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

NCT03566485 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: VICC BRE 17107NCI-2018-01159
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Estrogen Receptor-positive; HER2/Neu Negative

Outcome Measures

Primary Outcomes (4)

• Number of Participants With a Dose Limiting Toxicity (DLT) (Phase I)

  Assessment of DLT for the patients in the atezolizumab and idasanutiln arm of the study

  At 28 days

• Maximum Tolerated Dose (Phase I)

  Assessment of MTD for the atezolizumab and idasanutiln combination arm of the study

  At 28 days

• Recommended Phase II Dose (Phase I)

  Assessment of recommended phase II dose for the atezolizumab and idasanutiln combination arm of the study

  At 28 days

• Overall Response Rate (ORR; by Response Evaluation Criteria in Solid Tumors [RECIST]1.1) (Phase II)

  Assessment of clinical impact (anti-tumor effect) of the combination of atezolizumab and cobimetinib or idasanutiln in patients with metastatic ER \+ breast cancer by measure the rate (%) of complete and partial responses seen in patients with measurable disease. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  Up to 28 days after completion of study treatment, for a total of 2 years

Secondary Outcomes (5)

• Clinical Benefit Rate (CBR) (Phase II)

  At 6 months

• Immune Related Response Criteria (irRC) (Phase II)

  Up to 28 days after completion of study treatment, for a total of 2 years

• Progression-free Survival (PFS) (Phase II) in Days

  At 12 months

• Overall Survival (OS) (Phase II) in Days

  At 12 months

• Number of Adverse Events (Phase II)

  Up to 28 days after completion of study treatment, for a total of 2 years

Study Arms (2)

Phase 2 (atezolizumab, cobimetinib)

EXPERIMENTAL

Participants with 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 cobimetinib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Atezolizumab; Drug: Cobimetinib

Phase 1b - Atezolizumab 840mg IV + Idasanutlin 100mg PO

EXPERIMENTAL

Drug: Atezolizumab; Drug: Idasanutlin

Interventions

Atezolizumab DRUG

Given by IV

Phase 1b - Atezolizumab 840mg IV + Idasanutlin 100mg PO; Phase 2 (atezolizumab, cobimetinib)

Cobimetinib DRUG

Given by mouth

Phase 2 (atezolizumab, cobimetinib)

Idasanutlin DRUG

Given by mouth

Phase 1b - Atezolizumab 840mg IV + Idasanutlin 100mg PO

Eligibility Criteria

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

You may not qualify if:

• Prior therapy with anti-PD-L1 and anti-PD1 antibodies, MEK inhibitors or MDM2 antagonists.
• No more than 3 lines of chemotherapy in the metastatic setting
• No concurrent anticancer therapy. Required washout from prior therapy:
• Endocrine therapy: no required wash-out
• Chemotherapy: 14 days
• Major surgery: 14 days (provided wound healing is adequate)
• Radiation: 7 days
• Investigational/Biologic Therapy (half -life ≤ 40 hours): 14 days
• Investigational/Biologic Therapy (half -life \> 40 hours): 28 days
• Subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g. topical, ocular, intra-articular, intranasal, and inhaled);
• Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent are permitted;
• Adrenal replacement steroid doses including doses \> 10 mg daily prednisone are permitted;
• A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g. CT scan premedication against contrast dye allergy) or for treatment of non-autoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by a contact allergen) is permitted.
• Previous malignant disease other than breast cancer within the last 5 years, with the exception of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, or low-risk cancers considered curatively treated (i.e. complete remission achieved at least 2 years prior to first dose of study drugs AND additional therapy not required while receiving study treatment).
• All subjects with brain metastases, except those meeting the following criteria:

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• Genentech, Inc.: collaborator
• Stand Up To Cancer: collaborator

Study Sites (1)

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 3720932, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

atezolizumab; cobimetinib; RG7388

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Teresa Melton
• Organization: Vanderbilt-Ingram Cancer Center

teresa.melton@vumc.org

6159367423

Study Officials

• Ingrid Mayer, MD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 11, 2018
• First Posted: June 25, 2018
• Study Start: July 10, 2018
• Primary Completion: December 10, 2020
• Study Completion: December 10, 2020
• Last Updated: August 11, 2021
• Results First Posted: August 11, 2021

Record last verified: 2021-08

Locations

US (1)