NIMBUS: Nivolumab Plus Ipilimumab in Metastatic Hypermutated HER2-negative Breast Cancer

NCT03789110 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 18-561
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is studying a drug combination of nivolumab and ipilimumab as a possible treatment for hypermutated HER2 negative breast cancer. The drugs involved in this study are:

• Nivolumab (Opdivo ®)
• Ipilimumab (Yervoy ®)

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate of Nivolumab in Combination With Ipilimumab

  Overall Response Rate (ORR) is defined as the proportion of patients with complete or partial response evaluated by RECIST 1.1. Per RECIST 1.1: 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.

  2 years

Secondary Outcomes (4)

• Overall Response Rate of the Combination According to Immune-related Response Criteria

  2 years

• Clinical Benefit Rate

  2 Years

• Progression Free Survival

  2 years

• Overall Survival

  Participants were followed long-term for survival every 12 weeks from the end of treatment until death or lost to follow-up. Median follow-up in this study cohort was 9.7 months.

Study Arms (1)

Nivolumab+Ipilimumab

EXPERIMENTAL

* Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Nivolumab is called an anti- PD-1 or a checkpoint inhibitor and is an antibody (a type of human protein) designed to allow the body's own immune system to destroy tumors

Also known as: Opdivo

Nivolumab+Ipilimumab

Ipilimumab DRUG

Ipilimumab is called an anti-CTLA-4 and is a type of antibody that works to prevent the body's immune system from stopping to fight a specific cancer

Also known as: Yervoy

Nivolumab+Ipilimumab

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed invasive breast cancer, with metastatic disease. Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation.
• Patients must harbor tumors with total mutational burden (TMB) of at least 9 mutations per megabase assessed by a cancer-gene panel containing more than 300 genes, and performed in a CLIA verified laboratory. Tests like Foundation One, Oncopanel (DFCI), or IMPACT (MSKCC) are acceptable for including patients on this trial.
• Participants must have measurable disease by RECIST version 1.1.
• Participants must agree to undergo a research biopsy, if tumor is safely accessible, at baseline and at day 29 cycle 1 (+14 scheduling window). Previously collected archival tissue will be obtained on all participants. Participants for whom newly-obtained samples cannot be provided (e.g. inaccessible or participant safety concern) may submit an archived specimen (block or if not possible, 20 unstained slides).
• Prior chemotherapy: Participants may have received 0-3 prior chemotherapeutic regimens for metastatic breast cancer and must have been off treatment with chemotherapy for at least 14 days prior to study treatment initiation.
• Patients with hormone receptor positive breast cancer must have progressed on at least one prior line of endocrine therapy in the metastatic setting or have disease recurrence while on adjuvant endocrine therapy.
• Participants should also be adequately recovered from acute toxicities of prior treatment, with the exception of alopecia and peripheral sensory neuropathy.
• Prior biologic therapy: Patients must have discontinued all biologic therapy at least 14 days prior to study treatment initiation.
• Prior radiation therapy: Patients may have received prior radiation therapy in either the metastatic or early-stage setting. Radiation therapy must be completed 14 days prior to study treatment initiation.
• In all cases, there must be no ongoing complications from prior radiotherapy.
• The subject is ≥18 years old.
• ECOG performance status ≤1(Karnofsky ≥70%, see Appendix A).
• Participants must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/mcL
• platelets ≥100,000/mcL

You may not qualify if:

• Major surgery within 2 weeks before the first dose of study treatment.
• Concurrent administration of other anti-cancer therapy within 14 days of starting protocol therapy and during the course of this study.
• The participant has received another investigational agent within 14 days of the first dose of study drug.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody.
• Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms. Participants with a history of treated central nervous system (CNS) metastases are eligible. Treated brain metastases are defined as those having no evidence of progression for ≥ 2 weeks after treatment, and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging or CT scan) completed during screening. Subject must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily (or equivalent) for at least 7 days prior to first study treatment. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery, or a combination as deemed appropriate by the treating physician. Participants with CNS metastases treated by neurosurgical resection or brain biopsy performed within 28 days before study treatment initiation will be excluded.
• The subject has uncontrolled, significant intercurrent or recent illness. Individuals with a history of different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years or are deemed by the investigator to be at low risk for recurrence of that malignancy.
• Participant has an active infection requiring IV antibiotics at initiation of study therapy.
• Patient has a medical condition that requires chronic systemic steroid therapy or on any other form of immunosuppressive medication. For example, participants with autoimmune disease that requires systemic steroids or immunosuppression agents should be excluded. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Subjects with current pneumonitis, or requiring supplementary O2 therapy.
• The participant is known to be positive for human immunodeficiency virus (HIV), HepBsAg, or HCV RNA. HIV-positive participants on combination antiretroviral therapy are ineligible
• Participants with any other active malignancy requiring concurrent intervention.
• Known hypersensitivity to any of the components of ipilimumab or nivolumab.
• The participant has received a live vaccine within 28 days prior to the first dose of trial treatment and while participating in the trial. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine. The use of the inactivated seasonal influenza vaccine (Fluzone®) is allowed.
• The participant is pregnant or breastfeeding.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• Barroso-Sousa R, Zanudo JGT, Li T, Reddy SM, Emens LA, Kuntz TM, Silva CAC, AlDubayan SH, Chu H, Overmoyer B, Lange P, DiLullo MK, Montesion M, Kasparian J, Hughes ME, Attaya V, Basta A, Lin NU, Tayob N, Jeselsohn R, Mittendorf EA, Tolaney SM. Nivolumab plus low-dose ipilimumab in hypermutated HER2-negative metastatic breast cancer: a phase II trial (NIMBUS). Nat Commun. 2025 May 13;16(1):4430. doi: 10.1038/s41467-025-59695-1.

  PMID: 40360544 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Sara Tolaney
• Organization: Dana-Farber Cancer Institute

Sara_Tolaney@dfci.harvard.edu

617-632-5743

Study Officials

• Sara Tolaney, MD, MPH

  Dana-Farber Cancer Institute

  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: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator

Study Record Dates

• First Submitted: December 26, 2018
• First Posted: December 28, 2018
• Study Start: March 8, 2019
• Primary Completion: September 30, 2021
• Study Completion (Estimated): February 28, 2027
• Last Updated: April 28, 2026
• Results First Posted: September 27, 2022

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Requests may be directed to: \[contact information for Sponsor- Investigator or designee\]

Locations

US (3)