A Study of ALT-801 in Patients With Relapsed or Refractory Multiple Myeloma
Phase: PHASE1
Conditions: Relapsed or Refractory Multiple Myeloma
Sponsor: Altor BioScience

 
 
 
CLINICAL STUDY PROTOCOL 
 
 
Protocol Number: 
CA-ALT-801-01-11 
 
 
Protocol Title: 
A Study of ALT-801 in Patients with Relapsed 
or Refractory Multiple Myeloma 
 
 
 
Date of Protocol: 
 
Version# 01 
 
December 9, 2011 
 
 
 
 
Sponsor Contact: 
 
Hing C. Wong, Ph.D. 
Altor Bioscience Corporation. 
Miramar, Florida 33025 
Telephone: 
954-443-8600 
Safety Data Fax: 
954-443-8602 
 
 
 

   
 
 
 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CA-ALT-801-01-11 
 
 
Protocol Title: 
A Study of ALT-801 in Patients with Relapsed 
or Refractory Multiple Myeloma 
 
 
Date of Protocol: 
 
Version# 01 
 
December 9, 2011 
 
 
 
 
 
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) 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
SYNOPSIS .......................................................................................................................................... 7 
1. 
OBJECTIVES ........................................................................................................................... 12 
1.1 
PRIMARY OBJECTIVES .......................................................................................................... 12 
1.2 
SECONDARY OBJECTIVES ..................................................................................................... 12 
2. 
BACKGROUND ....................................................................................................................... 12 
2.1 
ALT-801 – GENERAL INFORMATION ................................................................................... 12 
2.2 
MULTIPLE MYELOMA .......................................................................................................... 12 
2.3 
IMMUNE-BASED THERAPIES FOR CANCER ............................................................................ 13 
2.4 
ENHANCED IMMUNE STIMULATORY ACTIVITY OF A TARGETED IL-2 FUSION PROTEIN ......... 14 
2.5 
TUMOR EFFICACY STUDIES OF ALT-801 IN ANIMAL MODELS .............................................. 15 
2.5.1 
Efficacy evaluation of ALT-801 dose regimens in xenograft tumor models .............. 15 
2.5.2 
Activity of ALT-801 against murine tumors including multiple myeloma in 
immunocompetent mice .............................................................................................................. 16 
2.6 
P53 OVEREXPRESSION AS AN IMMUNOTHERAPEUTIC TARGET FOR RELAPSED OR REFRACTORY 
MULTIPLE MYELOMA ....................................................................................................................... 18 
2.7 
NON-CLINICAL TOXICOLOGY ............................................................................................... 19 
2.7.1 
Single-dose toxicity study ........................................................................................... 19 
2.7.2 
Multi-dose toxicity study ............................................................................................ 19 
2.8 
PHARMACOKINETICS ........................................................................................................... 20 
2.8.1 
Non-clinical pharmacokinetics .................................................................................. 20 
2.8.2 
Clinical pharmacokinetics .......................................................................................... 21 
2.9 
HUMAN EXPERIENCE ........................................................................................................... 21 
2.9.1 
Phase I Study of ALT-801 in Patients with Progressive Metastatic Malignancies 
(CA-ALT-801-01-06) .................................................................................................................. 21 
2.9.1.1. 
Pharmacodynamics ............................................................................................. 21 
2.9.1.2. 
Tumor assessment .............................................................................................. 22 
2.9.1.3. 
Safety results ...................................................................................................... 23 
2.9.1.4. 
Immunogenicity ................................................................................................. 24 
2.9.1.5. 
Repeat treatment ................................................................................................. 24 
2.9.2 
Phase Ib/II Study of ALT-801 with Cisplatin in Patients with Metastatic Melanoma 
(CA-ALT-801-02-09) .................................................................................................................. 24 
3. 
RATIONALE FOR THE CURRENT STUDY ..................................................................... 25 
4. 
OVERALL STUDY DESIGN ................................................................................................. 27 
5. 
STUDY POPULATION ........................................................................................................... 29 
5.1 
INCLUSION CRITERIA ........................................................................................................... 29 
5.2 
EXCLUSION CRITERIA .......................................................................................................... 30 
5.3 
INCLUSION OF WOMEN AND MINORITIES .............................................................................. 30 
6. 
STUDY DESIGN ...................................................................................................................... 31 
6.1 
STUDY FLOW DIAGRAM ....................................................................................................... 31 
6.2 
SCREENING AND ENROLLMENT ............................................................................................ 31 

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6.3 
STUDY TREATMENT ............................................................................................................. 31 
6.3.1 
Treatment setting ........................................................................................................ 31 
6.3.2 
Treatment regimen and scheme .................................................................................. 32 
6.3.3 
Study drug preparation and administration ............................................................... 32 
6.3.4 
Pre- & Post- therapy interventions ............................................................................ 33 
6.4 
DURATION OF PATIENT PARTICIPATION ............................................................................... 34 
6.5 
DOSE CONFIRMATION PHASE ............................................................................................... 34 
6.6 
EXPANSION PHASE ............................................................................................................... 34 
6.7 
STOPPING RULES.................................................................................................................. 35 
6.8 
PATIENT MONITORING, RESPONSE EVALUATION, DISEASE PROGRESSION & SURVIVAL 
FOLLOW-UP ..................................................................................................................................... 35 
6.8.1 
Patient monitoring ...................................................................................................... 35 
6.8.2 
Response evaluation ................................................................................................... 35 
6.8.3 
Disease progression and survival follow-up .............................................................. 35 
6.9 
DOSE LIMITING TOXICITIES ................................................................................................. 35 
6.10 
STUDY TREATMENT DISCONTINUATION ............................................................................... 36 
6.10.1 
Study treatment discontinuation events ...................................................................... 36 
6.10.2 
Replacement of participants ....................................................................................... 36 
6.10.3 
Follow-ups after treatment discontinuation ............................................................... 36 
6.10.3.1. 
Discontinuation due to SAEs or on-going study drug related AEs .................... 36 
6.10.3.2. 
Discontinuation due to any other reasons........................................................... 36 
6.11 
STUDY TREATMENT INTERRUPTION ..................................................................................... 37 
6.11.1 
Kidney dysfunction ..................................................................................................... 37 
6.11.2 
Hematological dysfunction ......................................................................................... 37 
6.11.3 
Hypotension ................................................................................................................ 37 
6.11.4 
Allergic reactions and cytokine release syndrome/acute infusion reaction ............... 37 
6.12 
GENERAL SUPPORTIVE CARE GUIDELINES AND DRUG INTERACTION .................................... 37 
6.12.1 
Hypotension and capillary leak syndrome ................................................................. 38 
6.12.2 
Pulmonary dysfunction ............................................................................................... 38 
6.12.3 
Impaired kidney and liver functions ........................................................................... 38 
6.12.4 
Infection ...................................................................................................................... 38 
6.12.5 
Fever and chills .......................................................................................................... 38 
6.12.6 
Gastritis ...................................................................................................................... 38 
6.12.7 
Diarrhea, nausea and vomiting .................................................................................. 39 
6.12.8 
Pruritus and dermatitis .............................................................................................. 39 
6.12.9 
Acidosis ...................................................................................................................... 39 
6.12.10 
Life-threatening toxicities ...................................................................................... 39 
6.12.11 
Other supportive care ............................................................................................. 39 
6.12.12 
Drug interaction ..................................................................................................... 39 
7. 
STUDY DRUG: AVAILABILITY, ACCOUNTABILITY, PACKAGING & LABELING
 
41 
7.1 
AVAILABILITY ..................................................................................................................... 41 
7.2 
ACCOUNTABILITY ............................................................................................................... 41 
7.3 
PACKAGING ......................................................................................................................... 41 
7.4 
LABELING ............................................................................................................................ 41 
8. 
STUDY CALENDAR, CLINICAL PROCEDURES & TESTS .......................................... 42 

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8.1 
STUDY CALENDAR ............................................................................................................... 42 
8.2 
PROCEDURE AND TESTS ....................................................................................................... 43 
8.2.1 
HLA-A2 typing and assays for immune cell levels and phenotype ............................ 43 
8.2.2 
Presentation of HLA-A*0201/p53 aa264-272 complexes on tumor surfaces ............ 43 
8.2.3 
Medical history & prior therapy ................................................................................ 43 
8.2.4 
Pregnancy test ............................................................................................................ 43 
8.2.5 
Physical examination ................................................................................................. 43 
8.2.6 
Vital signs, body weight & height .............................................................................. 43 
8.2.7 
Cardiac assessment .................................................................................................... 43 
8.2.8 
Clinical blood tests ..................................................................................................... 43 
8.2.9 
Disease assessment tests and procedures .................................................................. 44 
8.2.10 
Adverse event assessment ........................................................................................... 44 
8.2.11 
Response assessment .................................................................................................. 44 
8.2.12 
Disease progression and survival follow-up .............................................................. 44 
8.2.13 
Pharmacokinetic (PK) testing .................................................................................... 45 
8.2.14 
Biomarker assays for IFNγ and TNFα ....................................................................... 45 
8.2.15 
Immunogenicity tests - detection of anti-ALT-801 and IL2-neutralizing antibodies . 45 
9. 
MEASUREMENT OF EFFECT ............................................................................................. 46 
9.1 
MEASURABLE DISEASE ........................................................................................................ 46 
9.2 
EFFECT ASSESSMENT SCHEDULE .......................................................................................... 46 
9.3 
METHODOLOGY OF RESPONSE EVALUATION ........................................................................ 46 
9.4 
RESPONSE EVALUATION CRITERIA ....................................................................................... 47 
9.5 
DISEASE PROGRESSION EVALUATION CRITERIA ................................................................... 48 
10. 
STATISTICAL ANALYSIS ................................................................................................ 49 
10.1 
STUDY OBJECTIVES ............................................................................................................. 49 
10.2 
SAMPLE SIZE ....................................................................................................................... 49 
10.3 
DATA COLLECTION .............................................................................................................. 49 
10.4 
DATA ANALYSIS .................................................................................................................. 49 
10.4.1 
Analysis of safety ........................................................................................................ 50 
10.4.2 
Analysis of response ................................................................................................... 50 
10.4.3 
Pharmacokinetics ....................................................................................................... 50 
11. 
REGULATORY AND REPORTING REQUIREMENTS .............................................. 51 
11.1 
ADVERSE EVENTS RECORDING, REPORTING AND COMMUNICATION ..................................... 51 
11.2 
ADVERSE EVENT TERMINOLOGY AND DEFINITIONS ............................................................. 51 
11.3 
ADVERSE EVENT REPORTING PROCEDURES ........................................................................ 52 
11.4 
ADVERSE EVENT EXPEDITED REPORTING GUIDELINES ....................................................... 53 
11.5 
SUBMISSION OF SERIOUS ADVERSE EVENT REPORTING ........................................................ 53 
11.6 
DATA REPORTING FORMS ................................................................................................... 53 
11.7 
REPORT /DATA SUBMISSION ADDRESS & CONTACT ............................................................. 54 
11.8 
PATIENT RECORDS, QUALITY ASSURANCE, RECORDS RETENTION ........................................ 54 
11.9 
METHOD OF REVIEW ............................................................................................................ 54 
11.10 
SPECIAL REGULATORY CONSIDERATIONS ........................................................................ 55 
11.10.1 
HIPAA .................................................................................................................... 55 
11.10.2 
Protocol amendments, informed consent, and IRB approval ................................. 55 
12. 
CONFIDENTIALITY .......................................................................................................... 55 

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13. 
ETHICAL STANDARDS & INVESTIGATOR OBLIGATIONS .................................. 55 
14. 
LIST OF EXPECTED ADVERSE EVENTS .................................................................... 56 
15. 
CTCAE .................................................................................................................................. 58 
REFERENCES ................................................................................................................................. 59 
APPENDIX A: ECOG ..................................................................................................................... 62 
APPENDIX B: NEW YORK HEART ASSOCIATION CLASSIFICATION ........................... 62 
APPENDIX C: ETHICAL STANDARDS ..................................................................................... 63 
APPENDIX D: INVESTIGATOR OBLIGATIONS .................................................................... 64 
APPENDIX E: CONTACT LIST - ALTOR .................................................................................. 68 
APPENDIX F: CONTACT LIST – DATA SAFETY MONITORING BOARD (DSMB) ........ 69 
APPENDIX G: CONTACT LIST - LABORATORIES ............................................................... 69 
APPROVAL PAGE .......................................................................................................................... 70 

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SYNOPSIS 
Sponsor: 
Altor Bioscience Corporation 
Protocol#: 
CA-ALT-801-01-11 
Study Drug Name: Not applicable 
Study Treatment 
Active agents: 
ALT-801 (c264scTCR-IL2), recombinant humanized, soluble single-chain 
TCR-cytokine fusion protein. 
Study Type: 
Interventional 
Study Phase: 
Ib/II 
Protocol Title: 
A Study of ALT-801 in Patients with Relapsed or Refractory Multiple 
Myeloma 
Objectives:   
To confirm the safety and tolerability of a well-tolerated dose level of ALT-
801 in patients with relapsed or refractory multiple myeloma.   
To estimate the anti-tumor activity of ALT-801 by radiologic or pathologic 
disease response, progression free survival, and overall survival in treated 
patients.  
To characterize the immunogenicity and pharmacokinetic profile of ALT-
801 in treated patients. 
To assess the relationship between tumor presentation of HLA-A*0201/p53 
aa 264-272 complex and the safety, immune response and clinical benefit of 
study treatment. 
Study Design: 
This is a Phase Ib/II, open-label, multi-center and competitive enrollment 
study of ALT-801 in patients who have relapsed or refractory multiple 
myeloma. 
 
There are two phases in this study: a dose confirmation phase to confirm a 
well-tolerated dose (TD) in this patient population and a two-stage 
expansion phase using the confirmed TD.  Each enrolled patient will receive 
up to two cycles of study treatment 
The study will be conducted in conformity with Good Clinical Practice 
(GCP).  
Treatments:  
All enrolled patients will receive up to two cycles of study treatment with a 
13-day rest period between cycles.  Each cycle consists of four doses of 
ALT-801 on Day #1, Day #3, Day #8, and Day #15 in the cycle.  The rest 
period may be extended to include an additional week. 
The schedule of study treatment is illustrated below: 
 
 
 
 
Treatment Week 
1 
2 
3 
4 
5 
6 
7 
Treatment Day 
1 
3 
8 
15 
Rest 
29 
31 
36 
43 
Dose# 
1 
2 
3 
4 
5 
6 
7 
8 
ALT-801 
X 
X 
X 
X 
X 
X 
X 
X 

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There are no restrictions on further therapies, such as chemotherapy, 
radiation therapy or surgery to be used after the protocol-specified therapy.  
Clearly, post-study further treatments could be of significant clinical benefit 
in selected patients, and these patients will be followed for outcome. 
Enrolled patients will receive the study treatment at qualified cancer 
treatment centers with adequate diagnostic and treatment facilities to provide 
appropriate management of therapy and complications. ALT-801 will be 
administered by intravenous infusion into a central or peripheral vein under 
the supervision of a qualified physician experienced in the use of anti-cancer 
agents including aldesleukin (Proleukin). 
Dose Confirmation 
Phase: 
In the dose-confirmation phase of the study, six patients will be enrolled at 
the dose level starting at 0.08 mg/kg, which is one of the well-tolerated dose 
levels in a Phase Ib/II study of ALT-801 in combination with cisplatin in 
patients with metastatic melanoma.  Enrolled patients will be monitored 
during the study treatment period for any Dose Limiting Toxicity (DLT).  
The tolerability of a dose level is defined as < 2 of 6 patients experiencing 
any DLT at this dose level.  If the tolerability of ALT-801 at a dose level 
cannot be confirmed, an additional six patients will be enrolled to repeat the 
dose confirmation phase with a step-down dose level that is 0.02 mg/kg 
lower than the previous tested dose level until a dose level is confirmed as 
the Tolerated Dose (TD). Below are the dose levels of the study drug during 
the dose confirmation phase of the study.   
  
 
 
 
 
DLT is defined as any toxicity of grade 3 that does not resolve to Grade 1 or 
lower within 72 hours and any toxicity of Grade 4 occurring during the study 
treatment period with exceptions and details described in the study protocol. 
Patients experiencing a DLT should discontinue study treatment.  Study 
treatment discontinuation due to adverse events experienced prior to study 
drug administration, disease progression or patient’s decision to withdraw 
from study treatment without occurrence of any study treatment 
discontinuation event will not necessarily define a DLT event.  Study 
treatment discontinuation events are defined in the protocol. 
 
 
Expansion 
Phase 
The two-stage expansion phase at the TD level will be conducted using a 
modified Simon two-stage design. Objective response (OR) (defined as 
complete response (CR) + partial response (PR)) will be evaluated and set 
thresholds of lack of efficacy (OR rate (ORR) = 20%) and an efficacy level 
of interest (ORR = 40%) will be selected.   
Cohort 
ALT-801 Dose (mg/kg) 
-2 
0.04 
-1 
0.06 
1 (initial) 
0.08 

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Stopping Rule: 
Patient enrollment will be temporarily suspended based on occurrence of any 
the following, and the sponsor, the Data Safety Monitoring Board and 
principal investigators will meet to discuss how to proceed with future 
patient enrollment in the study: 
• 
During the dose confirmation phase of the study, no dose level can be 
confirmed as the TD. 
• 
If at any time during the expansion phase of the study, more than 33% 
of patients experience a possible, probable or definite drug related DLT. 
Evaluations: 
Patients will be evaluated for clinical toxicities during the treatment.  
Patients’ blood samples will be collected to assess the pharmacokinetic 
profile and immunogenicity of the study drug. The anti-tumor response will 
be evaluated at week 8 and week 12 from the start of study treatment.  All 
patients who receive at least one dose of the study drug ALT-801 will be 
included in the anti-tumor response evaluation. 
Population: 
Patients of 18 years of age with relapsed or refractory multiple myeloma.  
Patients also need to have adequate cardiac, pulmonary, liver and kidney 
functions and to have an Eastern Cooperative Oncology Group (ECOG) 
performance status of 0, 1 or 2.  
Sample Size: 
A total of up to 18 assessable patients will be accrued to the dose confirmation 
phase of the study (Phase Ib).  Up to an additional 37 assessable patients will 
be enrolled at the expansion phase (Stage 1 and 2) of the study (Phase II).  A 
total of approximately 43 assessable patients will be enrolled and complete 
the study in the event that the TD is 0.08 mg/kg.  Assuming a 20% ineligible 
or non-assessable cases, a total of up to 52 patients may be accrued to the 
study. 
Primary 
Endpoints: 
For Phase Ib only: (1) Confirmation of a well-tolerated dose level of ALT-801.  
For Phase Ib & II: (2) Safety profile of ALT-801. 
 
(3) Disease response rate.  
Secondary  
Endpoints: 
(1) Duration of response. 
(2) Progression free survival. 
(3) Overall survival. 
(4) Immunogenicity and pharmacokinetics profile of ALT-801.  
(5) Relationship between tumor presentation of HLA-A*0201/p53 aa 264-
272 complexes and the safety, immune response and clinical benefit of 
study treatment. 
Pharmacokinetics 
& Biomarkers: 
Blood samples will be collected to assess typing for HLA-A2, immune cell 
levels and phenotype, pharmacokinetics and immunogenicity of the study 
drug ALT-801, and the serum levels of IFN-γ and TNF-α.  Unstained slides 
from a bone marrow biopsy will be used to test HLA-A*0201/p53 aa 264-
272 complex presentation. Blood samples for pharmacokinetic analysis of 

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ALT-801 will be taken on the first day of ALT-801 administration in the 
initial study treatment cycle. Venous blood will be obtained at Time 0 
(before the start of infusion), at 30 minutes (15 minutes after completion of 
infusion), and 1, 3 and 6 hours from Time 0 for the assessment of ALT-801 
serum concentration. Non-compartmental and compartmental analyses will 
be conducted.  In addition, the same blood samples collected for PK analysis 
will be used to assess the serum levels of IFN-γ and TNF-α.  Fresh blood 
samples for HLA-A2 typing, immune cell levels and phenotype testing will 
be collected before the start of first and fourth dose of study drug infusion in 
each treatment cycle.  HLA-A2 typing will be performed only once.  Bone 
marrow samples will be collected for future analysis of molecular markers 
associated with responses or resistance to ALT-801 in patients with relapsed 
or refractory multiple myeloma. 
Monitoring Tests: Blood samples for standard chemistry, and CBC with differential will be 
obtained at screening, on each study drug infusion day, and at follow-up 
visits.  Blood samples for immunogenicity testing, which include assays for 
anti-ALT-801 and IL-2 neutralizing antibodies, will be collected prior to 
dosing on the first ALT-801 infusion day and at Week 8 from the initial dose 
of study treatment. Blood and urine samples will be collected on each 
follow-up visit for response assessment.  
Response 
Assessment: 
There are two response assessments for treated patients: initial assessment at 
week 8 and confirmatory assessment at week 12 from the start of study 
treatment. After completion of study treatment, patients who have received 
at least one dose of study drug will have the response assessments.  
Responses will be evaluated according to the new International Uniform 
Response Criteria for Multiple Myeloma proposed by the International 
Myeloma Working Group. Baseline evaluations should be performed up to 
14 days before study treatment starts.  
Progression & 
Survival 
Assessment: 
Progression-free survival, overall survival, and duration of response of all 
treated patients will be assessed at every three months during year 1 and then 
every 6 months during years 2 and 3 from the start of study treatment, or 
through the point designated as the end of the study follow up. 
Adverse Events: 
All patients will be monitored and evaluated for clinical toxicities during the 
treatment period and queried at each follow-up visit for Adverse Events 
(AEs).  Patients may volunteer information concerning AEs.  All adverse 
events will be graded by using the NCI Common Terminology Criteria for 
Adverse Events version 4.0 (CTCAE v4.0), and logged in the patient Case 
Report Form.  The study centers should report all Serious Adverse Events 
(SAEs) and all events that trigger patient’s study treatment discontinuation 
to the sponsor via phone, fax or email (or a combination) no more than 24 
hours after learning of the event.  The sponsor will use the information to 
manage and coordinate the dose confirmation, cohort expansion and patient 
enrollment.  The sponsor will then inform all of the participating clinical 

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sites of the current dose level and the number of patients to be enrolled at 
that level, or of any patient enrollment suspension via phone, fax or email 
within 24 hours of learning of the event.  The study centers should report all 
other adverse events to the sponsor following the guidelines defined in the 
study protocol. All study drug related AEs that are both serious and 
unexpected will be reported to the FDA in an expedited manner in 
accordance with 21 CFR §312.32. 
Statistical Plan: 
For each cohort, all AEs will be tabulated and examined and all safety, 
pharmacokinetic and tumor response data will be evaluated. For estimation 
of duration of response and progression free survival, the Kaplan-Meier 
method will be used. P-values of ≤0.05 (two-sided) will be considered to 
indicate statistical significance.  

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8. 
STUDY CALENDAR, CLINICAL PROCEDURES & TESTS 
8.1 
Study calendar 
 
TESTS & PROCEDURES 
SCREEN/ 
BASELINE1 
TREATMENT 
CYCLE #1 
  
TREATMENT 
CYCLE  #2 
1ST 
ASSESSMENT 
2ND 
ASSESSMENT 
FOLLOW-UPS 
Study Month  
 
1 
 
2 
3 
6   9  
12  18  24   30  36  
Study Week  
 
1 
2 
3 
4 
5 
6 
7 
8 
12 
  
Day of Week 
 
M 
W  
M 
M 
 
M 
W 
M 
M 
  
 
 
Study Day  
 
1 
3 
8 
15 
16-28 
29 
31  
36  
43 
  
  
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
X 
X 
 
 
 
 
X 
 
 
 
X 
X 
 
Vital signs, weight, Height3 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Concurrent medication 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Adverse event assessment4 
X 
X  
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
CBC with Differential 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Blood Chemistry  
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
EKG 
X 
X5  
  
  
  
 
X  
  
  
  
 
 
 
Response evaluation6 
  
 
 
 
 
 
 
 
 
 
X 
X 
 
Serum quantitative immunoglobulins 
X 
 
 
 
 
 
 
 
 
 
X 
X 
 
SPEP 
X  
  
 
 
 
 
 
 
 
 
X 
X 
 
UPEP-random  
X 
 
 
 
 
 
 
 
 
 
X 
X 
 
SIFE 
X 
 
 
 
 
 
 
 
 
 
X 
X 
 
UIFE -random 
X 
 
 
 
 
 
 
 
 
 
X 
X 
 
Serum FLC assay6.1 
X  
 
 
 
 
 
 
 
 
 
X 
X 
 
Bone marrow plasma cell percentage6.2 
X  
 
 
 
 
 
 
 
 
 
X 
X 
 
Bone marrow immunohistochemistry or 
immunofluorescence6.3 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Soft tissue plasmacytomas assessment6.4 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Disease & survival follow-up7 
 
 
 
 
 
 
 
 
 
 
  
  
X  
X 
X 
X 
X 
X 
X 
Immune cell levels & phenotype8, 12 
 
X8 
 
 
X8 
 
X8 
 
 
X8 
 
 
 
HLA A2 Blood Typing9 & p53 tumor typing 
 
X 
 
 
 
 
 
 
 
 
 
 
 
PK, IFNγ, TNFα10,12 
 
X10 
 
 
 
 
 
 
 
 
 
 
 
Immunogenicity tests11, 12 
 
X11 
 
 
 
 
 
 
 
 
X 
 
 
Study drug (ALT-801)
 
a1  
a2 
a3 
a4 
 
a5 
a6 
a7 
a8 
  
  
 
1Screening/baseline evaluations are performed < 14 days prior to start of therapy.  If the patient's condition is deteriorating, laboratory evaluations should be repeated within 48 hours prior 
to initiation of study treatment infusion.  2Pregnancy test is for women with childbearing potential only.  3Vital signs (especially blood pressure), clinical status and laboratory tests should be 
reviewed before start of therapy. Vital signs will be evaluated every 2 hours after drug infusion and before discharge, and body weight before infusion on drug infusion day. 4Patients who 
have an on-going study drug-related SAE upon study completion or at discontinuation of study will be contacted by the investigator or his/her designee every week until the event is 
resolved or determined to be irreversible. 5If the screening EKG was performed within 14 days prior to start of study treatment, the EKG is not required 6Disease response and progression 
assessment will be evaluated using the new International Uniform Response Criteria for Multiple Myeloma proposed by the International Myeloma Working Group;. 6.1only when serum and 
urine M-protein are unmeasurable 6.2 only when serum and urine M-protein and serum FLC are unmeasurable and bone marrow plasma cell percentage > 30% at baseline; 6.3only when sCR 
is to be determined; 6.4only when present at baseline, and to confirm CR or PR by X-rays, MRI or CT scans. 7Information about tumor assessment & other therapies received after completion 
of study treatment will be collected if available.  8Fresh blood samples for HLA A2 blood typing, immune cell levels & phenotype testing will be collected before dosing. 9 Use the blood 
sample collected for immune cell levels & phenotype.10Collect blood samples at Time 0 (before drug infusion), at 30 min (15 min after completion of infusion, +/- 5 min), 1 hour (+/- 10 
min), 3 hour (+/- 30 min), 6 hour (+/- 60 min) from Time 0. IFNγ and TNFα assays are performed using the same samples and at the same schedule as PK.  11Use the sample collected 
before dosing for PK test. 12Residual samples may be used by Sponsor for research studies of other biomarkers.  

 
 
 
CLINICAL STUDY PROTOCOL 
 
 
Protocol Number: 
CA-ALT-801-01-11 
 
 
Protocol Title: 
A Study of ALT-801 in Patients with Relapsed 
or Refractory Multiple Myeloma 
 
 
 
Date of Protocol: 
 
Version# 01 
Version# 02 
 
December 9, 2011 
January 9, 2012 
 
 
 
Sponsor Contact: 
 
Hing C. Wong, Ph.D. 
Altor Bioscience Corporation. 
Miramar, Florida 33025 
Telephone: 
954-443-8600 
Safety Data Fax: 
954-443-8602 
 
 
 

   
 
 
 
INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
CA-ALT-801-01-11 
 
 
Protocol Title: 
A Study of ALT-801 in Patients with Relapsed 
or Refractory Multiple Myeloma 
 
 
Date of Protocol: 
 
Version# 01 
Version# 02 
 
December 9, 2011 
January 9, 2012 
 
 
 
 
 
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) 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
SYNOPSIS .......................................................................................................................................... 7 
1. 
OBJECTIVES ........................................................................................................................... 12 
1.1 
PRIMARY OBJECTIVES .......................................................................................................... 12 
1.2 
SECONDARY OBJECTIVES ..................................................................................................... 12 
2. 
BACKGROUND ....................................................................................................................... 12 
2.1 
ALT-801 – GENERAL INFORMATION ................................................................................... 12 
2.2 
MULTIPLE MYELOMA .......................................................................................................... 12 
2.3 
IMMUNE-BASED THERAPIES FOR CANCER ............................................................................ 13 
2.4 
ENHANCED IMMUNE STIMULATORY ACTIVITY OF A TARGETED IL-2 FUSION PROTEIN ......... 14 
2.5 
TUMOR EFFICACY STUDIES OF ALT-801 IN ANIMAL MODELS .............................................. 15 
2.5.1 Efficacy evaluation of ALT-801 dose regimens in xenograft tumor models .................. 15 
2.5.2 Activity of ALT-801 against murine tumors including multiple myeloma in 
immunocompetent mice .............................................................................................................. 16 
2.6 
P53 OVEREXPRESSION AS AN IMMUNOTHERAPEUTIC TARGET FOR RELAPSED OR REFRACTORY 
MULTIPLE MYELOMA ....................................................................................................................... 18 
2.7 
NON-CLINICAL TOXICOLOGY ............................................................................................... 19 
2.7.1 Single-dose toxicity study ............................................................................................... 19 
2.7.2 Multi-dose toxicity study ................................................................................................ 19 
2.8 
PHARMACOKINETICS ........................................................................................................... 20 
2.8.1 Non-clinical pharmacokinetics ...................................................................................... 20 
2.8.2 Clinical pharmacokinetics .............................................................................................. 21 
2.9 
HUMAN EXPERIENCE ........................................................................................................... 21 
2.9.1 Phase I Study of ALT-801 in Patients with Progressive Metastatic Malignancies (CA-
ALT-801-01-06) .......................................................................................................................... 21 
2.9.1.1. Pharmacodynamics ................................................................................................. 21 
2.9.1.2. Tumor assessment .................................................................................................. 22 
2.9.1.3. Safety results .......................................................................................................... 23 
2.9.1.4. Immunogenicity ..................................................................................................... 24 
2.9.1.5. Repeat treatment ..................................................................................................... 24 
2.9.2 Phase Ib/II Study of ALT-801 with Cisplatin in Patients with Metastatic Melanoma 
(CA-ALT-801-02-09) .................................................................................................................. 24 
3. 
RATIONALE FOR THE CURRENT STUDY ..................................................................... 25 
4. 
OVERALL STUDY DESIGN ................................................................................................. 27 
5. 
STUDY POPULATION ........................................................................................................... 29 
5.1 
INCLUSION CRITERIA ........................................................................................................... 29 
5.2 
EXCLUSION CRITERIA .......................................................................................................... 30 
5.3 
INCLUSION OF WOMEN AND MINORITIES .............................................................................. 30 
6. 
STUDY DESIGN ...................................................................................................................... 31 
6.1 
STUDY FLOW DIAGRAM ....................................................................................................... 31 
6.2 
SCREENING AND ENROLLMENT ............................................................................................ 31 

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6.3 
STUDY TREATMENT ............................................................................................................. 31 
6.3.1 Treatment setting ............................................................................................................ 31 
6.3.2 Treatment regimen and scheme ...................................................................................... 32 
6.3.3 Study drug preparation and administration ................................................................... 32 
6.3.4 Pre- & Post- therapy interventions ................................................................................ 33 
6.4 
DURATION OF PATIENT PARTICIPATION ............................................................................... 34 
6.5 
DOSE ESCALATION PHASE .................................................................................................... 34 
6.6 
EXPANSION PHASE ............................................................................................................... 34 
6.7 
STOPPING RULES.................................................................................................................. 35 
6.8 
PATIENT MONITORING, RESPONSE EVALUATION, DISEASE PROGRESSION & SURVIVAL 
FOLLOW-UP ..................................................................................................................................... 35 
6.8.1 Patient monitoring .......................................................................................................... 35 
6.8.2 Response evaluation ....................................................................................................... 35 
6.8.3 Disease progression and survival follow-up .................................................................. 35 
6.9 
DOSE LIMITING TOXICITIES ................................................................................................. 36 
6.10 
STUDY TREATMENT DISCONTINUATION ............................................................................... 36 
6.10.1 
Study treatment discontinuation events ...................................................................... 36 
6.10.2 
Replacement of participants ....................................................................................... 36 
6.10.3 
Follow-ups after treatment discontinuation ............................................................... 36 
6.10.3.1. 
Discontinuation due to SAEs or on-going study drug related AEs .................... 36 
6.10.3.2. 
Discontinuation due to any other reasons........................................................... 37 
6.11 
STUDY TREATMENT INTERRUPTION ..................................................................................... 37 
6.11.1 
Kidney dysfunction ..................................................................................................... 37 
6.11.2 
Hematological dysfunction ......................................................................................... 37 
6.11.3 
Hypotension ................................................................................................................ 37 
6.11.4 
Allergic reactions and cytokine release syndrome/acute infusion reaction ............... 37 
6.12 
GENERAL SUPPORTIVE CARE GUIDELINES AND DRUG INTERACTION .................................... 38 
6.12.1 
Hypotension and capillary leak syndrome ................................................................. 38 
6.12.2 
Pulmonary dysfunction ............................................................................................... 38 
6.12.3 
Impaired kidney and liver functions ........................................................................... 38 
6.12.4 
Infection ...................................................................................................................... 39 
6.12.5 
Fever and chills .......................................................................................................... 39 
6.12.6 
Gastritis ...................................................................................................................... 39 
6.12.7 
Diarrhea, nausea and vomiting .................................................................................. 39 
6.12.8 
Pruritus and dermatitis .............................................................................................. 39 
6.12.9 
Acidosis ...................................................................................................................... 39 
6.12.10 Life-threatening toxicities .......................................................................................... 39 
6.12.11 Other supportive care ................................................................................................. 39 
6.12.12 Drug interaction ......................................................................................................... 39 
7. 
STUDY DRUG: AVAILABILITY, ACCOUNTABILITY, PACKAGING & LABELING
 
41 
7.1 
AVAILABILITY ..................................................................................................................... 41 
7.2 
ACCOUNTABILITY ............................................................................................................... 41 
7.3 
PACKAGING ......................................................................................................................... 41 
7.4 
LABELING ............................................................................................................................ 41 
8. 
STUDY CALENDAR, CLINICAL PROCEDURES & TESTS .......................................... 42 

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8.1 
STUDY CALENDAR ............................................................................................................... 42 
8.2 
PROCEDURE AND TESTS ....................................................................................................... 43 
8.2.1 HLA-A2 typing and assays for immune cell levels and phenotype ................................ 43 
8.2.2 Presentation of HLA-A*0201/p53 aa264-272 complexes on tumor surfaces ................ 43 
8.2.3 Medical history & prior therapy .................................................................................... 43 
8.2.4 Pregnancy test ................................................................................................................ 43 
8.2.5 Physical examination ..................................................................................................... 43 
8.2.6 Vital signs, body weight & height .................................................................................. 43 
8.2.7 Cardiac assessment ........................................................................................................ 43 
8.2.8 Clinical blood tests ......................................................................................................... 43 
8.2.9 Disease assessment tests and procedures ...................................................................... 44 
8.2.10 
Adverse event assessment ........................................................................................... 44 
8.2.11 
Response assessment .................................................................................................. 44 
8.2.12 
Disease progression and survival follow-up .............................................................. 44 
8.2.13 
Pharmacokinetic (PK) testing .................................................................................... 45 
8.2.14 
Biomarker assays for IFNγ and TNFα ....................................................................... 45 
8.2.15 
Immunogenicity tests - detection of anti-ALT-801 and IL2-neutralizing antibodies . 45 
9. 
MEASUREMENT OF EFFECT ............................................................................................. 46 
9.1 
MEASURABLE DISEASE ........................................................................................................ 46 
9.2 
EFFECT ASSESSMENT SCHEDULE .......................................................................................... 46 
9.3 
METHODOLOGY OF RESPONSE EVALUATION ........................................................................ 46 
9.4 
RESPONSE EVALUATION CRITERIA ....................................................................................... 47 
9.5 
DISEASE PROGRESSION EVALUATION CRITERIA ................................................................... 48 
10. 
STATISTICAL ANALYSIS ................................................................................................ 49 
10.1 
STUDY OBJECTIVES ............................................................................................................. 49 
10.2 
SAMPLE SIZE ....................................................................................................................... 49 
10.3 
DATA COLLECTION .............................................................................................................. 49 
10.4 
DATA ANALYSIS .................................................................................................................. 49 
10.4.1 
Analysis of safety ........................................................................................................ 50 
10.4.2 
Analysis of response ................................................................................................... 50 
10.4.3 
Pharmacokinetics ....................................................................................................... 50 
11. 
REGULATORY AND REPORTING REQUIREMENTS .............................................. 51 
11.1 
ADVERSE EVENTS RECORDING, REPORTING AND COMMUNICATION ..................................... 51 
11.2 
ADVERSE EVENT TERMINOLOGY AND DEFINITIONS ............................................................. 51 
11.3 
ADVERSE EVENT REPORTING PROCEDURES ........................................................................ 52 
11.4 
ADVERSE EVENT EXPEDITED REPORTING GUIDELINES ....................................................... 53 
11.5 
SUBMISSION OF SERIOUS ADVERSE EVENT REPORTING ........................................................ 53 
11.6 
DATA REPORTING FORMS ................................................................................................... 53 
11.7 
REPORT /DATA SUBMISSION ADDRESS & CONTACT ............................................................. 54 
11.8 
PATIENT RECORDS, QUALITY ASSURANCE, RECORDS RETENTION ........................................ 54 
11.9 
METHOD OF REVIEW ............................................................................................................ 54 
11.10 
SPECIAL REGULATORY CONSIDERATIONS ........................................................................ 55 
11.10.1 HIPAA ........................................................................................................................ 55 
11.10.2 Protocol amendments, informed consent, and IRB approval ..................................... 55 
12. 
CONFIDENTIALITY .......................................................................................................... 55 

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13. 
ETHICAL STANDARDS & INVESTIGATOR OBLIGATIONS .................................. 55 
14. 
LIST OF EXPECTED ADVERSE EVENTS .................................................................... 56 
15. 
CTCAE .................................................................................................................................. 58 
REFERENCES ................................................................................................................................. 59 
APPENDIX A: ECOG ..................................................................................................................... 62 
APPENDIX B: NEW YORK HEART ASSOCIATION CLASSIFICATION ........................... 62 
APPENDIX C: ETHICAL STANDARDS ..................................................................................... 63 
APPENDIX D: INVESTIGATOR OBLIGATIONS .................................................................... 64 
APPENDIX E: CONTACT LIST - ALTOR .................................................................................. 68 
APPENDIX F: CONTACT LIST – DATA SAFETY MONITORING BOARD (DSMB) ........ 69 
APPENDIX G: CONTACT LIST - LABORATORIES ............................................................... 69 
APPROVAL PAGE .......................................................................................................................... 70 

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SYNOPSIS 
Sponsor: 
Altor Bioscience Corporation 
Protocol#: 
CA-ALT-801-01-11 
Study Drug Name: Not applicable 
Study Treatment 
Active agents: 
ALT-801 (c264scTCR-IL2), recombinant humanized, soluble single-chain 
TCR-cytokine fusion protein. 
Study Type: 
Interventional 
Study Phase: 
Ib/II 
Protocol Title: 
A Study of ALT-801 in Patients with Relapsed or Refractory Multiple 
Myeloma 
Objectives:   
To evaluate the safety and tolerability and to determine the maximum 
tolerated dose level (MTD) of ALT-801 in patients with relapsed or 
refractory multiple myeloma.   
To estimate the anti-tumor activity of ALT-801 by radiologic or pathologic 
disease response, progression free survival, and overall survival in treated 
patients.  
To characterize the immunogenicity and pharmacokinetic profile of ALT-
801 in treated patients. 
To assess the relationship between tumor presentation of HLA-A*0201/p53 
aa 264-272 complex and the safety, immune response and clinical benefit of 
study treatment. 
Study Design: 
This is a Phase Ib/II, open-label, multi-center and competitive enrollment 
study of ALT-801 in patients who have relapsed or refractory multiple 
myeloma. 
 
The study includes a dose escalation phase to determine the maximum 
tolerated dose level (MTD) using a (3+3) dose escalation design and a two-
stage expansion phase at the MTD using a Simon two-stage design. There 
are four escalating dose levels of ALT-801. Each enrolled patient will 
receive up to two cycles of study treatment 
The study will be conducted in conformity with Good Clinical Practice 
(GCP).  
Treatments:  
All enrolled patients will receive up to two cycles of study treatment with a 
13-day rest period between cycles.  Each cycle consists of four doses of 
ALT-801 on Day #1, Day #3, Day #8, and Day #15 in the cycle.  The rest 
period may be extended to include an additional week. 
The schedule of study treatment is illustrated below: 

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There are no restrictions on further therapies, such as chemotherapy, 
radiation therapy or surgery to be used after the protocol-specified therapy.  
Clearly, post-study further treatments could be of significant clinical benefit 
in selected patients, and these patients will be followed for outcome. 
Enrolled patients will receive the study treatment at qualified cancer 
treatment centers with adequate diagnostic and treatment facilities to provide 
appropriate management of therapy and complications. ALT-801 will be 
administered by intravenous infusion into a central or peripheral vein under 
the supervision of a qualified physician experienced in the use of anti-cancer 
agents including aldesleukin (Proleukin). 
Dose Escalation 
Phase: 
In this phase of the study, a minimum of 3 patients will be enrolled at each 
dose level.  All patients will be monitored for Dose Limiting Toxicity (DLT) 
during the treatment period. There are four escalating dose levels of ALT-
801 (0.04 mg/kg, 0.06 mg/kg and 0.08 mg/kg, and 0.10 mg/kg).  If 0/3 
patients have dose-limiting toxicity, the next cohort will be opened for 
enrollment. If one patient at a dose-level develops DLT, up to six patients 
will be enrolled at that dose level and each subsequent higher dose level.  If 
0 or 1 of 6 patients in a cohort of 6 patients experiences DLT, then the next 
cohort will be opened for enrollment. If 2 or more out of 3-6 patients in a 
dose escalation cohort experience DLT, that dose level will be designated as 
exceeding the maximum tolerated dose. If there are fewer than 6 enrolled 
patients in the dose level below this level, then additional patients (up to 6 
total) will be enrolled at that dose level. When there is a dose level with 0 or 
1 out of 6 patients with DLT, which is either the maximum planned dose 
level (level 4) or which is one level below a dose that was not tolerated, this 
dose level is defined as the maximum tolerated dose (MTD). If the MTD of 
ALT-801 cannot be reached during the dose escalation phase or more than 
one of six patients experience DLT at the initial dose (0.04 mg/kg), the 
sponsor, the Data Safety Monitoring Board and the principal investigators 
will meet to determine how to proceed with the study.  
Below are the dose levels of the study drug during the dose escalation phase 
of the study.   
Treatment Cycle 
Cycle #1 
 
Cycle #2 
Treatment Week 
1 
2 
3 
4 
5 
6 
7 
Treatment Day 
1 
3 
8 
15 
Rest 
29 
31 
36 
43 
Dose# 
1 
2 
3 
4 
5 
6 
7 
8 
ALT-801 
X 
X 
X 
X 
X 
X 
X 
X 

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DLT is defined as any toxicity of grade 3 that does not resolve to Grade 1 or 
lower within 72 hours and any toxicity of Grade 4 occurring during the study 
treatment period with exceptions and details described in the study protocol. 
Patients experiencing a DLT should discontinue study treatment.  Study 
treatment discontinuation due to adverse events experienced prior to study 
drug administration, disease progression or patient’s decision to withdraw 
from study treatment without occurrence of any study treatment 
discontinuation event will not necessarily define a DLT event.  Study 
treatment discontinuation events are defined in the protocol. 
 
 
Expansion 
Phase 
The two-stage expansion phase at the MTD level will be conducted using a 
Simon two-stage design. Objective response (OR) (defined as complete 
response (CR) + partial response (PR)) will be evaluated and set thresholds 
of lack of efficacy (OR rate (ORR) = 20%) and an efficacy level of interest 
(ORR = 40%) will be selected.   
Stopping Rule: 
Patient enrollment will be temporarily suspended based on occurrence of any 
the following, and the sponsor, the Data Safety Monitoring Board and 
principal investigators will meet to discuss how to proceed with future 
patient enrollment in the study: 
• 
During the dose escalation phase of the study, no dose level can be 
designated as the MTD. 
• 
If at any time during the expansion phase of the study, more than 33% 
of patients experience a possible, probable or definite drug related DLT. 
Evaluations: 
Patients will be evaluated for clinical toxicities during the treatment.  
Patients’ blood samples will be collected to assess the pharmacokinetic 
profile and immunogenicity of the study drug. The anti-tumor response will 
be evaluated at week 8 and week 12 from the start of study treatment.  All 
patients who receive at least one dose of the study drug ALT-801 will be 
included in the anti-tumor response evaluation. 
Population: 
Patients of 18 years of age with relapsed or refractory multiple myeloma.  
Patients also need to have adequate cardiac, pulmonary, liver and kidney 
functions and to have an Eastern Cooperative Oncology Group (ECOG) 
performance status of 0, 1 or 2.  
Sample Size: 
A total of up to 24 assessable patients will be accrued to the dose escalation 
phase of the study (Phase Ib).  Up to an additional 37 assessable patients will 
be enrolled at the expansion phase (Stage 1 and 2) of the study (Phase II).  A 
Cohort 
ALT-801 Dose (mg/kg) 
1 (initial) 
0.04 
2 
0.06 
3 
0.08 
4 
0.10 

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total of approximately 55 assessable patients will be enrolled to complete the 
study.  Assuming a 20% ineligible or non-assessable cases, a total of up to 
66 patients may be accrued to the study. 
 
Primary 
Endpoints: 
For Phase Ib only: (1) Determination of the MTD of ALT-801.  
For Phase Ib & II: (2) Safety profile of ALT-801. 
 
(3) Disease response rate.  
Secondary  
Endpoints: 
(1) Duration of response. 
(2) Progression free survival. 
(3) Overall survival. 
(4) Immunogenicity and pharmacokinetics profile of ALT-801.  
(5) Relationship between tumor presentation of HLA-A*0201/p53 aa 264-
272 complexes and the safety, immune response and clinical benefit of 
study treatment. 
Pharmacokinetics 
& Biomarkers: 
Blood samples will be collected to assess typing for HLA-A2, immune cell 
levels and phenotype, pharmacokinetics and immunogenicity of the study 
drug ALT-801, and the serum levels of IFN-γ and TNF-α.  Unstained slides 
from a bone marrow biopsy will be used to test HLA-A*0201/p53 aa 264-
272 complex presentation. Blood samples for pharmacokinetic analysis of 
ALT-801 will be taken on the first day of ALT-801 administration in the 
initial study treatment cycle. Venous blood will be obtained at Time 0 
(before the start of infusion), at 30 minutes (15 minutes after completion of 
infusion), and 1, 3 and 6 hours from Time 0 for the assessment of ALT-801 
serum concentration. Non-compartmental and compartmental analyses will 
be conducted.  In addition, the same blood samples collected for PK analysis 
will be used to assess the serum levels of IFN-γ and TNF-α.  Fresh blood 
samples for HLA-A2 typing, immune cell levels and phenotype testing will 
be collected before the start of first and fourth dose of study drug infusion in 
each treatment cycle.  HLA-A2 typing will be performed only once.  Bone 
marrow samples will be collected for future analysis of molecular markers 
associated with responses or resistance to ALT-801 in patients with relapsed 
or refractory multiple myeloma. 
Monitoring Tests: Blood samples for standard chemistry, and CBC with differential will be 
obtained at screening, on each study drug infusion day, and at follow-up 
visits.  Blood samples for immunogenicity testing, which include assays for 
anti-ALT-801 and IL-2 neutralizing antibodies, will be collected prior to 
dosing on the first ALT-801 infusion day and at Week 8 from the initial dose 
of study treatment. Blood and urine samples will be collected on each 
follow-up visit for response assessment.  
Response 
Assessment: 
There are two response assessments for treated patients: initial assessment at 
week 8 and confirmatory assessment at week 12 from the start of study 

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treatment. After completion of study treatment, patients who have received 
at least one dose of study drug will have the response assessments.  
Responses will be evaluated according to the new International Uniform 
Response Criteria for Multiple Myeloma proposed by the International 
Myeloma Working Group. Baseline evaluations should be performed up to 
14 days before study treatment starts.  
Progression & 
Survival 
Assessment: 
Progression-free survival, overall survival, and duration of response of all 
treated patients will be assessed at every three months during year 1 and then 
every 6 months during years 2 and 3 from the start of study treatment, or 
through the point designated as the end of the study follow up. 
Adverse Events: 
All patients will be monitored and evaluated for clinical toxicities during the 
treatment period and queried at each follow-up visit for Adverse Events 
(AEs).  Patients may volunteer information concerning AEs.  All adverse 
events will be graded by using the NCI Common Terminology Criteria for 
Adverse Events version 4.0 (CTCAE v4.0), and logged in the patient Case 
Report Form.  The study centers should report all Serious Adverse Events 
(SAEs) and all events that trigger patient’s study treatment discontinuation 
to the sponsor via phone, fax or email (or a combination) no more than 24 
hours after learning of the event.  The sponsor will use the information to 
manage and coordinate the dose escalation, cohort expansion and patient 
enrollment.  The sponsor will then inform all of the participating clinical 
sites of the current dose level and the number of patients to be enrolled at 
that level, or of any patient enrollment suspension via phone, fax or email 
within 24 hours of learning of the event.  The study centers should report all 
other adverse events to the sponsor following the guidelines defined in the 
study protocol. All study drug related AEs that are both serious and 
unexpected will be reported to the FDA in an expedited manner in 
accordance with 21 CFR §312.32. 
Statistical Plan: 
For each cohort, all AEs will be tabulated and examined and all safety, 
pharmacokinetic and tumor response data will be evaluated. For estimation 
of duration of response and progression free survival, the Kaplan-Meier 
method will be used. P-values of ≤0.05 (two-sided) will be considered to 
indicate statistical significance.  

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8. 
STUDY CALENDAR, CLINICAL PROCEDURES & TESTS 
8.1 
Study calendar 
 
TESTS & PROCEDURES 
SCREEN/ 
BASELINE1 
TREATMENT 
CYCLE #1 
  
TREATMENT 
CYCLE  #2 
1ST 
ASSESSMENT 
2ND 
ASSESSMENT 
FOLLOW-UPS 
Study Month  
 
1 
 
2 
3 
6   9  
12  18  24   30  36  
Study Week  
 
1 
2 
3 
4 
5 
6 
7 
8 
12 
  
Day of Week 
 
M 
W  
M 
M 
 
M 
W 
M 
M 
  
 
 
Study Day  
 
1 
3 
8 
15 
16-28 
29 
31  
36  
43 
  
  
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam 
X 
X 
 
 
 
 
X 
 
 
 
X 
X 
 
Vital signs, weight, Height3 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Concurrent medication 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Adverse event assessment4 
X 
X  
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
CBC with Differential 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
Blood Chemistry  
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
EKG 
X 
X5  
  
  
  
 
X  
  
  
  
 
 
 
Response evaluation6 
  
 
 
 
 
 
 
 
 
 
X 
X 
 
Serum quantitative immunoglobulins 
X 
 
 
 
 
 
 
 
 
 
X 
X 
 
SPEP 
X  
  
 
 
 
 
 
 
 
 
X 
X 
 
UPEP-random  
X 
 
 
 
 
 
 
 
 
 
X 
X 
 
SIFE 
X 
 
 
 
 
 
 
 
 
 
X 
X 
 
UIFE -random 
X 
 
 
 
 
 
 
 
 
 
X 
X 
 
Serum FLC assay6.1 
X  
 
 
 
 
 
 
 
 
 
X 
X 
 
Bone marrow plasma cell percentage6.2 
X  
 
 
 
 
 
 
 
 
 
X 
X 
 
Bone marrow immunohistochemistry or 
immunofluorescence6.3 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Soft tissue plasmacytomas assessment6.4 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Disease & survival follow-up7 
 
 
 
 
 
 
 
 
 
 
  
  
X  
X 
X 
X 
X 
X 
X 
Immune cell levels & phenotype8, 12 
 
X8 
 
 
X8 
 
X8 
 
 
X8 
 
 
 
HLA A2 Blood Typing9 & p53 tumor typing 
 
X 
 
 
 
 
 
 
 
 
 
 
 
PK, IFNγ, TNFα10,12 
 
X10 
 
 
 
 
 
 
 
 
 
 
 
Immunogenicity tests11, 12 
 
X11 
 
 
 
 
 
 
 
 
X 
 
 
Study drug (ALT-801)
 
a1  
a2 
a3 
a4 
 
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1Screening/baseline evaluations are performed < 14 days prior to start of therapy.  If the patient's condition is deteriorating, laboratory evaluations should be repeated within 48 hours prior 
to initiation of study treatment infusion.  2Pregnancy test is for women with childbearing potential only.  3Vital signs (especially blood pressure), clinical status and laboratory tests should be 
reviewed before start of therapy. Vital signs will be evaluated every 2 hours after drug infusion and before discharge, and body weight before infusion on drug infusion day. 4Patients who 
have an on-going study drug-related SAE upon study completion or at discontinuation of study will be contacted by the investigator or his/her designee every week until the event is 
resolved or determined to be irreversible. 5If the screening EKG was performed within 14 days prior to start of study treatment, the EKG is not required 6Disease response and progression 
assessment will be evaluated using the new International Uniform Response Criteria for Multiple Myeloma proposed by the International Myeloma Working Group;. 6.1only when serum and 
urine M-protein are unmeasurable 6.2 only when serum and urine M-protein and serum FLC are unmeasurable and bone marrow plasma cell percentage > 30% at baseline; 6.3only when sCR 
is to be determined; 6.4only when present at baseline, and to confirm CR or PR by X-rays, MRI or CT scans. 7Information about tumor assessment & other therapies received after completion 
of study treatment will be collected if available.  8Fresh blood samples for HLA A2 blood typing, immune cell levels & phenotype testing will be collected before dosing. 9 Use the blood 
sample collected for immune cell levels & phenotype.10Collect blood samples at Time 0 (before drug infusion), at 30 min (15 min after completion of infusion, +/- 5 min), 1 hour (+/- 10 
min), 3 hour (+/- 30 min), 6 hour (+/- 60 min) from Time 0. IFNγ and TNFα assays are performed using the same samples and at the same schedule as PK.  11Use the sample collected 
before dosing for PK test. 12Residual samples may be used by Sponsor for research studies of other biomarkers.