Cobimetinib and Atezolizumab in Treating Participants With Advanced or Refractory Rare Tumors

NCT03108131 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2016-0869NCI-2018-01399
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well cobimetinib and atezolizumab work in treating participants with rare tumors that have spread to other places in the body (advanced) or that does not respond to treatment (refractory). 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, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cobimetinib and atezolizumab may work better in treating participants with advanced or refractory rare tumors.

Conditions

Skin Squamous Cell Carcinoma; Appendix Adenocarcinoma; Rare Lesion; Locally Advanced Malignant Neoplasm; Locally Advanced Skin Squamous Cell Carcinoma; Metastatic Malignant Neoplasm; Metastatic Skin Squamous Cell Carcinoma; Metastatic Small Intestinal Adenocarcinoma; Rare Neoplastic Syndrome; Refractory Malignant Neoplasm; Stage IV Small Intestinal Adenocarcinoma AJCC v8; Unresectable Malignant Neoplasm

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  To evaluate the efficacy of cobimetinib plus atezolizumab (COTEZO) in cohorts of advanced rare tumors using objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Efficacy as determined by complete response and partial response.

  Patient will be on study up to 3 years

Secondary Outcomes (3)

• Disease Control Rate (DCR)

  3 years

• Progression-Free Survival (PFS)

  3 years

• Overall Survival

  3 years

Study Arms (1)

Treatment (cobimetinib, atezolizumab)

EXPERIMENTAL

Participants receive cobimetinib PO QD on days 1-21 and atezolizumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Atezolizumab; Drug: Cobimetinib

Interventions

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Treatment (cobimetinib, atezolizumab)

Cobimetinib DRUG

Given PO

Also known as: Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518

Treatment (cobimetinib, atezolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be informed of the investigational nature of this study and must be willing to give written informed consent in accordance with institutional and federal guidelines. Patients must be able to comply with the requirements and assessments of the study protocol
• Must have histologically or cytologically documented rare tumor as defined per protocol that is metastatic or locally advanced and unresectable. Patients with locally advanced cutaneous squamous cell carcinoma that are technically resectable but in whom surgery is expected to lead to substantial function impairment or disfigurement are eligible
• Must be refractory or intolerant to standard lines of therapy
• Must have completed prior chemotherapy, immunotherapy, or radiation therapy at least 14 days prior to start of treatment and all toxicity must be resolved to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade 1 (with the exception of CTCAE v4.0 grade 2 neuropathy) prior to start of treatment
• Presence of radiographically evaluable disease
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Tissue Parameters: a. Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (blocks are preferred) or at least 4 unstained slides, with an associated pathology report, for testing of tumor PD-L1 expression (tumor tissue from bone metastases is not evaluable for PD-L1 expression and is therefore not acceptable). b. Tumor tissue should be of good quality based on total and viable tumor content. Fine needle aspiration, brushing, cell pellet from pleural effusion, bone metastases, and lavage samples are not acceptable. For core-needle biopsy specimens, at least three cores should be submitted for evaluation. c. Patients who do not have tissue specimens meeting eligibility requirements must be willing to undergo a biopsy during the screening period
• Absolute neutrophil count (ANC) \>= 1,000/mcL (obtained within 14 days prior to enrollment)
• Platelets \>= 75,000/mcL (obtained within 14 days prior to enrollment)
• Hemoglobin \>= 9 g/dL (obtained within 14 days prior to enrollment)
• Calculated creatinine clearance \> 30 ml/min (obtained within 14 days prior to enrollment)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) =\< 3 x institutional upper limit of normal (IULN) without liver mets or =\< 5 x IULN with liver metastases (obtained within 14 days prior to enrollment)
• Bilirubin =\< 1.5 mg/dL (obtained within 14 days prior to enrollment)
• Able to swallow pills
• Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for \>= 1 year

You may not qualify if:

• Presence of brain metastases (unless they have been adequately treated with radiotherapy or surgery and stable for at least 30 days prior to enrollment provided patient is neurologically asymptomatic and without corticosteroid treatment for at least 7 days prior to enrollment)
• Uncontrolled intercurrent illness including, but not limited to diabetes, hypertension, severe infection, severe malnutrition, unstable angina, class III-IV New York Heart Association (NYHA) congestive heart failure, ventricular arrhythmias, active ischemic heart disease, or myocardial infarction within 6 months prior to enrollment
• History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration
• Patients will be excluded from study participation if they currently are known to have any of the following risk factors for RVO: a. Glaucoma with intraocular pressure \>= 21 mmHg b. Grade \>= 2 serum cholesterol c. Grade \>= 2 hypertriglyceridemia d. Grade \>= 2 or symptomatic hyperglycemia (fasting) e. Grade \>= 2 uncontrolled hypertension (patients with a history of hypertension controlled with anti-hypertensive medication to grade =\< 1 are eligible)
• Active malignancy (other than colorectal carcinoma \[CRC\]) or a history of prior malignancy within the past 3 years. Adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, ductal carcinoma in situ, other low grade lesions such as incidental appendix carcinoid, or any other cancer from which the patient has been disease and treatment free for two years are allowed. Prostate cancer patients on active surveillance are eligible
• Pregnant or nursing patients due to risk of fetal or nursing infant harm. Women/men of reproductive potential who do not agree to use an effective contraceptive method while on study and for at least 6 months after study treatment
• Left ventricular ejection fraction (LVEF) \< institutional lower limit of normal or \< 50%
• History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis a. Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. b. Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible. c. Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
• Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
• Rash must cover less than 10% of body surface area (BSA)
• Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
• No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• History of human immunodeficiency virus (HIV) infection or active hepatitis B (chronic or acute) or hepatitis C infection. a. Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive anti-HBc \[antibody to hepatitis B core antigen\] antibody test) are eligible. b. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
• Active tuberculosis or severe infections within 4 weeks prior to cycle 1, day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Adenocarcinoma, Mucinous; Neoplasm Metastasis; Neoplasms

Interventions

atezolizumab; cobimetinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Cystic, Mucinous, and Serous; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Kanwal Raghav
• Organization: The University of Texas MD Anderson Cancer Center

kpraghav@mdanderson.org

(917) 733-0356

Study Officials

• Kanwal P Raghav

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2017
• First Posted: April 11, 2017
• Study Start: April 7, 2017
• Primary Completion: April 2, 2024
• Study Completion: April 2, 2024
• Last Updated: May 28, 2025
• Results First Posted: May 28, 2025

Record last verified: 2025-05

Locations

US (1)