Stage II Melanoma
Conditions
Brief summary
This study's hypothesis is that patients with stage II melanoma who test positive for circulating tumor DNA are at a higher risk for recurrence and therefore adjuvant treatment is justified. In this study, the blood of consenting and eligible patients will be tested for ctDNA and those patients who test positive will be randomized on a 1:1 basis to either treatment with atezolizumab and tiragolumab or atezolizumab alone during Stage 1 of the study. If at least 3 patients in the atezolizumab + tiragolumab arm are shown to be ctDNA negative at C3D1, stage 2 of the study will begin enrollment. Stage 2 consists of 25 patients all enrolled to the atezolizumab + tiragolumab arm (no randomization and no atezolizumab monotherapy arm).Patients who test negative for ctDNA will be observed off protocol.
Interventions
DRUGAtezolizumab
Atezolizumab is provided by Genentech.
DRUGTiragolumab
Tiragolumab is provided by Genentech.
DEVICESignatera Assay
* To detect residual disease or to determine cancer recurrence with ctDNA * Step 2 screening (4-12 weeks after date of surgery), cycle 3 day 1, cycle 6 day 1, cycle 9 day 1, cycle 12 day 1, and end of treatment (optional)
Sponsors
Genentech, Inc.
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ctDNA Clearance Rate | Cycle 3 Day 1 (estimated to be 8 weeks) | -Defined as the proportion of ctDNA-positive participants having a ctDNA-negative test at Cycle 3 Day 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse-free Survival (RFS) | Through completion of follow-up (estimated to be 48 months) | -Defined as the duration of time from the date of randomization to the date of earliest disease relapse or death, whichever occurs first. |
| Distant Metastasis-free Survival (DMFS) | Through completion of follow-up (estimated to be 48 months) | -Defined as as the duration of time from the date of positive ctDNA being confirmed to the date of appearance of a distant metastasis or death, whichever occurs first. |
| Overall Survival (OS) | Through completion of follow-up (estimated to be 48 months) | -Defined as the duration of time from the date of positive ctDNA being confirmed to death from any cause. |
| Proportion of ctDNA-positive Participants Having a ctDNA-negative Test at Two Consecutive Measures | From baseline to end of treatment (estimated to be 12 months) | — |
| Number of Treatment Discontinuations Due to Treatment-related Adverse Events | From start of treatment through completion of treatment (estimated to be 12 months) | — |
| Assess the Impact of ctDNA Kinetics on Relapse-free Survival | Through completion of follow-up (estimated to be 48 months) | — |
| Assess the Impact of ctDNA Kinetics on Distant Metastasis-free Survival | Through completion of follow-up (estimated to be 48 months) | — |
| Number of Treatment-related Grade 3 or Greater Adverse Events | From start of treatment through 90 days after end of treatment (estimated to be 15 months) | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Unassigned Arm -Participants were enrolled but not assigned to treatment arm. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | ctDNA negative | 7 |
Baseline characteristics
| Characteristic | Unassigned Arm |
|---|---|
| Age, Continuous | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
ctDNA Clearance Rate
-Defined as the proportion of ctDNA-positive participants having a ctDNA-negative test at Cycle 3 Day 1
Time frame: Cycle 3 Day 1 (estimated to be 8 weeks)
Population: All participants enrolled did not start study treatment.
Secondary
Assess the Impact of ctDNA Kinetics on Distant Metastasis-free Survival
Time frame: Through completion of follow-up (estimated to be 48 months)
Population: All participants enrolled did not start study treatment.
Secondary
Assess the Impact of ctDNA Kinetics on Relapse-free Survival
Time frame: Through completion of follow-up (estimated to be 48 months)
Population: All participants enrolled did not start study treatment.
Secondary
Distant Metastasis-free Survival (DMFS)
-Defined as as the duration of time from the date of positive ctDNA being confirmed to the date of appearance of a distant metastasis or death, whichever occurs first.
Time frame: Through completion of follow-up (estimated to be 48 months)
Population: All participants enrolled did not start study treatment.
Secondary
Number of Treatment Discontinuations Due to Treatment-related Adverse Events
Time frame: From start of treatment through completion of treatment (estimated to be 12 months)
Population: All participants enrolled did not start study treatment.
Secondary
Number of Treatment-related Grade 3 or Greater Adverse Events
Time frame: From start of treatment through 90 days after end of treatment (estimated to be 15 months)
Population: All participants enrolled did not start study treatment.
Secondary
Overall Survival (OS)
-Defined as the duration of time from the date of positive ctDNA being confirmed to death from any cause.
Time frame: Through completion of follow-up (estimated to be 48 months)
Population: All participants enrolled did not start study treatment.
Secondary
Proportion of ctDNA-positive Participants Having a ctDNA-negative Test at Two Consecutive Measures
Time frame: From baseline to end of treatment (estimated to be 12 months)
Population: All participants enrolled did not start study treatment.
Secondary
Relapse-free Survival (RFS)
-Defined as the duration of time from the date of randomization to the date of earliest disease relapse or death, whichever occurs first.
Time frame: Through completion of follow-up (estimated to be 48 months)
Population: All participants enrolled did not start study treatment.