Clinical Trials Directory

Trials / Terminated

TerminatedNCT03566485

Atezolizumab and Cobimetinib or Idasanutlin in Participants With Stage IV or Unresectable Recurrent Estrogen Receptor Positive Breast Cancer

BRE 17107: A Phase Ib/II Trial of Atezolizumab (an Anti-PD-L1 Monoclonal Antibody) With Cobimetinib (a MEK1/2 Inhibitor) or Idasanutlin (an MDM2 Antagonist) in Metastatic ER+ Breast Cancer

Status
Terminated
Phase
Phase 1 / Phase 2
Study type
Interventional
Enrollment
12 (actual)
Sponsor
Vanderbilt-Ingram Cancer Center · Academic / Other
Sex
Female
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase I/II trial studies the side effects and best dose of idasanutlin when given together with atezolizumab, and to see how well atezolizumab and cobimetinib or idasanutlin work in treating participants with stage IV estrogen-receptor positive (ER+) breast cancer, or ER+ breast cancer that has come back (recurrent) and cannot be removed by surgery (unresectable). Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Cobimetinib and idasanutlin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab with cobimetinib or atezolizumab with idasanutlin may work better in treating participants with estrogen-receptor positive breast cancer.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety and tolerability of atezolizumab and idasanutlin in patients with estrogen receptor positive (ER+) metastatic breast cancer (mBC) (Phase I). II. To determine the anti-tumor effect of atezolizumab and cobimetinib or idasanutlin in patients with ER+ mBC (Phase II). SECONDARY OBJECTIVES: I. To determine the anti-tumor duration of effect of atezolizumab and cobimetinib or idasanutlin in patients with ER+ mBC (Phase II). II. To determine the safety and tolerability of atezolizumab and cobimetinib or idasanutlin in patients with ER+ mBC (Phase II). EXPLORATORY OBJECTIVES: I. To evaluate if CD8+ T cells are enhanced in the tumor with either MEK or MDM2 inhibition (Phase II). II. To evaluate if MHC-I/II and/or PD-L1 expression is enhanced with MEK inhibition (Phase II). III. To evaluate if T cell chemotractants (CCL5, CXCL9,10,11,13) are upregulated upon MDM2 antagonism (Phase II). IV. To determine if baseline or changes in PDL1 expression, MHC expression, presence of tumor infiltrating lymphocytes, neoantigen expression/ mutation burden (using ribonucleic acid \[RNA\]-and whole exome sequencing), CCL5, CXCL9, CXCL10, CXCL11, and CXCL13 correlate with clinical outcome (Phase II). V. To determine if immunological activity of MEK inhibition can be tracked noninvasively using Zr\^89-atezolizumab (Phase II). OUTLINE: This is a phase 1, dose-escalation study of idasanutlin followed by a phase II study. Participants are assigned to 1 of 2 arms. ARM I: Participants with TP53 gene mutation receive atezolizumab intravenously (IV) over 60 minutes starting with day 15 of course 1 and then on days 1 and 15 of subsequent courses, and cobimetinib orally (PO) daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Participants without TP53 gene mutation receive atezolizumab IV over 60 minutes starting with day 15 of course 1 and then on days 1 and 15 of subsequent courses, and idasanutlin PO daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed for 28 days.

Conditions

Interventions

TypeNameDescription
DRUGAtezolizumabGiven by IV
DRUGCobimetinibGiven by mouth
DRUGIdasanutlinGiven by mouth

Timeline

Start date
2018-07-10
Primary completion
2020-12-10
Completion
2020-12-10
First posted
2018-06-25
Last updated
2021-08-11
Results posted
2021-08-11

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT03566485. Inclusion in this directory is not an endorsement.