Trial Outcomes & Findings for Phase Ib/II Trial of Interleukin-2 and PD-1 Checkpoint Inhibitor, Nivolumab In Metastatic Clear Cell Renal Cell Cancer (NCT NCT02989714)

NCT ID: NCT02989714

Last Updated: 2021-07-13

Results Overview

This is the primary outcome for the Phase Ib portion of the trial. Events of interest are possibly immune-mediated and occur only after at least one dose of Nivolumab has been administered. Immune-mediated events of interest do not include those that are known to occur during high dose IL-2 monotherapy and are reversible. Grade assessed per CTCAE version 4.0.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

13 participants

Primary outcome timeframe

28 days from the first dose of Nivolumab

Results posted on

2021-07-13

Participant Flow

Participant milestones

Participant milestones
Measure	HD IL2 and Nivolumab Interleukin-2: 600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart Nivolumab: Nivolumab will be administered intravenously at 240 mg/dose over 60 minutes every 14 days, starting 1 week to 3 weeks after the start date of the first cycle of IL2 and continued for up to 48 weeks total in the absence of disease progression
Overall Study STARTED	13
Overall Study Started Nivolumab	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase Ib/II Trial of Interleukin-2 and PD-1 Checkpoint Inhibitor, Nivolumab In Metastatic Clear Cell Renal Cell Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HD IL2 and Nivolumab n=13 Participants Interleukin-2: 600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart Nivolumab: Nivolumab will be administered intravenously at 240 mg/dose over 60 minutes every 14 days, starting 1 week to 3 weeks after the start date of the first cycle of IL2 and continued for up to 48 weeks total in the absence of disease progression
Age, Continuous	60 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 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	2 Participants n=5 Participants
Race (NIH/OMB) White	11 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

PRIMARY outcome

Timeframe: 28 days from the first dose of Nivolumab

Population: Patients who received at least 1 dose of Nivolumab and Interleukin-2

This is the primary outcome for the Phase Ib portion of the trial. Events of interest are possibly immune-mediated and occur only after at least one dose of Nivolumab has been administered. Immune-mediated events of interest do not include those that are known to occur during high dose IL-2 monotherapy and are reversible. Grade assessed per CTCAE version 4.0.

Outcome measures

Outcome measures
Measure	HD IL2 and Nivolumab n=12 Participants Interleukin-2: 600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart Nivolumab: Nivolumab will be administered intravenously at 240 mg/dose over 60 minutes every 14 days, starting 1 week to 3 weeks after the start date of the first cycle of IL2 and continued for up to 48 weeks total in the absence of disease progression
The Number of Patients With Grade 3 and Grade 4 Adverse Events of Interest	0 Participants

PRIMARY outcome

Timeframe: 12 Weeks

Population: Patients who received at least 1 dose of Nivolumab and Interleukin-2

This is the primary outcome for the Phase II portion of the trial. Includes complete response (CR) + partial response (PR), measured by computerized tomography (CT) or magnetic resonance imaging (MRI) scan and assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Outcome measures

Outcome measures
Measure	HD IL2 and Nivolumab n=12 Participants Interleukin-2: 600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart Nivolumab: Nivolumab will be administered intravenously at 240 mg/dose over 60 minutes every 14 days, starting 1 week to 3 weeks after the start date of the first cycle of IL2 and continued for up to 48 weeks total in the absence of disease progression
The Number of Patients That Respond to Treatment	2 Participants

SECONDARY outcome

Timeframe: For the duration of the therapy plus 60 days post treatment

Population: Patients who received at least 1 dose of Nivolumab and Interleukin-2

Events of interest are possibly immune-mediated and occur only after at least one dose of Nivolumab has been administered. Immune-mediated events of interest do not include those that are known to occur during high dose IL-2 monotherapy and are reversible. Grade assessed per CTCAE version 4.0.

Outcome measures

Outcome measures
Measure	HD IL2 and Nivolumab n=12 Participants Interleukin-2: 600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart Nivolumab: Nivolumab will be administered intravenously at 240 mg/dose over 60 minutes every 14 days, starting 1 week to 3 weeks after the start date of the first cycle of IL2 and continued for up to 48 weeks total in the absence of disease progression
Number of Grade 3-5 Adverse Events of Interest	7 events

SECONDARY outcome

Timeframe: 24 Months

Population: Patients who received at least 1 dose of Nivolumab and Interleukin-2

Overall survival at 24 months following the first dose of study therapy; 24 month estimates were reported using the product limit method of Kaplan and Meier along with 95% confidence intervals.

Outcome measures

Outcome measures
Measure	HD IL2 and Nivolumab n=12 Participants Interleukin-2: 600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart Nivolumab: Nivolumab will be administered intravenously at 240 mg/dose over 60 minutes every 14 days, starting 1 week to 3 weeks after the start date of the first cycle of IL2 and continued for up to 48 weeks total in the absence of disease progression
Overall Survival at 24 Months	77.1 percentage of participants Interval 34.5 to 93.9

SECONDARY outcome

Timeframe: 24 Months

Population: Patients who received at least 1 dose of Nivolumab and Interleukin-2

PFS is defined as the time from start of study therapy with Nivolumab until progression or death; up to 24 months. Progressive disease is defined as At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	HD IL2 and Nivolumab n=12 Participants Interleukin-2: 600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart Nivolumab: Nivolumab will be administered intravenously at 240 mg/dose over 60 minutes every 14 days, starting 1 week to 3 weeks after the start date of the first cycle of IL2 and continued for up to 48 weeks total in the absence of disease progression
Progression Free Survival (PFS) at 24 Months	43.6 percentage of participants Interval 14.7 to 69.9

Adverse Events

HD IL2 and Nivolumab

Serious events: 3 serious events

Other events: 13 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	HD IL2 and Nivolumab n=13 participants at risk Interleukin-2: 600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart Nivolumab: Nivolumab will be administered intravenously at 240 mg/dose over 60 minutes every 14 days, starting 1 week to 3 weeks after the start date of the first cycle of IL2 and continued for up to 48 weeks total in the absence of disease progression
Injury, poisoning and procedural complications Fracture	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
General disorders Fatigue	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Gastrointestinal disorders Pancreatitis	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Gastrointestinal disorders Colitis	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)

Other adverse events

Other adverse events
Measure	HD IL2 and Nivolumab n=13 participants at risk Interleukin-2: 600,000 IU/kg/dose intravenously during two 5-day cycles 9 days apart Nivolumab: Nivolumab will be administered intravenously at 240 mg/dose over 60 minutes every 14 days, starting 1 week to 3 weeks after the start date of the first cycle of IL2 and continued for up to 48 weeks total in the absence of disease progression
Gastrointestinal disorders Abdominal pain	23.1% 3/13 • Number of events 3 • 60 days after end of treatment (Up to 14 months)
Renal and urinary disorders Acute kidney injury	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Investigations Alanine aminotransferase increased	84.6% 11/13 • Number of events 36 • 60 days after end of treatment (Up to 14 months)
Investigations Alkaline phosphatase increased	61.5% 8/13 • Number of events 16 • 60 days after end of treatment (Up to 14 months)
Immune system disorders Allergic reaction	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Blood and lymphatic system disorders Anemia	84.6% 11/13 • Number of events 25 • 60 days after end of treatment (Up to 14 months)
Metabolism and nutrition disorders Anorexia	38.5% 5/13 • Number of events 5 • 60 days after end of treatment (Up to 14 months)
Musculoskeletal and connective tissue disorders Arthralgia	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Musculoskeletal and connective tissue disorders Arthritis	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Investigations Aspartate aminotransferase increased	84.6% 11/13 • Number of events 33 • 60 days after end of treatment (Up to 14 months)
Musculoskeletal and connective tissue disorders Back pain	23.1% 3/13 • Number of events 3 • 60 days after end of treatment (Up to 14 months)
Gastrointestinal disorders Bloating	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Investigations Blood bilirubin increased	69.2% 9/13 • Number of events 18 • 60 days after end of treatment (Up to 14 months)
Investigations Cardiac troponin T increased	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Musculoskeletal and connective tissue disorders Chest wall pain	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
General disorders Chills	76.9% 10/13 • Number of events 18 • 60 days after end of treatment (Up to 14 months)
Renal and urinary disorders Chronic kidney disease	7.7% 1/13 • Number of events 4 • 60 days after end of treatment (Up to 14 months)
Gastrointestinal disorders Colitis	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Psychiatric disorders Confusion	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Gastrointestinal disorders Constipation	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Respiratory, thoracic and mediastinal disorders Cough	30.8% 4/13 • Number of events 4 • 60 days after end of treatment (Up to 14 months)
Investigations CPK increased	7.7% 1/13 • Number of events 3 • 60 days after end of treatment (Up to 14 months)
Investigations Creatinine increased	69.2% 9/13 • Number of events 35 • 60 days after end of treatment (Up to 14 months)
Metabolism and nutrition disorders Dehydration	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Gastrointestinal disorders Diarrhea	69.2% 9/13 • Number of events 18 • 60 days after end of treatment (Up to 14 months)
Nervous system disorders Dizziness	30.8% 4/13 • Number of events 4 • 60 days after end of treatment (Up to 14 months)
Gastrointestinal disorders Dry mouth	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Skin and subcutaneous tissue disorders Dry skin	30.8% 4/13 • Number of events 4 • 60 days after end of treatment (Up to 14 months)
Nervous system disorders Dysphasia	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
General disorders Edema face	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
General disorders Edema limbs	46.2% 6/13 • Number of events 6 • 60 days after end of treatment (Up to 14 months)
Nervous system disorders Encephalopathy	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Nervous system disorders Extrapyramidal disorder	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Eye disorders Eye disorders - Other	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Injury, poisoning and procedural complications Fall	23.1% 3/13 • Number of events 3 • 60 days after end of treatment (Up to 14 months)
General disorders Fatigue	84.6% 11/13 • Number of events 14 • 60 days after end of treatment (Up to 14 months)
General disorders Fever	23.1% 3/13 • Number of events 4 • 60 days after end of treatment (Up to 14 months)
Vascular disorders Flushing	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Injury, poisoning and procedural complications Fracture	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Renal and urinary disorders Hematuria	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Gastrointestinal disorders Hemorrhoids	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Metabolism and nutrition disorders Hypercalcemia	7.7% 1/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Metabolism and nutrition disorders Hyperglycemia	53.8% 7/13 • Number of events 42 • 60 days after end of treatment (Up to 14 months)
Metabolism and nutrition disorders Hyperkalemia	46.2% 6/13 • Number of events 11 • 60 days after end of treatment (Up to 14 months)
Endocrine disorders Hyperthyroidism	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Metabolism and nutrition disorders Hypoalbuminemia	76.9% 10/13 • Number of events 35 • 60 days after end of treatment (Up to 14 months)
Metabolism and nutrition disorders Hypocalcemia	69.2% 9/13 • Number of events 34 • 60 days after end of treatment (Up to 14 months)
Metabolism and nutrition disorders Hypoglycemia	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Metabolism and nutrition disorders Hypokalemia	30.8% 4/13 • Number of events 6 • 60 days after end of treatment (Up to 14 months)
Metabolism and nutrition disorders Hypomagnesemia	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Metabolism and nutrition disorders Hyponatremia	53.8% 7/13 • Number of events 12 • 60 days after end of treatment (Up to 14 months)
Metabolism and nutrition disorders Hypophosphatemia	15.4% 2/13 • Number of events 3 • 60 days after end of treatment (Up to 14 months)
Vascular disorders Hypotension	76.9% 10/13 • Number of events 16 • 60 days after end of treatment (Up to 14 months)
Endocrine disorders Hypothyroidism	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Respiratory, thoracic and mediastinal disorders Hypoxia	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
General disorders Infusion related reaction	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
General disorders Infusion site extravasation	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Psychiatric disorders Insomnia	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Blood and lymphatic system disorders Leukocytosis	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
General disorders Localized edema	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Investigations Lymphocyte count decreased	61.5% 8/13 • Number of events 32 • 60 days after end of treatment (Up to 14 months)
Investigations Lymphocyte count increased	38.5% 5/13 • Number of events 10 • 60 days after end of treatment (Up to 14 months)
Gastrointestinal disorders Mucositis oral	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Gastrointestinal disorders Nausea	69.2% 9/13 • Number of events 16 • 60 days after end of treatment (Up to 14 months)
Investigations Neutrophil count decreased	15.4% 2/13 • Number of events 3 • 60 days after end of treatment (Up to 14 months)
Gastrointestinal disorders Oral pain	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
General disorders Pain	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Musculoskeletal and connective tissue disorders Pain in extremity	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Infections and infestations Papulopustular rash	30.8% 4/13 • Number of events 4 • 60 days after end of treatment (Up to 14 months)
Nervous system disorders Paresthesia	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Nervous system disorders Peripheral sensory neuropathy	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Investigations Platelet count decreased	61.5% 8/13 • Number of events 20 • 60 days after end of treatment (Up to 14 months)
Respiratory, thoracic and mediastinal disorders Pneumonitis	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Respiratory, thoracic and mediastinal disorders Postnasal drip	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Nervous system disorders Presyncope	23.1% 3/13 • Number of events 3 • 60 days after end of treatment (Up to 14 months)
Respiratory, thoracic and mediastinal disorders Productive cough	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Skin and subcutaneous tissue disorders Pruritus	84.6% 11/13 • Number of events 20 • 60 days after end of treatment (Up to 14 months)
Skin and subcutaneous tissue disorders Rash maculo-papular	30.8% 4/13 • Number of events 5 • 60 days after end of treatment (Up to 14 months)
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	7.7% 1/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Cardiac disorders Sinus tachycardia	30.8% 4/13 • Number of events 5 • 60 days after end of treatment (Up to 14 months)
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Infections and infestations Skin infection	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Respiratory, thoracic and mediastinal disorders Sneezing	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Vascular disorders Superficial thrombophlebitis	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	7.7% 1/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Ear and labyrinth disorders Tinnitus	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Renal and urinary disorders Urinary tract obstruction	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Investigations Urine output decreased	23.1% 3/13 • Number of events 5 • 60 days after end of treatment (Up to 14 months)
Infections and infestations Vaginal infection	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Injury, poisoning and procedural complications Vascular access complication	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Cardiac disorders Ventricular tachycardia	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)
Gastrointestinal disorders Vomiting	61.5% 8/13 • Number of events 14 • 60 days after end of treatment (Up to 14 months)
Investigations Weight loss	15.4% 2/13 • Number of events 2 • 60 days after end of treatment (Up to 14 months)
Investigations White blood cell decreased	30.8% 4/13 • Number of events 10 • 60 days after end of treatment (Up to 14 months)
Injury, poisoning and procedural complications Wound dehiscence	7.7% 1/13 • Number of events 1 • 60 days after end of treatment (Up to 14 months)

Additional Information

Ajjai Alva, MD

University of Michigan Rogel Cancer Center

Phone: 734-936-0091

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place