Trial Outcomes & Findings for NIMBUS: Nivolumab Plus Ipilimumab in Metastatic Hypermutated HER2-negative Breast Cancer (NCT NCT03789110)

Last Updated: 2026-02-06

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

2 years

Results posted on

2026-02-06

Participant Flow

Participant milestones

Participant milestones
Measure	Nivolumab+Ipilimumab * Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks Nivolumab: 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 Ipilimumab: 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
Overall Study STARTED	30
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Nivolumab+Ipilimumab * Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks Nivolumab: 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 Ipilimumab: 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
Overall Study Adverse Event	2
Overall Study Physician Decision	1
Overall Study Withdrawal by Subject	2
Overall Study Lack of Efficacy	22
Overall Study still on treatment	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nivolumab+Ipilimumab n=30 Participants * Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks Nivolumab: 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 Ipilimumab: 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
Age, Categorical <=18 years	0 Participants n=192 Participants
Age, Categorical Between 18 and 65 years	21 Participants n=192 Participants
Age, Categorical >=65 years	9 Participants n=192 Participants
Age, Continuous	63 years n=192 Participants
Sex: Female, Male Female	30 Participants n=192 Participants
Sex: Female, Male Male	0 Participants n=192 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=192 Participants
Race (NIH/OMB) Asian	1 Participants n=192 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=192 Participants
Race (NIH/OMB) Black or African American	0 Participants n=192 Participants
Race (NIH/OMB) White	27 Participants n=192 Participants
Race (NIH/OMB) More than one race	2 Participants n=192 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=192 Participants
Region of Enrollment United States	30 participants n=192 Participants
ECOG Performance Status 0	22 Participants n=192 Participants
ECOG Performance Status 1	8 Participants n=192 Participants
Hormone Receptor (HR) Status HR +	21 Participants n=192 Participants
Hormone Receptor (HR) Status Triple Negative	9 Participants n=192 Participants
Prior lines of chemotherapy in the advanced setting	1.5 line n=192 Participants
PD-L1 positive cells Positive	4 Participants n=192 Participants
PD-L1 positive cells Negative	21 Participants n=192 Participants
PD-L1 positive cells Missing sample	4 Participants n=192 Participants
PD-L1 positive cells Specimen not adequate for evaluation	1 Participants n=192 Participants
TMB (mut/Mb)	10.9 mut/Mb n=192 Participants

PRIMARY outcome

Timeframe: 2 years

Population: The analysis population includes all patients who initiated protocol therapy

Outcome measures

Outcome measures
Measure	Nivolumab+Ipilimumab n=30 Participants * Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks Nivolumab: 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 Ipilimumab: 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
Overall Response Rate of Nivolumab in Combination With Ipilimumab	5 Participants

SECONDARY outcome

Timeframe: 2 years

Population: all patients who initiated protocol therapy

Overall Response Rate (ORR) is defined as the proportion of patients with complete or partial response evaluated by immune-related response criteria (irRC). Per irRC: irComplete Response (irCR): Complete disappearance of all tumor lesions (target an non-target) together with no new measurable/unmeasurable lesions for at least 4 weeks from the date of documentation of complete response. Immune-Related Partial Response (irPR): The sum of the products of the two largest perpendicular diameters of all target lesions is measured and captured as the SPD baseline. At each subsequent tumor assessment, the SPD of the two largest perpendicular diameters of all target lesions and of new measurable lesions are added together to provide the Immune Response Sum of Product Diameters (irSPD). A decrease, relative to baseline, of the irSPD compared to the previously SPD baseline of 50% or greater is considered an irPR.; Overall Response (OR) = irCR + irPR.

Outcome measures

Outcome measures
Measure	Nivolumab+Ipilimumab n=30 Participants * Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks Nivolumab: 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 Ipilimumab: 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
Overall Response Rate of the Combination According to Immune-related Response Criteria	6 Participants

SECONDARY outcome

Timeframe: 2 Years

Population: analysis population includes all patients who initiated protocol therapy

Clinical Benefit Rate (CBR) will be determined by looking at the number of subjects who have either a complete response, partial response, or stable disease for greater than or equal to 24 weeks, per RECIST 1.1

Outcome measures

Outcome measures
Measure	Nivolumab+Ipilimumab n=30 Participants * Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks Nivolumab: 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 Ipilimumab: 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
Clinical Benefit Rate	5 Participants

SECONDARY outcome

Timeframe: 2 years

Population: all patients who initiated protocol therapy

Progression free survival is defined from the study entry to first documented evidence of disease progression by RECIST 1.1 or death of any cause, whichever occurs first. Patients alive with no progression are censored at the last disease assessment.

Outcome measures

Outcome measures
Measure	Nivolumab+Ipilimumab n=30 Participants * Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks Nivolumab: 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 Ipilimumab: 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
Progression Free Survival	1.4 month Interval 1.3 to 4.6

SECONDARY outcome

Timeframe: 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.

Population: All patients who initiated protocol therapy

OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

Outcome measures

Outcome measures
Measure	Nivolumab+Ipilimumab n=30 Participants * Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks Nivolumab: 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 Ipilimumab: 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
Overall Survival	19.3 month Interval 5.2 to Follow-up is not long enough/data is not mature to provide upper bound confidence interval.

Adverse Events

Nivolumab+Ipilimumab

Serious events: 5 serious events

Other events: 24 other events

Deaths: 13 deaths

Serious adverse events

Serious adverse events
Measure	Nivolumab+Ipilimumab n=30 participants at risk * Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks Nivolumab: 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 Ipilimumab: 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
Metabolism and nutrition disorders Anorexia	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Cardiac disorders Atrial fibrillation	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Investigations Cardiac troponin T increased	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Psychiatric disorders Confusion	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Eye disorders Eyelid function disorder	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Metabolism and nutrition disorders Hypokalemia	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Metabolism and nutrition disorders Hyponatremia	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Nervous system disorders Lethargy	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Nervous system disorders Myasthenia gravis	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Cardiac disorders Myocarditis	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Investigations Platelet count decreased	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.3% 1/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.

Other adverse events

Other adverse events
Measure	Nivolumab+Ipilimumab n=30 participants at risk * Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks Nivolumab: 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 Ipilimumab: 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
Blood and lymphatic system disorders Anemia	10.0% 3/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Endocrine disorders Hypothyroidism	6.7% 2/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Gastrointestinal disorders Diarrhea	13.3% 4/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Gastrointestinal disorders Mucositis oral	6.7% 2/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
General disorders and administration site conditions Fatigue	30.0% 9/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
General disorders and administration site conditions Pain	10.0% 3/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Investigations Alanine aminotransferase increased	6.7% 2/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Investigations Aspartate aminotransferase increased	6.7% 2/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Investigations Neutrophil count decreased	6.7% 2/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Metabolism and nutrition disorders Anorexia	6.7% 2/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Musculoskeletal and connective tissue disorders Back pain	10.0% 3/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Musculoskeletal and connective tissue disorders Bone pain	6.7% 2/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Musculoskeletal and connective tissue disorders Pain in extremity	6.7% 2/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.7% 2/30 • AE data were collected every cycle from the time of the first dose of the study treatment, through the end of the treatment. Vital status was followed even after patients were off treatment. AEs, including overall mortality, were observed up to 30 months.

Additional Information

Sara Tolaney

Dana-Farber Cancer Institute

Phone: 617-632-5743

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place