Tiragolumab and Atezolizumab in Patients With Non-squamous Non-small Cell Lung Cancer (NSCLC) and Untreated Brain Metastases

Patients must have histologically or cytologically confirmed non-squamous NSCLC.

In patients treated with the combination of tiragolumab and atezolizumab, patients must have PDL1 TPS \>50%, as determined by an FDA-approved test.

Patients must have asymptomatic brain metastases with at least one untreated evaluable (per RANO-BM) brain metastasis of 5 mm or more. A growing lesion previously treated with whole brain radiotherapy is acceptable given the lower incidence of radiation necrosis. Lesions previously treated with SRS may not be used as target lesions.

o Patients are not required to have measurable disease outside the CNS per RECIST 1.1.

Prior chemotherapy, immunotherapy or radiation given with curative intent in early stage or locoregionally advanced NSCLC is permitted, if completed more than 12 months prior to initiation of study treatment.

Prior radiation with palliative intent in the metastatic setting to non-CNS lesions is permitted (no wash-out period).

Age ≥18 years.

ECOG performance status ≤ 1.

Life expectancy ≥12 weeks.

Patients must have normal organ and marrow function as defined below:

* Absolute neutrophil count ≥1,500/mcL

* Platelets ≥100,000/mcL

* Total bilirubin ≤ institutional upper limit of normal (ULN)

* AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN

* Creatinine Clearance (CrCl) ≥45 mL/min/1.73 m2

No known history of HIV, with the following exception: patients who are HIV positive are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/µL, and have an undetectable viral load.

Negative hepatitis B surface antigen (HBsAg) test at screening. If positive, an HBV DNA test must also be performed to determine if the patient has an HBV infection, which would render the patient ineligible. Patients receiving treatment with anti-viral therapy for HBV are excluded.

Negative hepatitis C antibody. If positive, an HCV RNA test must also be performed to determine if the patient has an HCV infection, which would render the patient ineligible.

Availability of a representative tumor specimen for exploratory biomarker research.

For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception:

Women must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 90 days after the final dose of tiragolumab, 5 months after the final dose of atezolizumab, and 6 months after the final dose of paclitaxel, pemetrexed, gemcitabine, carboplatin, or cisplatin.

* 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 (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a woman with a tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.

* 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 postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.

Women who would like to become pregnant after study treatment discontinuation should seek advice on oocyte cryopreservation prior to initiation of study treatment because of the possibility of irreversible infertility due to treatment with cisplatin and carboplatin.

For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:

* With a female partner of childbearing potential, 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, for 90 days after the final dose of tiragolumab, and for 6 months after the final dose of paclitaxel, pemetrexed, gemcitabine, carboplatin or cisplatin. Men must refrain from donating sperm during this same period.

* With a pregnant female partner, men must remain abstinent or use a condom during the treatment period for 90 days after the final dose of tiragolumab, and for 6 months after the final dose of paclitaxel, pemetrexed, gemcitabine, carboplatin, or cisplatin to avoid exposing 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 postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.

Men who would like to father a child after study treatment initiation should be advised regarding the conservation of sperm prior to treatment because of the possibility of irreversible infertility resulting from chemotherapies used in this study.

Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.

Ability to understand and the willingness to sign a written informed consent document.

What this study is about