Trial Outcomes & Findings for Ipilimumab and Nivolumab in Treating Patients With Recurrent Stage IV HER2 Negative Inflammatory Breast Cancer (NCT NCT02892734)

Last Updated: 2020-07-16

Results Overview

PFS in patients with newly recurrent HER2 negative IBC treated with nivolumab and ipilimumab as evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 assessed from the date of first study treatment to the date of disease progression or death from any cause, assessed up to 2 years.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2020-07-16

Participant Flow

The study opened to accrual on September 5, 2017 with a total accrual goal of 29. The first patient started treatment October 18, 2017. The study was closed permanently January 21 2019 with 3 patients treated on study.

Participant milestones

Participant milestones
Measure	Treatment (Nivolumab, Ipilimumab) Patients receive nivolumab 240mg IV over 30 minutes Q2W for the first 16 weeks then 480mg IV every 4 weeks thereafter. Patients will Ipilimumab 1mg/kg IV over 90 minutes Q6W in the absence of disease progression or unacceptable toxicity. 1 Cycle = 12 weeks. Scans every 12 weeks for disease assessment. Ipilimumab: Given IV Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV
Treatment on Study STARTED	3
Treatment on Study Completed 1st Cycle/Response at 12 Weeks	1
Treatment on Study Went on to Start Cycle 2	1
Treatment on Study COMPLETED	1
Treatment on Study NOT COMPLETED	2
Follow up for 2 Years STARTED	3
Follow up for 2 Years COMPLETED	0
Follow up for 2 Years NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Nivolumab, Ipilimumab) Patients receive nivolumab 240mg IV over 30 minutes Q2W for the first 16 weeks then 480mg IV every 4 weeks thereafter. Patients will Ipilimumab 1mg/kg IV over 90 minutes Q6W in the absence of disease progression or unacceptable toxicity. 1 Cycle = 12 weeks. Scans every 12 weeks for disease assessment. Ipilimumab: Given IV Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV
Treatment on Study Progressive Disease	2
Follow up for 2 Years Death	2
Follow up for 2 Years Study closed early	1

Baseline Characteristics

Ipilimumab and Nivolumab in Treating Patients With Recurrent Stage IV HER2 Negative Inflammatory Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Nivolumab, Ipilimumab) n=3 Participants Patients receive nivolumab 240mg IV over 30 minutes Q2W for the first 16 weeks then 480mg IV every 4 weeks thereafter. Patients will Ipilimumab 1mg/kg IV over 90 minutes Q6W in the absence of disease progression or unacceptable toxicity. 1 Cycle = 12 weeks. Scans every 12 weeks for disease assessment. Ipilimumab: Given IV Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Population: Data not collected and analyzed as study closed to accrual early due to slow accrual.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 12 weeks from treatment initiation for up to 2 years. Range of cycles patients completed 1-3 cycles (1 cycle =12 weeks)

Population: Sample size was too small for statistical analysis. Data collected shown but should be viewed as incomplete as based off of 1 patient. Only those patients who have measurable disease present at baseline, have received at least one dose of therapy, and have had their disease re-evaluated will be considered evaluable for response.

Evaluate the ORR according to RECIST criteria v1.1 in patients with recurrent Inflammatory Breast Cancer (IBC) treated with nivolumab and ipilimumab. ORR will be the number of patients with complete response plus the number of patients with partial response. Patients will have imaging scans every 12 weeks assessed up to 2 years. In general: Complete Response (CR): Disappearance of all target and non target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Treatment (Nivolumab, Ipilimumab) n=1 Participants Patients receive nivolumab 240mg IV over 30 minutes Q2W for the first 16 weeks then 480mg IV every 4 weeks thereafter. Patients will Ipilimumab 1mg/kg IV over 90 minutes Q6W in the absence of disease progression or unacceptable toxicity. 1 Cycle = 12 weeks. Scans every 12 weeks for disease assessment. Ipilimumab: Given IV Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV
Overall Response Rate (ORR)	0 patients

SECONDARY outcome

Timeframe: Every 12 weeks from treatment initiation for up to 2 years. Range of cycles patients completed 1-3 cycles (1 cycle =12 weeks)

Evaluate the CBR according to RECIST criteria v1.1 in patients with recurrent Inflammatory Breast Cancer (IBC) treated with nivolumab and ipilimumab. CBR will be the number of patients with complete response plus the number of patients with partial response plus those with stable disease. Patients will have imaging scans every 12 weeks assessed up to 2 years. In general: Complete Response (CR): Disappearance of all target and non target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Outcome measures

Outcome measures
Measure	Treatment (Nivolumab, Ipilimumab) n=1 Participants Patients receive nivolumab 240mg IV over 30 minutes Q2W for the first 16 weeks then 480mg IV every 4 weeks thereafter. Patients will Ipilimumab 1mg/kg IV over 90 minutes Q6W in the absence of disease progression or unacceptable toxicity. 1 Cycle = 12 weeks. Scans every 12 weeks for disease assessment. Ipilimumab: Given IV Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV
Clinical Benefit Rate (CBR)	1 number of patients

SECONDARY outcome

Timeframe: Up to 2 years

Population: OS was not calculated. Sample size was too small to warrant analysis due to the study closes before accrual was reached. Reported below is the number of patients alive at the time of reporting data (4/12/2019).

To assess overall survival in patients with recurrent HER2 negative IBC treated with nivolumab and ipilimumab, patients will be followed from the start of treatment until 2 years post-treatment or death, whichever occurs first, and average survival time will be measured.

Outcome measures

Outcome measures
Measure	Treatment (Nivolumab, Ipilimumab) n=3 Participants Patients receive nivolumab 240mg IV over 30 minutes Q2W for the first 16 weeks then 480mg IV every 4 weeks thereafter. Patients will Ipilimumab 1mg/kg IV over 90 minutes Q6W in the absence of disease progression or unacceptable toxicity. 1 Cycle = 12 weeks. Scans every 12 weeks for disease assessment. Ipilimumab: Given IV Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV
Overall Survival (OS)	1 patients

SECONDARY outcome

Timeframe: From the initiation of treatment until 12 weeks after study discontinuation. Range of cycles completed by patients 1-3 (1 cycle =12weeks)

Population: Data that was collected is reported.

Assess the safety and tolerability of nivolumab and ipilimumab in patients with recurrent Inflammatory Breast Cancer (IBC) by measuring the number, frequency, and severity of adverse events according to the National Cancer Institute Common Terminology Criteria Adverse events (CTCAE) v 4.03. AEs that were determined to be at least possibly related to study drug and grade 3-5 are reported. In general grading is as follows: Grade 1 - mild Grade 2 - moderate Grade 3 - severe Grade 4 - life threatening Grade 5 - fatal

Outcome measures

Outcome measures
Measure	Treatment (Nivolumab, Ipilimumab) n=3 Participants Patients receive nivolumab 240mg IV over 30 minutes Q2W for the first 16 weeks then 480mg IV every 4 weeks thereafter. Patients will Ipilimumab 1mg/kg IV over 90 minutes Q6W in the absence of disease progression or unacceptable toxicity. 1 Cycle = 12 weeks. Scans every 12 weeks for disease assessment. Ipilimumab: Given IV Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV
Number of Adverse Events of Nivolumab and Ipilimumab Combination Treatment	1 Adverse Events

OTHER_PRE_SPECIFIED outcome

Timeframe: At baseline

Assess the predictive value of baseline iSCORE using tissue samples.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At baseline

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At baseline

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At baseline

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Nivolumab, Ipilimumab)

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Nivolumab, Ipilimumab) n=3 participants at risk Patients receive nivolumab 240mg IV over 30 minutes Q2W for the first 16 weeks then 480mg IV every 4 weeks thereafter. Patients will Ipilimumab 1mg/kg IV over 90 minutes Q6W in the absence of disease progression or unacceptable toxicity. 1 Cycle = 12 weeks. Scans every 12 weeks for disease assessment. Ipilimumab: Given IV Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV
Respiratory, thoracic and mediastinal disorders Acute Hypoxic Respiratory Failure	33.3% 1/3 • Number of events 1 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Respiratory, thoracic and mediastinal disorders Pneumonitis	33.3% 1/3 • Number of events 1 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)

Other adverse events

Other adverse events
Measure	Treatment (Nivolumab, Ipilimumab) n=3 participants at risk Patients receive nivolumab 240mg IV over 30 minutes Q2W for the first 16 weeks then 480mg IV every 4 weeks thereafter. Patients will Ipilimumab 1mg/kg IV over 90 minutes Q6W in the absence of disease progression or unacceptable toxicity. 1 Cycle = 12 weeks. Scans every 12 weeks for disease assessment. Ipilimumab: Given IV Laboratory Biomarker Analysis: Correlative studies Nivolumab: Given IV
Gastrointestinal disorders Constipation	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
General disorders Fatigue	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Infections and infestations Upper Respiratory Infection	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Investigations Lymphocyte Count Decreased	66.7% 2/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Investigations Aspartate Aminotransferase Increased	66.7% 2/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Investigations Neutrophil Count Decreased	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Metabolism and nutrition disorders Hyperglycemia	66.7% 2/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Metabolism and nutrition disorders Hypoalbuminemia	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Metabolism and nutrition disorders Hypokalemia	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Musculoskeletal and connective tissue disorders Chest Wall Pain	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Musculoskeletal and connective tissue disorders Pain in extremity	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Nervous system disorders Headache	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Psychiatric disorders Insomnia	66.7% 2/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Psychiatric disorders Anxiety	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Reproductive system and breast disorders Breast Pain	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Respiratory, thoracic and mediastinal disorders Hoarseness	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Respiratory, thoracic and mediastinal disorders Pleural Effusion	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Skin and subcutaneous tissue disorders Erythema Multiforme	33.3% 1/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)
Vascular disorders Hypertension	66.7% 2/3 • Adverse events were collected from treatment initiation through 12 weeks post last dose of study drug with the range of cycles completed by patients 1 - 3. (1 Cycle = 12 Weeks)

Additional Information

William Gradishar, MD

Northwestern University

Phone: 312 695 4541

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place