| Eligibility |
Step One (Signatera Assay Development) Inclusion Criteria:
- Surgically resected and histologically/pathologically confirmed stage II cutaneous
melanoma. No more than 16 weeks may elapse between final surgical resection and
randomization. Treatment should start only after complete wound healing from the
surgery.
- Participants must not have been previously treated for melanoma beyond complete
surgical resection.
- At least 18 years of age.
- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).
Step One (Signatera Assay Development) Exclusion Criteria:
- A history of other malignancy with the exception of malignancies for which all
treatment was completed at least 2 years before registration and the patient has no
evidence of disease or malignancies in situ (such as DCIS), basal cell carcinoma, or
localized cutaneous squamous cell carcinomas.
- Currently receiving any other investigational agents.
- Prior history of pneumonitis
- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to atezolizumab and tiragolumab or other agents used in the
study.
- 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.
- 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 syndrome, Guillain-Barré syndrome,
or multiple sclerosis, with the exceptions listed below:
- 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
- Active tuberculosis.
- Prior allogeneic stem cell or solid organ transplantation
- Positive hepatitis B surface antigen (HBsAb) at screening.
- Positive hepatitis C virus (HCV) antibody test at screening (unless followed by a
negative HCV RNA test).
- Current treatment with anti-viral therapy for HBV
- Positive Epstein-Barr virus (EBV) viral capsid antigen 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.
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
anti-CTLA-4, anti-PD-1, anti-TIGIT, and anti-PD-L1 therapeutic antibodies.
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
or fusion proteins
- Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or
they have a history of AIDS-defining opportunistic infection within the 12 months
prior to registration. Concurrent treatment with effective ART according to DHHS
treatment guidelines is recommended.
Step Two (Randomization and Treatment) Inclusion Criteria:
- Positive ctDNA test.
- Normal bone marrow and organ function as defined below:
- Absolute neutrophil count = 1,500/mcL
- Lymphocyte count = 500/mcL
- Platelets = 100,000/mcL
- Hemoglobin = 9.0 g/dL (patients may be transfused to meet this criterion)
- Total bilirubin = 1.5 x IULN or direct bilirubin = IULN for participants with
total bilirubin levels > 1.5 x IULN; patients with known Gilbert disease must
have total bilirubin = 3 x IULN
- AST(SGOT)/ALT(SGPT) = 2.5 x IULN
- Alkaline phosphatase = 2.5 x IULN
- Creatinine clearance = 45 mL/min by Cockcroft-Gault
- Serum albumin = 2.5 g/dL
- INR or PT = 1.5 x IULN unless participant is receiving anticoagulant therapy as
long as PT or aPTT is within therapeutic range of intended use of anticoagulants
- aPTT = 1.5 x IULN unless participant is receiving anticoagulant therapy as long
as PT or aPTT is within therapeutic range of intended use of anticoagulants
- ECOG performance status = 1
- The effects of atezolizumab and tiragolumab on the developing human fetus are unknown.
For this reason, women of childbearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control, abstinence) prior to study
entry and for the duration of study participation, for 90 days after the final dose of
tiragolumab, and for 5 months after the final dose of atezolizumab. Should a woman
become pregnant or suspect she is pregnant while participating in this study, she must
inform her treating physician immediately. Men treated or enrolled on this protocol
must also agree to use adequate contraception prior to the study, for the duration of
the study, and 90 days after completion of the study
Step Two (Randomization and Treatment) Exclusion Criteria:
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of study entry.
- 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, within
90 days after the final dose of tiragolumab, or within 5 months after the final dose
of atezolizumab
- Treatment with systemic immunostimulatory agents (including, but not limited to,
interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is
longer) prior to initiation of study treatment.
- Treatment with systemic immunosuppressive medication (including, but not limited to,
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-tumor necrosis factor-a [TNF-a] 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
- 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.
- Major surgical procedure within 4 weeks prior to initiation of study treatment, or
anticipation of need for a major surgical procedure during the study.
- Severe infection within 4 weeks prior to initiation of study treatment, including, but
not limited to, hospitalization for complications of infection, bacteremia, or severe
pneumonia, or any active infection that, in the opinion of the investigator, could
impact patient safety
- 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.
- Treatment with systemic immunostimulatory agents (including, but not limited to,
interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is
longer) prior to initiation of study treatment.
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