Trial Outcomes & Findings for High-Dose Interleukin-2 (HDIL-2), Combined With recMAGE-A3 + AS15 ASCI (NCT NCT01266603)

Last Updated: 2020-02-19

Results Overview

To evaluate the objective response rate induced by the concurrent administration of HDIL-2 and recMAGE-A3 + AS15 ASCI in patients with MAGE-A3-positive, unresectable or metastatic melanoma. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: 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

COMPLETED

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

Until disease progression or up to 3 years & 9 months

Results posted on

2020-02-19

Participant Flow

Participant milestones

Participant milestones
Measure	High-dose Interleukin-2 (HDIL-2) + recMAGE-A3 Protein (MAGE-A3 In the induction phase, 300 ug of MAGE-A3 +AS15 were given via intramuscular injection every 2 weeks for 6 cycles and then every 3 weeks for 6 cycles. HDIL-2 was initiated on the day following MAGE-A3 CI immunization or up to eight cycles on weeks 1,3,9,11,18.21,27 and 30 at 720,000 IU/kg every 8 h for up to 14 doses each cycle. Following completion of of the 30-week induction HDIL-2 + MAGE-A3, patients who remained on study were continued on the maintenance MAGE-A3 alone alone given every 6 weeks for 4 cycles, then every 12 weeks for 4 cycles, and then every 24 weeks for 4 cycles.
Overall Study STARTED	44
Overall Study MAGE-A3 Positive Tumor	18
Overall Study Patients Evaluable for Safety	17
Overall Study Patients Evaluable for Response	16
Overall Study Continued to Maintenance- MAGE-A3	4
Overall Study Maintenance Completion	2
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	42

Reasons for withdrawal

Reasons for withdrawal
Measure	High-dose Interleukin-2 (HDIL-2) + recMAGE-A3 Protein (MAGE-A3 In the induction phase, 300 ug of MAGE-A3 +AS15 were given via intramuscular injection every 2 weeks for 6 cycles and then every 3 weeks for 6 cycles. HDIL-2 was initiated on the day following MAGE-A3 CI immunization or up to eight cycles on weeks 1,3,9,11,18.21,27 and 30 at 720,000 IU/kg every 8 h for up to 14 doses each cycle. Following completion of of the 30-week induction HDIL-2 + MAGE-A3, patients who remained on study were continued on the maintenance MAGE-A3 alone alone given every 6 weeks for 4 cycles, then every 12 weeks for 4 cycles, and then every 24 weeks for 4 cycles.
Overall Study Adverse Event	1
Overall Study Lack of Efficacy	14
Overall Study Withdrawal by Subject	1
Overall Study Failed screening; MAGE-A3 negative	26

Baseline Characteristics

High-Dose Interleukin-2 (HDIL-2), Combined With recMAGE-A3 + AS15 ASCI

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	High-dose Interleukin-2 (HDIL-2) + recMAGE-A3 Protein (MAGE-A3 n=17 Participants In the induction phase, 300 ug of MAGE-A3 +AS15 were given via intramuscular injection every 2 weeks for 6 cycles and then every 3 weeks for 6 cycles. HDIL-2 was initiated on the day following MAGE-A3 CI immunization or up to eight cycles on weeks 1,3,9,11,18.21,27 and 30 at 720,000 IU/kg every 8 h for up to 14 doses each cycle. Following completion of of the 30-week induction HDIL-2 + MAGE-A3, patients who remained on study were continued on the maintenance MAGE-A3 alone alone given every 6 weeks for 4 cycles, then every 12 weeks for 4 cycles, and then every 24 weeks for 4 cycles.
Age, Continuous	55 Years n=5 Participants
Sex: Female, Male Female	7 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	17 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	17 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	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Until disease progression or up to 3 years & 9 months

Outcome measures

Outcome measures
Measure	High-dose Interleukin-2 (HDIL-2) + recMAGE-A3 Protein (MAGE-A3 n=16 Participants In the induction phase, 300 ug of MAGE-A3 +AS15 were given via intramuscular injection every 2 weeks for 6 cycles and then every 3 weeks for 6 cycles. HDIL-2 was initiated on the day following MAGE-A3 CI immunization or up to eight cycles on weeks 1,3,9,11,18.21,27 and 30 at 720,000 IU/kg every 8 h for up to 14 doses each cycle. Following completion of of the 30-week induction HDIL-2 + MAGE-A3, patients who remained on study were continued on the maintenance MAGE-A3 alone alone given every 6 weeks for 4 cycles, then every 12 weeks for 4 cycles, and then every 24 weeks for 4 cycles.
Objective Response Rate	25 percentage of participants

SECONDARY outcome

Timeframe: Until treatment completed or up to 3 years & 9 months

To evaluate the safety and toxicity profile of HDIL-2 in combination with recMAGE-A3 + AS15 ASCI in participants with MAGE-A3-positive, unresectable or metastatic melanoma

Outcome measures

Outcome measures
Measure	High-dose Interleukin-2 (HDIL-2) + recMAGE-A3 Protein (MAGE-A3 n=17 Participants In the induction phase, 300 ug of MAGE-A3 +AS15 were given via intramuscular injection every 2 weeks for 6 cycles and then every 3 weeks for 6 cycles. HDIL-2 was initiated on the day following MAGE-A3 CI immunization or up to eight cycles on weeks 1,3,9,11,18.21,27 and 30 at 720,000 IU/kg every 8 h for up to 14 doses each cycle. Following completion of of the 30-week induction HDIL-2 + MAGE-A3, patients who remained on study were continued on the maintenance MAGE-A3 alone alone given every 6 weeks for 4 cycles, then every 12 weeks for 4 cycles, and then every 24 weeks for 4 cycles.
Rate of SAEs	1 participants

SECONDARY outcome

Timeframe: Until treatment completed or up to 3 years & 9 months.

To evaluate the rate of stable disease, progression-free survival and the overall survival of patients with MAGE-A3- positive, unresectable or metastatic melanoma who received the combination of HDIL-2 and recMAGE-A3 + AS15 ASCI.

Outcome measures

Outcome measures
Measure	High-dose Interleukin-2 (HDIL-2) + recMAGE-A3 Protein (MAGE-A3 n=17 Participants In the induction phase, 300 ug of MAGE-A3 +AS15 were given via intramuscular injection every 2 weeks for 6 cycles and then every 3 weeks for 6 cycles. HDIL-2 was initiated on the day following MAGE-A3 CI immunization or up to eight cycles on weeks 1,3,9,11,18.21,27 and 30 at 720,000 IU/kg every 8 h for up to 14 doses each cycle. Following completion of of the 30-week induction HDIL-2 + MAGE-A3, patients who remained on study were continued on the maintenance MAGE-A3 alone alone given every 6 weeks for 4 cycles, then every 12 weeks for 4 cycles, and then every 24 weeks for 4 cycles.
Progression-free Survival	3.6 Months Interval 1.8 to 12.0

Adverse Events

High-dose Interleukin-2 (HDIL-2) + recMAGE-A3 Protein (MAGE-A3

Serious events: 1 serious events

Other events: 17 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	High-dose Interleukin-2 (HDIL-2) + recMAGE-A3 Protein (MAGE-A3 n=17 participants at risk In the induction phase, 300 ug of MAGE-A3 +AS15 were given via intramuscular injection every 2 weeks for 6 cycles and then every 3 weeks for 6 cycles. HDIL-2 was initiated on the day following MAGE-A3 CI immunization or up to eight cycles on weeks 1,3,9,11,18.21,27 and 30 at 720,000 IU/kg every 8 h for up to 14 doses each cycle. Following completion of of the 30-week induction HDIL-2 + MAGE-A3, patients who remained on study were continued on the maintenance MAGE-A3 alone alone given every 6 weeks for 4 cycles, then every 12 weeks for 4 cycles, and then every 24 weeks for 4 cycles.
Renal and urinary disorders Renal Insufficiency	5.9% 1/17 • Throughout treatment up to 3 years & 9 months.
Metabolism and nutrition disorders Hyperuricemia	5.9% 1/17 • Throughout treatment up to 3 years & 9 months.
Gastrointestinal disorders Diarrhea	5.9% 1/17 • Throughout treatment up to 3 years & 9 months.
Endocrine disorders Hypothyroidism	5.9% 1/17 • Throughout treatment up to 3 years & 9 months.
Cardiac disorders Hypotension	5.9% 1/17 • Throughout treatment up to 3 years & 9 months.
Renal and urinary disorders Acute kidney injury	5.9% 1/17 • Throughout treatment up to 3 years & 9 months.
Cardiac disorders Ventricular Tachycardia	5.9% 1/17 • Throughout treatment up to 3 years & 9 months.
Gastrointestinal disorders Gastroperesis	5.9% 1/17 • Throughout treatment up to 3 years & 9 months.

Other adverse events

Other adverse events
Measure	High-dose Interleukin-2 (HDIL-2) + recMAGE-A3 Protein (MAGE-A3 n=17 participants at risk In the induction phase, 300 ug of MAGE-A3 +AS15 were given via intramuscular injection every 2 weeks for 6 cycles and then every 3 weeks for 6 cycles. HDIL-2 was initiated on the day following MAGE-A3 CI immunization or up to eight cycles on weeks 1,3,9,11,18.21,27 and 30 at 720,000 IU/kg every 8 h for up to 14 doses each cycle. Following completion of of the 30-week induction HDIL-2 + MAGE-A3, patients who remained on study were continued on the maintenance MAGE-A3 alone alone given every 6 weeks for 4 cycles, then every 12 weeks for 4 cycles, and then every 24 weeks for 4 cycles.
Blood and lymphatic system disorders Anemia	82.4% 14/17 • Throughout treatment up to 3 years & 9 months.
Metabolism and nutrition disorders Anorexia	35.3% 6/17 • Throughout treatment up to 3 years & 9 months.
Musculoskeletal and connective tissue disorders Arthralgia	41.2% 7/17 • Throughout treatment up to 3 years & 9 months.
General disorders Chills	58.8% 10/17 • Throughout treatment up to 3 years & 9 months.
Gastrointestinal disorders Constipation	23.5% 4/17 • Throughout treatment up to 3 years & 9 months.
Respiratory, thoracic and mediastinal disorders Cough	17.6% 3/17 • Throughout treatment up to 3 years & 9 months.
Renal and urinary disorders Decreased Urinary Output	5.9% 1/17 • Throughout treatment up to 3 years & 9 months.
Gastrointestinal disorders Diarrhea	41.2% 7/17 • Throughout treatment up to 3 years & 9 months.
Skin and subcutaneous tissue disorders Dry Skin	88.2% 15/17 • Throughout treatment up to 3 years & 9 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	17.6% 3/17 • Throughout treatment up to 3 years & 9 months.
General disorders Edema	82.4% 14/17 • Throughout treatment up to 3 years & 9 months.
General disorders Fatigue	82.4% 14/17 • Throughout treatment up to 3 years & 9 months.
General disorders Fever	29.4% 5/17 • Throughout treatment up to 3 years & 9 months.
Nervous system disorders Headache	41.2% 7/17 • Throughout treatment up to 3 years & 9 months.
Metabolism and nutrition disorders Hyperglycemia	35.3% 6/17 • Throughout treatment up to 3 years & 9 months.
Metabolism and nutrition disorders Hyperkalemia	23.5% 4/17 • Throughout treatment up to 3 years & 9 months.
Metabolism and nutrition disorders Hypermagenesemia	5.9% 1/17 • Throughout treatment up to 3 years & 9 months.
Vascular disorders Hypertension	11.8% 2/17 • Throughout treatment up to 3 years & 9 months.
Metabolism and nutrition disorders Hyperuricemia	23.5% 4/17 • Throughout treatment up to 3 years & 9 months.
Metabolism and nutrition disorders Hypoalbunemia	82.4% 14/17 • Throughout treatment up to 3 years & 9 months.
Metabolism and nutrition disorders Hypoglycemia	29.4% 5/17 • Throughout treatment up to 3 years & 9 months.
Metabolism and nutrition disorders Hyponatremia	11.8% 2/17 • Throughout treatment up to 3 years & 9 months.
Metabolism and nutrition disorders Hypophosphatemia	17.6% 3/17 • Throughout treatment up to 3 years & 9 months.
Vascular disorders Hypotension	41.2% 7/17 • Throughout treatment up to 3 years & 9 months.
Investigations Increased Alanine Aminotransferase	17.6% 3/17 • Throughout treatment up to 3 years & 9 months.
Investigations Increased Alkaline Phosphatase	17.6% 3/17 • Throughout treatment up to 3 years & 9 months.
Investigations Increased Aspartate Aminotransferase	29.4% 5/17 • Throughout treatment up to 3 years & 9 months.
Investigations Increased Bilirrubin	35.3% 6/17 • Throughout treatment up to 3 years & 9 months.
Renal and urinary disorders Increased Creatinine	35.3% 6/17 • Throughout treatment up to 3 years & 9 months.
General disorders Injection Site Reaction	29.4% 5/17 • Throughout treatment up to 3 years & 9 months.
Investigations Lymphopenia	23.5% 4/17 • Throughout treatment up to 3 years & 9 months.
Musculoskeletal and connective tissue disorders Myalgia	58.8% 10/17 • Throughout treatment up to 3 years & 9 months.
Gastrointestinal disorders Nausea	64.7% 11/17 • Throughout treatment up to 3 years & 9 months.
Skin and subcutaneous tissue disorders Pain	70.6% 12/17 • Throughout treatment up to 3 years & 9 months.
Nervous system disorders Peripheral Sensory Neuropathy	41.2% 7/17 • Throughout treatment up to 3 years & 9 months.
Skin and subcutaneous tissue disorders Pruritis	70.6% 12/17 • Throughout treatment up to 3 years & 9 months.
Skin and subcutaneous tissue disorders Rash	47.1% 8/17 • Throughout treatment up to 3 years & 9 months.
Investigations Thrombocytopenia	11.8% 2/17 • Throughout treatment up to 3 years & 9 months.
Ear and labyrinth disorders Tinnitus	17.6% 3/17 • Throughout treatment up to 3 years & 9 months.
Cardiac disorders Ventricular tachycardia	11.8% 2/17 • Throughout treatment up to 3 years & 9 months.
Gastrointestinal disorders Vomiting	41.2% 7/17 • Throughout treatment up to 3 years & 9 months.
Investigations Weight Loss	17.6% 3/17 • Throughout treatment up to 3 years & 9 months.

Additional Information

Dr. Michael A Davies, BA,MD,PHD/Melanoma Medical Oncology

U T MD Anderson Cancer Center

Phone: 713-792-3454

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place