Tiragolumab With Atezolizumab Plus Bevacizumab in Previously-Treated Advanced Non-squamous NSCLC

  • STATUS
    Recruiting
  • End date
    Jul 14, 2024
  • participants needed
    42
  • sponsor
    Georgetown University
Updated on 14 May 2022

Summary

To evaluate the efficacy of tiragolumab with atezolizumab and bevacizumab in previously-treated advanced non-squamous NSCLC.

Details
Condition Non-squamous Non-small-cell Lung Cancer
Treatment bevacizumab, Atezolizumab, Tiragolumab
Clinical Study IdentifierNCT04958811
SponsorGeorgetown University
Last Modified on14 May 2022

Eligibility

Yes No Not Sure

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
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
defined as clinical stability on unchanged dose of therapeutic anticoagulation
for ≥14 days
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
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
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
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
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures, and agreement to refrain from donating sperm, as
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
defined
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
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
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
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
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence
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
of active pneumonitis on screening chest computed tomography (CT) scan
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
History of radiation pneumonitis in the radiation field (fibrosis) is
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
permitted
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
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
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
History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) or clinically significant hemorrhage within 1 month of study treatment initiation
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
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
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
days prior to initiation of study treatment
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note