A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803, a Novel Recombinant IL-15 Complex in Patients With Advanced Solid Tumors: Melanoma, Renal Cell, Non-Small Cell Lung and Squamous Cell Head and Neck Cancer
Phase: PHASE1
Conditions: Advanced Solid Tumors
Sponsor: Altor BioScience

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: April 8, 2013 
 
1 
NCI Protocol #: 
CITN06-ALT-803 
 
Local Protocol #: 
CA-ALT-803-01-13 
 
TITLE: A Phase 1/2 Study of the Clinical and Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with Advanced Melanoma  
 
(Advanced Melanoma – ICD-10053571) 
 
 
 
 
 
 
 
 
 
Sponsor:  
 
 
 
 
 
 
 
Coordinating Center: 
 
 
Cancer Immunotherapy Trials Network, Fred Hutchinson 
Cancer Research Center 
 
*Principal Investigator: 
Kim Margolin, MD 
 
University of Washington, Seattle Cancer Care Alliance 
 
825 East Lake Ave E, G4810 
 
Seattle WA 98109-1023 
 
Telephone: 206-288-7341 
 
Fax: 206-288-6681 
 
kmargoli@seattlecca.org 
 
Co-Investigators: 
Adil Daud, MD 
 
University of California San Francisco 
 
(415) 353-7392 
 
 
adaud@medicine.ucsf.edu 
 
 
 
Marc Ernstoff, MD 
 
Dartmouth Hitchcock Medical Center 
 
(603) 650-5534 
 
marc.s.ernstoff@hitchcock.org  
 
 
Thomas Waldmann, MD 
 
National Cancer Institute 
 
(301) 496-6656 
 
tawald@mail.nih.gov 
 
 
 
  
 
  Hing C. Wong, Ph.D. 
  Altor Bioscience Corporation. 
  Miramar, Florida 33025 
  Telephone: 
954-443-8600 
  Safety Data Fax: 
954-443-8602 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: April 8, 2013 
 
2 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CA-ALT-803-01-13 
 
 
Protocol Title: 
A Phase 1/2 Study of the Clinical and 
Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with 
Advanced Melanoma  
 
 
Date of Protocol: 
 
Version # 01 
April 8, 2013 
 
 
Sponsor Contact:  
 
Hing C. Wong, Ph.D. 
Altor Bioscience Corporation. 
Miramar, Florida 33025 
Telephone: 
954-443-8600 
Safety Data Fax: 
954-443-8602 
 
 
By my signature below, I hereby attest that I have read, and that I understand and will abide by 
all the conditions, instructions, and restrictions contained in the attached protocol. 
 
Additionally, I will not initiate this study without approval of the appropriate Institutional 
Review Board (IRB), and I understand that any changes in the protocol must be approved in 
writing by the sponsor, the IRB, and, in certain cases the FDA, before they can be implemented, 
except where necessary to eliminate hazards to subjects. 
 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Principal Investigator’s Name (Print) 
 
 
 
 
 
 
 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: April 8, 2013 
 
3 
Statistician: 
 
Study Coordinator: N/A  
Zoe Moodie, PhD 
 
Fred Hutchinson Cancer Research Center  
 
1100 Fairview Ave N, Mail Stop M2-C200 
 
Seattle, WA 98109 
  
 (206) 667-7077 
 
Fax: (206) 667-4378 
 
zoe@fhcrc.org 
 
 
Responsible Research Nurse: N/A  
Responsible Data Manager: N/A  
 
 
 
NCI-Supplied Agent(s): N/A  
 
Other Agent(s): ALT-803: a “recombinant human superagonist interleukin-15 (IL-15) complex” 
(AKA, IL-15N72D:IL-15RαSu/IgG1 Fc complex) NSC#: TBD 
  
 
Investigational Agent  
IND# 
IND Sponsor  
ALT-803 
TBD 
Altor Bioscience Corporation  
 
Protocol Type / Version # / Version Date: 
Original/Version 1/April 8, 2013 
 
 
 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: April 8, 2013 
 
4 
SCHEMA 
 
Regimen Description 
Agent 
Pre-Medications: 
Precautions 
Dose 
Route 
Schedule 
Cycle Length 
ALT-803 
*1 dose of 
antipyretic 
medication within 
30 min of ALT-803 
administration 
 
*1 dose of 
antipyretic 
medication 4 h after 
ALT-803 
administration 
0.003 mg/kg 
or 
0.006 mg/kg 
or 
0.01 mg/kg 
or 
0.02 mg/kg 
or 
0.03 mg/kg 
IV 
D1, W1 
D1, W2 
D1, W3 
D1, W4 
42 days 
(4 weeks on, 2 weeks off) 
With up to 4 cycles in the 
absence of unacceptable 
toxicity and disease 
progression 
*Non-steroidal anti-inflammatory medication such as acetaminophen, ibuprofen, Naproxen or 
aspirin may be given per physician discretion. Not to exceed standard maximum thresholds: 
 
Acetaminophen: not to exceed 3000 mg (3 g) in 24 hours 
Ibuprofen: not to exceed 2400 mg in 24 hours 
Naproxen: not to exceed 1100 mg in 24 hours 
Aspirin: not to exceed 3800 mg in 24 hours 
 
 
Dose Escalation Schedule 
Dose Level 
Dose of ALT-803 
Level -1 
0.001 mg/kg (only if the first level is too toxic) 
Level 1 
0.003 mg/kg 
Level 2 
0.006 mg/kg 
Level 3 
0.01 mg/kg 
Level 4 
0.02 mg/kg 
Level 5 
0.03 mg/kg 
 
 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: April 8, 2013 
 
51 
 
10. STUDY CALENDAR 
 
Baseline evaluations are to be conducted within 1 to 30 days before start of protocol therapy, as indicated in the study calendar, except 
for pregnancy testing, which must be performed within 48 hours prior to initial ALT-803 administration. Scans and x-rays must be 
performed within 30 days before the start of therapy. In the event that the patient’s condition is changing, laboratory evaluations 
should be repeated within 24 hours before initiating the next cycle of therapy. Please refer to the study calendar below for specific 
timing of required evaluations. 
 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
F/U 14 
days post 
last 
injection 
6 
Month 
F/U 
Visit 
 
Within 30 d 
Within 14 d 
W1 
D1 
W2 
D8 
W3 
D15 
W4 
D22 
W5 
D29 
W6 
D36 
W1 
D1 
W2 
D8 
W3 
D15 
W4 
D22 
W5 
D29 
W6 
D36 
 
 
ALT-803*(A) 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant meds 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
Vital signs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
Performance status 
 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
CBC w/diff, plts 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
PT/PTT 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistrya 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Antinuclear antibody 
(ANA) 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
Electrocardiogram (ECG)b 
 
 
Xb Xb 
 
 
 
 
Xb 
Xb 
Xb 
 
 
 
 
Xb 
 
 
ECHO (as indicated)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event evaluation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor measurementsc 
X 
Tumor measurements are repeated every 8 ± 1 week and 16 ± 2 weeks  
X 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: April 8, 2013 
 
52 
CT, MRI, or PET of chest, 
abdomen, pelvisd 
X 
Documentation (radiologic) must be provided for patients removed from study for progressive disease. 
 
CT or MRI Braind [as 
indicated for symptoms 
only] 
X 
If negative at baseline, to be repeated only with symptoms  
X 
Radiologic evaluation by 
RECIST 1.1 
X 
Radiologic measurements should be performed every 8 ± 1 week and 16 ± 2 weeks  
X 
B-HCGe 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
EBV serostatus 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CMV serostatus 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid studies: TSH, T4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
PK  
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
WB Immunophenotypingg 
 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 
IFN-γ ELISPOTg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
NK-cell functiong 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
Plasma cytokinesg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
Serum Ab to ALT-803g 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
PBMC 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
X 
Serum 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
Abbreviations: Ab, antibodies; CBC, complete blood count; CT, computed tomography; MRI, magnetic resonance imaging; NK, natural killer; PET, positron emission 
tomography; PK, pharmacokinetics; PPT, partial thromboplastin time; PT, prothrombin time  
*(A), Agent 
a Blood chemistries include: creatinine, glucose, total protein, blood urea nitrogen (BUN), total carbon dioxide (CO2), albumin, total bilirubin, phosphorus, 
alkaline phosphatase, aspartate transaminae (AST), and alanine transaminase (ALT) 
b ECGs are to be done before ALT-803 injections on Day 1 and 6 hours after the first ALT-803 injection (Day1) of all treatment cycles. In addition an ECG is to 
be done at the end of treatment, i.e., end of cycle 1, or after subsequent cycles have been completed. 
c baseline tumor assessment scans should be done 1 to 30 days before beginning treatment. 
d CT, MRI, or PET is acceptable for imaging assessment purposes  
e Pregnancy test may be done up to 48 hours before ALT-803 administration 
f See pharmacokinetic flow sheet for specific draw times 
g Blood for WB Immunophenotyping, IFN-γ ELISPOT, NK-cell function, plasma cytokines, and serum Ab to ALT-803 must be drawn before the patient 
receives ALT-803 injections on Days 1, 8, 15 and 22 of each treatment cycle.  

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: May 6, 2013 
 
1 
NCI Protocol #: 
CITN06-ALT-803 
 
Local Protocol #: 
CA-ALT-803-01-13 
 
TITLE: A Phase 1/2 Study of the Clinical and Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with Advanced Melanoma  
 
(Advanced Melanoma – ICD-10053571) 
 
 
 
 
 
 
 
 
 
Sponsor:  
 
 
 
 
 
 
 
Coordinating Center: 
 
 
Cancer Immunotherapy Trials Network, Fred Hutchinson 
Cancer Research Center 
 
*Principal Investigator: 
Kim Margolin, MD 
 
University of Washington, Seattle Cancer Care Alliance 
 
825 East Lake Ave E, G4810 
 
Seattle WA 98109-1023 
 
Telephone: 206-288-7341 
 
Fax: 206-288-6681 
 
kmargoli@seattlecca.org 
 
Co-Investigators: 
Adil Daud, MD 
 
University of California San Francisco 
 
(415) 353-7392 
 
 
adaud@medicine.ucsf.edu 
 
 
 
Marc Ernstoff, MD 
 
Dartmouth Hitchcock Medical Center 
 
(603) 650-5534 
 
marc.s.ernstoff@hitchcock.org  
 
 
Thomas Waldmann, MD 
 
National Cancer Institute 
 
(301) 496-6656 
 
tawald@mail.nih.gov 
 
 
 
  
 
  Hing C. Wong, Ph.D. 
  Altor Bioscience Corporation. 
  Miramar, Florida 33025 
  Telephone: 
954-443-8600 
  Safety Data Fax: 
954-443-8602 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: May 6, 2013 
 
2 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CA-ALT-803-01-13 
 
 
Protocol Title: 
A Phase 1/2 Study of the Clinical and 
Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with 
Advanced Melanoma  
 
 
Date of Protocol: 
 
Version # 01 
Version # 02 
April 8, 2013 
May 6, 2013 
 
Sponsor Contact:  
 
Hing C. Wong, Ph.D. 
Altor Bioscience Corporation. 
Miramar, Florida 33025 
Telephone: 
954-443-8600 
Safety Data Fax: 
954-443-8602 
 
 
By my signature below, I hereby attest that I have read, and that I understand and will abide by 
all the conditions, instructions, and restrictions contained in the attached protocol. 
 
Additionally, I will not initiate this study without approval of the appropriate Institutional 
Review Board (IRB), and I understand that any changes in the protocol must be approved in 
writing by the sponsor, the IRB, and, in certain cases the FDA, before they can be implemented, 
except where necessary to eliminate hazards to subjects. 
 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Principal Investigator’s Name (Print) 
 
 
 
 
 
 
 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: May 6, 2013 
 
3 
Statistician: 
 
Study Coordinator: N/A  
Zoe Moodie, PhD 
 
Fred Hutchinson Cancer Research Center  
 
1100 Fairview Ave N, Mail Stop M2-C200 
 
Seattle, WA 98109 
  
 (206) 667-7077 
 
Fax: (206) 667-4378 
 
zoe@fhcrc.org 
 
 
Responsible Research Nurse: N/A  
Responsible Data Manager: N/A  
 
 
 
NCI-Supplied Agent(s): N/A  
 
Other Agent(s): ALT-803: a “recombinant human superagonist interleukin-15 (IL-15) complex” 
(AKA, IL-15N72D:IL-15RαSu/IgG1 Fc complex) NSC#: TBD 
  
 
Investigational Agent  
IND# 
IND Sponsor  
ALT-803 
118280 
Altor Bioscience Corporation  
 
Protocol Type / Version # / Version Date: 
Version 2/May 6, 2013 
 
 
 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: May 6, 2013 
 
4 
SCHEMA 
 
Regimen Description 
Agent 
Pre-Medications: 
Precautions 
Dose 
Route 
Schedule 
Cycle Length 
ALT-803 
*1 dose of 
antipyretic 
medication within 
30 min of ALT-803 
administration 
 
*1 dose of 
antipyretic 
medication 4 h after 
ALT-803 
administration 
0.003 mg/kg 
or 
0.006 mg/kg 
or 
0.01 mg/kg 
or 
0.02 mg/kg 
or 
0.03 mg/kg 
IV 
D1, W1 
D1, W2 
D1, W3 
D1, W4 
42 days 
(4 weeks on, 2 weeks off) 
With up to 4 cycles in the 
absence of unacceptable 
toxicity and disease 
progression 
*Non-steroidal anti-inflammatory medication including agents such as acetaminophen, 
ibuprofen, or Naproxen may be given per physician discretion. Not to exceed standard maximum 
thresholds, for example: 
 
Acetaminophen: not to exceed 3000 mg (3 g) in 24 hours 
Ibuprofen: not to exceed 2400 mg in 24 hours 
Naproxen: not to exceed 1100 mg in 24 hours 
 
 
Dose Escalation Schedule 
Dose Level 
Dose of ALT-803 
Level -1 
0.001 mg/kg (only if the first level is too toxic) 
Level 1 
0.003 mg/kg 
Level 2 
0.006 mg/kg 
Level 3 
0.01 mg/kg 
Level 4 
0.02 mg/kg 
Level 5 
0.03 mg/kg 
 
 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: May 6, 2013 
 
53 
10. STUDY CALENDAR 
 
Baseline evaluations are to be conducted within 1 to 30 days before start of protocol therapy, as indicated in the study calendar, except 
for pregnancy testing, which must be performed within 48 hours prior to initial ALT-803 administration. Scans and x-rays must be 
performed within 30 days before the start of therapy. In the event that the patient’s condition is changing, laboratory evaluations 
should be repeated within 24 hours before initiating the next cycle of therapy. Please refer to the study calendar below for specific 
timing of required evaluations. 
 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
F/U 14 
days post 
last 
injection 
6 
Month 
F/U 
Visit 
 
Within 30 d 
Within 14 d 
W1 
D1 
W2 
D8 
W3 
D15 
W4 
D22 
W5 
D29 
W6 
D36 
W1 
D1 
W2 
D8 
W3 
D15 
W4 
D22 
W5 
D29 
W6 
D36 
 
 
ALT-803*(A) 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant meds 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam# 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
Vital signs with oxygen 
saturation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
Performance status 
 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
CBC w/diff, plts 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
PT/PTT 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistrya 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Antinuclear antibody 
(ANA) 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
Electrocardiogram (ECG)b 
 
 
Xb Xb 
 
 
 
 
Xb 
Xb 
Xb 
 
 
 
 
Xb 
 
 
ECHO (as indicated)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pulmonary function test 
(spirometry) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: May 6, 2013 
 
54 
Adverse event evaluation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor measurementsc 
X 
Tumor measurements are repeated every 8 ± 1 week and 16 ± 2 weeks  
X 
CT, MRI, or PET of chest, 
abdomen, pelvisd 
X 
Documentation (radiologic) must be provided for patients removed from study for progressive disease. 
 
CT or MRI Braind [as 
indicated for symptoms 
only] 
X 
If negative at baseline, to be repeated only with symptoms  
X 
Radiologic evaluation by 
RECIST 1.1 
X 
Radiologic measurements should be performed every 8 ± 1 week and 16 ± 2 weeks  
X 
B-HCGe 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
EBV serostatus 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CMV serostatus 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid studies: TSH, T4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
PK  
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
WB Immunophenotypingg 
 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 
IFN-γ ELISPOTg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
NK-cell functiong 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
Plasma cytokinesg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
Serum Ab to ALT-803g 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
PBMC 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
X 
Serum 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
Abbreviations: Ab, antibodies; CBC, complete blood count; CT, computed tomography; MRI, magnetic resonance imaging; NK, natural killer; PET, positron emission 
tomography; PK, pharmacokinetics; PPT, partial thromboplastin time; PT, prothrombin time  
*(A), Agent 
# Physical exam must always include neurological assessment.  In addition, all patients will have formal ophthalmologic testing prior to starting therapy and 
repeated if clinically indicated. 
a Blood chemistries include: creatinine, glucose, total protein, blood urea nitrogen (BUN), total carbon dioxide (CO2), albumin, total bilirubin, phosphorus, 
alkaline phosphatase, aspartate transaminase (AST), and alanine transaminase (ALT) 
b ECGs are to be done before ALT-803 injections on Day 1 and 4, 12 and 24 hours post-dose.  ECGs are to be repeated before and at 4 hours (the end of the    
   outpatient observation period) following each subsequent dose.   
c Baseline tumor assessment scans should be done 1 to 30 days before beginning treatment. 
d CT, MRI, or PET is acceptable for imaging assessment purposes  
e Pregnancy test may be done up to 48 hours before ALT-803 administration 
f See pharmacokinetic flow sheet for specific draw times 
g Blood for WB Immunophenotyping, IFN-γ ELISPOT, NK-cell function, plasma cytokines, and serum Ab to ALT-803 must be drawn before the patient  
   receives ALT-803 injections on Days 1, 8, 15 and 22 of each treatment cycle.  

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: July 26, 2013 
 
1 
NCI Protocol #: 
CITN06-ALT-803 
 
Local Protocol #: 
CA-ALT-803-01-13 
 
TITLE: A Phase 1/2 Study of the Clinical and Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with Advanced Melanoma  
 
(Advanced Melanoma – ICD-10053571) 
 
 
 
 
 
 
 
 
 
Sponsor:  
 
 
 
 
 
 
 
Coordinating Center: 
 
 
Cancer Immunotherapy Trials Network, Fred Hutchinson 
Cancer Research Center 
 
*Principal Investigator: 
Kim Margolin, MD 
 
University of Washington, Seattle Cancer Care Alliance 
 
825 East Lake Ave E, G4810 
 
Seattle WA 98109-1023 
 
Telephone: 206-288-7341 
 
Fax: 206-288-6681 
 
kmargoli@seattlecca.org 
 
Co-Investigators: 
Adil Daud, MD 
 
University of California San Francisco 
 
(415) 353-7392 
 
 
adaud@medicine.ucsf.edu 
 
 
 
Marc Ernstoff, MD 
 
Dartmouth Hitchcock Medical Center 
 
(603) 650-5534 
 
marc.s.ernstoff@hitchcock.org  
 
 
Thomas Waldmann, MD 
 
National Cancer Institute 
 
(301) 496-6656 
 
tawald@mail.nih.gov 
 
 
 
  
 
  Hing C. Wong, Ph.D. 
  Altor Bioscience Corporation. 
  Miramar, Florida 33025 
  Telephone: 
954-443-8600 
  Safety Data Fax: 
954-443-8602 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: July 26, 2013 
 
2 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CA-ALT-803-01-13 
 
 
Protocol Title: 
A Phase 1/2 Study of the Clinical and 
Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with 
Advanced Melanoma  
 
 
Date of Protocol: 
 
Version # 01 
Version # 02 
Version # 03 
April 8, 2013 
May 6, 2013 
July 26, 2013 
 
Sponsor Contact:  
 
Hing C. Wong, Ph.D. 
Altor Bioscience Corporation. 
Miramar, Florida 33025 
Telephone: 
954-443-8600 
Safety Data Fax: 
954-443-8602 
 
 
By my signature below, I hereby attest that I have read, and that I understand and will abide by 
all the conditions, instructions, and restrictions contained in the attached protocol. 
 
Additionally, I will not initiate this study without approval of the appropriate Institutional 
Review Board (IRB), and I understand that any changes in the protocol must be approved in 
writing by the sponsor, the IRB, and, in certain cases the FDA, before they can be implemented, 
except where necessary to eliminate hazards to subjects. 
 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Principal Investigator’s Name (Print) 
 
 
 
 
 
 
 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: July 26, 2013 
 
3 
Statistician: 
 
Study Coordinator: N/A  
Zoe Moodie, PhD 
 
Fred Hutchinson Cancer Research Center  
 
1100 Fairview Ave N, Mail Stop M2-C200 
 
Seattle, WA 98109 
  
 (206) 667-7077 
 
Fax: (206) 667-4378 
 
zoe@fhcrc.org 
 
 
Responsible Research Nurse: N/A  
Responsible Data Manager: N/A  
 
 
 
NCI-Supplied Agent(s): N/A  
 
Other Agent(s): ALT-803: a “recombinant human superagonist interleukin-15 (IL-15) complex” 
(AKA, IL-15N72D:IL-15RαSu/IgG1 Fc complex) NSC#: TBD 
  
 
Investigational Agent  
IND# 
IND Sponsor  
ALT-803 
118280 
Altor Bioscience Corporation  
 
Protocol Type / Version # / Version Date: 
Version 3/July 26, 2013 
 
 
 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: July 26, 2013 
 
4 
SCHEMA 
 
Regimen Description 
Agent 
Pre-Medications: 
Precautions 
Dose 
Route 
Schedule 
Cycle Length 
ALT-803 
*1 dose of 
antipyretic 
medication within 
30 min of ALT-803 
administration 
 
*1 dose of 
antipyretic 
medication 4 h after 
ALT-803 
administration 
0.001 mg/kg 
or 
0.003 mg/kg 
or 
0.006 mg/kg 
or 
0.01 mg/kg 
or 
0.02 mg/kg 
or 
0.03 mg/kg 
IV 
D1, W1 
D1, W2 
D1, W3 
D1, W4 
42 days 
(4 weeks on, 2 weeks off) 
With up to 4 cycles in the 
absence of unacceptable 
toxicity and disease 
progression 
*Non-steroidal anti-inflammatory medication including agents such as acetaminophen, 
ibuprofen, or Naproxen may be given per physician discretion. Not to exceed standard maximum 
thresholds, for example: 
 
Acetaminophen: not to exceed 3000 mg (3 g) in 24 hours 
Ibuprofen: not to exceed 2400 mg in 24 hours 
Naproxen: not to exceed 1100 mg in 24 hours 
 
 
Dose Escalation Schedule 
Dose Level 
Dose of ALT-803 
Level -1 
0.0005 mg/kg (only if the first level is too toxic) 
Level 1 
0.001 mg/kg  
Level 2 
0.003 mg/kg 
Level 3 
0.006 mg/kg 
Level 4 
0.01 mg/kg 
Level 5 
0.02 mg/kg 
Level 6 
0.03 mg/kg 
 
 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: July 26, 2013 
 
53 
10. STUDY CALENDAR 
 
Baseline evaluations are to be conducted within 1 to 30 days before start of protocol therapy, as indicated in the study calendar, except 
for pregnancy testing, which must be performed within 48 hours prior to initial ALT-803 administration. Scans and x-rays must be 
performed within 30 days before the start of therapy. In the event that the patient’s condition is changing, laboratory evaluations 
should be repeated within 24 hours before initiating the next cycle of therapy. Please refer to the study calendar below for specific 
timing of required evaluations. 
 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
F/U 14 
days post 
last 
injection 
6 
Month 
F/U 
Visit 
 
Within 30 d 
Within 14 d 
W1 
D1 
W2 
D8 
W3 
D15 
W4 
D22 
W5 
D29 
W6 
D36 
W1 
D1 
W2 
D8 
W3 
D15 
W4 
D22 
W5 
D29 
W6 
D36 
 
 
ALT-803*(A) 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant meds 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam# 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
Vital signs with oxygen 
saturation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
Performance status 
 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
CBC w/diff, plts 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
PT/PTT 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistrya 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Antinuclear antibody 
(ANA) 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
Electrocardiogram (ECG)b 
 
 
Xb Xb 
 
 
 
 
Xb 
Xb 
Xb 
 
 
 
 
Xb 
 
 
ECHO (as indicated)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pulmonary function test 
(spirometry) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

NCI Protocol #:CITN06-ALT-803 
CONFIDENTIAL 
Version Date: July 26, 2013 
 
54 
Adverse event evaluation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor measurementsc 
X 
Tumor measurements are repeated every 8 ± 1 week and 16 ± 2 weeks  
X 
CT, MRI, or PET of chest, 
abdomen, pelvisd 
X 
Documentation (radiologic) must be provided for patients removed from study for progressive disease. 
 
CT or MRI Braind [as 
indicated for symptoms 
only] 
X 
If negative at baseline, to be repeated only with symptoms  
X 
Radiologic evaluation by 
RECIST 1.1 
X 
Radiologic measurements should be performed every 8 ± 1 week and 16 ± 2 weeks  
X 
B-HCGe 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
EBV serostatus 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CMV serostatus 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid studies: TSH, T4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
PK  
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
WB Immunophenotypingg 
 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 
IFN-γ ELISPOTg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
NK-cell functiong 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
Plasma cytokinesg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
Serum Ab to ALT-803g 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
PBMC 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
X 
Serum 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
Abbreviations: Ab, antibodies; CBC, complete blood count; CT, computed tomography; MRI, magnetic resonance imaging; NK, natural killer; PET, positron emission 
tomography; PK, pharmacokinetics; PPT, partial thromboplastin time; PT, prothrombin time  
*(A), Agent 
# Physical exam must always include neurological assessment.  In addition, all patients will have formal ophthalmologic testing prior to starting therapy and 
repeated if clinically indicated. 
a Blood chemistries include: creatinine, glucose, total protein, blood urea nitrogen (BUN), total carbon dioxide (CO2), albumin, total bilirubin, phosphorus, 
alkaline phosphatase, aspartate transaminase (AST), and alanine transaminase (ALT) 
b ECGs are to be done before ALT-803 injections on Day 1 and 4, 12 and 24 hours post-dose.  ECGs are to be repeated before and at 4 hours (the end of the    
   outpatient observation period) following each subsequent dose.   
c Baseline tumor assessment scans should be done 1 to 30 days before beginning treatment. 
d CT, MRI, or PET is acceptable for imaging assessment purposes  
e Pregnancy test may be done up to 48 hours before ALT-803 administration 
f See pharmacokinetic flow sheet for specific draw times 
g Blood for WB Immunophenotyping, IFN-γ ELISPOT, NK-cell function, plasma cytokines, and serum Ab to ALT-803 must be drawn before the patient  
   receives ALT-803 injections on Days 1, 8, 15 and 22 of each treatment cycle.  

NCI Protocol #:CITN-06-ALT-803 
CONFIDENTIAL 
Version Date: December 02, 2013 
 
1 
NCI Protocol #: 
CITN-06-ALT-803 
 
Local Protocol #: 
CA-ALT-803-01-13 
 
TITLE: A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with Advanced Melanoma  
 
(Advanced Melanoma – ICD-10053571) 
 
 
Sponsor:  
 
 
 
 
 
 
 
Coordinating Center: 
 
 
Cancer Immunotherapy Trials Network, Fred Hutchinson 
Cancer Research Center 
 
*Principal Investigator: 
Kim Margolin, MD 
 
University of Washington, Seattle Cancer Care Alliance 
 
825 East Lake Ave E, G4810 
 
Seattle WA 98109-1023 
 
Telephone: 206-288-7341 
 
Fax: 206-288-6681 
 
kmargoli@seattlecca.org 
 
Co-Investigators: 
Adil Daud, MD 
 
University of California San Francisco 
 
(415) 353-7392 
 
 
adaud@medicine.ucsf.edu 
 
 
 
Marc Ernstoff, MD 
 
Dartmouth Hitchcock Medical Center 
 
(603) 650-5534 
 
marc.s.ernstoff@hitchcock.org  
 
 
Thomas Waldmann, MD 
 
National Cancer Institute 
 
(301) 496-6656 
 
tawald@mail.nih.gov 
 
The University of Washington and USCF will participate to the dose-escalation phase of the 
trial. Dartmouth and the NCI will be added in the expansion phase of the trial. 
 
 
 Hing C. Wong, Ph.D. 
 Altor Bioscience Corporation. 
 Miramar, Florida 33025 
 Telephone: 
954-443-8600 
 Safety Data Fax: 
954-443-8602 

NCI Protocol #:CITN-06-ALT-803 
CONFIDENTIAL 
Version Date: December 02, 2013 
 
2 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CA-ALT-803-01-13 
 
 
Protocol Title: 
A Phase 1 Study of the Clinical and 
Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with 
Advanced Melanoma  
 
 
Date of Protocol: 
 
Version # 01 
Version # 02 
Version # 03 
Version # 04 
 
April 8, 2013 
May 6, 2013 
July 26, 2013 
December 02, 2013 
 
Sponsor Contact:  
 
Hing C. Wong, Ph.D. 
Altor Bioscience Corporation. 
Miramar, Florida 33025 
Telephone: 
954-443-8600 
Safety Data Fax: 
954-443-8602 
 
 
By my signature below, I hereby attest that I have read, and that I understand and will abide by 
all the conditions, instructions, and restrictions contained in the attached protocol. 
 
Additionally, I will not initiate this study without approval of the appropriate Institutional 
Review Board (IRB), and I understand that any changes in the protocol must be approved in 
writing by the sponsor, the IRB, and, in certain cases the FDA, before they can be implemented, 
except where necessary to eliminate hazards to subjects. 
 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Principal Investigator’s Name (Print) 
 
 
 
 
 
 

NCI Protocol #:CITN-06-ALT-803 
CONFIDENTIAL 
Version Date: December 02, 2013 
 
3 
Statistician: 
 
Study Coordinator: N/A  
Zoe Moodie, PhD 
 
Fred Hutchinson Cancer Research Center  
 
1100 Fairview Ave N, Mail Stop M2-C200 
 
Seattle, WA 98109 
  
 (206) 667-7077 
 
Fax: (206) 667-4378 
 
zoe@fhcrc.org 
 
 
Responsible Research Nurse: N/A  
Responsible Data Manager: N/A  
 
 
 
NCI-Supplied Agent(s): N/A  
 
Other Agent(s): ALT-803: a “recombinant human superagonist interleukin-15 (IL-15) complex” 
(AKA, IL-15N72D: IL-15RαSu/IgG1 Fc complex) NSC#: TBD 
  
 
Investigational Agent  
IND# 
IND Sponsor  
ALT-803 
118280 
Altor Bioscience Corporation  
 
Protocol Type / Version # / Version Date: 
Amendment/Version 1.0/November 22, 2013 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

NCI Protocol #:CITN-06-ALT-803 
CONFIDENTIAL 
Version Date: December 02, 2013 
 
4 
CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION 
 
To submit site registration 
documents: 
For patient enrollments:  
Submit study data    
CTSU Regulatory Office 
1818 Market Street, Suite 1100 
Philadelphia, PA 19103 
Phone – 1-866-651-CTSU 
Fax – 215-569-0206 
Email: 
CTSURegulatory@ctsu.coccg.o
rg (for submitting regulatory 
documents only) 
Please refer to the patient enrollment 
section for instructions on using the 
Oncology Patient Enrollment Network 
(OPEN) at 
https://www.ctsu.org/OPEN_SYSTEM/ 
or https://OPEN.ctsu.org. 
 
Contact the CTSU Help Desk with any 
OPEN-related questions at 
ctsucontact@westat.com. 
Data collection for this 
study will be done via 
Medidata Rave (Axio 
Research).   
 
Please see the data 
submission section of the 
protocol for further 
instructions.  
 
 
   
The current version of the study protocol and all supporting documents must be downloaded from the 
protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org.   
For patient eligibility or treatment-related questions: 
Contact the CITN Coordinating Center at citn@fhcrc.org or 206-667-6606 
For questions unrelated to patient eligibility, treatment, or clinical data submission contact the CTSU 
Help Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com.  All calls and 
correspondence will be triaged to the appropriate CTSU representative. 
The CTSU Web site is located at   https://www.ctsu.org 
 
 
 

NCI Protocol #:CITN-06-ALT-803 
CONFIDENTIAL 
Version Date: December 02, 2013 
 
5 
SCHEMA 
 
Regimen Description 
Agent 
Pre-Medications: 
Precautions 
Dose 
Route 
Schedule 
Cycle Length 
ALT-803 
*1 dose of 
antipyretic 
medication within 
30 min of ALT-803 
administration 
 
*1 dose of 
antipyretic 
medication 4 h after 
ALT-803 
administration 
0.3 μg/kg or 
0.5 μg/kg or 
1 μg/kg or 
3 μg/kg or 
6 μg/kg 
IV 
D1, W1 
D1, W2 
D1, W3 
D1, W4 
42 days 
(4 weeks on, 2 weeks off) 
With up to 4 cycles in the 
absence of unacceptable 
toxicity and disease 
progression** 
*Non-steroidal anti-inflammatory medication including agents such as acetaminophen, 
ibuprofen, or Naproxen may be given per physician discretion. Not to exceed standard maximum 
thresholds: 
 
Acetaminophen: not to exceed 3000 mg (3 g) in 24 hours 
Ibuprofen: not to exceed 2400 mg in 24 hours 
Naproxen: not to exceed 1100 mg in 24 hours 
 
** Additional cycles beyond the 4th cycle may be considered for patients continuing to benefit 
and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
 
Dose Escalation Schedule 
Dose Level 
Dose of ALT-803 
Level -1 
0.1 μg/kg (only if the first level is too toxic) 
Level 1 
0.3 μg/kg 
Level 2 
0.5 μg/kg 
Level 3 
1 μg/kg 
Level 4 
3 μg/kg 
Level 5 
6 μg/kg 
 
 

NCI Protocol #:CITN-06-ALT-803 
CONFIDENTIAL 
Version Date: December 02, 2013 
 
57 
10. STUDY CALENDAR 
 
Baseline evaluations are to be conducted within 1 to 30 days before start of protocol therapy, as indicated in the study calendar, except 
for pregnancy testing, which must be performed within 48 hours prior to initial ALT-803 administration. Scans and x-rays must be 
performed within 30 days before the start of therapy. In the event that the patient’s condition is changing, laboratory evaluations 
should be repeated within 24 hours before initiating the next cycle of therapy. Please refer to the study calendar below for specific 
timing of required evaluations. 
 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 d 
post 
last inf. 
6 
Mo 
1 yeari 
 
Within 
30 d 
Within 
14 d 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
ALT-803*(A) 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant meds 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examh 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
Vital signs with oxygen 
saturation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
Performance status 
 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
CBC w/diff, plts 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PT/PTT 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistrya 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Antinuclear antibody 
(ANA) 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
Electrocardiogram (ECG)b  
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
ECHO (as indicated)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event evaluation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor measurementsc 
X 
Tumor measurements are repeated every 6 ± 1 week and 12 ± 2 weeks  
X 
 
CT, MRI, or PET of chest, 
X 
Documentation (radiologic) must be provided for patients removed from study for progressive disease. 
 
 

NCI Protocol #:CITN-06-ALT-803 
CONFIDENTIAL 
Version Date: December 02, 2013 
 
58 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 d 
post 
last inf. 
6 
Mo 
1 yeari 
abdomen, pelvisd 
CT or MRI Braind [as 
indicated for symptoms 
only] 
X 
If negative at baseline, to be repeated only with symptoms  
X 
 
Radiologic evaluation by 
RECIST 1.1 
X 
Radiologic measurements should be performed every 6 ± 1 week and 12 ± 2 weeks  
X 
 
B-HCGe 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid studies: TSH, T4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
PKf  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WB Immunophenotypingg 
 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 
 
IFN-γ ELISPOTg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
NK-cell functiong 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Plasma cytokinesg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Serum Ab to ALT-803g 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
Other laboratoriesj 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum  
 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Abbreviations: Ab, antibodies; CBC, complete blood count; CT, computed tomography; MRI, magnetic resonance imaging; NK, natural killer; PET, positron emission 
tomography; PK, pharmacokinetics; PTT, partial thromboplastin time; PT, prothrombin time  
*(A), Agent 
a Blood chemistries include: creatinine, glucose, total protein, blood urea nitrogen (BUN), total carbon dioxide (CO2), albumin, total bilirubin, phosphorus, alkaline phosphatase, 
aspartate transaminase (AST), and alanine transaminase (ALT) 
b ECGs are to be done before ALT-803 infusions on Day 1 and 4, 12 and 24 hours after the first ALT-803 infusion (Cycle 1, Week 1, Day1). As clinically indicated, ECGs are to 
be obtained to evaluate for cardiac toxicity during subsequent doses and cycles of therapy and follow-up visits.  
c Baseline tumor assessment scans should be done 1 to 30 days before beginning treatment. 
d CT, MRI, or PET is acceptable for imaging assessment purposes  
e Pregnancy test may be done up to 48 hours before ALT-803 administration 
f See pharmacokinetic flow sheet for specific draw times 
g Blood for WB Immunophenotyping, IFN-γ ELISPOT, NK-cell function, plasma cytokines, and serum Ab to ALT-803 must be drawn before the patient receives ALT-803 
infusions on Days 1, 8, 15, and 22 of each treatment cycle.  
h Physical exam must always include neurological assessment. In addition, all patients will have formal ophthalmologic testing prior to starting therapy and repeated if clinically 
indicated.  
iAdditional cycles beyond the 4th cycle may be considered for patients continuing to benefit and tolerating therapy, upon discussion among the sponsor and Principal 
Investigator. 
jOther labs include: Lactate dehydrogenase, magnesium, phosphate, creatinine kinase and troponin I; must be drawn before and at 12 and 24 hours after the first ALT-803 
dose.

NCI Protocol #: CITN-06-ALT-803 
Version Date: October 08, 2014 
 
1 
 
NCI Protocol #: 
CITN-06-ALT-803 
 
Local Protocol #: 
CA-ALT-803-01-13 
 
TITLE: A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with Advanced Melanoma  
 
(Advanced Melanoma – ICD-10053571) 
 
 
Sponsor:  
 
 
 
 
 
 
 
Coordinating Center: 
 
 
Cancer Immunotherapy Trials Network, Fred Hutchinson 
Cancer Research Center 
 
*Principal Investigator: 
Kim Margolin, MD 
 
Stanford University, Division of Oncology 
 
269 Campus Drive, CCSR 4115A 
 
Stanford CA 94305-5151 
 
kmargoli@stanford.edu 
 
Co-Investigators: 
Adil Daud, MD 
 
University of California San Francisco 
 
(415) 353-7392 
 
adaud@medicine.ucsf.edu 
 
 
Lionel Lewis, MD 
 
Dartmouth Hitchcock Medical Center 
 
(603) 650-8685 
 
lionel.lewis@dartmouth.edu 
 
 
 
Sylvia Lee, MD 
 
Seattle Cancer Care Alliance 
 
(206) 667-2218 
 
smlee@fhcrc.org 
 
 
Shernan Holtan, MD 
 
University of Minnesota 
 
(612) 301-1095 
 
sgholtan@umn.edu 
 
 
 Hing C. Wong, Ph.D. 
 Altor Bioscience Corporation. 
 Miramar, Florida 33025 
 Telephone: 
954-443-8600 
 Safety Data Fax: 
954-443-8602 

NCI Protocol #: CITN-06-ALT-803 
Version Date: October 08, 2014 
 
2 
 
 
Howard L. Kaufman, MD, FACS 
 
Rutgers University 
 
(732) 235-6807 
 
Howard.kaufman@rutgers.edu 
 
 
 
Thomas Waldmann, MD 
 
National Cancer Institute 
 
(301) 496-6656 
 
tawald@mail.nih.gov 
 
The SCCA, UCSF, Dartmouth, University of Minnesota, Rutgers University and Stanford 
University will participate to the dose-escalation phase of the trial. NCI will be added in the 
expansion phase of the trial. 

NCI Protocol #: CITN-06-ALT-803 
Version Date: October 08, 2014 
 
3 
 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CA-ALT-803-01-13 
 
 
Protocol Title: 
A Phase 1 Study of the Clinical and 
Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with 
Advanced Melanoma  
 
 
Date of Protocol: 
 
Version # 01 
Version # 02 
Version # 03 
Version # 04 
Version # 05 
April 8, 2013 
May 6, 2013 
July 26, 2013 
December 02, 2013 
October 08, 2014 
 
Sponsor Contact:  
 
Hing C. Wong, Ph.D. 
Altor Bioscience Corporation. 
Miramar, Florida 33025 
Telephone: 
954-443-8600 
Safety Data Fax: 
954-443-8602 
 
By my signature below, I hereby attest that I have read, and that I understand and will abide by 
all the conditions, instructions, and restrictions contained in the attached protocol. 
 
Additionally, I will not initiate this study without approval of the appropriate Institutional 
Review Board (IRB), and I understand that any changes in the protocol must be approved in 
writing by the sponsor, the IRB, and, in certain cases the FDA, before they can be implemented, 
except where necessary to eliminate hazards to subjects. 
 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Principal Investigator’s Name (Print) 
 
 
 
 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: October 08, 2014 
 
4 
 
Statistician: 
 
Study Coordinator: N/A  
Zoe Moodie, PhD 
 
Fred Hutchinson Cancer Research Center  
 
1100 Fairview Ave N, Mail Stop M2-C200 
 
Seattle, WA 98109 
  
 (206) 667-7077 
 
Fax: (206) 667-4378 
 
zoe@fhcrc.org 
 
 
Responsible Research Nurse: N/A  
Responsible Data Manager: N/A  
 
 
 
NCI-Supplied Agent(s): N/A  
 
Other Agent(s): ALT-803: a “recombinant human superagonist interleukin-15 (IL-15) complex” 
(AKA, IL-15N72D: IL-15RαSu/IgG1 Fc complex) NSC#: TBD 
  
 
Investigational Agent  
IND# 
IND Sponsor  
ALT-803 
118280 
Altor Bioscience Corporation  
 
Protocol Type / Version # / Version Date: 
Amendment /Version 3.0 /August 27, 2014 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: October 08, 2014 
 
5 
 
CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION 
 
To submit site registration 
documents: 
For patient enrollments:  
Submit study data    
CTSU Regulatory Office 
1818 Market Street, Suite 1100 
Philadelphia, PA 19103 
Phone – 1-866-651-CTSU 
Fax – 215-569-0206 
Email: 
CTSURegulatory@ctsu.coccg.o
rg (for submitting regulatory 
documents only) 
Please refer to the patient enrollment 
section for instructions on using the 
Oncology Patient Enrollment Network 
(OPEN) at 
https://www.ctsu.org/OPEN_SYSTEM/ 
or https://OPEN.ctsu.org. 
 
Contact the CTSU Help Desk with any 
OPEN-related questions at 
ctsucontact@westat.com. 
Data collection for this 
study will be done via 
Medidata Rave (Axio 
Research).   
 
Please see the data 
submission section of the 
protocol for further 
instructions.  
 
 
   
The current version of the study protocol and all supporting documents must be downloaded from the 
protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org.   
For patient eligibility or treatment-related questions: 
Contact the CITN Coordinating Center at citn@fhcrc.org or 206-667-6606 
For questions unrelated to patient eligibility, treatment, or clinical data submission contact the 
CTSU Help Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com.  All calls and 
correspondence will be triaged to the appropriate CTSU representative. 
The CTSU Web site is located at   https://www.ctsu.org 
 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: October 08, 2014 
 
6 
 
SCHEMA 
 
Regimen Description 
Agent 
Pre-Medications: 
Precautions 
Dose 
Route 
Schedule 
Cycle Length 
ALT-803 
*1 dose of 
antipyretic 
medication within 
30 min of ALT-803 
administration 
 
*1 dose of 
antipyretic 
medication 4 h after 
ALT-803 
administration 
0.3 μg/kg or 
0.5 μg/kg or 
1 μg/kg or 
3 μg/kg or 
6 μg/kg 
IV 
D1, W1 
D1, W2 
D1, W3 
D1, W4 
42 days 
(4 weeks on, 2 weeks off) 
With up to 4 cycles in the 
absence of unacceptable 
toxicity and disease 
progression** 
*Non-steroidal anti-inflammatory medication including agents such as acetaminophen, 
ibuprofen, or Naproxen may be given per physician discretion. Not to exceed standard maximum 
thresholds: 
 
Acetaminophen: not to exceed 3000 mg (3 g) in 24 hours 
Ibuprofen: not to exceed 2400 mg in 24 hours 
Naproxen: not to exceed 1100 mg in 24 hours 
 
** Additional cycles beyond the 4th cycle may be considered for patients continuing to benefit 
and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
 
Dose Escalation Schedule 
Dose Level 
Dose of ALT-803 
Level -1 
0.1 μg/kg (only if the first level is too toxic) 
Level 1 
0.3 μg/kg 
Level 2 
0.5 μg/kg 
Level 3 
1 μg/kg 
Level 4 
3 μg/kg 
Level 5 
6 μg/kg 
 
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: October 08, 2014 
 
59 
 
10. STUDY CALENDAR 
Baseline evaluations are to be conducted within 1 to 30 days before start of protocol therapy, as indicated in the study calendar, except for 
pregnancy testing, which must be performed within 48 hours prior to initial ALT-803 administration. Scans and x-rays must be performed within 
30 days before the start of therapy. In the event that the patient’s condition is changing, laboratory evaluations should be repeated within 24 hours 
before initiating the next cycle of therapy. Please refer to the study calendar below for specific timing of required evaluations. 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 d 
post 
last inf. 
6 
Mo 1 yeari 
 
Within 
30 d 
Within 
14 d 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
ALT-803*(A) 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant meds 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examh 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
Vital signs with oxygen 
saturation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
Performance status 
 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
CBC w/diff, plts 
 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PT/PTT 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistrya 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Antinuclear antibody 
(ANA) 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
Electrocardiogram (ECG)b  
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
ECHO (as indicated)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event evaluation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor measurementsc 
X 
Tumor measurements are repeated every 6 ± 1 week and 12 ± 2 weeks  
X 
 
CT, MRI, or PET of chest, 
abdomen, pelvisd 
X 
Documentation (radiologic) must be provided for patients removed from study for progressive disease. 
 
 
CT or MRI Braind [as 
indicated for sympt only] 
X 
If negative at baseline, to be repeated only with symptoms  
X 
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: October 08, 2014 
 
60 
 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 d 
post 
last inf. 
6 
Mo 1 yeari 
 
Within 
30 d 
Within 
14 d 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
Radiologic evaluation by 
RECIST 1.1 
X 
Radiologic measurements should be performed every 6 ± 1 week and 12 ± 2 weeks  
X 
 
B-HCGe 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid studies: TSH, T4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
PKf  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WB Immunophenotypingg 
 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 
 
IFN-γ ELISPOTg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
NK-cell functiong 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Plasma cytokinesg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Kyn/Trp ratiog 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Serum Ab to ALT-803g 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
Other laboratoriesj 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum  
 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Abbreviations: Ab, antibodies; CBC, complete blood count; CT, computed tomography; MRI, magnetic resonance imaging; NK, natural killer; PET, positron emission 
tomography; PK, pharmacokinetics; PTT, partial thromboplastin time; PT, prothrombin time  
*(A): Agent 
a Blood chemistries include: creatinine, glucose, total protein, blood urea nitrogen (BUN), total carbon dioxide (CO2), albumin, total bilirubin, phosphorus, alkaline phosphatase, 
aspartate transaminase (AST), and alanine transaminase (ALT) 
b ECGs are to be done before ALT-803 infusions on Day 1 and 4, 12 and 24 hours after the first ALT-803 infusion (Cycle 1, Week 1, Day1). As clinically indicated, ECGs are to 
be obtained to evaluate for cardiac toxicity during subsequent doses and cycles of therapy and follow-up visits.  
c Baseline tumor assessment scans should be done 1 to 30 days before beginning treatment. 
d CT, MRI, or PET is acceptable for imaging assessment purposes  
e Pregnancy test may be done up to 48 hours before ALT-803 administration 
f See pharmacokinetic flow sheet for specific draw times 
g Blood for WB Immunophenotyping, IFN-γ ELISPOT, NK-cell function, plasma cytokines, Kyn/Trp ratio and serum Ab to ALT-803 must be drawn before the patient receives 
ALT-803 infusions on Days 1, 8, 15, and 22 of each treatment cycle.  
h Physical exam must always include neurological assessment. In addition, a funduscopic exam, conducted by the investigator with a hand-held ophthalmoscope, must be done 
prior to starting therapy (Cycle 1, Day 1, Week 1) and repeated if clinically indicated (See Section 6.0 for additional details).  
iAdditional cycles beyond the 4th cycle may be considered for patients continuing to benefit and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
jOther labs include: Lactate dehydrogenase, magnesium, phosphate, CK and troponin I or T; must be drawn before and at 12 and 24 hours after the first ALT-803 dose. 
kCBC w/diff, plts (Cycle 1, Week 1, Day 1); must be drawn before and at 12 and 24 hours after the first ALT-803 dose.  

NCI Protocol #: CITN-06-ALT-803 
Version Date: November 20, 2014 
 
1 
 
NCI Protocol #: 
CITN-06-ALT-803 
 
Local Protocol #: 
CA-ALT-803-01-13 
 
TITLE: A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with Advanced Solid Tumors: Melanoma, Renal Cell, 
Non-Small Cell Lung and Squamous Cell Head and Neck Cancer 
 
 
 
Sponsor:  
 
 
 
 
 
 
 
Coordinating Center: 
 
 
Cancer Immunotherapy Trials Network, Fred Hutchinson 
Cancer Research Center 
 
*Principal Investigator: 
Kim Margolin, MD 
 
Stanford University, Division of Oncology 
 
269 Campus Drive, CCSR 4115A 
 
Stanford CA 94305-5151 
 
(650) 725-5421 
 
kmargoli@stanford.edu 
 
Co-Investigators: 
Lionel Lewis, MD 
 
Dartmouth Hitchcock Medical Center 
 
(603) 650-8685 
 
lionel.lewis@dartmouth.edu 
 
 
 
Sylvia Lee, MD 
 
Seattle Cancer Care Alliance 
 
(206) 667-2218 
 
smlee@fhcrc.org 
 
 
Shernan Holtan, MD 
 
University of Minnesota 
 
(612) 301-1095 
 
sgholtan@umn.edu 
 
 
 
 
 
 
 
 Hing C. Wong, Ph.D. 
 Altor Bioscience Corporation. 
 Miramar, Florida 33025 
 Telephone: 
954-443-8600 
 Safety Data Fax: 
954-443-8602 

NCI Protocol #: CITN-06-ALT-803 
Version Date: November 20, 2014 
 
2 
 
 
Howard L. Kaufman, MD, FACS 
 
Rutgers University 
 
(732) 235-6807 
 
Howard.kaufman@rutgers.edu 
 
 
 
Marc Ernstoff, MD 
 
Cleveland Clinic Foundation 
 
(216) 444-0888 
 
ernstom@ccf.org 
 
 
 
Thomas Waldmann, MD 
 
National Cancer Institute 
 
(301) 496-6656 
 
tawald@mail.nih.gov 
 
The SCCA, Cleveland Clinic Foundation, UCSF, Dartmouth, University of Minnesota, Rutgers 
University and Stanford University will participate to the dose-escalation phase of the trial. NCI 
will be added in the expansion phase of the trial. 

NCI Protocol #: CITN-06-ALT-803 
Version Date: November 20, 2014 
 
3 
 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CA-ALT-803-01-13 
 
 
Protocol Title: 
A Phase 1 Study of the Clinical and 
Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with 
Advanced Solid Tumors: Melanoma, Renal 
Cell, Non-Small Cell Lung and Squamous Cell 
Head and Neck Cancer  
 
 
Date of Protocol: 
 
Version # 01 
Version # 02 
Version # 03 
Version # 04 
Version # 05 
Version # 06 
 
April 8, 2013 
May 6, 2013 
July 26, 2013 
December 02, 2013 
October 08, 2014 
November 20, 2014 
 
Sponsor Contact:  
 
 
Hing C. Wong, Ph.D. 
Altor Bioscience Corporation. 
Miramar, Florida 33025 
Telephone: 
954-443-8600 
Safety Data Fax: 
954-443-8602 
 
By my signature below, I hereby attest that I have read, and that I understand and will abide by 
all the conditions, instructions, and restrictions contained in the attached protocol. 
 
Additionally, I will not initiate this study without approval of the appropriate Institutional 
Review Board (IRB), and I understand that any changes in the protocol must be approved in 
writing by the sponsor, the IRB, and, in certain cases the FDA, before they can be implemented, 
except where necessary to eliminate hazards to subjects. 
 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Principal Investigator’s Name (Print) 
 
 
 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: November 20, 2014 
 
4 
 
Statistician: 
 
Study Coordinator: N/A  
Zoe Moodie, PhD 
 
Fred Hutchinson Cancer Research Center  
 
1100 Fairview Ave N, Mail Stop M2-C200 
 
Seattle, WA 98109 
  
 (206) 667-7077 
 
Fax: (206) 667-4378 
 
zoe@fhcrc.org 
 
 
Responsible Research Nurse: N/A  
Responsible Data Manager: N/A  
 
 
 
NCI-Supplied Agent(s): N/A  
 
Other Agent(s): ALT-803: a “recombinant human superagonist interleukin-15 (IL-15) complex” 
(AKA, IL-15N72D: IL-15RαSu/IgG1 Fc complex) NSC#: TBD 
  
 
Investigational Agent  
IND# 
IND Sponsor  
ALT-803 
118280 
Altor Bioscience Corporation  
 
Protocol Type / Version # / Version Date: 
Amendment /Version 4.0 /October 30, 2014 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: November 20, 2014 
 
5 
 
CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION 
 
To submit site registration 
documents: 
For patient enrollments:  
Submit study data    
CTSU Regulatory Office 
1818 Market Street, Suite 1100 
Philadelphia, PA 19103 
Phone – 1-866-651-CTSU 
Fax – 215-569-0206 
Email: 
CTSURegulatory@ctsu.coccg.o
rg (for submitting regulatory 
documents only) 
Please refer to the patient enrollment 
section for instructions on using the 
Oncology Patient Enrollment Network 
(OPEN) at 
https://www.ctsu.org/OPEN_SYSTEM/ 
or https://OPEN.ctsu.org. 
 
Contact the CTSU Help Desk with any 
OPEN-related questions at 
ctsucontact@westat.com. 
Data collection for this 
study will be done via 
Medidata Rave (Axio 
Research).   
 
Please see the data 
submission section of the 
protocol for further 
instructions.  
 
 
   
The current version of the study protocol and all supporting documents must be downloaded from the 
protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org.   
For patient eligibility or treatment-related questions: 
Contact the CITN Coordinating Center at citn@fhcrc.org or 206-667-6606 
For questions unrelated to patient eligibility, treatment, or clinical data submission contact the 
CTSU Help Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com.  All calls and 
correspondence will be triaged to the appropriate CTSU representative. 
The CTSU Web site is located at   https://www.ctsu.org 
 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: November 20, 2014 
 
6 
 
SCHEMA 
 
Regimen Description 
Agent 
Pre-Medications: 
Precautions 
Dose 
Route 
Schedule 
Cycle Length 
ALT-803 
*1 dose of 
antipyretic 
medication within 
30 min of ALT-803 
administration 
 
*1 dose of 
antipyretic 
medication 4 h after 
ALT-803 
administration 
0.3 μg/kg or 
0.5 μg/kg or 
1 μg/kg or 
3 μg/kg or 
6 μg/kg 
IV 
D1, W1 
D1, W2 
D1, W3 
D1, W4 
42 days 
(4 weeks on, 2 weeks off) 
With up to 4 cycles in the 
absence of unacceptable 
toxicity and disease 
progression** 
*Non-steroidal anti-inflammatory medication including agents such as acetaminophen, 
ibuprofen, or Naproxen may be given per physician discretion. Not to exceed standard maximum 
thresholds: 
 
Acetaminophen: not to exceed 3000 mg (3 g) in 24 hours 
Ibuprofen: not to exceed 2400 mg in 24 hours 
Naproxen: not to exceed 1100 mg in 24 hours 
 
** Additional cycles beyond the 4th cycle may be considered for patients continuing to benefit 
and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
 
Dose Escalation Schedule 
Dose Level 
Dose of ALT-803 
Level -1 
0.1 μg/kg (only if the first level is too toxic) 
Level 1 
0.3 μg/kg 
Level 2 
0.5 μg/kg 
Level 3 
1 μg/kg 
Level 4 
3 μg/kg 
Level 5 
6 μg/kg 
 
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: November 20, 2014 
 
59 
 
10. STUDY CALENDAR 
Baseline evaluations are to be conducted within 1 to 30 days before start of protocol therapy, as indicated in the study calendar, except for 
pregnancy testing, which must be performed within 48 hours prior to initial ALT-803 administration. Scans and x-rays must be performed within 
30 days before the start of therapy. In the event that the patient’s condition is changing, laboratory evaluations should be repeated within 24 hours 
before initiating the next cycle of therapy. Please refer to the study calendar below for specific timing of required evaluations. 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 d 
post 
last inf. 
6 
Mo 1 yeari 
 
Within 
30 d 
Within 
14 d 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
ALT-803*(A) 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant meds 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examh 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
Vital signs with oxygen 
saturation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
Performance status 
 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
CBC w/diff, plts 
 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PT/PTT 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistrya 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Antinuclear antibody 
(ANA) 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
Electrocardiogram (ECG)b  
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
ECHO (as indicated)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event evaluation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor measurementsc 
X 
Tumor measurements are repeated every 6 ± 1 week and 12 ± 2 weeks  
X 
 
CT, MRI, or PET of chest, 
abdomen, pelvisd 
X 
Documentation (radiologic) must be provided for patients removed from study for progressive disease. 
 
 
CT or MRI Braind [as 
indicated for sympt only] 
X 
If negative at baseline, to be repeated only with symptoms  
X 
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: November 20, 2014 
 
60 
 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 d 
post 
last inf. 
6 
Mo 1 yeari 
 
Within 
30 d 
Within 
14 d 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
Radiologic evaluation by 
RECIST 1.1 
X 
Radiologic measurements should be performed every 6 ± 1 week and 12 ± 2 weeks  
X 
 
B-HCGe 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid studies: TSH, T4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
PKf  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WB Immunophenotypingg 
 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 
 
IFN-γ ELISPOTg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
NK-cell functiong 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Plasma cytokinesg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Kyn/Trp ratiog 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Serum Ab to ALT-803g 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
Other laboratoriesj 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum  
 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Abbreviations: Ab, antibodies; CBC, complete blood count; CT, computed tomography; MRI, magnetic resonance imaging; NK, natural killer; PET, positron emission 
tomography; PK, pharmacokinetics; PTT, partial thromboplastin time; PT, prothrombin time  
*(A): Agent 
a Blood chemistries include: creatinine, glucose, total protein, blood urea nitrogen (BUN), total carbon dioxide (CO2), albumin, total bilirubin, phosphorus, alkaline phosphatase, 
aspartate transaminase (AST), and alanine transaminase (ALT) 
b ECGs are to be done before ALT-803 infusions on Day 1 and 4, 12 and 24 hours after the first ALT-803 infusion (Cycle 1, Week 1, Day1). As clinically indicated, ECGs are to 
be obtained to evaluate for cardiac toxicity during subsequent doses and cycles of therapy and follow-up visits.  
c Baseline tumor assessment scans should be done 1 to 30 days before beginning treatment. 
d CT, MRI, or PET is acceptable for imaging assessment purposes  
e Pregnancy test may be done up to 48 hours before ALT-803 administration 
f See pharmacokinetic flow sheet for specific draw times 
g Blood for WB Immunophenotyping, IFN-γ ELISPOT, NK-cell function, plasma cytokines, Kyn/Trp ratio and serum Ab to ALT-803 must be drawn before the patient receives 
ALT-803 infusions on Days 1, 8, 15, and 22 of each treatment cycle.  
h Physical exam must always include neurological assessment. In addition, a funduscopic exam, conducted by the investigator with a hand-held ophthalmoscope, must be done 
prior to starting therapy (Cycle 1, Day 1, Week 1) and repeated if clinically indicated (See Section 6.0 for additional details).  
iAdditional cycles beyond the 4th cycle may be considered for patients continuing to benefit and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
jOther labs include: Lactate dehydrogenase, magnesium, phosphate, CK and troponin I or T; must be drawn before and at 12 and 24 hours after the first ALT-803 dose. 
kCBC w/diff, plts (Cycle 1, Week 1, Day 1); must be drawn before and at 12 and 24 hours after the first ALT-803 dose.  

NCI Protocol #: CITN-06-ALT-803 
Version Date: January 26, 2015 
 
1 
 
NCI Protocol #: 
CITN-06-ALT-803 
 
Local Protocol #: 
CA-ALT-803-01-13 
 
TITLE: A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with Advanced Solid Tumors: Melanoma, Renal Cell, 
Non-Small Cell Lung and Squamous Cell Head and Neck Cancer 
 
 
 
Sponsor:  
 
 
 
 
 
 
 
Coordinating Center: 
 
 
Cancer Immunotherapy Trials Network, Fred Hutchinson 
Cancer Research Center 
 
*Principal Investigator: 
Kim Margolin, MD 
 
Stanford University, Division of Oncology 
 
269 Campus Drive, CCSR 4115A 
 
Stanford CA 94305-5151 
 
(650) 725-5421 
 
kmargoli@stanford.edu 
 
Co-Investigators: 
Lionel Lewis, MD 
 
Dartmouth Hitchcock Medical Center 
 
(603) 650-8685 
 
lionel.lewis@dartmouth.edu 
 
 
 
Sylvia Lee, MD 
 
Seattle Cancer Care Alliance 
 
(206) 667-2218 
 
smlee@fhcrc.org 
 
 
Shernan Holtan, MD 
 
University of Minnesota 
 
(612) 301-1095 
 
sgholtan@umn.edu 
 
 
 
 
 
 
 
 Hing C. Wong, Ph.D. 
 Altor Bioscience Corporation. 
 Miramar, Florida 33025 
 Telephone: 
954-443-8600 
 Safety Data Fax: 
954-443-8602 

NCI Protocol #: CITN-06-ALT-803 
Version Date: January 26, 2015 
 
2 
 
 
Howard L. Kaufman, MD, FACS 
 
Rutgers University 
 
(732) 235-6807 
 
Howard.kaufman@rutgers.edu 
 
 
 
Marc Ernstoff, MD 
 
Cleveland Clinic Foundation 
 
(216) 444-0888 
 
ernstom@ccf.org 
 
 
 
Thomas Waldmann, MD 
 
National Cancer Institute 
 
(301) 496-6656 
 
tawald@mail.nih.gov 
 
The SCCA, Cleveland Clinic Foundation, UCSF, Dartmouth, University of Minnesota, Rutgers 
University and Stanford University will participate to the dose-escalation phase of the trial. NCI 
will be added in the expansion phase of the trial. 

NCI Protocol #: CITN-06-ALT-803 
Version Date: January 26, 2015 
 
3 
 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CA-ALT-803-01-13 
 
 
Protocol Title: 
A Phase 1 Study of the Clinical and 
Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with 
Advanced Solid Tumors: Melanoma, Renal Cell, 
Non-Small Cell Lung and Squamous Cell Head 
and Neck Cancer  
 
 
Date of Protocol: 
 
Version # 01 
Version # 02 
Version # 03 
Version # 04 
Version # 05 
Version # 06 
Version # 07 
April 8, 2013 
May 6, 2013 
July 26, 2013 
December 02, 2013 
October 08, 2014 
November 20, 2014 
January 26, 2015 
 
Sponsor Contact:  
 
 
Hing C. Wong, Ph.D. 
Altor Bioscience Corporation. 
Miramar, Florida 33025 
Telephone: 
954-443-8600 
Safety Data Fax: 
954-443-8602 
 
By my signature below, I hereby attest that I have read, and that I understand and will abide by 
all the conditions, instructions, and restrictions contained in the attached protocol. 
 
Additionally, I will not initiate this study without approval of the appropriate Institutional 
Review Board (IRB), and I understand that any changes in the protocol must be approved in 
writing by the sponsor, the IRB, and, in certain cases the FDA, before they can be implemented, 
except where necessary to eliminate hazards to subjects. 
 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Principal Investigator’s Name (Print) 
 
 
 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: January 26, 2015 
 
4 
 
Statistician: 
 
Study Coordinator: N/A  
Zoe Moodie, PhD 
 
Fred Hutchinson Cancer Research Center  
 
1100 Fairview Ave N, Mail Stop M2-C200 
 
Seattle, WA 98109 
  
 (206) 667-7077 
 
Fax: (206) 667-4378 
 
zoe@fhcrc.org 
 
 
Responsible Research Nurse: N/A  
Responsible Data Manager: N/A  
 
 
 
NCI-Supplied Agent(s): N/A  
 
Other Agent(s): ALT-803: a “recombinant human superagonist interleukin-15 (IL-15) complex” 
(AKA, IL-15N72D: IL-15RαSu/IgG1 Fc complex) NSC#: TBD 
  
 
Investigational Agent  
IND# 
IND Sponsor  
ALT-803 
118280 
Altor Bioscience Corporation  
 
Protocol Type / Version # / Version Date: 
Amendment /Version 5.0 /January 21, 2015 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: January 26, 2015 
 
5 
 
CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION 
 
To submit site registration 
documents: 
For patient enrollments:  
Submit study data    
CTSU Regulatory Office 
1818 Market Street, Suite 1100 
Philadelphia, PA 19103 
Phone – 1-866-651-CTSU 
Fax – 215-569-0206 
Email: 
CTSURegulatory@ctsu.coccg.o
rg (for submitting regulatory 
documents only) 
Please refer to the patient enrollment 
section for instructions on using the 
Oncology Patient Enrollment Network 
(OPEN) at 
https://www.ctsu.org/OPEN_SYSTEM/ 
or https://OPEN.ctsu.org. 
 
Contact the CTSU Help Desk with any 
OPEN-related questions at 
ctsucontact@westat.com. 
Data collection for this 
study will be done via 
Medidata Rave (Axio 
Research).   
 
Please see the data 
submission section of the 
protocol for further 
instructions.  
 
 
   
The current version of the study protocol and all supporting documents must be downloaded from the 
protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org.   
For patient eligibility or treatment-related questions: 
Contact the CITN Coordinating Center at citn@fhcrc.org or 206-667-6606 
For questions unrelated to patient eligibility, treatment, or clinical data submission contact the 
CTSU Help Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com.  All calls and 
correspondence will be triaged to the appropriate CTSU representative. 
The CTSU Web site is located at   https://www.ctsu.org 
 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: January 26, 2015 
 
6 
 
SCHEMA 
 
Regimen Description 
Agent 
Pre-Medications: 
Precautions 
Dose 
Route 
Schedule 
Cycle Length 
ALT-803 
*1 dose of 
antipyretic 
medication within 
30 min of ALT-803 
administration 
 
*1 dose of 
antipyretic 
medication 4 h after 
ALT-803 
administration 
0.3 μg/kg or 
0.5 μg/kg or 
1 μg/kg or 
3 μg/kg or 
6 μg/kg 
IV 
D1, W1 
D1, W2 
D1, W3 
D1, W4 
42 days 
(4 weeks on, 2 weeks off) 
With up to 4 cycles in the 
absence of unacceptable 
toxicity and disease 
progression** 
*Non-steroidal anti-inflammatory medication including agents such as acetaminophen, 
ibuprofen, or Naproxen may be given per physician discretion. Not to exceed standard maximum 
thresholds: 
 
Acetaminophen: not to exceed 3000 mg (3 g) in 24 hours 
Ibuprofen: not to exceed 2400 mg in 24 hours 
Naproxen: not to exceed 1100 mg in 24 hours 
 
** Additional cycles beyond the 4th cycle may be considered for patients continuing to benefit 
and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
 
Dose Escalation Schedule 
Dose Level 
Dose of ALT-803 
Level -1 
0.1 μg/kg (only if the first level is too toxic) 
Level 1 
0.3 μg/kg 
Level 2 
0.5 μg/kg 
Level 3 
1 μg/kg 
Level 4 
3 μg/kg 
Level 5 
6 μg/kg 
 
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: January 26, 2015 
 
59 
 
10. STUDY CALENDAR 
Baseline evaluations are to be conducted within 1 to 30 days before start of protocol therapy, as indicated in the study calendar, except for 
pregnancy testing, which must be performed within 48 hours prior to initial ALT-803 administration. Scans and x-rays must be performed within 
30 days before the start of therapy. In the event that the patient’s condition is changing, laboratory evaluations should be repeated within 24 hours 
before initiating the next cycle of therapy. Please refer to the study calendar below for specific timing of required evaluations. 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 d 
post 
last inf. 
6 
Mo 1 yeari 
 
Within 
30 d 
Within 
14 d 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
ALT-803*(A) 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant meds 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examh 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
Vital signs with oxygen 
saturation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
Performance status 
 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
CBC w/diff, plts 
 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PT/PTT 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistrya 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Antinuclear antibody 
(ANA) 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
Electrocardiogram (ECG)b  
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
ECHO (as indicated)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event evaluation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor measurementsc 
X 
Tumor measurements are repeated every 6 ± 1 week and 12 ± 2 weeks  
X 
 
CT, MRI, or PET of chest, 
abdomen, pelvisd 
X 
Documentation (radiologic) must be provided for patients removed from study for progressive disease. 
 
 
CT or MRI Braind [as 
indicated for sympt only] 
X 
If negative at baseline, to be repeated only with symptoms  
X 
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: January 26, 2015 
 
60 
 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 d 
post 
last inf. 
6 
Mo 1 yeari 
 
Within 
30 d 
Within 
14 d 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
W1 
D1±1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
Radiologic evaluation by 
RECIST 1.1 
X 
Radiologic measurements should be performed every 6 ± 1 week and 12 ± 2 weeks  
X 
 
B-HCGe 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid studies: TSH, T4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
PKf  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WB Immunophenotypingg 
 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
 
 
IFN-γ ELISPOTg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
NK-cell functiong 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Plasma cytokinesg 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Kyn/Trp ratiog 
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Serum Ab to ALT-803g 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
Other laboratoriesj 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum  
 
 
 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Abbreviations: Ab, antibodies; CBC, complete blood count; CT, computed tomography; MRI, magnetic resonance imaging; NK, natural killer; PET, positron emission 
tomography; PK, pharmacokinetics; PTT, partial thromboplastin time; PT, prothrombin time  
*(A): Agent 
a Blood chemistries include: creatinine, glucose, total protein, blood urea nitrogen (BUN), total carbon dioxide (CO2), albumin, total bilirubin, phosphorus, alkaline phosphatase, 
aspartate transaminase (AST), and alanine transaminase (ALT) 
b ECGs are to be done before ALT-803 infusions on Day 1 and 4, 12 and 24 hours after the first ALT-803 infusion (Cycle 1, Week 1, Day1). As clinically indicated, ECGs are to 
be obtained to evaluate for cardiac toxicity during subsequent doses and cycles of therapy and follow-up visits.  
c Baseline tumor assessment scans should be done 1 to 30 days before beginning treatment. 
d CT, MRI, or PET is acceptable for imaging assessment purposes  
e Pregnancy test may be done up to 48 hours before ALT-803 administration 
f See pharmacokinetic flow sheet for specific draw times 
g Blood for WB Immunophenotyping, IFN-γ ELISPOT, NK-cell function, plasma cytokines, Kyn/Trp ratio and serum Ab to ALT-803 must be drawn before the patient receives 
ALT-803 infusions on Days 1, 8, 15, and 22 of each treatment cycle.  
h Physical exam must always include neurological assessment. In addition, a funduscopic exam, conducted by the investigator with a hand-held ophthalmoscope, must be done 
prior to starting therapy (Cycle 1, Day 1, Week 1) and repeated if clinically indicated (See Section 6.0 for additional details).  
iAdditional cycles beyond the 4th cycle may be considered for patients continuing to benefit and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
jOther labs include: Lactate dehydrogenase, magnesium, phosphate, CK and troponin I or T; must be drawn before and at 12 and 24 hours after the first ALT-803 dose. 
kCBC w/diff, plts (Cycle 1, Week 1, Day 1); must be drawn before and at 12 and 24 hours after the first ALT-803 dose.  

NCI Protocol #: CITN-06-ALT-803 
Version Date: June 11, 2015 
 
1 
 
NCI Protocol #: 
CITN-06-ALT-803 
 
Local Protocol #: 
CA-ALT-803-01-13 
 
TITLE: A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with Advanced Solid Tumors: Melanoma, Renal Cell, 
Non-Small Cell Lung and Squamous Cell Head and Neck Cancer 
 
 
 
Sponsor:  
 
 
 
 
 
 
 
Coordinating Center: 
 
 
Cancer Immunotherapy Trials Network, Fred Hutchinson 
Cancer Research Center 
 
*Principal Investigator: 
Marc Ernstoff, MD 
 
Cleveland Clinic Foundation 
 
9500 Euclid Avenue 
 
Cleveland, OH 44195 
 
(216) 444-0888 
 
ernstom@ccf.org  
 
Co-Investigators: 
Lionel Lewis, MD 
 
Dartmouth Hitchcock Medical Center 
 
(603) 650-8685 
 
lionel.lewis@dartmouth.edu 
 
 
 
Sylvia Lee, MD 
 
Seattle Cancer Care Alliance 
 
(206) 667-2218 
 
smlee@fhcrc.org 
 
 
Shernan Holtan, MD 
 
University of Minnesota 
 
(612) 301-1095 
 
sgholtan@umn.edu 
 
 
 
 
 
 
 
 Hing C. Wong, Ph.D. 
 Altor Bioscience Corporation. 
 Miramar, Florida 33025 
 Telephone: 
954-443-8600 
 Safety Data Fax: 
954-443-8602 

NCI Protocol #: CITN-06-ALT-803 
Version Date: June 11, 2015 
 
2 
 
 
Howard L. Kaufman, MD, FACS 
 
Rutgers University 
 
(732) 235-6807 
 
Howard.kaufman@rutgers.edu 
 
 
 
Vamsidhar Velcheti, MD 
 
Cleveland Clinic Foundation 
 
(216) 444-8665 
 
velchev@ccf.org 
 
 
 
Thomas Waldmann, MD 
 
National Cancer Institute 
 
(301) 496-6656 
 
tawald@mail.nih.gov 
 
The SCCA, Cleveland Clinic Foundation, UCSF, University of Minnesota and Rutgers 
University will participate to the dose-escalation phase of the trial. NCI will be added in the 
expansion phase of the trial. 

NCI Protocol #: CITN-06-ALT-803 
Version Date: June 11, 2015 
 
3 
 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CA-ALT-803-01-13 
 
 
Protocol Title: 
A Phase 1 Study of the Clinical and 
Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with 
Advanced Solid Tumors: Melanoma, Renal Cell, 
Non-Small Cell Lung and Squamous Cell Head 
and Neck Cancer  
 
 
Date of Protocol: 
 
Version # 01 
Version # 02 
Version # 03 
Version # 04 
Version # 05 
Version # 06 
Version # 07 
Version #08 
April 8, 2013 
May 6, 2013 
July 26, 2013 
December 02, 2013 
October 08, 2014 
November 20, 2014 
January 26, 2015 
June 11, 2015 
 
Sponsor Contact:  
 
 
Hing C. Wong, Ph.D. 
Altor Bioscience Corporation. 
Miramar, Florida 33025 
Telephone: 
954-443-8600 
Safety Data Fax: 
954-443-8602 
 
By my signature below, I hereby attest that I have read, and that I understand and will abide by 
all the conditions, instructions, and restrictions contained in the attached protocol. 
 
Additionally, I will not initiate this study without approval of the appropriate Institutional 
Review Board (IRB), and I understand that any changes in the protocol must be approved in 
writing by the sponsor, the IRB, and, in certain cases the FDA, before they can be implemented, 
except where necessary to eliminate hazards to subjects. 
 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Principal Investigator’s Name (Print) 
 
 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: June 11, 2015 
 
4 
 
Statistician: 
 
Study Coordinator: N/A  
Zoe Moodie, PhD 
 
Fred Hutchinson Cancer Research Center  
 
1100 Fairview Ave N, Mail Stop M2-C200 
 
Seattle, WA 98109 
  
 (206) 667-7077 
 
Fax: (206) 667-4378 
 
zoe@fhcrc.org 
 
 
Responsible Research Nurse: N/A  
Responsible Data Manager: N/A  
 
 
 
NCI-Supplied Agent(s): N/A  
 
Other Agent(s): ALT-803: a “recombinant human superagonist interleukin-15 (IL-15) complex” 
(AKA, IL-15N72D: IL-15RαSu/IgG1 Fc complex) NSC#: TBD 
  
 
Investigational Agent  
IND# 
IND Sponsor  
ALT-803 
118280 
Altor Bioscience Corporation  
 
Protocol Type / Version # / Version Date: 
Amendment /Version 6.0 /June 3, 2015 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: June 11, 2015 
 
5 
 
CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION 
 
To submit site registration 
documents: 
For patient enrollments:  
Submit study data    
CTSU Regulatory Office 
1818 Market Street, Suite 1100 
Philadelphia, PA 19103 
Phone – 1-866-651-CTSU 
Fax – 215-569-0206 
Email: 
CTSURegulatory@ctsu.coccg.o
rg (for submitting regulatory 
documents only) 
Please refer to the patient enrollment 
section for instructions on using the 
Oncology Patient Enrollment Network 
(OPEN) at 
https://www.ctsu.org/OPEN_SYSTEM/ 
or https://OPEN.ctsu.org. 
 
Contact the CTSU Help Desk with any 
OPEN-related questions at 
ctsucontact@westat.com. 
Data collection for this 
study will be done via 
Medidata Rave (Axio 
Research).   
 
Please see the data 
submission section of the 
protocol for further 
instructions.  
 
 
   
The current version of the study protocol and all supporting documents must be downloaded from the 
protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org.   
For patient eligibility or treatment-related questions: 
Contact the CITN Coordinating Center at citn@fhcrc.org or 206-667-6606 
For questions unrelated to patient eligibility, treatment, or clinical data submission contact the 
CTSU Help Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com.  All calls and 
correspondence will be triaged to the appropriate CTSU representative. 
The CTSU Web site is located at   https://www.ctsu.org 
 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: June 11, 2015 
 
6 
 
SCHEMA 
 
Regimen Description 
Agent 
Pre-Medications: 
Precautions 
Dose 
Route 
Schedule 
Cycle Length 
ALT-803 
*1 dose of 
antipyretic 
medication within 
30 min of ALT-803 
administration 
 
*1 dose of 
antipyretic 
medication 4 h after 
ALT-803 
administration 
0.3 μg/kg or 
0.5 μg/kg or 
1 μg/kg or 
3 μg/kg or 
6 μg/kg 
IV 
D1, W1 
D1, W2 
D1, W3 
D1, W4 
42 days 
(4 weeks on, 2 weeks off) 
With up to 4 cycles in the 
absence of unacceptable 
toxicity and disease 
progression** 
*Non-steroidal anti-inflammatory medication including agents such as acetaminophen, 
ibuprofen, or Naproxen may be given per physician discretion. Not to exceed standard maximum 
thresholds: 
 
Acetaminophen: not to exceed 3000 mg (3 g) in 24 hours 
Ibuprofen: not to exceed 2400 mg in 24 hours 
Naproxen: not to exceed 1100 mg in 24 hours 
 
** Additional cycles beyond the 4th cycle may be considered for patients continuing to benefit 
and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
 
Dose Escalation Schedule 
Dose Level 
Dose of ALT-803 
Level -1 
0.1 μg/kg (only if the first level is too toxic) 
Level 1 
0.3 μg/kg 
Level 2 
0.5 μg/kg 
Level 3 
1 μg/kg 
Level 4 
3 μg/kg 
Level 5 
6 μg/kg 
 
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: June 11, 2015 
 
61 
 
10. STUDY CALENDAR 
Baseline evaluations are to be conducted within 1 to 30 days before start of protocol therapy, as indicated in the study calendar, except for pregnancy testing, 
which must be performed within 48 hours prior to initial ALT-803 administration. Scans and x-rays must be performed within 30 days before the start of 
therapy. In the event that the patient’s condition is changing, laboratory evaluations should be repeated within 24 hours before initiating the next cycle of 
therapy. Please refer to the study calendar below for specific timing of required evaluations. 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 days 
post last 
infusion 
6 
Mo 
1  
yeari 
 
Within 
30 days 
Within 
14 days 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
D1±1 
D4±1 
D1±1 
D4±1 
ALT-803*(A) 
 
 
X 
 
X 
X 
X 
 
 
X 
 
X 
X 
X 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant meds 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examh 
 
X 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
Vital signs with oxygen 
saturation 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
 
 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Performance status 
 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
X 
CBC w/diff, plts 
 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PT/PTT 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistrya 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Antinuclear antibody (ANA) 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
Electrocardiogram (ECG)b 
 
 
X 
 
X 
X 
X 
 
 
X 
 
X 
X 
X 
 
 
X 
X 
X 
ECHO (as indicated)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event evaluation 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor measurementsc 
X 
Tumor measurements are repeated every 6 ± 1 week and 12 ± 2 weeks  
X 
 
CT, MRI, or PET of chest, 
abdomen, pelvisd 
X 
Documentation (radiologic) must be provided for patients removed from study for progressive disease. 
 
 
CT or MRI Braind [as 
indicated for sympt only] 
X 
If negative at baseline, to be repeated only with symptoms  
X 
 
Radiologic evaluation by 
RECIST 1.1 
X 
Radiologic measurements should be performed every 6 ± 1 week and 12 ± 2 weeks  
X 
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: June 11, 2015 
 
62 
 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 days 
post last 
infusion 
6 
Mo 
1  
yeari 
 
Within 
30 days 
Within 
14 days 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
D1±1 
D4±1 
D1±1 
D4±1 
B-HCGe 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid studies: TSH, T4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
PKf  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WB Immunophenotypingg 
 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
 
 
X 
 
 
 
 
IFN-γ ELISPOTg 
 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
NK-cell functiong 
 
 
X 
X 
X 
 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
Plasma cytokinesg 
 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
Kyn/Trp ratiog 
 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
Serum Ab to ALT-803g 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
Other laboratoriesj 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Storage (optional) 
 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: Ab, antibodies; CBC, complete blood count; CT, computed tomography; MRI, magnetic resonance imaging; NK, natural killer; PET, positron emission tomography; PK, 
pharmacokinetics; PTT, partial thromboplastin time; PT, prothrombin time  
*(A): Agent 
a Blood chemistries include: creatinine, glucose, total protein, blood urea nitrogen (BUN), total carbon dioxide (CO2), albumin, total bilirubin, phosphorus, alkaline phosphatase, aspartate 
transaminase (AST), and alanine transaminase (ALT) 
b ECGs are to be done before ALT-803 infusions on Day 1 and 4, 12 and 24 hours after the first ALT-803 infusion (Cycle 1, Week 1, Day1). As clinically indicated, ECGs are to be obtained to 
evaluate for cardiac toxicity during subsequent doses and cycles of therapy and follow-up visits.  
c Baseline tumor assessment scans should be done 1 to 30 days before beginning treatment. 
d CT, MRI, or PET is acceptable for imaging assessment purposes  
e Pregnancy test may be done up to 48 hours before ALT-803 administration 
f See pharmacokinetic flow sheet for specific draw times 
g Blood for WB Immunophenotyping, IFN-γ ELISPOT, NK-cell function, plasma cytokines, Kyn/Trp ratio and serum Ab to ALT-803 must be drawn before the patient receives ALT-803 infusions 
on Days 1, 8, 15, and 22 of each treatment cycle.  
h Physical exam must always include neurological assessment. In addition, a funduscopic exam, conducted by the investigator with a hand-held ophthalmoscope, must be done prior to starting 
therapy (Cycle 1, Day 1, Week 1) and repeated if clinically indicated (See Section 6.0 for additional details).  
iAdditional cycles beyond the 4th cycle may be considered for patients continuing to benefit and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
jOther labs include: Lactate dehydrogenase, magnesium, phosphate, CK and troponin I or T; must be drawn before and at 12 and 24 hours after the first ALT-803 dose. 
kCBC w/diff, plts (Cycle 1, Week 1, Day 1); must be drawn before and at 12 and 24 hours after the first ALT-803 dose.  

NCI Protocol #: CITN-06-ALT-803 
Version Date: August 5, 2015 
 
1 
 
NCI Protocol #: 
CITN-06-ALT-803 
 
Local Protocol #: 
CA-ALT-803-01-13 
 
TITLE: A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with Advanced Solid Tumors: Melanoma, Renal Cell, 
Non-Small Cell Lung and Squamous Cell Head and Neck Cancer 
 
 
 
Sponsor:  
 
 
 
 
 
 
 
Coordinating Center: 
 
 
Cancer Immunotherapy Trials Network, Fred Hutchinson 
Cancer Research Center 
 
*Principal Investigator: 
Marc Ernstoff, MD 
 
Cleveland Clinic Foundation 
 
9500 Euclid Avenue 
 
Cleveland, OH 44195 
 
(216) 444-0888 
 
ernstom@ccf.org  
 
Co-Investigators: 
Lionel Lewis, MD 
 
Dartmouth Hitchcock Medical Center 
 
(603) 650-8685 
 
lionel.lewis@dartmouth.edu 
 
 
 
Sylvia Lee, MD 
 
Seattle Cancer Care Alliance 
 
(206) 667-2218 
 
smlee@fhcrc.org 
 
 
Shernan Holtan, MD 
 
University of Minnesota 
 
(612) 301-1095 
 
sgholtan@umn.edu 
 
 
 
 
 
 
 
 Hing C. Wong, Ph.D. 
 Altor Bioscience Corporation. 
 Miramar, Florida 33025 
 Telephone: 
954-443-8600 
 Safety Data Fax: 
954-443-8602 

NCI Protocol #: CITN-06-ALT-803 
Version Date: August 5, 2015 
 
2 
 
 
Howard L. Kaufman, MD, FACS 
 
Rutgers University 
 
(732) 235-6807 
 
Howard.kaufman@rutgers.edu 
 
 
 
Vamsidhar Velcheti, MD 
 
Cleveland Clinic Foundation 
 
(216) 444-8665 
 
velchev@ccf.org 
 
 
 
Thomas Waldmann, MD 
 
National Cancer Institute 
 
(301) 496-6656 
 
tawald@mail.nih.gov 
 
The SCCA, Cleveland Clinic Foundation, UCSF, University of Minnesota and Rutgers 
University will participate to the dose-escalation phase of the trial. NCI will be added in the 
expansion phase of the trial. 

NCI Protocol #: CITN-06-ALT-803 
Version Date: August 5, 2015 
 
3 
 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CA-ALT-803-01-13 
 
 
Protocol Title: 
A Phase 1 Study of the Clinical and 
Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with 
Advanced Solid Tumors: Melanoma, Renal Cell, 
Non-Small Cell Lung and Squamous Cell Head 
and Neck Cancer  
 
 
Date of Protocol: 
 
Version # 01 
Version # 02 
Version # 03 
Version # 04 
Version # 05 
Version # 06 
Version # 07 
Version # 08 
Version # 09 
April 8, 2013 
May 6, 2013 
July 26, 2013 
December 02, 2013 
October 08, 2014 
November 20, 2014 
January 26, 2015 
June 11, 2015 
August 5, 2015 
 
Sponsor Contact:  
 
 
Hing C. Wong, Ph.D. 
Altor Bioscience Corporation. 
Miramar, Florida 33025 
Telephone: 
954-443-8600 
Safety Data Fax: 
954-443-8602 
 
By my signature below, I hereby attest that I have read, and that I understand and will abide by 
all the conditions, instructions, and restrictions contained in the attached protocol. 
 
Additionally, I will not initiate this study without approval of the appropriate Institutional 
Review Board (IRB), and I understand that any changes in the protocol must be approved in 
writing by the sponsor, the IRB, and, in certain cases the FDA, before they can be implemented, 
except where necessary to eliminate hazards to subjects. 
 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Principal Investigator’s Name (Print) 
 
 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: August 5, 2015 
 
4 
 
Statistician: 
 
Study Coordinator: N/A  
Zoe Moodie, PhD 
 
Fred Hutchinson Cancer Research Center  
 
1100 Fairview Ave N, Mail Stop M2-C200 
 
Seattle, WA 98109 
  
 (206) 667-7077 
 
Fax: (206) 667-4378 
 
zoe@fhcrc.org 
 
 
Responsible Research Nurse: N/A  
Responsible Data Manager: N/A  
 
 
 
NCI-Supplied Agent(s): N/A  
 
Other Agent(s): ALT-803: a “recombinant human superagonist interleukin-15 (IL-15) complex” 
(AKA, IL-15N72D: IL-15RαSu/IgG1 Fc complex) NSC#: TBD 
  
 
Investigational Agent  
IND# 
IND Sponsor  
ALT-803 
118280 
Altor Bioscience Corporation  
 
Protocol Type / Version # / Version Date: 
Amendment /Version 7.0 /July 28, 2015 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: August 5, 2015 
 
5 
 
CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION 
 
To submit site registration 
documents: 
For patient enrollments:  
Submit study data    
CTSU Regulatory Office 
1818 Market Street, Suite 1100 
Philadelphia, PA 19103 
Phone – 1-866-651-CTSU 
Fax – 215-569-0206 
Email: 
CTSURegulatory@ctsu.coccg.o
rg (for submitting regulatory 
documents only) 
Please refer to the patient enrollment 
section for instructions on using the 
Oncology Patient Enrollment Network 
(OPEN) at 
https://www.ctsu.org/OPEN_SYSTEM/ 
or https://OPEN.ctsu.org. 
 
Contact the CTSU Help Desk with any 
OPEN-related questions at 
ctsucontact@westat.com. 
Data collection for this 
study will be done via 
Medidata Rave (Axio 
Research).   
 
Please see the data 
submission section of the 
protocol for further 
instructions.  
 
 
   
The current version of the study protocol and all supporting documents must be downloaded from the 
protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org.   
For patient eligibility or treatment-related questions: 
Contact the CITN Coordinating Center at citn@fhcrc.org or 206-667-6606 
For questions unrelated to patient eligibility, treatment, or clinical data submission contact the 
CTSU Help Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com.  All calls and 
correspondence will be triaged to the appropriate CTSU representative. 
The CTSU Web site is located at   https://www.ctsu.org 
 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: August 5, 2015 
 
6 
 
SCHEMA 
 
Regimen Description 
Agent 
Pre-Medications: 
Precautions 
Dose 
Route 
Schedule 
Cycle Length 
ALT-803 
*1 dose of 
antipyretic 
medication within 
30 min of ALT-803 
administration 
 
*1 dose of 
antipyretic 
medication 4 h after 
ALT-803 
administration 
0.3 μg/kg or 
0.5 μg/kg or 
1 μg/kg or 
3 μg/kg or 
6 μg/kg 
IV 
D1, W1 
D1, W2 
D1, W3 
D1, W4 
42 days 
(4 weeks on, 2 weeks off) 
With up to 4 cycles in the 
absence of unacceptable 
toxicity and disease 
progression** 
6 μg/kg 
10 μg/kg 
15 μg/kg 
20 μg/kg 
 
SQ 
*Non-steroidal anti-inflammatory medication including agents such as acetaminophen, 
ibuprofen, or Naproxen may be given per physician discretion. Not to exceed standard maximum 
thresholds: 
 
Acetaminophen: not to exceed 3000 mg (3 g) in 24 hours 
Ibuprofen: not to exceed 2400 mg in 24 hours 
Naproxen: not to exceed 1100 mg in 24 hours 
 
** Additional cycles beyond the 4th cycle may be considered for patients continuing to benefit 
and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
 
Dose Escalation Schedule 
Dose Level 
Dose of ALT-803 
Route of Administration 
Level -1 
0.1 μg/kg (only if the first level is too toxic) 
IV 
Level 1 
0.3 μg/kg 
IV 
Level 2 
0.5 μg/kg 
IV 
Level 3 
1 μg/kg 
IV 
Level 4 
3 μg/kg 
IV 
Level 5 
6 μg/kg 
IV 
Level 5a1 
6 μg/kg 
SQ 
Level 6 
10 μg/kg 
SQ 
Level 7 
15 μg/kg 
SQ 
Level 82 
20 μg/kg 
SQ 
1With protocol version #9, ALT-803 dosing is changed from IV to SQ, and dose level 5 is repeated to confirm 
safety with the new route of administration. 
2The dose of ALT-803 will be increased in increments of 5 μg/kg if a minimum of three patients have been 
treated at dose level 8 (20 μg/kg), and the Maximum Tolerated Dose (MTD) and Optimum Biological Dose 
(OBD) have not been identified. Enrollment will continue until the MTD/OBD is identified.  
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: August 5, 2015 
 
62 
 
10. STUDY CALENDAR 
Baseline evaluations are to be conducted within 1 to 30 days before start of protocol therapy, as indicated in the study calendar, except for pregnancy testing, 
which must be performed within 48 hours prior to initial ALT-803 administration. Scans and x-rays must be performed within 30 days before the start of 
therapy. In the event that the patient’s condition is changing, laboratory evaluations should be repeated within 24 hours before initiating the next cycle of 
therapy. Please refer to the study calendar below for specific timing of required evaluations. 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 days 
post last 
dose 
6 
Mo 
1  
yeari 
 
Within 
30 days 
Within 
14 days 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
D1±1 
D4±1 
D1±1 
D4±1 
ALT-803*(A) 
 
 
X 
 
X 
X 
X 
 
 
X 
 
X 
X 
X 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant meds 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examh 
 
X 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
Vital signs with oxygen 
saturation 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
 
 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Performance status 
 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
X 
CBC w/diff, plts 
 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PT/PTT 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistrya 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Antinuclear antibody (ANA) 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
Electrocardiogram (ECG)b 
 
 
X 
 
X 
X 
X 
 
 
X 
 
X 
X 
X 
 
 
X 
X 
X 
ECHO (as indicated)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event evaluation 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor measurementsc 
X 
Tumor measurements are repeated every 6 ± 1 week and 12 ± 2 weeks  
X 
 
CT, MRI, or PET of chest, 
abdomen, pelvisd 
X 
Documentation (radiologic) must be provided for patients removed from study for progressive disease. 
 
 
CT or MRI Braind [as 
indicated for sympt only] 
X 
If negative at baseline, to be repeated only with symptoms  
X 
 
Radiologic evaluation by 
RECIST 1.1 
X 
Radiologic measurements should be performed every 6 ± 1 week and 12 ± 2 weeks  
X 
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: August 5, 2015 
 
63 
 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 days 
post last 
dose 
6 
Mo 
1  
yeari 
 
Within 
30 days 
Within 
14 days 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
D1±1 
D4±1 
D1±1 
D4±1 
Injection Site Evaluation 
 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
 
 
X 
 
 
B-HCGe 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid studies: TSH, T4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
PKf  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WB Immunophenotypingg 
 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
 
 
X 
 
 
 
 
IFN-γ ELISPOTg 
 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
NK-cell functiong 
 
 
X 
X 
X 
 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
Plasma cytokinesg 
 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
Kyn/Trp ratiog 
 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
Serum Ab to ALT-803g 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
Other laboratoriesj 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Storage (optional) 
 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: Ab, antibodies; CBC, complete blood count; CT, computed tomography; MRI, magnetic resonance imaging; NK, natural killer; PET, positron emission tomography; PK, 
pharmacokinetics; PTT, partial thromboplastin time; PT, prothrombin time  
*(A): Agent 
a Blood chemistries include: creatinine, glucose, total protein, blood urea nitrogen (BUN), total carbon dioxide (CO2), albumin, total bilirubin, phosphorus, alkaline phosphatase, aspartate 
transaminase (AST), and alanine transaminase (ALT) 
b ECGs are to be done before ALT-803 administration on Day 1 and 4, 12 and 24 hours after the first ALT-803 dose (Cycle 1, Week 1, Day1). As clinically indicated, ECGs are to be obtained to 
evaluate for cardiac toxicity during subsequent doses and cycles of therapy and follow-up visits.  
c Baseline tumor assessment scans should be done 1 to 30 days before beginning treatment. 
d CT, MRI, or PET is acceptable for imaging assessment purposes  
e Pregnancy test may be done up to 48 hours before ALT-803 administration 
f See pharmacokinetic flow sheet for specific draw times 
g Blood for WB Immunophenotyping, IFN-γ ELISPOT, NK-cell function, plasma cytokines, Kyn/Trp ratio and serum Ab to ALT-803 must be drawn before the patient receives the dose of ALT-
803 on Days 1, 8, 15, and 22 of each treatment cycle.  
h Physical exam must always include neurological assessment. In addition, a funduscopic exam, conducted by the investigator with a hand-held ophthalmoscope, must be done prior to starting 
therapy (Cycle 1, Day 1, Week 1) and repeated if clinically indicated (See Section 6.0 for additional details).  
iAdditional cycles beyond the 4th cycle may be considered for patients continuing to benefit and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
jOther labs include: Lactate dehydrogenase, magnesium, phosphate, CK and troponin I or T; must be drawn before and at 12 and 24 hours after the first ALT-803 dose. 
kCBC w/diff, plts (Cycle 1, Week 1, Day 1); must be drawn before and at 12 and 24 hours after the first ALT-803 dose.  

NCI Protocol #: CITN-06-ALT-803 
Version Date: April 13, 2016 
 
1 
 
NCI Protocol #: 
CITN-06-ALT-803 
 
Local Protocol #: 
CA-ALT-803-01-13 
 
TITLE: A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with Advanced Solid Tumors: Melanoma, Renal Cell, 
Non-Small Cell Lung and Squamous Cell Head and Neck Cancer 
 
 
 
Sponsor:  
 
 
 
 
 
 
 
Coordinating Center: 
 
 
Cancer Immunotherapy Trials Network, Fred Hutchinson 
Cancer Research Center 
 
*Principal Investigator: 
Marc Ernstoff, MD 
 
Roswell Park Cancer Institute 
 
Elm & Carlton Streets 
 
Buffalo, NY 14263 
 
(716) 845-4101 
 
marc.ernstoff@roswellpark.org 
 
 
 
 
Co-Principal Investigator: 
Kim Margolin, MD 
 
City of Hope 
 
(626) 218-0496 
 
kmargolin@coh.org 
  
 
Co-Investigators: 
Lionel Lewis, MD 
 
Dartmouth Hitchcock Medical Center 
 
(603) 650-8685 
 
lionel.lewis@dartmouth.edu 
 
 
 
Sylvia Lee, MD 
 
Seattle Cancer Care Alliance 
 
(206) 667-2218 
 
smlee@fhcrc.org 
 
 
Shernan Holtan, MD 
 
 
 Hing C. Wong, Ph.D. 
 Altor Bioscience Corporation. 
 Miramar, Florida 33025 
 Telephone: 
954-443-8600 
 Safety Data Fax: 
954-443-8602 

NCI Protocol #: CITN-06-ALT-803 
Version Date: April 13, 2016 
 
2 
 
 
University of Minnesota 
 
(612) 301-1095 
 
sgholtan@umn.edu 
 
 
 
 
 
 
Howard L. Kaufman, MD, FACS 
 
Rutgers University 
 
(732) 235-6807 
 
Howard.kaufman@rutgers.edu 
 
 
 
Vamsidhar Velcheti, MD 
 
Cleveland Clinic Foundation 
 
(216) 444-8665 
 
velchev@ccf.org 
 
 
 
Thomas Waldmann, MD 
 
National Cancer Institute 
 
(301) 496-6656 
 
tawald@mail.nih.gov 
 
The SCCA, Cleveland Clinic Foundation, UCSF, University of Minnesota and Rutgers 
University will participate to the dose-escalation phase of the trial. NCI will be added in the 
expansion phase of the trial. 

NCI Protocol #: CITN-06-ALT-803 
Version Date: April 13, 2016 
 
3 
 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CA-ALT-803-01-13 
 
 
Protocol Title: 
A Phase 1 Study of the Clinical and 
Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with 
Advanced Solid Tumors: Melanoma, Renal Cell, 
Non-Small Cell Lung and Squamous Cell Head 
and Neck Cancer  
 
 
Date of Protocol: 
 
Version # 01 
Version # 02 
Version # 03 
Version # 04 
Version # 05 
Version # 06 
Version # 07 
Version # 08 
Version # 09 
April 8, 2013 
May 6, 2013 
July 26, 2013 
December 02, 2013 
October 08, 2014 
November 20, 2014 
January 26, 2015 
June 11, 2015 
August 5, 2015 
Version # 10 
 
Sponsor Contact:  
April 13, 2016 
 
 
Hing C. Wong, Ph.D. 
Altor Bioscience Corporation. 
Miramar, Florida 33025 
Telephone: 
954-443-8600 
Safety Data Fax: 
954-443-8602 
 
By my signature below, I hereby attest that I have read, and that I understand and will abide by 
all the conditions, instructions, and restrictions contained in the attached protocol. 
 
Additionally, I will not initiate this study without approval of the appropriate Institutional 
Review Board (IRB), and I understand that any changes in the protocol must be approved in 
writing by the sponsor, the IRB, and, in certain cases the FDA, before they can be implemented, 
except where necessary to eliminate hazards to subjects. 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Principal Investigator’s Name (Print) 
 
 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: April 13, 2016 
 
4 
 
Statistician: 
 
Study Coordinator: N/A  
Zoe Moodie, PhD 
 
Fred Hutchinson Cancer Research Center  
 
1100 Fairview Ave N, Mail Stop M2-C200 
 
Seattle, WA 98109 
  
 (206) 667-7077 
 
Fax: (206) 667-4378 
 
zoe@fhcrc.org 
 
 
Responsible Research Nurse: N/A  
Responsible Data Manager: N/A  
 
 
 
NCI-Supplied Agent(s): N/A  
 
Other Agent(s): ALT-803: a “recombinant human superagonist interleukin-15 (IL-15) complex” 
(AKA, IL-15N72D: IL-15RαSu/IgG1 Fc complex) NSC#: TBD 
  
 
Investigational Agent  
IND# 
IND Sponsor  
ALT-803 
118280 
Altor Bioscience Corporation  
 
Protocol Type / Version # / Version Date: 
Amendment /Version 8.0 /March 31, 2016 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: April 13, 2016 
 
5 
 
CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION 
 
To submit site registration 
documents: 
For patient enrollments:  
Submit study data    
CTSU Regulatory Office 
1818 Market Street, Suite 1100 
Philadelphia, PA 19103 
Phone – 1-866-651-CTSU 
Fax – 215-569-0206 
Email: 
CTSURegulatory@ctsu.coccg.o
rg (for submitting regulatory 
documents only) 
Please refer to the patient enrollment 
section for instructions on using the 
Oncology Patient Enrollment Network 
(OPEN) at 
https://www.ctsu.org/OPEN_SYSTEM/ 
or https://OPEN.ctsu.org. 
 
Contact the CTSU Help Desk with any 
OPEN-related questions at 
ctsucontact@westat.com. 
Data collection for this 
study will be done via 
Medidata Rave (Axio 
Research).   
 
Please see the data 
submission section of the 
protocol for further 
instructions.  
 
 
   
The current version of the study protocol and all supporting documents must be downloaded from the 
protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org.   
For patient eligibility or treatment-related questions: 
Contact the CITN Coordinating Center at citn@fhcrc.org or 206-667-6606 
For questions unrelated to patient eligibility, treatment, or clinical data submission contact the 
CTSU Help Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com.  All calls and 
correspondence will be triaged to the appropriate CTSU representative. 
The CTSU Web site is located at   https://www.ctsu.org 
 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: April 13, 2016 
 
6 
 
SCHEMA 
 
Regimen Description 
Agent 
Pre-Medications: 
Precautions 
Dose 
Route 
Schedule 
Cycle Length 
ALT-803 
*1 dose of 
antipyretic 
medication within 
30 min of ALT-803 
administration 
 
*1 dose of 
antipyretic 
medication 4 h after 
ALT-803 
administration 
0.3 μg/kg or 
0.5 μg/kg or 
1 μg/kg or 
3 μg/kg or 
6 μg/kg 
IV 
D1, W1 
D1, W2 
D1, W3 
D1, W4 
42 days 
(4 weeks on, 2 weeks off) 
With up to 4 cycles in the 
absence of unacceptable 
toxicity and disease 
progression** 
6 μg/kg 
10 μg/kg 
15 μg/kg 
20 μg/kg 
 
SQ 
*Non-steroidal anti-inflammatory medication including agents such as acetaminophen, 
ibuprofen, or Naproxen may be given per physician discretion. Not to exceed standard maximum 
thresholds: 
 
Acetaminophen: not to exceed 3000 mg (3 g) in 24 hours 
Ibuprofen: not to exceed 2400 mg in 24 hours 
Naproxen: not to exceed 1100 mg in 24 hours 
 
** Additional cycles beyond the 4th cycle may be considered for patients continuing to benefit 
and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
 
Dose Escalation Schedule 
Dose Level 
Dose of ALT-803 
Route of Administration 
Level -1 
0.1 μg/kg (only if the first level is too toxic) 
IV 
Level 1 
0.3 μg/kg 
IV 
Level 2 
0.5 μg/kg 
IV 
Level 3 
1 μg/kg 
IV 
Level 4 
3 μg/kg 
IV 
Level 5 
6 μg/kg 
IV 
Level 5a1 
6 μg/kg 
SQ 
Level 6 
10 μg/kg 
SQ 
Level 7 
15 μg/kg 
SQ 
Level 82 
20 μg/kg 
SQ 
1With protocol version #9, ALT-803 dosing is changed from IV to SQ, and dose level 5 is repeated to confirm safety 
with the new route of administration. 
2The dose of ALT-803 will be increased in increments of 5 μg/kg if a minimum of three patients have been treated 
at dose level 8 (20 μg/kg), and the Maximum Tolerated Dose (MTD) and Optimum Biological Dose (OBD) have not 
been identified. Enrollment will continue until the MTD/OBD is identified.  
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: April 13, 2016 
 
62 
 
10. STUDY CALENDAR 
Baseline evaluations are to be conducted within 1 to 30 days before start of protocol therapy, as indicated in the study calendar, except for pregnancy testing, 
which must be performed within 48 hours prior to initial ALT-803 administration. Scans and x-rays must be performed within 30 days before the start of 
therapy. In the event that the patient’s condition is changing, laboratory evaluations should be repeated within 24 hours before initiating the next cycle of 
therapy. Please refer to the study calendar below for specific timing of required evaluations. 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 days 
post last 
dose 
6 
Mo 
1  
yeari 
 
Within 
30 days 
Within 
14 days 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
D1±1 
D4±1 
D1±1 
D4±1 
ALT-803*(A) 
 
 
X 
 
X 
X 
X 
 
 
X 
 
X 
X 
X 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant meds 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examh 
 
X 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
Vital signs with oxygen 
saturation 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
 
 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Performance status 
 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
X 
CBC w/diff, plts 
 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PT/PTT 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistrya 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Antinuclear antibody (ANA) 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
Electrocardiogram (ECG)b 
 
 
X 
 
X 
X 
X 
 
 
X 
 
X 
X 
X 
 
 
X 
X 
X 
ECHO (as indicated)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event evaluation 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor measurementsc 
X 
Tumor measurements are repeated every 6 ± 1 week and 12 ± 2 weeks  
X 
 
CT, MRI, or PET of chest, 
abdomen, pelvisd 
X 
Documentation (radiologic) must be provided for patients removed from study for progressive disease. 
 
 
CT or MRI Braind [as 
indicated for sympt only] 
X 
If negative at baseline, to be repeated only with symptoms  
X 
 
Radiologic evaluation by 
RECIST 1.1 
X 
Radiologic measurements should be performed every 6 ± 1 week and 12 ± 2 weeks  
X 
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: April 13, 2016 
 
63 
 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 days 
post last 
dose 
6 
Mo 
1  
yeari 
 
Within 
30 days 
Within 
14 days 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
D1±1 
D4±1 
D1±1 
D4±1 
Injection Site Evaluation 
 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
 
 
X 
 
 
B-HCGe 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid studies: TSH, T4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
PKf  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WB Immunophenotypingg 
 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
 
 
X 
 
 
 
 
IFN-γ ELISPOTg 
 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
NK-cell functiong 
 
 
X 
X 
X 
 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
Plasma cytokinesg 
 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
Kyn/Trp ratiog 
 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
Serum Ab to ALT-803g 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
Other laboratoriesj 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Storage (optional) 
 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: Ab, antibodies; CBC, complete blood count; CT, computed tomography; MRI, magnetic resonance imaging; NK, natural killer; PET, positron emission tomography; PK, 
pharmacokinetics; PTT, partial thromboplastin time; PT, prothrombin time  
*(A): Agent 
a Blood chemistries include: creatinine, glucose, total protein, blood urea nitrogen (BUN), total carbon dioxide (CO2), albumin, total bilirubin, phosphorus, alkaline phosphatase, aspartate 
transaminase (AST), and alanine transaminase (ALT) 
b ECGs are to be done before ALT-803 administration on Day 1 and 4, 12 and 24 hours after the first ALT-803 dose (Cycle 1, Week 1, Day1). As clinically indicated, ECGs are to be obtained to 
evaluate for cardiac toxicity during subsequent doses and cycles of therapy and follow-up visits.  
c Baseline tumor assessment scans should be done 1 to 30 days before beginning treatment. 
d CT, MRI, or PET is acceptable for imaging assessment purposes  
e Pregnancy test may be done up to 48 hours before ALT-803 administration 
f See pharmacokinetic flow sheet for specific draw times 
g Blood for WB Immunophenotyping, IFN-γ ELISPOT, NK-cell function, plasma cytokines, Kyn/Trp ratio and serum Ab to ALT-803 must be drawn before the patient receives the dose of ALT-
803 on Days 1, 8, 15, and 22 of each treatment cycle.  
h Physical exam must always include neurological assessment. In addition, a funduscopic exam, conducted by the investigator with a hand-held ophthalmoscope, must be done prior to starting 
therapy (Cycle 1, Day 1, Week 1) and repeated if clinically indicated (See Section 6.0 for additional details).  
iAdditional cycles beyond the 4th cycle may be considered for patients continuing to benefit and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
jOther labs include: Lactate dehydrogenase, magnesium, phosphate, CK and troponin I or T; must be drawn before and at 12 and 24 hours after the first ALT-803 dose. 
kCBC w/diff, plts (Cycle 1, Week 1, Day 1); must be drawn before and at 12 and 24 hours after the first ALT-803 dose.  

NCI Protocol #: CITN-06-ALT-803 
Version Date: August 9, 2016 
 
1 
 
NCI Protocol #: 
CITN-06-ALT-803 
 
Local Protocol #: 
CA-ALT-803-01-13 
 
TITLE: A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803, a Novel 
Recombinant IL-15 Complex in Patients with Advanced Solid Tumors: Melanoma, Renal Cell, 
Sarcoma, Colon, Non-Hodgkin Lymphoma, Non-Small Cell Lung and Squamous Cell Head 
and Neck Cancer and Cutaneous Squamous Cell Cancer 
 
 
 
Sponsor:  
 
 
 
 
 
 
 
Coordinating Center: 
 
 
Cancer Immunotherapy Trials Network, Fred Hutchinson 
Cancer Research Center 
 
*Principal Investigator: 
Marc Ernstoff, MD 
 
Roswell Park Cancer Institute 
 
Elm & Carlton Streets 
 
Buffalo, NY 14263 
 
(716) 845-4101 
 
marc.ernstoff@roswellpark.org 
 
 
 
 
Co-Principal Investigator: 
Kim Margolin, MD 
 
City of Hope 
 
(626) 218-0496 
 
kmargolin@coh.org 
  
 
Jeffrey S. Miller 
 
University of Minnesota 
 
(612) 625-7409 
 
Mille011@umn.edu 
 
Co-Investigators: 
Lionel Lewis, MD 
 
Dartmouth Hitchcock Medical Center 
 
(603) 650-8685 
 
lionel.lewis@dartmouth.edu 
 
 
 
 
 
 
 Hing C. Wong, Ph.D. 
 Altor Bioscience Corporation. 
 Miramar, Florida 33025 
 Telephone: 
954-443-8600 
 Safety Data Fax: 
954-443-8602 

NCI Protocol #: CITN-06-ALT-803 
Version Date: August 9, 2016 
 
2 
 
 
Sylvia Lee, MD 
 
Seattle Cancer Care Alliance 
 
(206) 667-2218 
 
smlee@fhcrc.org 
 
 
Shernan Holtan, MD 
 
University of Minnesota 
 
(612) 301-1095 
 
sgholtan@umn.edu 
 
 
 
Howard L. Kaufman, MD, FACS 
 
Rutgers University 
 
(732) 235-6807 
 
Howard.kaufman@rutgers.edu 
 
 
 
Vamsidhar Velcheti, MD 
 
Cleveland Clinic Foundation 
 
(216) 444-8665 
 
velchev@ccf.org 
 
 
 
Thomas Waldmann, MD 
 
National Cancer Institute 
 
(301) 496-6656 
 
tawald@mail.nih.gov 
 
The SCCA, Cleveland Clinic Foundation, University of Minnesota and Rutgers University will 
participate to the dose-escalation phase of the trial. NCI will be added in the expansion phase of 
the trial. 

NCI Protocol #: CITN-06-ALT-803 
Version Date: August 9, 2016 
 
3 
 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CA-ALT-803-01-13 
 
 
Protocol Title: 
A Phase 1 Study of the Clinical and Immunologic Effects 
of ALT-803, a Novel Recombinant IL-15 Complex in 
Patients with Advanced Solid Tumors: Melanoma, Renal 
Cell, Sarcoma, Colon, Non-Hodgkin Lymphoma,  Non-
Small Cell Lung and Squamous Cell Head and Neck 
Cancer and Cutaneous Squamous Cell Cancer 
 
 
Date of Protocol: 
 
Version # 01 
Version # 02 
Version # 03 
Version # 04 
Version # 05 
Version # 06 
Version # 07 
Version # 08 
Version # 09 
April 8, 2013 
May 6, 2013 
July 26, 2013 
December 02, 2013 
October 08, 2014 
November 20, 2014 
January 26, 2015 
June 11, 2015 
August 5, 2015 
Version # 10 
Version # 11 
 
Sponsor Contact:  
April 13, 2016 
August 9, 2016 
 
 
Hing C. Wong, Ph.D. 
Altor Bioscience Corporation. 
Miramar, Florida 33025 
Telephone: 
954-443-8600 
Safety Data Fax: 
954-443-8602 
 
By my signature below, I hereby attest that I have read, and that I understand and will abide by 
all the conditions, instructions, and restrictions contained in the attached protocol. 
 
Additionally, I will not initiate this study without approval of the appropriate Institutional 
Review Board (IRB), and I understand that any changes in the protocol must be approved in 
writing by the sponsor, the IRB, and, in certain cases the FDA, before they can be implemented, 
except where necessary to eliminate hazards to subjects. 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
 
 
 
 
 
 
Principal Investigator’s Name (Print) 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: August 9, 2016 
 
4 
 
 
Statistician: 
 
Study Coordinator: N/A  
Zoe Moodie, PhD 
 
Fred Hutchinson Cancer Research Center  
 
1100 Fairview Ave N, Mail Stop M2-C200 
 
Seattle, WA 98109 
  
 (206) 667-7077 
 
Fax: (206) 667-4378 
 
zoe@fhcrc.org 
 
 
Responsible Research Nurse: N/A  
Responsible Data Manager: N/A  
 
 
 
NCI-Supplied Agent(s): N/A  
 
Other Agent(s): ALT-803: a “recombinant human superagonist interleukin-15 (IL-15) complex” 
(AKA, IL-15N72D: IL-15RαSu/IgG1 Fc complex) NSC#: TBD 
  
 
Investigational Agent  
IND# 
IND Sponsor  
ALT-803 
118280 
Altor Bioscience Corporation  
 
Protocol Type / Version # / Version Date: 
Amendment 9 /Version 2.0 /July 13, 2016 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: August 9, 2016 
 
5 
 
CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION 
 
To submit site registration 
documents: 
For patient enrollments:  
Submit study data    
CTSU Regulatory Office 
1818 Market Street, Suite 1100 
Philadelphia, PA 19103 
Phone – 1-866-651-CTSU 
Fax – 215-569-0206 
Email: 
CTSURegulatory@ctsu.coccg.o
rg (for submitting regulatory 
documents only) 
Please refer to the patient enrollment 
section for instructions on using the 
Oncology Patient Enrollment Network 
(OPEN) at 
https://www.ctsu.org/OPEN_SYSTEM/ 
or https://OPEN.ctsu.org. 
 
Contact the CTSU Help Desk with any 
OPEN-related questions at 
ctsucontact@westat.com. 
Data collection for this 
study will be done via 
Medidata Rave (Axio 
Research).   
 
Please see the data 
submission section of the 
protocol for further 
instructions.  
 
 
   
The current version of the study protocol and all supporting documents must be downloaded from the 
protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org.   
For patient eligibility or treatment-related questions: 
Contact the CITN Coordinating Center at citn@fhcrc.org or 206-667-6606 
For questions unrelated to patient eligibility, treatment, or clinical data submission contact the 
CTSU Help Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com.  All calls and 
correspondence will be triaged to the appropriate CTSU representative. 
The CTSU Web site is located at   https://www.ctsu.org 
 
 
 

NCI Protocol #: CITN-06-ALT-803 
Version Date: August 9, 2016 
 
6 
 
SCHEMA 
 
Regimen Description 
Agent 
Pre-Medications: 
Precautions 
Dose 
Route 
Schedule 
Cycle Length 
ALT-803 
*1 dose of 
antipyretic 
medication within 
30 min of ALT-803 
administration 
 
*1 dose of 
antipyretic 
medication 4 h after 
ALT-803 
administration 
0.3 μg/kg or 
0.5 μg/kg or 
1 μg/kg or 
3 μg/kg or 
6 μg/kg 
IV 
D1, W1 
D1, W2 
D1, W3 
D1, W4 
42 days 
(4 weeks on, 2 weeks off) 
With up to 4 cycles in the 
absence of unacceptable 
toxicity and disease 
progression** 
6 μg/kg 
10 μg/kg 
15 μg/kg 
20 μg/kg 
 
SQ 
 
 
10 µg/kg + 
15 µg/kg SQ  
15 µg/kg +  
15 µg/kg SQ 
20 µg/kg + 
15 µg/kg SQ 
IT 
followed 
by SQ 
D1, W1 
(IT) 
D1, W2 
(SQ) 
D1, W3 
(SQ) 
D1, W4 
(SQ) 
42 days 
(4 weeks on, 2 weeks off) 
With up to 4 cycles in the 
absence of unacceptable 
toxicity and disease 
progression** 
 
Cycle 1 only: pre and 
post treatment biopsy 
*Non-steroidal anti-inflammatory medication including agents such as acetaminophen, 
ibuprofen, or Naproxen may be given per physician discretion. Not to exceed standard maximum 
thresholds: 
 
Acetaminophen: not to exceed 3000 mg (3 g) in 24 hours 
Ibuprofen: not to exceed 2400 mg in 24 hours 
Naproxen: not to exceed 1100 mg in 24 hours 
 
** Additional cycles beyond the 4th cycle may be considered for patients continuing to benefit 
and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
 
Dose Escalation Schedule 
Cohort 1 
Dose Level 
Dose of ALT-803 
Route of Administration 
Level -1 
0.1 μg/kg (only if the first level is too toxic) 
IV 
Level 1 
0.3 μg/kg 
IV 
Level 2 
0.5 μg/kg 
IV 
Level 3 
1 μg/kg 
IV 
Level 4 
3 μg/kg 
IV 
Level 5 
6 μg/kg 
IV 
Cohort 23 

NCI Protocol #: CITN-06-ALT-803 
Version Date: August 9, 2016 
 
7 
 
Level 5a1 
6 μg/kg 
SQ 
Level 6 
10 μg/kg 
SQ 
Level 7 
15 μg/kg 
SQ 
Level 82 
20 μg/kg 
SQ 
Cohort 33,4 
Level 1 
10 µg/kg  
IT (Week 1) 
15 µg/kg 
SQ (Week 2, 3, 4) 
Level 2 
15 µg/kg 
IT (Week 1) 
15 µg/kg 
SQ (Week 2, 3, 4) 
Level 32 
20 µg/kg 
IT (Week 1) 
15 µg/kg 
SQ (Week 2, 3, 4) 
1With protocol version #9, ALT-803 dosing is changed from IV to SQ, and dose level 5 is repeated to confirm safety 
with the new route of administration. 
2The dose of ALT-803 will be increased in increments of 5 μg/kg if a minimum of three patients have been treated 
at dose level 8 in Cohort 2 or dose level 3 in Cohort 3, and the Maximum Tolerated Dose (MTD) and Optimum 
Biological Dose (OBD) have not been identified. Enrollment will continue until the MTD/OBD is identified.  
3Cohort 2 and Cohort 3 enrollment will occur in parallel. The treatment cohort assignment (Cohort 2 vs Cohort 
3) is at the Investigator and patient discretion. Cohort 3 will be receiving both IT injection and SQ injections and 
must be amenable to undergoing pre and post-treatment biopsy.  
4Cohort 3, dose escalation only for the IT portion; SQ dose remains constant at 15 µg/kg. 
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: August 9, 2016 
 
68 
 
10. STUDY CALENDAR 
Baseline evaluations are to be conducted within 1 to 30 days before start of protocol therapy, as indicated in the study calendar, except for pregnancy testing, 
which must be performed within 48 hours prior to initial ALT-803 administration. Scans and x-rays must be performed within 30 days before the start of 
therapy. In the event that the patient’s condition is changing, laboratory evaluations should be repeated within 24 hours before initiating the next cycle of 
therapy. Please refer to the study calendar below for specific timing of required evaluations. 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 days 
post last 
dose 
6 
Mo 
1  
yeari 
 
Within 
30 days 
Within 
14 days 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
D1±1 
D4±1 
D1±1 
D4±1 
ALT-803 
 
 
Xl 
 
X 
X 
X 
 
 
Xl 
 
X 
X 
X 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant meds 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examh 
 
X 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
Vital signs with oxygen 
saturation 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
 
 
X 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Performance status 
 
X 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
X 
X 
CBC w/diff, plts 
 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PT/PTT 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum chemistrya 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Antinuclear antibody (ANA) 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
X 
Electrocardiogram (ECG)b 
 
 
X 
 
X 
X 
X 
 
 
X 
 
X 
X 
X 
 
 
X 
X 
X 
ECHO (as indicated)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse event evaluation 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Tumor measurementsc 
X 
Tumor measurements are repeated every 6 ± 1 week and 12 ± 2 weeks  
X 
 
CT, MRI, or PET of chest, 
abdomen, pelvisd 
X 
Documentation (radiologic) must be provided for patients removed from study for progressive disease. 
 
 
CT or MRI Braind [as 
indicated for sympt only] 
X 
If negative at baseline, to be repeated only with symptoms  
X 
 
Radiologic evaluation by 
RECIST 1.1 
X 
Radiologic measurements should be performed every 6 ± 1 week and 12 ± 2 weeks  
X 
 

NCI Protocol #: CITN-06-ALT-803 
 
Version Date: August 9, 2016 
 
69 
 
 
 
 
 
F/U 
  
Pre-study 
(screening) 
Cycle 1 (Weeks) 
Cycle 2 (Weeks) 
14 days 
post last 
dose 
6 
Mo 
1  
yeari 
 
Within 
30 days 
Within 
14 days 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
Week 1 
W2 
D8±1 
W3 
D15±1 
W4 
D22±1 
W5 
D29±1 
W6 
D36±1 
 
 
 
D1±1 
D4±1 
D1±1 
D4±1 
Injection Site Evaluation 
 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
 
 
X 
 
 
B-HCGe 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid studies: TSH, T4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
PKf  
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WB Immunophenotypingg 
 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
 
 
X 
 
 
 
 
IFN-γ ELISPOTg 
 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
NK-cell functiong 
 
 
X 
X 
X 
 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
Plasma cytokinesg 
 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
Kyn/Trp ratiog 
 
 
X 
 
 
 
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
Serum Ab to ALT-803g 
 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
 
 
Other laboratoriesj 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Storage (optional) 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Biopsym 
 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: Ab, antibodies; CBC, complete blood count; CT, computed tomography; MRI, magnetic resonance imaging; NK, natural killer; PET, positron emission tomography; PK, 
pharmacokinetics; PTT, partial thromboplastin time; PT, prothrombin time  
a Blood chemistries include: creatinine, glucose, total protein, blood urea nitrogen (BUN), total carbon dioxide (CO2), albumin, total bilirubin, phosphorus, alkaline phosphatase, aspartate 
transaminase (AST), and alanine transaminase (ALT) 
b ECGs are to be done before ALT-803 administration on Day 1 and 4, 12 and 24 hours after the first ALT-803 dose (Cycle 1, Week 1, Day1). As clinically indicated, ECGs are to be obtained to 
evaluate for cardiac toxicity during subsequent doses and cycles of therapy and follow-up visits.  
c Baseline tumor assessment scans should be done 1 to 30 days before beginning treatment. 
d CT, MRI, or PET is acceptable for imaging assessment purposes  
e Pregnancy test may be done up to 48 hours before ALT-803 administration 
f See pharmacokinetic flow sheet for specific draw times 
g Blood for WB Immunophenotyping, IFN-γ ELISPOT, NK-cell function, plasma cytokines, Kyn/Trp ratio and serum Ab to ALT-803 must be drawn before the patient receives the dose of ALT-
803 on Days 1, 8, 15, and 22 of each treatment cycle.  
h Physical exam must always include neurological assessment. In addition, a funduscopic exam, conducted by the investigator with a hand-held ophthalmoscope, must be done prior to starting 
therapy (Cycle 1, Day 1, Week 1) and repeated if clinically indicated (See Section 6.0 for additional details).  
iAdditional cycles beyond the 4th cycle may be considered for patients continuing to benefit and tolerating therapy, upon discussion among the sponsor and Principal Investigator. 
jOther labs include: Lactate dehydrogenase, magnesium, phosphate, CK and troponin I or T; must be drawn before and at 12 and 24 hours after the first ALT-803 dose. 
kCBC w/diff, plts (Cycle 1, Week 1, Day 1); must be drawn before and at 12 and 24 hours after the first ALT-803 dose.  
lCohort 3 only, intratumoral injection (Week 1, Day 1 of each treatment cycle) 
mCohort 3 only, biopsy must be done before ALT-803 administration