Phase 2
N=64
Vemurafenib, Cobimetinib, Atezolizumab, and Tiragolumab in Treating Patients With High-Risk Stage III Melanoma
Clinical Stage III Cutaneous Melanoma AJCC v8 · Pathologic Stage III Cutaneous Melanoma AJCC v8 · Pathologic Stage IIIA Cutaneous Melanoma AJCC v8 · Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 · Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
Bottom Line
View on ClinicalTrials.gov: NCT03554083 ↗Enrolled (actual)
64
Serious AEs
32.8%
Results posted
May 2026
Primary outcome: Primary: Pathologic Complete Response Rate (pCR) — 66.7; 13.3; 38.2 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Atezolizumab (Drug); Cobimetinib (Drug); Tiragolumab (Biological); Vemurafenib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Mayo Clinic
- Primary completion
- Apr 2025
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Pathologic Complete Response Rate (pCR) |
66.7; 13.3; 38.2 | — |
| PRIMARY Median Recurrence-free (RFS) Rate (Adjuvant Phase) |
NA; 40.8; NA | — |
| SECONDARY Incidence of Adverse Events Per Common Terminology Criteria for Adverse Events (CTCAE) |
12; 9; 10 | — |
Summary
This trial studies how well vemurafenib, cobimetinib, and atezolizumab work in treating patients with high-risk stage III melanoma. Vemurafenib and cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab and tiragolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving vemurafenib, cobimetinib, and atezolizumab may work better in treating high-risk stage III melanoma. Giving atezolizumab and tiragolumab together may also work better in treating high-risk stage III melanoma.
Eligibility Criteria
Inclusion Criteria
- PRE-REGISTRATION: Age >= 18 years
- PRE-REGISTRATION: High-risk stage III melanoma, defined as (any of the following):
- Recurrent nodal metastasis, or
- Clinically detectable nodal metastasis, or
- Metastatic involvement of more than one nodal basin
- NOTE: For the purpose of pre-registration, high-risk stage III melanoma is defined based on clinical and imaging assessment (positron emission tomography/computed tomography [PET/CT], CT, or magnetic resonance imaging [MRI]). Histologic confirmation of nodal metastatic disease is not needed at the time of pre-registration, provided there is histologic confirmation of primary melanoma or a prior lymph node metastasis.
- PRE-REGISTRATION: Willing to submit archival tissue from a lymph node biopsy or undergo a needle biopsy (with clip placement) for BRAF testing and for research purposes.
- PRE-REGISTRATION: Willing to forego anticancer treatments or investigational agents during pre-registration period.
- PRE-REGISTRATION: The following laboratory values obtained = = 26 weeks.
- REGISTRATION: Absolute neutrophil count (ANC) >= 1500/mm^3 obtained = = 100,000/mm^3 obtained = = 9.0 g/dL obtained = = 45 mL/min on the basis of measured CrCl from a 24-hour urine collection or Cockcroft-Gault glomerular filtration rate estimation obtained = = 50% or institutional lower limit of normal (LLN) = = 28 days prior to pre-registration.
- PRE-REGISTRATION: Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
- PRE-REGISTRATION: For patients with concurrent diagnosis of primary melanoma with nodal involvement, major surgical procedure other than lymph node biopsy or wide local excision of primary melanoma =< 4 weeks prior to pre-registration, or anticipation of need for a major surgical procedure for reasons other than melanoma during the course of the study.
- PRE-REGISTRATION: For patients with nodal recurrence, surgical procedure or anti-cancer therapy for this recurrence (other than lymph node biopsy) or anticipation of need for a major surgical procedure for reasons other than melanoma during the course of the study.
- PRE-REGISTRATION: Prior radiotherapy for melanoma.
- PRE-REGISTRATION: History of non-nodal melanoma metastasis or central nervous system (CNS) lesion(s) proven or clinically suspected to be metastasis.
- PRE-REGISTRATION: Active malignancy (other than melanoma) or malignancy =< 3 years prior to pre-registration.
- NOTE: Exceptions: Asymptomatic papillary thyroid cancer (not requiring treatment), resected basal cell carcinoma (BCC), resected cutaneous squamous cell carcinoma (SCC), resected carcinoma in situ of the cervix, resected carcinoma in situ of the breast, in situ prostate cancer, non-muscle-invasive bladder cancer, Stage I uterine cancer, or other curatively treated malignancies from which the patient has been disease-free for at least 3 years prior to pre registration.
- PRE-REGISTRATION: Prior allogeneic stem cell or solid organ transplantation.
- PRE-REGISTRATION: 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 CT scan.
- PRE-REGISTRATION: History of autoimmune disease requiring systemic immunosuppressive or immune-modulatory therapy =< 5 years prior to pre-registration.
- NOTE: Exceptions are allowed for hypothyroidism on thyroid replacement therapy; or Type 1 diabetes on insulin regimen.
- PRE-REGISTRATION: Active psoriasis requiring therapy (systemic or topical).
- PRE-REGISTRATION: Known clinically significant liver disease, including alcoholism, cirrhosis, fatty liver, and other inherited liver disease as well as active viral disease.
- PRE-REGISTRATION: Arms A and B only: History of or evidence of retinal pathology on ophthalmologic examination including but not limited to:
- Neurosensory retinal detachment
- Central serous c
Data sourced from ClinicalTrials.gov (NCT03554083). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.