBV viral capsid antigen antibody (IgM) testing 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.
- Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
- History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death as assessed and confirmed by the study PI. Possible examples include: adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
- Severe infection within 3 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection (including COVID-19), bacteremia, or severe pneumonia
- Prior allogeneic stem cell or solid organ transplantation
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the view of the investigator, 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
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment
- Prior immune-related adverse event resulting in permanent discontinuation of immune checkpoint blockade therapy including but not limited to anti-PD-1, anti-PD-L1 and anti-CTLA4 therapeutic antibodies (cohort A only) that, in the view of the investigator, could compromise health and safety of prospective patient if enrolled in the study
- Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg). Anti-hypertensive therapy to achieve these parameters is allowable
- Prior history of hypertensive crisis or hypertensive encephalopathy
- Significant vascular and cardiovascular disease (e.g., New York Heart Association Class II or greater heart failure, unstable arrhythmia, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis - including but not limited to myocardial infarction, transient ischemic attack, stroke or unstable angina) within 6 months prior to study treatment initiation
- History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) or clinically significant hemorrhage within 1 month of study treatment initiation
- Evidence of bleeding diathesis or significant coagulopathy (in absence of therapeutic anticoagulation)
- Current or recent (within 10 days of first dose of study treatment) use of aspirin (>325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, < 7 days prior to the first dose of study treatment
- History of abdominal or tracheoesophageal fistula or GI perforation within 6 months prior to treatment initiation
- Clinical signs or symptoms of GI obstruction
- Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
- Proteinuria, as demonstrated by urine dipstick or > 1.0 g of protein in a 24-hour urine collection. All patients with ≥ 2+ protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection for protein
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 study treatment, 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 after PI confirmation has been obtained.
- Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 6 months after the final dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Tiragolumab plus atezolizumab and bevacizumab
Tiragolumab 600mg IV will be administered together with atezolizumab 1200mg IV and bevacizumab 15mg/kg IV every 3 weeks (q3w) until progressive disease or unacceptable toxicity.
|
600mg IV administered every 3 weeks.
1200mg IV administered every 3 weeks.
15mg/kg IV administered every 3 weeks.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: Up to end of treatment (average 9 months)
|
As defined by investigator-assessed ORR according to RECIST v1.1
|
Up to end of treatment (average 9 months)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival (PFS)
Time Frame: Up to 5 years
|
Up to 5 years
|
|
Overall Survival (OS)
Time Frame: Up to 5 years
|
Up to 5 years
|
|
Duration of Response (DOR)
Time Frame: Up to 5 years
|
Up to 5 years
|
|
Incidence of Treatment-Related Adverse Events
Time Frame: At the end of each cycle of therapy (every ~21 days)
|
Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
|
At the end of each cycle of therapy (every ~21 days)
|
6-month PFS rate
Time Frame: Up to 5 years
|
Up to 5 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Joshua Reuss, MD, Georgetown University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bevacizumab
- Atezolizumab
Other Study ID Numbers
- STUDY00003943
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Non-squamous Non-small-cell Lung Cancer
-
Peking University First HospitalMerck Sharp & Dohme LLCNot yet recruitingAdvanced Non-squamous Non-small-cell Lung Cancer | Metastatic Non-squamous Non Small Cell Lung Cancer | Recurrent Non-Squamous Non-Small Cell Lung CancerChina
-
Western Regional Medical CenterTerminatedNon-squamous Cell Non-Metastatic Non-Small Cell Lung Cancer | Squamous Cell Non-Metastatic Non-Small Cell Lung CancerUnited States
-
AIO-Studien-gGmbHAstraZenecaTerminatedNSCLC | Non-squamous Non-small Cell Lung Cancer Stage II | Non-squamous Non-small Cell Lung Cancer Stage IIIA | Non-squamous Non-small Cell Lung Cancer Stage IIIB | Activating EGFR MutationGermany
-
Bristol-Myers SquibbNo longer availableNon-squamous Non-Small Cell Lung Cancer | Squamous Non-Small Cell Lung CancerBrazil, Canada
-
National Cancer Institute (NCI)Active, not recruitingStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage IV Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Metastatic Lung Non-Squamous Non-Small Cell Carcinoma | Unresectable Lung Non-Small Cell Carcinoma | Unresectable Lung Non-Squamous Non-Small Cell Carcinoma | Metastatic...United States
-
National Cancer Institute (NCI)Active, not recruitingStage IIIA Lung Non-Small Cell Cancer AJCC v7 | Advanced Lung Non-Squamous Non-Small Cell Carcinoma | Metastatic Lung Non-Squamous Non-Small Cell Carcinoma | Stage IIIB Lung Non-Small Cell Cancer AJCC v7 | Stage IV Lung Non-Small Cell Cancer AJCC v7 | Stage III Lung Non-Small Cell Cancer AJCC...United States
-
Hoffmann-La RocheCompletedNon-Squamous Non-Small Cell Lung Cancer, Squamous Non-Small Cell Lung CancerSpain, Italy, Poland, Brazil, Turkey, Serbia, France, Korea, Republic of, Romania, Hungary, Russian Federation, United States, United Kingdom, Germany, Greece, Japan, Thailand, Ukraine, China
-
European Organisation for Research and Treatment...WithdrawnSquamous Non-small Cell Lung Cancer | Non-Squamous Non-small Cell Lung Cancer
-
National Cancer Institute (NCI)RecruitingStage IV Lung Cancer AJCC v8 | Stage IIIB Lung Cancer AJCC v8 | Advanced Lung Non-Squamous Non-Small Cell Carcinoma | Metastatic Lung Non-Squamous Non-Small Cell Carcinoma | Recurrent Lung Non-Squamous Non-Small Cell CarcinomaUnited States
-
Calithera Biosciences, IncTerminatedNon-Small Cell Lung Cancer | Non-squamous Non-small-cell Lung Cancer | Non-Squamous Non-Small Cell Neoplasm of Lung | KEAP1 Gene Mutation | NFE2L2 Gene Mutation | NRF2 MutationUnited States
Clinical Trials on Tiragolumab
-
Yonsei UniversityNot yet recruitingNon-small Cell Lung CancerKorea, Republic of
-
Alain AlgaziGenentech, Inc.RecruitingCarcinoma | Cancer | Head and Neck Cancer | Squamous Cell CarcinomaUnited States
-
Hoffmann-La RocheActive, not recruitingEsophageal Squamous Cell CarcinomaUnited States, France, Spain, Australia, Korea, Republic of, Argentina, Belgium, China, Portugal, Taiwan, Japan, Germany, Poland, Thailand, United Kingdom, Switzerland, Turkey, Russian Federation, Morocco, Greece, Italy, New Zealand, South Africa and more
-
Hoffmann-La RocheActive, not recruiting
-
Hoffmann-La RocheActive, not recruitingEsophageal CancerKorea, Republic of, China, Hong Kong, Thailand, Taiwan
-
Hoffmann-La RocheActive, not recruitingNon-small Cell Lung Cancer (NSCLC)United States, Belgium, Korea, Republic of, Canada, China, Denmark, Spain, Thailand, United Kingdom, Taiwan, Brazil, Germany, Mexico, Italy, Switzerland, Hong Kong, Japan, France, Turkey, New Zealand, Kenya, Poland
-
Hoffmann-La RocheRecruitingUrothelial CancerKorea, Republic of, United States, Brazil, China, France, Germany, Mexico, Poland, Denmark, Turkey, Australia, Greece, Spain, United Kingdom, Italy
-
M.D. Anderson Cancer CenterRecruitingMetastatic MalignancyUnited States
-
Washington University School of MedicineGenentech, Inc.Terminated
-
Hoffmann-La RocheActive, not recruitingSquamous Cell Carcinoma of Head and NeckUnited States, Korea, Republic of, United Kingdom, Czechia, New Zealand, France, Spain, Greece, Thailand, Taiwan, Hungary, Italy, Poland