Trial Outcomes & Findings for Comparison of High-dose IL-2 and High-dose IL-2 With Radiation Therapy in Patients With Metastatic Melanoma. (NCT NCT01416831)

Last Updated: 2025-03-17

Results Overview

Determine the best overall tumor response rate of high dose IL-2 versus SBRT + high-dose IL-2 using RECIST v1.1 assessed by CT/MRI, criteria applied to all target and non-target lesions with the exclusion of sites treated with SBRT. For patients who have SBRT after progression on IL-2 monotherapy, the response rate will be recorded, but not counted as a response for the primary objective. Overall response rate (ORR) includes all measurable and non-measurable target lesions except the lesions treated by SBRT, which were assessed separately. Both CT and positron emission tomography imaging were employed to assess response. Complete Response: disappearance of all target/non-target lesions and no abnormalities on PET; Partial Response: ≥30% decrease in sum of longest diameter (LD) of target lesions; Progressive Disease: ≥20% increase in sum of LD recorded since tx start or appearance of ≥1 new lesions; Stable Disease: Neither qualifying for PR nor PD since tx started.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

At the end of Cycle 2 (Week 14).

Results posted on

2025-03-17

Participant Flow

A total of 63 potential patients were screened for eligibility at Providence Cancer Institute Franz Clinic and Compass Oncology East Clinic from 2011 to 2017.

Of the 50 patients who signed consent, six were excluded (3 due to rapid melanoma progression during screening, 2 due to cardiac ischemia on exercise tolerance testing, and 1 due to insurance issues). Of the 44 enrolled patients, 20 were assigned to Arm A, and 7 of those patients chose to participate in the optional crossover portion of the study.

Participant milestones

Participant milestones
Measure	Arm A: IL-2 Monotherapy Patients receive standard high-dose IL-2 therapy, with an opportunity to crossover to the experimental arm if there is disease progression noted after two cycles of high-dose IL-2. Crossover patients will be included in Arm A. High-dose IL-2: IL-2 will be given on a Monday at a dose of 600,000 IU per kilogram IV every 8 hours for up to 14 doses each cycle. The second cycle is planned 16 days after cycle 1 but may be delayed up to one week to allow toxicity to resolve. The maximum number of doses that can be given during two cycles will be 28 doses. Patients who respond after two cycles can receive 4 more cycles of IL-2. Patients with disease progression after 2 cycles may elect to receive radiation before a 3rd cycle of IL-2. If patients crossover, IL-2 will be given on the Monday following the last dose of radiation, at a dose of 600,000 IU per kilogram IV every 8 hours for a maximum of 14 doses each cycle. Another cycle is planned 16 days after cycle 3 but may be delayed up to one week to allow toxicity to resolve.	Arm B: SBRT + IL-2 Patients 1-20 who are assigned to receive radiation therapy will receive a single dose of radiation before IL-2; patients 21-44 assigned to receive radiation will receive two doses of radiation before receiving high-dose IL-2. Radiation therapy and high-dose IL-2: Patients 1 - 20 will receive a single fraction of radiation. Patients 21 through the completion of the study will receive two fractions. The dose for all patients will be 20 Gy per fraction to the prescription line at the edge of the planning treatment volume (PTV) with the last dose delivered on a Friday before IL-2 administration. For patients receiving two radiation doses, the doses can be administered on the Wednesday and Friday before IL-2 starts. Patients who are assigned to IL-2 monotherapy and have progressive disease after two IL-2 cycles are then eligible to receive SBRT before cycle 3 of IL-2 commences, single fraction for patients 1-20 and two fractions for patients 21- end of study.
Cycles 1 & 2 (Weeks 1-14) STARTED	20	24
Cycles 1 & 2 (Weeks 1-14) COMPLETED	19	22
Cycles 1 & 2 (Weeks 1-14) NOT COMPLETED	1	2
SBRT Crossover Period STARTED	7	0
SBRT Crossover Period COMPLETED	7	0
SBRT Crossover Period NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: IL-2 Monotherapy Patients receive standard high-dose IL-2 therapy, with an opportunity to crossover to the experimental arm if there is disease progression noted after two cycles of high-dose IL-2. Crossover patients will be included in Arm A. High-dose IL-2: IL-2 will be given on a Monday at a dose of 600,000 IU per kilogram IV every 8 hours for up to 14 doses each cycle. The second cycle is planned 16 days after cycle 1 but may be delayed up to one week to allow toxicity to resolve. The maximum number of doses that can be given during two cycles will be 28 doses. Patients who respond after two cycles can receive 4 more cycles of IL-2. Patients with disease progression after 2 cycles may elect to receive radiation before a 3rd cycle of IL-2. If patients crossover, IL-2 will be given on the Monday following the last dose of radiation, at a dose of 600,000 IU per kilogram IV every 8 hours for a maximum of 14 doses each cycle. Another cycle is planned 16 days after cycle 3 but may be delayed up to one week to allow toxicity to resolve.	Arm B: SBRT + IL-2 Patients 1-20 who are assigned to receive radiation therapy will receive a single dose of radiation before IL-2; patients 21-44 assigned to receive radiation will receive two doses of radiation before receiving high-dose IL-2. Radiation therapy and high-dose IL-2: Patients 1 - 20 will receive a single fraction of radiation. Patients 21 through the completion of the study will receive two fractions. The dose for all patients will be 20 Gy per fraction to the prescription line at the edge of the planning treatment volume (PTV) with the last dose delivered on a Friday before IL-2 administration. For patients receiving two radiation doses, the doses can be administered on the Wednesday and Friday before IL-2 starts. Patients who are assigned to IL-2 monotherapy and have progressive disease after two IL-2 cycles are then eligible to receive SBRT before cycle 3 of IL-2 commences, single fraction for patients 1-20 and two fractions for patients 21- end of study.
Cycles 1 & 2 (Weeks 1-14) Death	1	2

Baseline Characteristics

Comparison of High-dose IL-2 and High-dose IL-2 With Radiation Therapy in Patients With Metastatic Melanoma.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: IL-2 Monotherapy n=20 Participants Patients receive standard high-dose IL-2 therapy, with an opportunity to crossover to the experimental arm if there is disease progression noted after two cycles of high-dose IL-2. Crossover patients will be included in Arm A. High-dose IL-2: IL-2 will be given on a Monday at a dose of 600,000 IU per kilogram IV every 8 hours for up to 14 doses each cycle. The second cycle is planned 16 days after cycle 1 but may be delayed up to one week to allow toxicity to resolve. The maximum number of doses that can be given during two cycles will be 28 doses. Patients who respond after two cycles can receive 4 more cycles of IL-2. Patients with disease progression after 2 cycles may elect to receive radiation before a 3rd cycle of IL-2. If patients crossover, IL-2 will be given on the Monday following the last dose of radiation, at a dose of 600,000 IU per kilogram IV every 8 hours for a maximum of 14 doses each cycle. Another cycle is planned 16 days after cycle 3 but may be delayed up to one week to allow toxicity to resolve.	Arm B: SBRT + IL-2 n=24 Participants Patients 1-20 who are assigned to receive radiation therapy will receive a single dose of radiation before IL-2; patients 21-44 assigned to receive radiation will receive two doses of radiation before receiving high-dose IL-2. Radiation therapy and high-dose IL-2: Patients 1 - 20 will receive a single fraction of radiation. Patients 21 through the completion of the study will receive two fractions. The dose for all patients will be 20 Gy per fraction to the prescription line at the edge of the planning treatment volume (PTV) with the last dose delivered on a Friday before IL-2 administration. For patients receiving two radiation doses, the doses can be administered on the Wednesday and Friday before IL-2 starts. Patients who are assigned to IL-2 monotherapy and have progressive disease after two IL-2 cycles are then eligible to receive SBRT before cycle 3 of IL-2 commences, single fraction for patients 1-20 and two fractions for patients 21- end of study.	Total n=44 Participants Total of all reporting groups
Age, Continuous	57.5 years n=5 Participants	53 years n=7 Participants	57 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	18 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants	24 Participants n=7 Participants	44 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	24 Participants n=7 Participants	44 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	24 participants n=7 Participants	44 participants n=5 Participants
BRAF Status Mutated	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
BRAF Status Wild Type	5 Participants n=5 Participants	14 Participants n=7 Participants	19 Participants n=5 Participants
BRAF Status Unknown	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: At the end of Cycle 2 (Week 14).

Population: There will be a comparison of the overall tumor response of patients receiving one versus two SBRT doses. Responses from patients who participated in the crossover portion of the study were excluded.

Outcome measures

Outcome measures
Measure	Arm A: IL-2 Monotherapy n=20 Participants Patients receive standard high-dose IL-2 therapy, with an opportunity to crossover to the experimental arm if there is disease progression noted after two cycles of high-dose IL-2. Crossover patients will be included in Arm A. High-dose IL-2: IL-2 will be given on a Monday at a dose of 600,000 IU per kilogram IV every 8 hours for up to 14 doses each cycle. The second cycle is planned 16 days after cycle 1 but may be delayed up to one week to allow toxicity to resolve. The maximum number of doses that can be given during two cycles will be 28 doses. Patients who respond after two cycles can receive 4 more cycles of IL-2. Patients with disease progression after 2 cycles may elect to receive radiation before a 3rd cycle of IL-2. If patients crossover, IL-2 will be given on the Monday following the last dose of radiation, at a dose of 600,000 IU per kilogram IV every 8 hours for a maximum of 14 doses each cycle. Another cycle is planned 16 days after cycle 3 but may be delayed up to one week to allow toxicity to resolve.	Arm B: SBRT + IL-2 n=24 Participants Patients 1-20 who are assigned to receive radiation therapy will receive a single dose of radiation before IL-2; patients 21-44 assigned to receive radiation will receive two doses of radiation before receiving high-dose IL-2. Radiation therapy and high-dose IL-2: Patients 1 - 20 will receive a single fraction of radiation. Patients 21 through the completion of the study will receive two fractions. The dose for all patients will be 20 Gy per fraction to the prescription line at the edge of the planning treatment volume (PTV) with the last dose delivered on a Friday before IL-2 administration. For patients receiving two radiation doses, the doses can be administered on the Wednesday and Friday before IL-2 starts. Patients who are assigned to IL-2 monotherapy and have progressive disease after two IL-2 cycles are then eligible to receive SBRT before cycle 3 of IL-2 commences, single fraction for patients 1-20 and two fractions for patients 21- end of study.
Best Overall Tumor Response of High Dose IL-2 vs. SBRT + High Dose IL-2 Overall Response Rate (ORR)	54 percentage of participants	35 percentage of participants
Best Overall Tumor Response of High Dose IL-2 vs. SBRT + High Dose IL-2 Complete Response (CR)	15 percentage of participants	21 percentage of participants
Best Overall Tumor Response of High Dose IL-2 vs. SBRT + High Dose IL-2 Partial Response (PR)	20 percentage of participants	33 percentage of participants
Best Overall Tumor Response of High Dose IL-2 vs. SBRT + High Dose IL-2 Stable Disease (SD)	25 percentage of participants	21 percentage of participants
Best Overall Tumor Response of High Dose IL-2 vs. SBRT + High Dose IL-2 Progressive Disease (PD)	40 percentage of participants	25 percentage of participants

SECONDARY outcome

Timeframe: 7 weeks following Cycle 2 (Week 21).

Population: This measure is specifically for patients enrolled into IL-2 monotherapy cohort who then opted for radiation therapy in addition to IL-2.

Measure the response rate of patients who have disease progression after the first IL-2 cycles (using RECIST criteria) who received SBRT prior to cycle 3 of IL-2.

Outcome measures

Outcome measures
Measure	Arm A: IL-2 Monotherapy n=7 Participants Patients receive standard high-dose IL-2 therapy, with an opportunity to crossover to the experimental arm if there is disease progression noted after two cycles of high-dose IL-2. Crossover patients will be included in Arm A. High-dose IL-2: IL-2 will be given on a Monday at a dose of 600,000 IU per kilogram IV every 8 hours for up to 14 doses each cycle. The second cycle is planned 16 days after cycle 1 but may be delayed up to one week to allow toxicity to resolve. The maximum number of doses that can be given during two cycles will be 28 doses. Patients who respond after two cycles can receive 4 more cycles of IL-2. Patients with disease progression after 2 cycles may elect to receive radiation before a 3rd cycle of IL-2. If patients crossover, IL-2 will be given on the Monday following the last dose of radiation, at a dose of 600,000 IU per kilogram IV every 8 hours for a maximum of 14 doses each cycle. Another cycle is planned 16 days after cycle 3 but may be delayed up to one week to allow toxicity to resolve.	Arm B: SBRT + IL-2 Patients 1-20 who are assigned to receive radiation therapy will receive a single dose of radiation before IL-2; patients 21-44 assigned to receive radiation will receive two doses of radiation before receiving high-dose IL-2. Radiation therapy and high-dose IL-2: Patients 1 - 20 will receive a single fraction of radiation. Patients 21 through the completion of the study will receive two fractions. The dose for all patients will be 20 Gy per fraction to the prescription line at the edge of the planning treatment volume (PTV) with the last dose delivered on a Friday before IL-2 administration. For patients receiving two radiation doses, the doses can be administered on the Wednesday and Friday before IL-2 starts. Patients who are assigned to IL-2 monotherapy and have progressive disease after two IL-2 cycles are then eligible to receive SBRT before cycle 3 of IL-2 commences, single fraction for patients 1-20 and two fractions for patients 21- end of study.
Response Rate in Crossover Patients CR	1 Count of participants	—
Response Rate in Crossover Patients PR	2 Count of participants	—
Response Rate in Crossover Patients SD	0 Count of participants	—
Response Rate in Crossover Patients PD	4 Count of participants	—

Adverse Events

Arm A: IL-2 Monotherapy

Serious events: 17 serious events

Other events: 2 other events

Deaths: 16 deaths

Arm B: SBRT + IL-2

Serious events: 17 serious events

Other events: 0 other events

Deaths: 18 deaths

Serious adverse events

Other adverse events

Additional Information

Brendan Curti, M.D.

Earle A. Chiles Research Institute, Providence Cancer Institute

Phone: 503-215-6588

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm A: IL-2 Monotherapy n=20 participants at risk Patients receive standard high-dose IL-2 therapy, with an opportunity to crossover to the experimental arm if there is disease progression noted after two cycles of high-dose IL-2. Crossover patients will be included in Arm A. High-dose IL-2: IL-2 will be given on a Monday at a dose of 600,000 IU per kilogram IV every 8 hours for up to 14 doses each cycle. The second cycle is planned 16 days after cycle 1 but may be delayed up to one week to allow toxicity to resolve. The maximum number of doses that can be given during two cycles will be 28 doses. Patients who respond after two cycles can receive 4 more cycles of IL-2. Patients with disease progression after 2 cycles may elect to receive radiation before a 3rd cycle of IL-2. If patients crossover, IL-2 will be given on the Monday following the last dose of radiation, at a dose of 600,000 IU per kilogram IV every 8 hours for a maximum of 14 doses each cycle. Another cycle is planned 16 days after cycle 3 but may be delayed up to one week to allow toxicity to resolve.	Arm B: SBRT + IL-2 n=31 participants at risk Patients 1-20 who are assigned to receive radiation therapy will receive a single dose of radiation before IL-2; patients 21-44 assigned to receive radiation will receive two doses of radiation before receiving high-dose IL-2. Radiation therapy and high-dose IL-2: Patients 1 - 20 will receive a single fraction of radiation. Patients 21 through the completion of the study will receive two fractions. The dose for all patients will be 20 Gy per fraction to the prescription line at the edge of the planning treatment volume (PTV) with the last dose delivered on a Friday before IL-2 administration. For patients receiving two radiation doses, the doses can be administered on the Wednesday and Friday before IL-2 starts. Patients who are assigned to IL-2 monotherapy and have progressive disease after two IL-2 cycles are then eligible to receive SBRT before cycle 3 of IL-2 commences, single fraction for patients 1-20 and two fractions for patients 21- end of study. Patients 25-31 are those who participated in the optional crossover period from Arm A and are included in the at risk figure.
Gastrointestinal disorders Abdominal Pain	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Investigations Alkaline Phosphate Increased	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Investigations ALT (SGPT) Increased	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Blood and lymphatic system disorders Anemia	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Metabolism and nutrition disorders Anorexia	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Metabolism and nutrition disorders Arthralgia	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Investigations AST (SGOT) Increased	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Blood and lymphatic system disorders Bilirubin Increased/Elevated	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Vascular disorders Capillary leak pulmonary	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
General disorders Chills	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Psychiatric disorders Confusion	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Gastrointestinal disorders Constipation	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Respiratory, thoracic and mediastinal disorders Cough	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Investigations Creatinine Increased	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Gastrointestinal disorders Diarrhea	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Nervous system disorders Dizziness	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Nervous system disorders Drowsiness	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
General disorders Edema, lower extremity	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Skin and subcutaneous tissue disorders Erythroderma	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
General disorders Fatigue	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Psychiatric disorders Hallucinations	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Metabolism and nutrition disorders Hyperglycemia	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Metabolism and nutrition disorders Hypocalcemia	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Metabolism and nutrition disorders Hypokalemia	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Metabolism and nutrition disorders Hypomagnesemia	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Metabolism and nutrition disorders Hyponatremia	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Metabolism and nutrition disorders Hypophosphatemia	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Metabolism and nutrition disorders Metabolic acidosis	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Gastrointestinal disorders Mucositis	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Musculoskeletal and connective tissue disorders Myalgias	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Investigations Oliguria	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Gastrointestinal disorders Pain, abdominal	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Musculoskeletal and connective tissue disorders Pain, knee	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Investigations Platelet count decreased	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Injury, poisoning and procedural complications Dry Desquamation	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Skin and subcutaneous tissue disorders Skin, Itching	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Cardiac disorders Tachycardia	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Skin and subcutaneous tissue disorders Vitiligo, upper extremity	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Psychiatric disorders Vivid Dreams	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
General disorders Azotemia	5.0% 1/20 • Number of events 1 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.
Investigations White Blood Cells Decreased	10.0% 2/20 • Number of events 2 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.	0.00% 0/31 • Screening through Week 7 (or 8 if IL-2 restaging) and during the optional crossover phase, up to 7 weeks. All adverse events reported during the course of the study.