A Phase 2 Study of Duvelisib in Subjects With Refractory Indolent Non-Hodgkin Lymphoma
Phase: PHASE2
Conditions: Indolent Non-Hodgkin Lymphoma
Sponsor: SecuraBio

Protocol IPI-145-06 
Verastem, Inc. 
IPI-145 
30 October 2017 (Amendment 4, Global) CONFIDENTIAL 
Page 1 of 88 
STUDY PROTOCOL 
IPI-145-06 
Protocol Title 
A Phase 2 Study of IPI-145 in Subjects with Refractory 
Indolent Non-Hodgkin Lymphoma 
Protocol Number 
IPI-145-06 
Phase: 
IND Number 
EudraCT 
Phase 2 
112,486 
2013-004008-20 
Date of Protocol 
Previous Version 
30 October 2017 (Amendment 4, Global) 
03 November 2015 (Amendment 3, Global) 
30 April 2015 (Amendment 2, Global) 
08 April 2014 (Amendment 1, Global) 
20 December 2013 (Amendment 1, UK only) 
02 April 2013 (Original) 
Sponsor: 
Verastem, Inc. 
117 Kendrick Street, Suite 500 
Needham, MA  02494 
Not for Distribution – Do Not Copy 
This study protocol contains confidential information and is the proprietary property of Verastem, Inc. The 
protocol is for use by the Principal Investigator and his/her designated representatives participating in this 
investigational trial. This protocol may not be copied or made available for review by an unauthorized person 
or firm without the prior written authorization of Verastem, Inc.
NCT #: NCT01882803

Protocol IPI-145-06 
 
Verastem, Inc. 
IPI-145 
30 October 2017 (Amendment 4, Global) CONFIDENTIAL 
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INVESTIGATOR PROTOCOL APPROVAL 
A Phase 2 Study of IPI-145 in Subjects with Refractory Indolent Non-Hodgkin Lymphoma 
 
I agree to the terms of this study protocol.  I will conduct the study according to the procedures 
specified herein, and according to principles of Good Clinical Practice and local regulations and 
requirements. 
 
Institution/Clinic:  
___________________________________________ 
 
Principal Investigator ___________________________________________ 
 
Print Name:  ______________________________________ 
 
Signature:  
______________________________________ 
 
Date (mm/dd/yyyy):    ______________________________ 
 
 
 

Protocol IPI-145-06 
 
Verastem, Inc. 
IPI-145 
30 October 2017 (Amendment 4, Global) CONFIDENTIAL 
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CONTACT INFORMATION 
 
Sponsor: 
Verastem, Inc. 
117 Kendrick Street, Suite 500 
Needham, MA  02494 
 
For urgent study-related questions, please call the Medical Monitor at one of the following 
numbers: 
• US/Canada (toll free): 
 
• International: 
 

Protocol IPI-145-06 
 
Verastem, Inc. 
IPI-145 
30 October 2017 (Amendment 4, Global) CONFIDENTIAL 
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TABLE OF CONTENTS 
 
Section 
Page 
INVESTIGATOR PROTOCOL APPROVAL .....................................................................2 
SPONSOR PROTOCOL APPROVAL..................................................................................3 
CONTACT INFORMATION .................................................................................................4 
TABLE OF CONTENTS ........................................................................................................5 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ......................................9 
PROTOCOL SYNOPSIS ......................................................................................................14 
1 
BACKGROUND AND RATIONALE ............................................................30 
1.1 
INTRODUCTION ..............................................................................................30 
1.2 
BACKGROUND ................................................................................................30 
1.2.1 
Functions of PI3K-δ and PI3K-γ ........................................................................30 
1.2.2 
Indolent non-Hodgkin Lymphoma .....................................................................31 
1.3 
IPI-145 ................................................................................................................32 
1.3.1 
IPI-145, a Potent PI3K-δ,γ Inhibitor ...................................................................32 
1.3.2 
Non-Clinical Summary of IPI-145 .....................................................................32 
1.3.3 
Clinical Experience in Humans ..........................................................................32 
1.3.3.1 
Study IPI-145-01 (Phase 1, first in human study) ..............................................32 
1.3.3.2 
Study IPI-145-02 (Phase 1, Hematologic Malignancies) ...................................34 
1.4 
RATIONALE FOR IPI-145 AS A POTENTIAL THERAPY FOR SUBJECTS 
WITH INDOLENT NHL....................................................................................36 
1.5 
DETERMINATION OF STARTING DOSE AND REGIMEN ........................36 
1.6 
SUMMARY ........................................................................................................36 
2 
STUDY OBJECTIVES ....................................................................................38 
2.1 
PRIMARY OBJECTIVES ..................................................................................38 
2.2 
SECONDARY OBJECTIVES ...........................................................................38 
2.3 
EXPLORATORY OBJECTIVES.......................................................................38 
3 
STUDY ENDPOINTS.......................................................................................39 
3.1 
PRIMARY ENDPOINT .....................................................................................39 
3.2 
SECONDARY ENDPOINTS .............................................................................39 
3.3 
EXPLORATORY ENDPOINTS ........................................................................39 

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30 October 2017 (Amendment 4, Global) CONFIDENTIAL 
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4 
STUDY DESIGN...............................................................................................40 
4.1 
SCHEDULE OF ADMINISTRATION ..............................................................40 
4.2 
DOSE INTERRUPTION/HOLD/MODIFICATION GUIDELINES ................40 
4.3 
ADDITIONAL CYCLES ...................................................................................43 
4.4 
TREATMENT DISCONTINUATION ..............................................................43 
4.5 
STUDY DISCONTINUATION .........................................................................44 
5 
STUDY POPULATION ...................................................................................45 
5.1 
ENTRY CRITERIA ............................................................................................45 
5.1.1 
Inclusion Criteria ................................................................................................45 
5.1.2 
Exclusion Criteria ...............................................................................................46 
6 
STUDY PROCEDURES AND ASSESSMENTS ...........................................48 
6.1 
INFORMED CONSENT ....................................................................................48 
6.2 
SCREENING PERIOD.......................................................................................48 
6.2.1 
Medical History, Physical Examination, and Screening Assessments ...............48 
6.2.2 
Contraception ......................................................................................................49 
6.3 
TREATMENT PERIOD .....................................................................................50 
6.3.1 
Physical Examination and Vital signs ................................................................50 
6.3.2 
ECOG Performance Status .................................................................................50 
6.3.3 
B symptoms ........................................................................................................50 
6.3.4 
12-Lead ECG ......................................................................................................50 
6.3.5 
Clinical Laboratory Tests....................................................................................50 
6.3.6 
Study Drug Administration, Criteria for Treatment, and Drug Self-administration 
Diary ...................................................................................................................51 
6.3.7 
Adverse Events ...................................................................................................52 
6.3.8 
Concomitant Medication and Therapies .............................................................52 
6.3.8.1 
Antiemetics and Antidiarrheals ..........................................................................52 
6.3.8.2 
Hematopoietic Growth Factors ...........................................................................52 
6.3.8.3 
Use with caution: Medications that are Substrates of CYP3A or CYP2C8 .......53 
6.3.8.4 
Prohibited: Medications or Food that Inhibit or Induce CYP3A ........................53 
6.3.8.5 
Prohibited: Use of Vaccines ...............................................................................54 
6.3.8.6 
Prohibited:  Immunosuppressants .......................................................................54 
6.3.8.7 
Prohibited: PI3K and BTK Inhibitors .................................................................54 
6.3.8.8 
Prohibited:  Other Anticancer Therapies or Investigational Agents ...................54 
6.3.8.9 
Use with caution:  Medications that are Substrates or Inhibitors of P-glycoprotein 
(P-gp) ..................................................................................................................54 
6.3.8.10 
Photosafety..........................................................................................................55 
6.3.8.11 
Other Concomitant Therapies .............................................................................55 
6.3.9 
Subject-reported Outcomes Assessment .............................................................55 
6.3.10 
Pharmacokinetic Sampling .................................................................................55 
6.3.11 
Biomarker Assessments ......................................................................................55 
6.3.12 
Pharmacogenomic Sample Collection (Optional) ..............................................56 
6.3.13 
Indolent NHL Response Assessments ................................................................57 
6.4 
END OF TREATMENT VISIT ..........................................................................58 
6.5 
POST-TREATMENT PERIOD ..........................................................................59 

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6.5.1 
Safety Follow up Visit (30 Days Post-Treatment)..............................................59 
6.5.2 
Long-term Follow-up ..........................................................................................59 
6.6 
MISSED VISITS ................................................................................................59 
7 
INVESTIGATIONAL MEDICINAL PRODUCT .........................................60 
7.1 
DESCRIPTION OF INVESTIGATIONAL MEDICINAL PRODUCT ............60 
7.2 
DOSAGE AND ADMINISTRATION ...............................................................60 
7.2.1 
Dosage ................................................................................................................60 
7.2.2 
Administration ....................................................................................................60 
7.3 
PACKAGING AND LABELING ......................................................................61 
7.4 
STORAGE AND HANDLING ..........................................................................61 
7.5 
INVESTIGATIONAL MEDICINAL PRODUCT ACCOUNTABILITY .........61 
7.6 
ASSIGNMENT TO TREATMENT ...................................................................61 
7.7 
ASSESSMENT OF COMPLIANCE ..................................................................62 
7.8 
TREATMENT OF OVERDOSE ........................................................................62 
8 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS .......................63 
8.1 
DEFINITIONS....................................................................................................63 
8.1.1 
Adverse Event .....................................................................................................63 
8.1.2 
Adverse Reactions and Suspected Adverse Reactions .......................................63 
8.1.3 
Serious Adverse Event ........................................................................................63 
8.2 
PROCEDURES FOR ELICITING, RECORDING, AND REPORTING 
ADVERSE EVENTS ..........................................................................................64 
8.2.1 
Eliciting and Recording Adverse Events ............................................................64 
8.2.1.1 
Relationship to Study drug .................................................................................64 
8.2.1.2 
Adverse Event Severity ......................................................................................65 
8.2.2 
Specific Instructions for Recording Adverse Events on the eCRF .....................65 
8.2.2.1 
Diagnosis versus Signs and Symptoms ..............................................................65 
8.2.2.2 
Adverse Events Occurring Secondary to Other Events ......................................65 
8.2.2.3 
Persistent or Recurrent Adverse Events..............................................................66 
8.2.2.4 
Abnormal Laboratory Values .............................................................................66 
8.2.2.5 
New Cancers .......................................................................................................66 
8.2.2.6 
Medication Errors, Misuse and Abuse of Study Drug ........................................66 
8.2.3 
Reporting of Serious Adverse Events .................................................................67 
8.2.3.1 
Immediate Reporting of Serious Adverse Events by Investigator to Sponsor ...67 
8.2.3.2 
Immediate Reporting of Medical Events of Interest ...........................................67 
8.2.3.3 
Reporting of Serious Adverse Events to the Institutional Review Board (IRB)/ 
Ethics Committee (EC) .......................................................................................68 
8.2.3.4 
Reporting of Serious Adverse Events to Regulatory Authorities .......................68 
8.2.4 
Pregnancy and In Utero Drug Exposure .............................................................68 
9 
STATISTICAL METHODS ............................................................................70 
9.1 
SAMPLE SIZE DETERMINATION .................................................................70 
9.2 
RANDOMIZATION AND STRATIFICATION ...............................................70 
9.3 
ANALYSIS SETS ..............................................................................................70 
9.4 
EFFICACY ANALYSES ...................................................................................70 

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9.4.1 
Analysis of Primary Endpoint ............................................................................71 
9.4.2 
Analyses of Secondary Endpoints ......................................................................71 
9.5 
SAFETY ANALYSES .......................................................................................71 
9.6 
PHARMACOKINETIC ANALYSES ................................................................72 
9.7 
ANALYSIS OF OTHER ENDPOINTS .............................................................72 
9.7.1 
Biomarker Analyses ............................................................................................72 
9.7.2 
Analyses of Health-Related QoL ........................................................................72 
9.8 
INTERIM AND FINAL ANALYSeS ................................................................72 
9.8.1 
Interim Analysis ..................................................................................................72 
9.8.2 
Final Analysis .....................................................................................................73 
10 
STUDY ADMINISTRATION .........................................................................74 
10.1 
GOOD CLINICAL PRACTICE STATEMENT ................................................74 
10.2 
INFORMED CONSENT ....................................................................................74 
10.3 
SUBJECT CONFIDENTIALITY.......................................................................74 
10.4 
INSTITUTIONAL REVIEW BOARD/ ETHICS COMMITTEE 
REQUIREMENTS..............................................................................................75 
10.5 
CASE REPORT FORMS AND SOURCE DOCUMENTATION .....................75 
10.6 
SPONSOR MONITORING ................................................................................75 
10.7 
INDEPENDENT DATA MONITORING COMMITTEE .................................75 
10.8 
QUALITY ASSURANCE ..................................................................................76 
10.9 
STUDY OR CLINICAL SITE TERMINATION ...............................................76 
10.10 
DURATION OF THE STUDY, EXPECTED DURATION OF SUBJECT 
PARTICIPATION, AND END OF STUDY ......................................................76 
10.11 
RECORDS RETENTION...................................................................................76 
10.12 
PUBLICATIONS................................................................................................76 
11 
REFERENCES..................................................................................................77 
APPENDICES ........................................................................................................................80 
 
Appendix 1: Known CYP3A or CYP2C8 Substrates ..........................................................80 
Appendix 2: Medications or Foods Known to Inhibit or Induce CYP3A .........................81 
Appendix 3: P-gp Substrates and Medications that are Inhibitors of P-gp ......................83 
Appendix 4: ECOG Performance Status ..............................................................................85 
Appendix 5: Examples of Suitable Prior Chemotherapy ....................................................86 
Appendix 6: QoL Instrument - EQ-5D Questionnaire ........................................................87 
 

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IPI-145 
30 October 2017 (Amendment 4, Global) CONFIDENTIAL 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
Abbreviation 
 
Definition 
ADME 
Absorption, distribution, metabolism, and excretion 
AE 
Adverse Event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase  
AKT (PKB) 
A serine/threonine protein kinase 
aPTT 
Activated partial thromboplastin time 
ASCO 
American Society of Clinical Oncology 
AST 
Aspartate aminotransferase 
AUC 
Area under the curve 
BCR 
B-cell receptor 
βhCG 
β human chorionic gonadotropin 
BID 
BTK 
Twice a day 
Bruton’s Tyrosine Kinase 
ºC 
Degrees Celsius 
C5a 
A protein fragment released from complement component C5 
CAL-101 (GS-1101) 
 
A PI3K-δ inhibitor in clinical development for patients with 
hematologic malignancies, also known as idelalisib or Zydelig™ 
CEC 
Central Ethics Committee 
CLL 
Chronic lymphocytic leukemia 
Cmax 
Maximum concentration 
CNS 
Central nervous system 
CMV 
Cytomegalovirus 
COPD 
Chronic obstructive pulmonary disease 
CR 
Complete response 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events  
CYP 
Cytochrome P450 
DDI 
Drug-drug interaction 
DNA 
Deoxyribonucleic acid 

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IPI-145 
30 October 2017 (Amendment 4, Global) CONFIDENTIAL 
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Abbreviation 
 
Definition 
DOR 
Duration of response 
DMC 
Data monitoring committee 
EC 
Ethics Committee 
ECOG 
Eastern Cooperative Oncology Group 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EoT 
End of Treatment 
EQ-5D 
EuroQol – 5D (health-related QoL assessment) 
FAS 
Full analysis set 
FCεRI 
High-affinity IgE receptor 
FCγRII 
Fc fragment of IgG, low affinity IIa, receptor (CD32) 
FDA 
Food and Drug Administration 
FL 
Follicular lymphoma 
GLP 
Good laboratory practice 
GPCR 
G-protein coupled receptor 
GRAS 
Generally Regarded as Safe 
h 
Hour(s) 
HBcAb 
Hepatitis B core antibody 
HBsAg 
Hepatitis B surface antigen 
HCV Ab  
Hepatitis C virus antibodies 
HIV 
Human immunodeficiency virus 
HSCT 
Hematopoietic stem cell transplant 
IC50 
Half maximal inhibitory concentration 
ICH 
International Conference on Harmonisation 
IEC 
IRB 
Independent Ethics Committee 
Institutional Review Board 
Ig 
Immunoglobulin  
in 
Inches 
Infinity 
Infinity Pharmaceuticals, Inc. 
iNHL 
Indolent non-Hodgkin lymphoma 

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IPI-145 
30 October 2017 (Amendment 4, Global) CONFIDENTIAL 
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Abbreviation 
 
Definition 
INR 
International normalized ratio 
IPI-145 
(S)-3-(1-(9H-
purin-6-ylamino)ethyl)-8-chloro-2-phenylisoquinolin-1(2H)-one, 
also known as duvelisib 
IRB 
Institutional Review Board 
IV 
Intravenous(ly) 
IWG 
International Working Group 
kg 
Kilogram(s) 
KPS 
Karnofsky Performance Status 
L 
Liter(s) 
LC/MS/MS 
Liquid chromatography-tandem mass spectrometry method.   
LDH 
LEC 
Lactate dehydrogenase 
Local Ethics Committee 
m 
Meter(s) 
MAD 
Multiple ascending dose 
MedDRA 
MEOI 
Medical Dictionary for Regulatory Activities 
Medical Event of Interest 
mg 
Milligram(s) 
mL 
Milliliter(s) 
MRI 
Magnetic resonance imaging 
µg 
Microgram(s) 
µM 
Micromolar 
MTD 
Maximum tolerated dose 
MZL 
Marginal zone lymphoma 
N 
Number 
NCI 
National Cancer Institute 
ng 
Nanogram(s) 
nM 
Nanomolar 
NK 
Natural killer 
ORR 
Overall response rate 
OS 
Overall survival 

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30 October 2017 (Amendment 4, Global) CONFIDENTIAL 
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Abbreviation 
 
Definition 
PCR 
Polymerase chain reaction 
PD 
Progressive disease 
PDK-1 
3-phosphoinositide dependent protein kinase-1 
PET 
Positron emission tomography 
PFS 
Progression-free survival 
P-gp 
P-glycoprotein 
PI3K 
Phosphoinositide-3-kinase 
PIP3 
Phosphatidylinositol (3,4,5)-trisphosphate 
PK 
Pharmacokinetics 
PO 
Oral(ly) 
PR 
Partial response 
PT 
Prothrombin time 
PTEN 
Phosphatase and tensin homolog 
QD 
Once a day 
QoL 
Quality of life 
RAS 
Protein subfamily of small GTPases involved in cellular signal 
transduction 
RBC 
Red blood cell 
RIT 
Radioimmunotherapy 
SAD 
Single ascending dose 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SCF 
Stem cell factor 
SD 
Stable disease 
SE 
Standard error 
SH2 
Sarc homology 2 
SLL 
Small lymphocytic lymphoma 
SOC 
Standard of care 
T1/2 
TTR 
Terminal elimination half-life 
Time to Response 
ULN 
Upper limit of normal 

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30 October 2017 (Amendment 4, Global) CONFIDENTIAL 
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Abbreviation 
 
Definition 
TAMs 
Tumor-associated macrophages 
TEAE 
Treatment-emergent adverse events 
Tmax 
Time to maximum concentration 
UV 
Ultraviolet 
WBC 
White blood cell 
WCBP 
Women of child-bearing potential 

Protocol IPI-145-06 
 
Verastem, Inc. 
IPI-145 
30 October 2017 (Amendment 4, Global) CONFIDENTIAL 
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PROTOCOL SYNOPSIS 
Study Title: 
A Phase 2 Study of IPI-145 in Subjects with Refractory 
Indolent Non-Hodgkin Lymphoma 
Protocol Number 
IPI-145-06 
Study Phase 
2 
Investigational Agent 
IPI-145 (duvelisib) 
Study Objectives: 
Primary Objective: 
To evaluate the antitumor activity of IPI-145 administered to 
subjects diagnosed with indolent non-Hodgkin lymphoma 
(iNHL) (defined as follicular lymphoma [FL], marginal zone 
lymphoma [MZL; splenic, nodal and extranodal], or small 
lymphocytic lymphoma [SLL]) whose disease is refractory 
to rituximab and to either chemotherapy or 
radioimmunotherapy (RIT). 
Secondary Objectives: 
• To evaluate the safety of IPI-145 in all subjects 
• To evaluate additional efficacy parameters in all 
subjects 
• To evaluate the pharmacokinetics (PK) of IPI-145 
and, if applicable, its metabolite(s) 
Exploratory Objectives: 
• To evaluate whether baseline values or treatment-
related changes in biomarkers correlate with IPI-145 
clinical activity, safety and/or resistance in iNHL 
• To evaluate whether tumor genomic or 
pharmacogenomic markers correlate with IPI-145 
clinical activity, safety, PK and/or resistance in iNHL 
• To evaluate the health-related quality of life (QoL) of 
subjects 
Study Endpoints: 
Primary Endpoint 
Overall Response Rate (ORR), with overall response defined 
as best response of complete response/remission (CR) or 
partial response/remission (PR), according to the revised 
International Working Group (IWG) Criteria1  
 

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Secondary Endpoints 
• Treatment-emergent adverse events (TEAEs), ECG 
measures, and changes in safety laboratory values  
• Duration of response (DOR), defined as the time 
from the first documentation of response to the first 
documentation of progressive disease (PD) or death 
due to any cause 
• Progression-free survival (PFS), defined as the time 
from the first dose of study treatment to the first 
documentation of PD or death due to any cause 
• Overall survival (OS) defined as the time from the 
first dose of study treatment to the date of death 
• Time to response (TTR), defined as the time from the 
first dose of study treatment to the first 
documentation of response (complete or partial) 
• PK parameters derived from plasma IPI-145 
concentrations and, if applicable, its metabolite(s) 
Exploratory Endpoints 
• Lymph node response rate (LNR rate), with LNR 
defined as ≥ 50% reduction in the Sum of the 
Products of the Perpendicular Diameters (SPD) of 
nodal target lesions 
• 
Serum, plasma and tissue biomarkers and blood 
immunophenotype 
• 
Germline DNA sequence variations  
• Tumor genomic features (e.g. DNA sequence 
variation, DNA copy number variation, and/or RNA 
expression)  
• Health-related QoL of subjects as assessed by the 
following subject-reported questionnaire:  
o EuroQol-5D (EQ-5D), a standardized 
instrument for use as a measure of health-
related QoL 
Study Treatment: 
IPI-145 is administered orally as a capsule formulation. The 
IPI-145 drug product is supplied as 5 mg and 25 mg 
formulated capsules.  
 
 

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Study Design: 
 
Study IPI-145-06 is a Phase 2, open-label, single arm 
efficacy and safety study of IPI-145 administered orally to 
subjects diagnosed with iNHL (FL, MZL, or SLL) whose 
disease is refractory to rituximab and to either chemotherapy 
or RIT.   
Schedule of Administration 
Subjects will be given a starting dose of 25 mg IPI-145 
orally twice daily (BID) during each 28-day treatment cycle, 
for up to 13 cycles.  To receive additional cycles of IPI-145 
beyond 13 cycles, subjects must have documented evidence 
of response (CR or PR) or stable disease (SD) at the Cycle 
14 Day 1 response assessment according to the revised IWG 
criteria 1. These subjects may continue to receive IPI-145 
treatment until disease progression or unacceptable toxicity. 
Study Population: 
This study anticipates enrolling approximately 120 subjects 
with a diagnosis of iNHL whose disease is refractory to 
rituximab and to either chemotherapy or RIT.  This will 
include approximately 80 subjects with FL. Total enrollment 
may exceed 120 subjects in order to enroll a sufficient 
number of FL subjects. 
Study Duration: 
Following treatment with IPI-145, study subjects will be 
followed for survival for up to 3 years from the date of their 
first dose of study drug.   
It is anticipated that the entire study will accrue subjects over 
approximately 30 months from the enrollment of the first 
subject. 
It is anticipated that the total duration of the study will be 
approximately 66 months. 
Study Centers: 
Enrollment is anticipated at approximately 100 sites.  
Approximately 40 sites will be initiated in the US, with the 
remainder of sites outside the US.    
Inclusion Criteria: 
Subjects are eligible for inclusion in the study if they meet 
the following criteria: 
1. Age 18 years or older.  
2. Subjects who have been diagnosed with indolent NHL 
[defined as FL, MZL (splenic, nodal and extranodal), or 
SLL] that has progressed. 
a. For subjects for whom the most recent biopsy was 
performed >36 months before the first dose of 

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IPI-145, a repeat biopsy to confirm histology 
should be performed, unless medically 
contraindicated. 
b. For subjects who progressed within 2 months of 
initiating last prior chemotherapy, a repeat biopsy 
to confirm histology should be performed, unless 
medically contraindicated. 
3. Subjects must have disease that is refractory to a 
chemotherapy regimen or RIT.  The chemotherapy 
regimen (with or without rituximab) must contain at least 
one alkylating agent or purine nucleoside antagonist. See 
Appendix 5 for examples of suitable prior chemotherapy. 
Refractory is defined as either:  
a. Lack of a CR or PR while receiving the 
chemotherapy regimen or RIT  
or 
b. PD within 6 months of the last dose of the 
chemotherapy regimen or RIT documented by 
computed tomography (CT), PET/CT or MRI 
obtained within 6 months after the last dose 
Note: Subjects exhibiting clinical progression within 6 
months after the last dose of a chemotherapy regimen or 
RIT who are unable to undergo CT, PET/CT or MRI 
scans within the 6 month timeframe are allowed up to an 
additional 30 days to confirm radiologic progression. 
4. Subjects must have disease that is refractory to 
rituximab.  Refractory is defined as any of the following: 
a. Lack of a CR or PR during treatment with a full 
course of single-agent rituximab (≥4 doses of 
375 mg/m2, weekly) or ≥2 doses of ≥375 mg/m2 of 
rituximab in combination with chemotherapy  
b. PD within 6 months of the last dose of a full course 
of single-agent rituximab or rituximab in 
combination with chemotherapy 
c. PD during, or within 6 months of the last dose of 
rituximab maintenance therapy 
5. Measurable disease with a lymph node or tumor mass 
≥1.5 cm in at least one dimension by CT, PET/CT or 
MRI. 

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6. Eastern Cooperative Oncology Group (ECOG) 
performance status 0-2 (corresponds to Karnofsky 
Performance Status [KPS] ≥60%). 
7. Adequate renal function, defined as serum creatinine ≤2 
× upper limit of normal (ULN).  
8. Adequate hepatic function, defined as total bilirubin ≤1.5 
× ULN (unless elevated due to Gilbert’s syndrome) and 
aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT) levels ≤3 × ULN. 
9. Negative serum or urine β human chorionic gonadotropin 
(βhCG) pregnancy test within 1 week before first dose of 
study drug if the subject is a woman of childbearing 
potential (WCBP) (defined as a sexually mature woman 
who has not undergone surgical sterilization or who has 
not been naturally post-menopausal for at least 
24 consecutive months for women ≤55 years or 12 
consecutive months for women >55 years).   
10. Willingness of male and female subjects who are not 
surgically sterile or postmenopausal to use medically 
acceptable methods of birth control for the duration of 
the study, including 30 days after the last dose of 
IPI-145. Sexually active men, and women using oral 
contraceptive pills, should also use barrier contraception. 
11. Ability to adhere to the study visit schedule and all 
protocol requirements. 
12. Signed and dated institutional review board 
(IRB)/independent ethics committee (IEC)-approved 
informed consent form before any study specific-
screening procedures are performed. 
Exclusion Criteria:  
 
Subjects are to be excluded from the study if they meet any 
of the following criteria: 
1. Candidate for potentially curative therapies at the time of 
informed consent, in the opinion of the investigator. 
2. Prior treatment with any PI3K inhibitor or Bruton’s 
Tyrosine Kinase (BTK) inhibitor 
3. Prior history of allogeneic hematopoietic stem cell 
transplant (HSCT). 
4. Major surgery within 28 days before the first dose of 
study drug.  

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5. Prior chemotherapy, cancer immunosuppressive therapy, 
or other investigational agents within 4 weeks before 
first dose of study drug.  
6. Ongoing treatment with chronic immunosuppressants 
(e.g. cyclosporine) or systemic steroids >20 mg 
prednisone (or equivalent) once daily (QD). 
7. Grade 3B FL and/or clinical evidence of transformation 
to a more aggressive subtype of lymphoma.  
8. Symptomatic central nervous system (CNS) NHL; a 
lumbar puncture is not required unless CNS involvement 
with NHL is clinically suspected. 
9. Ongoing systemic bacterial, fungal, or viral infections at 
the time of initiation of study treatment (defined as 
requiring therapeutic dosing of an antimicrobial, 
antifungal or antiviral agent) 
a. Subjects on antimicrobial, antifungal or antiviral 
prophylaxis are not specifically excluded if all other 
inclusion/exclusion criteria are met and there is no 
presence of active infection. 
10. Human immunodeficiency virus (HIV) infection. 
11. Baseline QTcF >500 ms (average of triplicate readings). 
NOTE: This criterion does not apply to subjects with a 
right or left bundle branch block (BBB). 
12. Prior, current or chronic hepatitis B or hepatitis C 
infection, positive result for hepatitis C virus antibodies 
(HCV Ab) or hepatitis B surface antigen (HBsAg) or 
hepatitis B core antibody (HBcAb).  
13. Unable to receive prophylactic treatment for 
pneumocystis, herpes simplex virus (HSV) or herpes 
zoster (VZV) at time of initiation of study treatment. 
14. History of chronic liver disease, such as cirrhosis or 
chronic hepatitis due to any cause, or suspicion of 
alcohol abuse (iNHL in the liver is not an exclusion). 
15. Unstable or severe uncontrolled medical condition (e.g., 
unstable cardiac function, unstable pulmonary 
condition).  Any important medical illness or abnormal 
laboratory finding that would, in the investigator’s 
judgment, increase the subject’s risk to participating in 
this study. 
16. Concurrent active malignancy other than nonmelanoma 
skin cancer or carcinoma in situ of the cervix; bladder 

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cancer or prostate cancer not requiring treatment.  
Subjects with previous malignancies are eligible 
provided that they have been disease free for 2 years or 
more. 
17. History of stroke, unstable angina, myocardial infarction, 
or ventricular arrhythmia requiring medication or 
mechanical control within the last 6 months prior to first 
dose of study drug. 
18. Prior surgery or gastrointestinal dysfunction that may 
affect absorption of study drug (e.g. gastric bypass, 
gastrectomy). 
19. Use of live or live attenuated vaccines within 30 days 
prior to signing ICF.  
20. Administration of medications or foods that are strong 
inhibitors or inducers of CYP3A within 2 weeks prior to 
the first dose of study drug. 
21. Female subjects who are pregnant or breastfeeding. 
Statistical 
Methodology: 
Sample Size Determination 
This study will test the null hypothesis that the ORR is ≤30% 
against the alternative that ORR is ≥45%. Using a group 
sequential design with 1 interim analysis, 120 subjects will 
provide >90% power to achieve a one-sided overall 
significance level of 0.025.  The interim analysis will occur 
approximately 4 months after at least 30 subjects (25% of 
the total) have initiated treatment with IPI-145.  The 
cumulative Type II error to be spent at the interim and final 
analyses are 0.02 and 0.1, respectively.  The interim analysis 
is intended for futility only and hence no Type I error will be 
spent. 
Analysis Sets 
The Full Analysis Set (FAS) will include all subjects who 
were treated with at least one dose of IPI-145. The FAS will 
be the primary analysis set for all efficacy and safety 
analyses.   
The Evaluable Analysis Set (EAS) will include all subjects 
who had no major protocol violations and who remained in 
the treatment phase of the study for at least 8 weeks with an 
adequate baseline tumor assessment and at least 1 adequate 
post baseline tumor assessment. Subjects with documented 
disease progression before 8 weeks of treatment should be 

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considered as “early progression” subjects and, therefore, 
should be considered evaluable. 
Primary Efficacy Analysis 
ORR will be tested against the null (≤30%) by 1-sided exact 
binomial test at the 0.025 level.  The estimated ORR along 
with the 2-sided 95% exact confidence interval will be 
provided.  Missing data will be imputed by assuming that 
any subjects not exhibiting a response (CR or PR) are non-
responders. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 1: Study Assessments for IPI-145 Monotherapy 
 
Screening 
Day 
 -30 to -1 
Cycle 1, Cycle 2 & 
Cycle 3 
(28-Day Cycle 
Length) 
Cycle 4, Cycle 5,  
Cycle 6 & Cycle 7 
(28-Day Cycle 
Length) 
Cycle 8 and beyond – 
every second cycle  
(28-Day Cycle Length) 
End of Treatment 
(EoT) 
(within 7 days 
following the 
decision to 
discontinue study 
treatment) s 
Safety Follow-up 
(30+7 days from 
last dose) t 
Day 
Day 
Day 
 1 (±4) u 
15 (±3) 
1 (±4) 
1 (±4) 
Informed Consent 
X 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
Histologic confirmation of indolent B-cell 
lymphoma (FL, MZL, or SLL) 
  X a 
 
 
 
 
 
 
Medical History, Demographics 
X 
 
 
 
 
 
 
Cancer History 
X 
 
 
 
 
 
 
Follicular Lymphoma International Prognostic 
Index (FLIPI) score at time of Screening 
X 
 
 
 
 
 
 
Hepatitis Serology, CMV/EBV serology or viral 
load, HIV 
  X b 
 
 
 
 
 
 
Physical Examination/Vital Signs d 
  X c  
X 
X 
X 
X 
X 
 
ECG (12-lead) 
X 
See Table 2 
 
 
 
 
Bone marrow biopsy and/or bone marrow 
aspiration 
  X e 
See Table 3 
 
 
CT scans of the chest, abdomen and pelvis 
  X f 
See Table 3 
 
 
ECOG Performance Status 
X 
 
 
 
 
 
 
B symptoms 
X 
X 
 
X 
X 
 
 
Serum/Urine βhCG Pregnancy Test 
  X g 
  X g 
 
  X g 
  X g 
 
 
Blood chemistry j 
    X c,h 
  X h 
 
  X h 
  X h 
 X h 
 
Liver Function Tests j 
   X c,i 
 X i 
 X i 
 X i 
  X i 
X i 
 
Hematology j 
    X c,k 
  X k 
 X k 
 X k 
  X k 
X k 
 
Coagulation j 
   X c,l 
 X l 
 
 
 
 
 
Urinalysis j 
    X c,m 
  X m 
 
   X m 
 
 
 
Prior/Concomitant Medications n 
X 
X 
X 
X 
X 
X 
  X t 
Prior/Concomitant Procedures o 
X 
X 
X 
X 
X 
X 
  X t 
AE/SAE Assessment 
  X p 
X 
X 
X 
X 
X 
  X t 
Quality of Life (QoL) (EQ-5D) 
  X q 
  X q 
 
  X q 
  X q 
  X q 
 
Drug Self-administration Diary 
 
X 
 
 
 
 
IPI-145 Administration 
 
  X r 
  X r 
  X r 
 
 

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a. 
Histologic confirmation based on biopsy obtained <36 months prior to Cycle 1, Day 1 should be performed unless medically contraindicated.  For 
subjects who progressed within 2 months of initiating most recent chemotherapy, a repeat biopsy to confirm histology should be performed. 
b. 
All subjects will be assayed for anti-hepatitis C antibody (anti-HCV) and hepatitis B surface antigen (HBsAg) and core antibody (HBcAb) at Screening.  
Subjects with a positive anti-HCV or positive HBsAg or HBcAb test will be excluded from enrolling in the study.  All subjects will also be assayed for 
cytomegalovirus and Epstein-Barr virus [CMV and EBV (Ag and Ab)] via a serology or viral load detection via polymerase chain reaction (PCR) assay at 
Screening. Subjects without documentation of a prior negative HIV test result (e.g. antibody, antigen or PCR-based test) are required to undergo an HIV 
test during Screening. Only subjects with a negative HIV result will be eligible for the study. 
c. 
Clinically significant findings after the time of informed consent should be recorded as an AE from all subjects (excluding screen failures). Events 
meeting serious criteria will be reported to the Sponsor as an SAE for all subjects from time of informed consent (including screen failures). 
d. 
Complete physical exam at Screening: includes assessment of liver/spleen size and clinical assessment of tumor masses (if evaluable by physical exam), 
height and weight and vital signs (including temperature, blood pressure, pulse rate and respiratory rate). At all other visits, a focused physical exam 
should be performed, which includes vital signs, assessment of liver/spleen size, clinical assessment of tumor masses and other clinically significant 
findings (new or previously noted at Screening).  If physical examination at Screening is performed within 7 days of Cycle 1, Day 1, these Screening 
results can be used in place of the Cycle 1, Day 1 focused physical examination.   
e. 
Bone marrow biopsy and/or bone marrow aspiration are to be performed at Screening for subjects where bone marrow biopsies and aspirates are a 
necessary part of the subject’s clinical staging or who have ≥Grade 3 cytopenias at Screening.  If a previous bone marrow biopsy and aspirate has been 
performed within 60 days of Cycle 1, Day 1 and frozen aspirate sample and unstained slides or blocks are available, these results can be used in place of 
the Screening assessment.  If bone marrow aspirate and/or bone marrow biopsy is performed, the Screening and the first post-Screening bone marrow 
biopsies and/or aspirate samples should be sent for biomarker analysis (along with the corresponding pathology report) if available. See the IPI-145-06 
Laboratory Manual for further instructions regarding the handling, shipping, and storage of the samples. 
f. 
CT scans of the chest, abdomen and pelvis are required for all subjects.  Other scans may be performed (e.g. head/neck CT) if clinically indicated or to 
evaluate a site of known disease.  18-FDG-PET/CT or MRIs may be used instead of CT scans, but the same method must be used throughout the study. 
Copies of all scans will be sent for independent review of response assessment.  Please refer to complete imaging schedule per Table 3.  
g. 
A serum/urine βhCG pregnancy test will be performed at Screening, on Day 1 of each Cycle, and when clinically indicated while receiving IPI-145 for 
WCBP.  The test must be performed within 7 days of first dose to confirm eligibility.  If the Screening test was within 7 days of first dose, it does not 
need to be repeated on Cycle 1 Day 1. 
h. 
Blood chemistry laboratory parameters include: albumin, total protein, uric acid, sodium, potassium, calcium, phosphorous, chloride, bicarbonate (or 
CO2), blood urea nitrogen (BUN) or urea, creatinine, lipase, amylase, magnesium, and glucose.  If the Screening chemistry evaluations are performed 
within 7 days of Cycle 1, Day 1, these Screening results can be used in place of the Cycle 1, Day 1 blood chemistry results.  All clinically significant 
laboratory findings, including but not limited to those findings resulting in a drug interruption/reduction/discontinuation or requiring medical intervention 
should be reported as an AE (see protocol Section 8.1.1 for definition of an AE).   
i. 
Liver function tests to include lactate dehydrogenase (LDH), serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), total and 
direct bilirubin, and alkaline phosphatase (ALP).  If the Screening liver function tests are performed within 7 days of Cycle 1, Day 1 then these Screening 
results can be used in place of the Cycle 1, Day 1 liver function tests results. Blood samples should be drawn and results reviewed within 72 hours prior to 
the clinic visit.  All clinically significant laboratory findings, including but not limited to those findings resulting in a drug 
interruption/reduction/discontinuation or requiring medical intervention should be reported as an AE (see protocol Section 8.1.1 for definition of an AE).   
j. 
Additional (unscheduled) assessments should be done as clinically indicated. 

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k. 
Hematology laboratory parameters to include: hemoglobin, hematocrit, platelets, and white blood cell count with 5-part differential (manual or 
automated) [for an absolute neutrophil count (ANC), neutrophils, lymphocytes and monocytes, eosinophils and basophils].  If the Screening hematology 
evaluations are performed within 7 days of Cycle 1 Day 1, then these Screening results can be used in place of the Cycle 1 Day 1 hematology results.  
Blood samples should be drawn and results reviewed within 72 hours prior to the clinic visit.  Clinically significant laboratory findings, including but not 
limited to those findings resulting in a drug interruption/reduction/discontinuation or requiring medical intervention should be reported as an AE (see 
protocol Section 8.1.1 for definition of an AE). 
l. 
Coagulation evaluation will occur at Screening and on Day 1 of Cycles 1, 2, and 3 for all subjects.  Coagulation laboratory parameters include 
prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (aPTT).  If the screening coagulation evaluations 
are performed within 7 days of Cycle 1 Day 1, these Screening results can be used in place of the Cycle 1 Day 1 coagulation results.  Blood samples 
should be drawn and results reviewed within 72 hours prior to the clinic visit.  Clinically significant laboratory findings including but not limited to those 
findings resulting in a drug interruption/reduction/discontinuation or requiring medical intervention should be reported as an adverse event (see protocol 
Section 8.1.1 for definition of an AE). 
m. 
Complete urinalysis with qualitative analysis for protein will be performed at Screening, at Cycle 3, Day 1 and at Cycle 7, Day 1.  Positive results 
(protein >30 mg/dL) will require quantitative analysis (assessment of urine protein to creatinine ratio) if not previously noted as part of medical history.  
Clinically significant laboratory findings including but not limited to those resulting in a drug interruption/reduction/discontinuation or requiring medical 
intervention should be reported as an adverse event (see protocol Section 8.1.1 for definition of an AE).  
n. 
For a period of 14 days prior to Cycle 1 Day 1 and throughout study treatment, subjects must avoid the concomitant use of drugs or foods that are strong 
inducers and inhibitors of CYP3A4.  Moderate or weak inducers/inhibitors may be used with caution (See Appendix 2).  
o. 
Prior/concomitant procedures should include all transfusions.  If the subject is transfusion-dependent at Screening, transfusion history from the previous 3 
months will be collected. 
p. 
Adverse events will be collected from time of informed consent through the 30-day post-treatment visit for all subjects (excluding screen failures).  SAEs 
will be collected from the time of informed consent (including screen failures) through 30 days after the last dose of study drug for all subjects.  All AEs 
will be followed until resolution, return to baseline or it is determined the event is considered chronic.  See Section 8.1.1 of the protocol for more 
information regarding AE/SAE collection and reporting. 
q. 
Quality of life assessment includes the EQ-5D questionnaire. Conducted at Screening, and on Day 1 of Cycle 3, Cycle 5, Cycle 7, and Cycle 10, and Day 
1 of every 4th cycle thereafter while on treatment (i.e. Cycle 14, 18, 22, etc.), and, when possible, at End of Treatment (EoT) (if >1 months from last 
administered questionnaire). 
r. 
IPI-145 capsules will be administered twice daily (BID) in 28-day cycles.  IPI-145 doses will be dispensed at a minimum monthly through Cycle 8 and 
every two months thereafter so the subject has enough IPI-145 doses until at least the next dispensation visit, taking into account the dispensation visit 
window.  The ±4 day window for Day 1 in relevant Cycles does not apply to dose administration as dosing is daily.  Doses should be taken every 12 hours 
within ±2 hours of the scheduled dose. Missed doses outside this window or vomited doses should not be taken or repeated. 
s. 
An End of Treatment (EoT) visit is to be performed for all subjects who permanently discontinue study treatment within 7 days following the decision to 
discontinue study treatment. EoT assessments need not be repeated if performed within the previous 14 days, or 30 days for CT scan. 
t. 
All subjects will have a Safety follow-up visit approximately 30 (+7) days after the last dose of study drug.  If possible, this visit should occur prior to the 
initiation of any subsequent anticancer therapy.  Assessments should include collection of AEs/SAEs and concomitant medications/procedures.  This can 
be performed by telephone call, as long as the subject does not require laboratory and/or other procedures related to any new or ongoing AEs, in which 
case a clinical visit will be required. 

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u. 
Visit window does not apply to Cycle 1, Day 1. 

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Table 2: Pharmacokinetic and Biomarker Assessments 
 
Cycle 1  
(28-Day Cycle Length) 
Cycle 2 
(28-Day Cycle 
Length) 
Cycle 3  
(28-Day Cycle 
Length) 
Cycles 5, 7, 10 & 14  
(28-Day Cycle 
Length) 
End of 
Treatment 
(EoT) 
(within 7 days 
following the 
decision to 
discontinue 
study 
treatment) 
Day 1 
Day 15 (±3) 
Day 1 (±4) 
Day 1 (±4) 
Day 1 (±4) 
Time (hr) relative to IPI-145 administration 
Pre-
dose 
Pre-
dose 
+1 
+4 
Anytime 
during the visit 
Anytime 
during the 
visit 
Anytime during 
the visit 
Pharmacokinetic blood sample collection a 
 
 X b 
X 
X 
X 
X 
 
 
ECG (12-lead) 
  X c 
 X c 
 X c 
 X c 
 
 
 
 
Serum and plasma biomarkers  
X 
X 
 
 
X 
X 
X 
X 
Immunoglobulin blood levels d 
X 
 
 
 
 
X 
X 
X 
Immunophenotyping evaluations (e.g. B/T-lymphocyte 
panel) e 
X 
 
 
 
X 
X 
X 
X 
Archival tumor tissue f 
X 
 
 
 
 
 
 
 
Optional pharmacogenomics blood sample g 
X 
 
 
 
 
 
 
 
Optional tumor tissue biopsy (e.g. accessible involved 
lymph nodes) before treatment, on study, and at 
progression h 
X 
X 
 
 
 
X i 
a. 
PK blood samples for IPI-145 plasma concentration determination will be collected from all subjects on Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 3 Day 1. An additional blood sample 
for PK is requested at the start and end of any drug interruption/hold for an AE, when feasible.   
b. 
On Cycle 1 Day 15, the morning dose of study medication will be administered in the clinic in order to accommodate PK sampling. 
c. 
Assessment of the QT interval (for corrected QT [QTc] determination) will be performed as marked in the above table.  All ECGs are to be performed in triplicate, within  
approximately a 5 minute time period 
d. 
Immunoglobulin evaluation (to be done locally) includes IgA, IgG, IgM, and where routinely performed, IgE.  
e. 
Immunophenotyping evaluation will be performed by a central lab.  Samples will be collected from all subjects on Day 1 of Cycles 1, 2, 3, 5, 7, 10, 14 and at EoT. An 
immunophenotyping sample is also requested at the start and end of any drug hold/interruption for an AE, when feasible. 
f. 
Tumor tissue is not required for enrollment, but should be submitted from all enrolled subjects, if available.  Lymph node or other archival soft tissue that did not undergo 
decalcification is preferred.  A fine needle aspirate cell block is also acceptable. Bone marrow biopsies are acceptable only if a soft tissue sample is not available.  In cases where bone 
marrow biopsies and bone marrow aspirates are a necessary part of the subject’s clinical care, leftover blocks or unstained slides are requested.  A screening bone marrow biopsy may 
also serve as archival tumor tissue. Corresponding pathology reports should also be submitted, if available.  See the IPI-145-06 Laboratory Manual for further instructions regarding 
the handling, shipping, and storage of the samples. 
g. 
Collected on a single occasion from subjects who provide additional optional informed consent for pharmacogenomics research.  It is recommended that the pharmacogenomics blood 
sample be collected prior to dosing on Cycle 1 Day 1. Subjects who do not wish to participate in the pharmacogenomics research may still participate in the clinical study. 

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h. 
Optional tumor tissue biopsy sample collection for subjects who provide additional informed consent.  Cycle 1 Day 1 biopsy is pre-IPI-145 therapy and may be collected at any time 
during the Screening period.   The on-treatment biopsy at Cycle 1 Day 15 may be collected at any time during the clinic visit.  For subjects with measurable disease in the blood, a 
whole blood sample may be collected in place of tumor tissue, if applicable. 
i. 
Optional tumor tissue biopsy sample collection only for subjects with disease progression who provide additional informed consent. 
 

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Table 3: On-Treatment iNHL Response Assessments 
Assessments 
On-Treatment Assessments 
End of Treatment (EoT) 
(within 7 days following the 
decision to discontinue study 
treatment) 
Cycles 3, 5, 7 & 10 
 
(Day -7 to Day 1 of Each 
Cycle) 
Cycles 14 & 18 
& Every 4th Cycle 
Thereafter  
 
(Day -7 to Day 1 of 
Each cycle) 
CT scans of chest, abdomen and pelvis a, b 
X 
X 
X c 
Bone marrow aspirate and/or biopsy d 
X 
X 
 
Focused physical examination and assessment of 
B symptoms 
X 
X 
X 
Response Assessment e  
X 
X 
X 
a. CT scans of the chest, abdomen and pelvis are required for all subjects to document measureable disease at Screening and will be performed within 7 days prior to 
initiating the next cycle of study treatment (i.e. Day -7 to Day 1) of Cycles 3, 5, 7, 10 and at every fourth cycle thereafter (Cycle 14, 18, 22, etc.) while on-treatment with 
IPI-145.  Other scans may be performed (e.g. head/neck CT) if clinically indicated or to evaluate a site of known disease. Copies of all scans will be sent for independent 
review of response assessment.  
b. 18-FDG PET/CT scan or MRI may be substituted if clinically indicated, but the modality chosen to evaluate each individual subject should be the same throughout the 
duration of the study.  The frequency provided is the minimum required for study participation. 
c. Scans will be performed at the EoT if the subject is discontinued for reasons other than radiologic disease progression and a previous assessment has not been performed 
within 30 days of the EoT visit. 
d. Bone marrow biopsy and/or bone marrow aspirate required only for subjects who otherwise meet the criteria for a CR unless the subject had an adequate bone marrow 
biopsy at Screening that was negative for lymphoma or unless the subject had previously undergone a bone marrow procedure confirming the CR. If bone marrow 
aspirate and/or bone marrow biopsy is performed, bone marrow biopsies and/or aspirate samples (along with corresponding pathology report, if available) should be sent 
for biomarker analysis if available.  
e. Response assessment is determined using information from objective measurements of available CT scan, focused physical exam, bone marrow biopsy as relevant, and 
assessment of B symptoms. 

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Table 4: Long-term Follow-up Assessments for IPI-145 Monotherapy 
 
Disease follow-up a 
Survival Follow-up c 
≤ 12 months from 1st 
Dose of IPI-145 
>12 months from 1st Dose 
of IPI-145 
Every 12 weeks 
Every 16 weeks 
Response assessment b 
X 
 
Survival  
 
X 
a. 
For subjects who discontinue study treatment for reasons other than radiologic disease progression, response assessments (as shown in Table 3) will be performed during 
long-term follow-up.  The same tumor assessments utilized during the treatment phase of the trial should be used during long-term follow-up. The first disease assessment 
follow-up should occur approximately 12-16 weeks after the last on-treatment/end-of-treatment tumor assessment. Response assessments following the long-term follow-
up disease assessment schedule will occur for 2 years after the first dose of IPI-145 or until progression is documented or other anticancer therapy is initiated, whichever 
occurs first.   
b. 
Response assessment is determined using information from objective measurements of available CT scan, focused physical exam, bone marrow biopsy as relevant, and 
assessment of B symptoms. 
c. 
For all subjects who discontinue treatment from IPI-145, survival follow-up will occur every 6 months (± 4 weeks) from IPI-145 treatment discontinuation for up to 3 years 
after their first dose of IPI-145. This assessment can be conducted by telephone interview.  Information on initiation of other anticancer therapy will also be collected and is 
to include start date and therapy name(s), of other subsequent therapies if applicable. 
 
 
 
 

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1 
BACKGROUND AND RATIONALE 
1.1 
INTRODUCTION 
IPI-145 is a potent phosphoinositide-3-kinase (PI3K)-δ,γ inhibitor being developed by Verastem, 
Inc. (Verastem).  PI3K-δ and PI3K-γ isoforms are necessary for adaptive and innate immunity, 
and are important mediators in inflammatory disorders and hematologic malignancies.  
Therefore, IPI-145 is being developed as an orally administered potential therapeutic in 
hematologic malignancy and inflammatory disease indications.  This study is an evaluation of 
IPI-145 in iNHL subjects whose disease is refractory to rituximab and to either chemotherapy or 
radioimmunotherapy (RIT).   
1.2 
BACKGROUND 
1.2.1 
Functions of PI3K-δ and PI3K-γ  
There are four mammalian isoforms of class 1 PI3Ks: PI3K-α, β,δ (class 1a PI3Ks) and PI3K-γ 
(a class 1b PI3K).  These PI3Ks catalyze the production of phosphatidylinositol (3,4,5)-
trisphosphate (PIP3), leading to activation of the downstream effector pathways important for 
cellular survival, differentiation, and function.  PI3K-α and PI3K-β are widely expressed, and are 
important mediators of signaling from cell surface receptors.  PI3K-α is the isoform most often 
found mutated in cancers, and has a role in insulin signaling and glucose homeostasis.2, 3  PI3K-β 
is activated in cancers where phosphatase and tensin homolog (PTEN) is deleted.  Both isoforms 
are targets of small molecule therapeutics in development for cancer.  PI3K-δ and P13K-γ are 
preferentially expressed in leukocytes, and are important in leukocyte function.   
PI3K-δ is activated by cellular receptors (e.g., receptor tyrosine kinases) through interaction with 
the SH2 domains of the PI3K regulatory subunit (p85), or through direct interaction with RAS.   
PI3K-γ is associated with G-protein coupled receptors (GPCRs), is responsible for the very rapid 
induction of PIP3 in response to GPCRs, and can be also activated by RAS downstream of other 
receptors.  PIP3 produced by PI3K activates effector pathways downstream through interaction 
with pleckstrin homology (PH) domain containing enzymes (e.g., PDK-1 and AKT [PKB]).4   
It is clear that both PI3K-δ and PI3K-γ isoforms are important for chemotaxis and cell migration, 
and have independent roles in models of inflammatory diseases.5  The roles of PI3K-δ and 
PI3K-γ in different immune cell types are outlined below. 
B-Cells 
PI3K-δ is important in B-cell function including development, activation, chemotaxis, migration, 
and homing to lymphoid tissue, and inhibitors of PI3K-δ block these functions.3, 4, 6-12 

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T-Cells 
In T-cells, PI3K-δ has demonstrated a role in receptor and cytokine signaling.  PI3K-δ is 
important for T-cell function including proliferation, activation, and differentiation.3, 13-21 
Neutrophils 
PI3K-δ along with PI3K-γ, are important in the response to immune complexes and FCγRII 
signaling in neutrophils, including migration, and the neutrophil respiratory burst.  PI3K-γ is also 
critical for the migration and function of tumor associated neutrophils, suggesting a role in tumor 
immunity and cancer progression.22  As such, PI3K-δ and PI3K-γ are central mediators of 
autoimmune disease and cancer.23-27 
Macrophages/Monocytes 
In macrophages collected from patients with chronic obstructive pulmonary disease (COPD), 
glucocorticoid responsiveness can be restored by treatment of the cells with inhibitors of PI3K-δ.  
Macrophages rely on PI3K-δ and PI3K-γ for responses to immune complexes through the Arthus 
reaction (FCγR and C5a signaling).26, 28, 29  PI3K-γ is also critical for the migration and function 
of tumor associated macrophages suggesting a role in tumor immunity and cancer progression.22 
Mast Cells 
In mast cells, stem cell factor- (SCF) and IL-3-dependent proliferation, differentiation and 
function are PI3K-δ and PI3K-γ dependent, as is chemotaxis.  The allergen/IgE cross-linking of 
FCεR1 resulting in cytokine release and mast cell degranulation is inhibited by treatment with 
PI3K-δ inhibitors, suggesting a role for PI3K-δ in allergic disease.30-32  
NK Cells 
Natural killer (NK) cells are dependent on both PI3K-δ and PI3K-γ for efficient migration.  NK 
cell activity against viral targets is impaired in PI3K-δ kinase-dead mice, while the activity 
against tumors is unaffected.33-36 
1.2.2 
Indolent non-Hodgkin Lymphoma 
Non- Hodgkin lymphoma (NHL) is the seventh most common cancer in male and female adults 
in the US,37 representing the ninth and sixth leading cause of cancer deaths for men and women, 
respectively. 37  In Europe, it is the eighth most commonly diagnosed cancer, and the tenth most 
common cause of death from cancer in adults. The majority (>90%) of NHL represents 
malignancies of B-lymphocyte lineage and express CD20.  There are approximately 14 classes of 
indolent and aggressive B-cell lymphoma classified according to morphology, 
immunophenotyping, genetics and clinical factors.38  The most common of the indolent B-cell 
lymphomas is follicular lymphoma, comprising approximately 22% of all B-cell lymphomas. 
Less common are small lymphocytic lymphoma (SLL, approximately 6%), and marginal zone B-
cell lymphoma, malt-type or nodal-type, approximately 5% and 1% of all B-cell lymphomas, 
respectively. 
Indolent lymphomas tend to grow slowly. Even without treatment, subjects with indolent 
lymphoma often live for many years without major problems from their disease. For some 
subjects, no treatment is recommended until symptoms develop. With treatment, the expected 
median survival time is approximately 8 to 10 years. Overall response rates of ≥ 80% can be 

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expected with initial treatment.  However, indolent lymphoma is considered incurable and almost 
all patients relapse with the response and duration of response to subsequent therapies decreasing 
with each line of therapy.39, 40 
Rituximab, an anti-CD20 therapy, is commonly used as a single agent or in combination with 
cytotoxic chemotherapy for the treatment of B-cell NHL. The addition of polychemotherapy 
regimens to rituximab treatment has resulted in greater disease responses and longer duration of 
response in first-, second-, and later lines of therapy.  However, there is an increasing need for 
effective treatments for patients with iNHL who, due to the incurable nature of this disease, 
eventually develop disease refractory to treatment with rituximab and chemotherapy.  No 
standard of care exists in the refractory setting, with the treatment regimen primarily being 
determined by prior therapies.  Therapies utilized in the refractory setting include additional 
chemotherapy, stem cell transplantation, and RIT.  However, all these therapies are associated 
with lower response rates in patients refractory to chemotherapy and rituximab.  In addition, 
stem cell transplantation is associated with significant toxicity, especially in elderly patients or 
those patients with comorbidities.  RIT is associated with significant myelosuppression.  Patients 
whose iNHL has not responded or has progressed within 6 months of either a rituximab 
containing chemotherapy regimen or RIT represent a population which would benefit from the 
development of novel anticancer agents. 
1.3 
IPI-145 
1.3.1 
IPI-145, a Potent PI3K-δ,γ Inhibitor 
PI3K-δ and PI3K-γ contribute to the development and maintenance of inflammatory and 
autoimmune diseases, and hematologic malignancies.3, 4, 8, 41  IPI-145 is a potent PI3K-δ,γ 
inhibitor being developed as a potential therapeutic in hematologic malignancy and 
inflammatory disease indications. 
1.3.2 
Non-Clinical Summary of IPI-145 
See the IPI-145 Investigator’s Brochure for detailed summaries on pharmacology, toxicology, 
and absorption, distribution, metabolism, and excretion (ADME) of IPI-145. 
1.3.3 
Clinical Experience in Humans 
1.3.3.1 
Study IPI-145-01 (Phase 1, first in human study) 
Study IPI-145-01 was a randomized, double-blind, placebo-controlled, Phase 1 study in healthy 
adult subjects.  Study objectives were to evaluate the safety, tolerability, PK and 
pharmacodynamics (PD) of single and multiple ascending doses of IPI-145 and to assess the 
effect of food and ketoconazole on the PK of IPI-145. This study is complete and data are 
summarized below.   
One-hundred and six (106) subjects were enrolled overall, which included 36 subjects in the 
single ascending dose (SAD) portion (24 active treatment; 12 placebo), 48 subjects in the 
multiple ascending dose (MAD) portion (36 active treatment; 12 placebo), 6 subjects in the food 
effect (FE) effect portion (consisting of IPI-145 dosing with sequential fed and fasting portions), 

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and 16 subjects in the drug-drug interaction (DDI) portion (consisting of IPI-145 dosing periods 
with and without ketoconazole).  The total subject exposure to IPI-145 is summarized in Table 5. 
 
Table 5: Subject Exposure (Study IPI-145-01) 
PART 
Treatment Exposure 
Duration of 
Treatment 
Total Exposure 
per Subject 
(mg) 
Total No. of 
Subjects 
Exposed 
 SAD  
Placebo SD 
1 day 
0 
12 
 
1 mg IPI-145 SD 
1 day 
1 
4 
 
2 mg IPI-145 SD 
1 day 
2 
4 
 
5 mg IPI-145 SD 
1 day 
5 
4 
 
10 mg IPI-145 SD 
1 day 
10 
4 
 
20 mg IPI-145 SD 
1 day 
20 
4 
 
30 mg IPI-145 SD 
1 day 
30 
4 
 MAD  
Placebo Q12h or Q24h 
14 days 
0 
12 
 
1 mg IPI-145 Q12h* 
14 days 
26 
9 
 
2 mg IPI-145 Q12h* 
14 days 
52 
9 
 
5 mg IPI-145 Q12h* 
14 days 
130 
9 
 
10 mg IPI-145 Q24h 
14 days 
140 
9 
 FE  
25 mg IPI-145 Fasted-Fed 
2 days 
50 
3 
 
25 mg IPI-145 Fed-Fasted 
2 days 
50 
3 
DDI 
10 mg IPI-145 SD 
2 days 
20 
16 
SD = single dose; Q12h = once every 12 hrs; Q24h = once every 24 hrs; SAD = single ascending dose; MAD = 
multiple ascending dose; FE = food effect; DDI = drug-drug interaction. *includes QD dosing on Days 1 and 14. 
IPI-145 was well tolerated at the doses evaluated. There were no deaths and no serious adverse 
events (SAEs).  Dose escalation proceeded as planned in both the SAD and MAD portions, to a 
pre-determined exposure limit based on the findings in the 28-day nonclinical toxicology study 
in rats.  
No clinically significant safety laboratory or ECG abnormalities were observed during any 
portion of the study.   
Pharmacokinetic assessments demonstrated that IPI-145 is rapidly absorbed following single and 
multiple dose oral administration, with the maximum plasma concentration observed typically 
1 hr after dosing.  Across the dose ranges evaluated, IPI-145 exposure increased proportionally 
to dose.  The mean elimination half-life ranged from 6.5 to 11.7 hr after repeat dosing and did 
not depend on the dose level administered.  IPI-145 accumulation was less than 2-fold following 
14 days of Q12 hr oral administration.   
Data from the DDI portion indicated that concomitant administration of 200 mg Q12hr 
ketoconazole increased exposure to IPI 145.  On average, Cmax, AUC0-last and AUC0-inf increased 

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by approximately 66%, 285% and 295%, respectively, in the presence of ketoconazole compared 
to IPI-145 administered alone.   
See the IPI-145 Investigator’s Brochure for further information. 
1.3.3.2 
Study IPI-145-02 (Phase 1, Hematologic Malignancies) 
A Phase 1 dose-escalation study (IPI-145-02) to evaluate the safety, PK and biological activity of 
orally administered IPI-145 in subjects with advanced hematologic malignancies is currently 
ongoing. Sequential cohorts of subjects have been enrolled at progressively higher dose levels 
(ranging from 8 mg to 100 mg given orally BID continuously in 28-day cycles) with expansion 
cohorts of subjects with select hematologic malignancies.  Dose limiting toxicities (DLTs) of 
Grade 3 rash and Grade 3 alanine aminotransferase (ALT])/aspartate aminotransferase (AST) 
elevations were experienced by two subjects receiving 100 mg BID.  Therefore, the maximum 
tolerated dose (MTD) has been determined to be 75 mg BID.    
Clinical Safety 
A total of 193 subjects have been enrolled in study IPI-145-02 as of 28 October 2013.  Of these, 
32 (17% of enrollment) are iNHL subjects (including follicular and marginal zone lymphoma 
subtypes). Other populations include relapsed/refractory chronic lymphocytic leukemia/small 
lymphocytic leukemia (CLL/SLL), n=52 (27%), treatment-naïve CLL, n=15 (8%) and other 
diagnoses, n=109 (56%). 
Across the population of subjects enrolled, 122 are male and 71 female with a median age of 66 
years. IPI-145 doses administered include 8 mg BID (n=1), 15 mg BID (n=6), 25 mg BID 
(n=61), 35 mg BID (n=3), 50 mg BID (n=3), 60 mg BID (n=4) 75 mg BID (n=112), and 100 mg 
BID (n=3). Subjects with iNHL were enrolled at 15 mg BID (n=1), 25 mg BID (n=15), 50 mg 
BID (n=1) and 75 mg BID (n=15). 
As of 28 October 2013, across all subjects in all dose cohorts, the median number of treatment 
cycles was 4.1 cycles, with 42% of subjects continuing on treatment.  Subjects who received 25 
mg BID had a median time on treatment of 4.7 cycles. 
Subjects with iNHL (n=32) had a median 8.5 cycles of treatment (range 0.1 to 22.7 cycles) and 
subjects dosed with 25 mg BID had a median of 9.8 cycles of treatment (range: 0.1 to 20.7 
cycles). 
In all subjects across all dose cohorts, treatment-emergent adverse events (TEAEs) have 
occurred in 180 (93%) subjects, including 56 subjects (92%) in the 25 mg BID dose group. The 
most common TEAEs (≥ 20%) in all dose groups combined included fatigue (32%), ALT or 
AST increased (combined, 32%), diarrhea (27%), pyrexia (25%), nausea (24%), cough (22%) 
and neutropenia (20%).  Related Grade ≥3 TEAEs occurred in 102 subjects (53%).  The most 
common related Grade ≥3 TEAEs (≥ 5%) included ALT or AST increased (combined, 16%), 
neutropenia (13%) and neutrophil count decreased (5%).  
Across all 32 iNHL subjects, TEAEs have occurred in 31 (97%) subjects.  The most common 
TEAEs (≥ 20%) in all dose groups combined included: ALT or AST increased (combined, 53%), 
pyrexia (41%), rash (combined terms, 41%), fatigue (34%), diarrhea (34%), nausea (34%), 
neutropenia (31%) and cough (31%).  Related Grade ≥3 TEAEs occurred in 22 subjects (69%),  
The most common related Grade ≥3 TEAEs (≥5%) included: ALT or AST increased (combined, 

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34%), neutropenia (25%), diarrhea (16%), anemia (9%), febrile neutropenia (9%), neutrophil 
count decreased (6%) and pneumonitis (6%). 
In iNHL subjects in the 25 mg BID group, TEAEs have occurred in 15 subjects (100%).  The 
most common TEAEs (≥ 20%) included: ALT or AST increased (combined, 53%), nausea 
(40%), rash (combined terms, 27%), vomiting (27%), diarrhea (27%), neutropenia (27%), 
pyrexia (20%), fatigue (20%) and cough (20%).  Related Grade ≥3 TEAEs occurred in 11 (73%) 
of iNHL subjects in the 25 mg BID group. The most common related Grade ≥3 TEAEs (≥ 5%) 
included: ALT or AST increased (combined, 40%).  
Related SAEs in subjects with iNHL occurred in 11 (34%) subjects overall, including 4 (27%) 
subjects in the 25 mg BID group and 6 (40%) subjects in the 75 mg BID group.  Related SAEs 
occurring in more than one subject with iNHL (all doses) included: diarrhea (2 [6%]), 
pneumonitis (2 [6%]), pneumonia (2 [6%]), pyrexia (2 [6%]), and febrile neutropenia (2 [6%]). 
The two subjects with febrile neutropenia were in the 75 mg BID dose group. There were no 
related SAEs occurring in more than one subject in the 25 mg BID group.   
As of 28 October 2013, two subjects with iNHL in the 75 mg BID group had fatal SAEs.  One 
subject with marginal zone lymphoma had an SAE of colitis, which was improving, however the 
subject’s respiratory status declined during hospitalization and the subject died of respiratory 
failure. The second subject, diagnosed with lymphoplasmacytic lymphoma had fatal SAEs of 
fungal pneumonia and disease progression with onset dates one week after discontinuing IPI-145 
for neutropenia.  The events were fatal approximately one month after onset and were considered 
related to IPI-145 by the Investigator.    
Clinical Efficacy 
Tumor response was evaluated in Study IPI-145-02 based on disease-specific standard criteria. 
Clinical activity was observed in all populations and at all dose levels evaluated.  
As of 28 October 2013, 29 subjects with iNHL (including follicular and marginal zone 
lymphoma) have been evaluated for response.  The ORR (defined as CR and PR) was 62%, 
including 3 CR and 15 PR.  Eight (8) subjects had stable disease (SD), and 2 subjects had 
progressive disease (PD).  The overall response rate was 67% for subjects who received ≤25 mg 
BID and 57% for subjects who received >25 mg BID.  The median time to response was 1.8 
months (range: 1.5 to 4.1), with no variation between dose groups (median 1.8 months for 25 mg 
BID; 1.8 for 75 mg BID). 
Clinical Pharmacokinetics 
Preliminary PK data from Study IPI-145-02 demonstrate IPI-145 is rapidly absorbed following 
oral dosing in subjects with advanced hematologic malignancies, with the maximum plasma 
concentration (Cmax) generally achieved at approximately 1 hour post-dose.  Steady state 
exposure over the dosing interval (AUC0-12) is proportional to dose.  Following repeat dose 
administration of 25 mg BID, mean Cmax and AUC0-12 values are 1460 ng/mL and 8129 
ng*h/mL, respectively.  IPI-145 elimination half-life (t1/2) does not appear to vary with dose and 
the mean t1/2 was 4.5 hours following 25 mg BID administration. 

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1.4 
RATIONALE FOR IPI-145 AS A POTENTIAL THERAPY FOR SUBJECTS 
WITH INDOLENT NHL 
PI3K-δ and PI3K-γ are expressed in hematopoietic cells, and are critical for the ability of normal 
immune cells to respond to survival and differentiation signals in their environment.  In cancer 
patients, where the pathways mediated by PI3K-δ,γ contribute to survival, proliferation, and 
differentiation of cancer cells, treatment with IPI-145 may be beneficial.  The tumor 
microenvironment plays an important role in the development and maintenance of cancer cells.42  
Cancer cells through the expression of various cytokines, growth factors, and chemokines recruit 
multiple cell types including myeloid cells capable of differentiating into tumor-associated 
macrophages (TAMs) which promote angiogenesis and augment tumor growth.43  Therefore, 
agents that target TAMs as well as other types of infiltrating leukocytes are of potential 
therapeutic interest in oncology.   
PI3Ks play pivotal roles in cell signaling and regulate a variety of cellular functions relevant to 
oncogenesis. Impaired development and function of B and T lymphocytes has been demonstrated 
in PI3K-δ and PI3K-γ isoform knockout mice, supporting the development of PI3K-δ,γ specific 
inhibitors for B- and T-cell lymphoid malignancies.  
1.5 
DETERMINATION OF STARTING DOSE AND REGIMEN 
In Study IPI-145-02, responses (CR and PR) have been observed in subjects with iNHL at doses 
≤25 mg BID.  Overall, as of 28 October 2013, 193 subjects have been dosed with IPI-145, 
including 32 subjects with iNHL.   Of the 32 iNHL subjects, 15 have been dosed with IPI-145 at 
25 mg BID, with a median time on treatment of 4.7 cycles. 
The clinical safety data as of 28 October 2013 for patients on 25 mg BID in the overall 
population (n=61) and in the iNHL population (n=15) suggest this dose is well tolerated with a 
safety profile similar to what might be expected in patients with advanced hematologic 
malignancies.  Frequently occurring adverse events (>20%) in the iNHL population receiving 25 
mg BID included ALT or AST increased (combined terms) (53%), nausea (40%), rash 
(combined terms, 27%), vomiting (27%), diarrhea (27%), neutropenia (27%), pyrexia (20%), 
fatigue (20%) and cough (20%).  Among the 29 evaluable subjects with iNHL, the best ORR was 
62% (3 CR, 15 PR) with 8 SD and 2 PD.  The overall response rate was 67% for subjects who 
received ≤25 mg BID and 57% for subjects who received >25 mg BID.  The median time to 
response was 1.8 months (range: 1.5 to 4.1), with no variation between dose groups.   
Based on the safety and clinical activity of IPI-145 observed to date in Study IPI-145-02, a dose 
of 25 mg BID has been selected to evaluate in iNHL patients in the Phase 2 setting.  
1.6 
SUMMARY 
Effective treatment for patients who have been diagnosed with iNHL who have not responded to 
or have progressed within 6 months of a rituximab containing chemotherapy regimen or RIT is 
an area of high unmet medical need.  IPI-145 is a potent PI3K-δ,γ inhibitor being developed as a 
potential therapeutic in hematologic malignancy and inflammatory disease indications.  Initial 
experience of IPI-145 in the treatment of patients with relapsed/refractory iNHL suggests a 
therapeutic potential for IPI-145 in high risk iNHL. 

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Therefore, Verastem, Inc. is conducting a Phase 2 clinical trial to evaluate the safety and efficacy 
of IPI-145 as a monotherapy in subjects with iNHL that is refractory to rituximab and to either 
chemotherapy or RIT. 
 
 

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2 
STUDY OBJECTIVES 
2.1 
PRIMARY OBJECTIVES 
The primary objective of this trial is to evaluate the antitumor activity of IPI-145 administered to 
subjects diagnosed with iNHL (defined as FL, MZL [splenic, nodal and extranodal], or SLL) 
whose disease is refractory to rituximab and to either chemotherapy or radioimmunotherapy 
(RIT). 
2.2 
SECONDARY OBJECTIVES 
The secondary objectives of the study are: 
• To evaluate the safety of IPI-145 in all subjects 
• To evaluate additional efficacy parameters in all subjects 
• To evaluate the PK of IPI-145 and, if applicable, its metabolite(s) 
2.3 
EXPLORATORY OBJECTIVES 
The exploratory objectives of the study are: 
• To evaluate whether baseline values or treatment-related changes in biomarkers correlate 
with IPI-145 clinical activity, safety and/or resistance in iNHL. 
• To evaluate whether tumor genomic or pharmacogenomic markers correlate with IPI-145 
clinical activity, safety, PK and/or resistance in iNHL 
• To evaluate the health-related quality of life (QoL) of subjects 
 
 

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3 
STUDY ENDPOINTS 
3.1 
PRIMARY ENDPOINT 
The primary endpoint of the study is the Overall Response Rate (ORR), with overall response 
defined as best response of complete response/remission (CR) or partial response/remission (PR) 
according to the revised International Working Group (IWG) Criteria1  
3.2 
SECONDARY ENDPOINTS 
The secondary endpoints of the study are: 
• Treatment-emergent adverse events (TEAEs), ECG measures, and changes in safety 
laboratory values  
• Duration of response (DOR) defined as the time from the first documentation of  
response to the first documentation of progressive disease (PD) or death due to any cause 
• Progression-free survival (PFS) defined as the time from the first dose of study treatment 
to the first documentation of PD or death due to any cause  
• Overall survival (OS) defined as the time from the first dose of study treatment to the 
date of death 
• Time to response (TTR), defined as the time from the first dose of study treatment to the 
first documentation of response (complete or partial)  
• PK parameters derived from plasma IPI-145 concentrations and, if applicable, its 
metabolite(s) 
3.3 
EXPLORATORY ENDPOINTS 
The exploratory endpoints of the study are: 
• Lymph node response rate (LNR rate), with LNR defined as ≥ 50% reduction in the Sum 
of the Products of the Perpendicular Diameters (SPD) of nodal target lesions 
• Serum, plasma and tissue biomarkers, and blood immunophenotype 
• Germline DNA sequence variations  
• Tumor genomic features (e.g. DNA sequence variation, DNA copy number variation, 
and/or RNA expression)  
• Health-related QoL of subjects as assessed by the following subject-reported 
questionnaire:  
o EuroQol-5D (EQ-5D), a standardized instrument for use as a measure of health-
related QoL 
 

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4 
STUDY DESIGN 
This is an open-label, single arm efficacy and safety study of IPI-145 administered orally to 
subjects who have been diagnosed with iNHL (FL, MZL, or SLL) whose disease is refractory to 
rituximab and to either chemotherapy or RIT.  Approximately 120 subjects will be enrolled. 
Enrollment is anticipated at approximately 100 sites with approximately 40 sites in the US and 
the remainder of sites outside of the US.  It is anticipated that the entire study will accrue 
subjects over approximately 30 months. 
4.1 
SCHEDULE OF ADMINISTRATION  
Subjects will receive a starting dose of 25 mg IPI-145 BID over the course of 28-day treatment 
cycles for up to 13 cycles.   
After completing 13 treatment cycles of IPI-145, subjects who have documented evidence of 
response (CR or PR) or SD at the Cycle 14 Day 1 response assessment according to the revised 
IWG criteria1 may continue to receive additional cycles of IPI-145until disease progression or 
unacceptable toxicity.  Treatment continuation assessments will be made thereafter at the start of 
every fourth cycle according to Table 3. 
4.2 
DOSE INTERRUPTION/HOLD/MODIFICATION GUIDELINES 
Subjects will be monitored continuously for toxicity while on study treatment.  Toxicity will be 
assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events 
(NCI-CTCAE) Version 4.03.  If a subject has an adverse event at least possibly related to study 
drug, then dose interruptions/holds with possible modifications should be made according to 
Table 6 below.  Deviations from these guidelines may occur based on the clinical judgment of 
the Investigator with notification to the Medical Monitor/Sponsor.  There should be no attempt to 
make up for missed doses. 

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Table 6: Dose Interruption/Hold/Modifications for IPI-145-Related Toxicities  
IPI-145-related Toxicities a, b 
Dose Interruption/Hold/Modification/Recommendation for 
IPI-145 c 
Non-hematologic: 
Grade 2 or higher Pneumonitis/Pneumonia 
Or 
Grade 3 or higher all other Nonhematologic  
First occurrence: 
Withhold until return to ≤ Grade 1 or baseline level; re-challenge 
therapy at original dose level. 
Second occurrence of same AE:  
Withhold until return to ≤ Grade 1 or baseline level; re-initiate 
therapy at one dose level lower from current dose. 
Third occurrence of same AE: 
Withhold until return to ≤ Grade 1 or baseline level; re-initiate 
therapy at one dose level lower from current dose. 
Fourth occurrence of same AE: 
Discontinue subject from study drug 
Hematologic: 
Grade 3 or higher febrile neutropenia 
Or 
New Grade 4 neutropenia >7 days duration 
Or 
Grade 3 or higher thrombocytopenia with 
Grade ≥2 hemorrhage 
Or  
New Grade 4 thrombocytopenia of any 
duration requiring transfusion support. 
Recommendations for implementation of dose interruption  
Immediate hold for Grade 4 or higher nonhematologic toxicities and Grade 3 or higher febrile neutropenia 
For all other events, reduce from BID dosing to QD for two days, then hold 
a. 
IPI-145 Related = possible, probable, or definite relationship to IPI-145 as defined in Section 8.2.1. 
b. Toxicity grades are defined per CTCAE Version 4.03.  Note if parameter is not defined by CTCAE, then AE 
grading criteria (Section 8.2.1) should be utilized. 
c. 
Refer to Table 7 for IPI-145 dose levels. 
 
Treatment Interruption for Nonhematologic Toxicity 
Treatment with IPI-145 should be interrupted for the following nonhematologic toxicities: 
• 
Grade 2 or higher pneumonitis/pneumonia, defined as symptomatic and requiring 
medical intervention, including oral antimicrobials and/or steroids  
o Subjects who develop new pulmonary symptoms (e.g. cough, shortness of breath, 
dyspnea on exertion) or new radiographic findings should have IPI-145 held and 
receive empiric antimicrobial coverage while undergoing evaluation. 
Corticosteroids for symptomatic treatment of pneumonitis is recommended (and 
allowed per protocol). Restarting treatment with IPI-145 is allowed after complete 
resolution of symptoms.  
• Grade 3 or higher other nonhematologic toxicity including the following: 

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o Infections: Subjects who develop infections requiring IV 
antibiotics/antifungals/anti-virals should have IPI-145 held until infection resolves 
(subject may restart IPI-145 while completing a course of oral therapy).  
Prophylaxis to prevent recurrence/opportunistic infections will not preclude the 
subject from restarting treatment.  
o Hepatic events: Subjects who develop Grade 3 or higher transaminase 
(ALT/AST) elevations with or without clinical symptoms should have IPI-145 
held until return to ≤ Grade 1. Additional work-up to evaluate viral infection/re-
activation, exposure to environmental toxins (e.g. alcohol/con-meds), or other 
causes is recommended before restarting treatment with IPI-145. 
o Gastrointestinal: Subjects who develop Grade 3 or higher nausea, vomiting or 
diarrhea despite optimal treatment should have IPI-145 held until resolution of 
symptoms.  Evaluation of concomitant medications, gastrointestinal infections or 
inflammatory bowel (via endoscopy and biopsy) should be considered with 
persistent diarrhea or recurrence with restarting IPI-145. Corticosteroids 
(budesonide) with taper are allowed if colitis is suspected/cannot be ruled out. 
o Skin rash: Subjects who develop Grade 3 or higher skin rashes should have IPI-
145 held until return to ≤ Grade 1.  In the setting of new Grade 1-2 skin rash early 
intervention is recommended to ameliorate risk of worsening symptoms. 
Evaluation of concomitant medications, environmental exposure, infections or 
other contributing factors is recommended. 
o Cardiac: Subjects who develop new Grade 3 or higher cardiac events should have 
IPI-145 held until resolution of symptoms.  This includes new Grade 3 QTcF 
prolongation only if >20 ms increase from Baseline. A new Grade 3 QTcF 
prolongation (>20 ms from baseline) requires triplicate ECGs with the average 
measurement used and the use of Fridericia’s correction method (QTcF).  For 
subjects with a right or left BBB, a new Grade 3 QTc prolongation is defined as 
an increase in QTcF of >100 ms from the pre-dose ECG to any post dose ECG as 
the QRS interval is prolonged at Baseline (by approximately 40 ms) in subjects 
with a BBB 
Subjects requiring treatment interruption should be re-evaluated at least weekly until the toxicity 
improves to ≤ Grade 1 or returns to Baseline level. IPI-145 dose will be restarted at doses 
described in Table 7. 
Treatment Interruption for Hematologic Toxicity 
Worsening or transient Grade 3 or higher neutropenia, anemia, and/or thrombocytopenia caused 
by the subject’s existing disease or by IPI-145 are to be expected. Blood counts should be 
monitored as described in the protocol with the frequency increased as clinically indicated in the 
setting of new or worsening Grade 3 or higher cytopenias.  IPI-145 dosing may be interrupted at 
any time, at the discretion of the treating physician. 
Treatment with IPI-145 should be interrupted for the following symptomatic hematologic 
toxicities: 
• Grade 3 or higher febrile neutropenia 
• Grade 3 or higher thrombocytopenia associated with Grade 2 or higher hemorrhage 

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The subject should be re-evaluated at least weekly until the toxicity improves to ≤Grade 1 or 
returns to Baseline.  
A dose may be withheld up to 42 days for toxicity.  Doses withheld for >42 days due to 
treatment-related toxicity will result in permanent discontinuation from treatment.  Any subject 
who requires reduction to less than 10 mg BID due to repeat occurrence of the same treatment-
related toxicity will be permanently discontinued from treatment.  Any subject who requires 
reduction to less than 5 mg BID for different treatment-related toxicities will be permanently 
discontinued from study treatment.  Dose levels are shown in Table 7. 
Table 7: IPI-145 Dosing Levels 
Dose Level 
Dose (mg)  
1 
25 BID 
-1 
15 BID 
-2 
10 BID 
-3 
5 BID 
 
Subjects who have a dose reduction due to a toxicity may be eligible for a dose increase back to 
the dose level prior to the reduction (i.e. the starting dose or dose of previous reduction if subject 
was dose reduced more than one level) if the following criteria are met: 
1. Subject has tolerated the lower treatment dose for >1 treatment cycle 
2. Subject has recovered to baseline levels from the toxicity which caused the dose 
reduction 
4.3 
ADDITIONAL CYCLES 
Subjects with documented evidence of response (CR or PR) or SD at the Cycle 14 Day 1 
response assessment according to the revised IWG criteria1 may receive continued treatment 
with IPI-145 beyond the initial 13 cycles until disease progression or unacceptable toxicity.  
Treatment discontinuation from the study is described in Section 4.4. 
4.4 
TREATMENT DISCONTINUATION 
A subject should be withdrawn from the study treatment if, in the opinion of the investigator, it is 
medically necessary, or if it is the wish of the subject. However, every effort should be made to 
keep the subject on study treatment. Subjects will be withdrawn from study treatment in case of 
any of the following reasons: 
• An adverse event that requires permanent discontinuation of IPI-145 
• Protocol-specified disease progression 
• Subject death 
• Noncompliance to protocol  

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• Investigator decision 
• Subject becomes pregnant 
• Termination of the study by sponsor 
• Voluntary withdrawal from treatment by subject 
In addition to the above reasons, other circumstances may necessitate discontinuation of a 
subject from the study treatment, as judged by the investigator or sponsor.  
If a subject does not return for a scheduled visit, then every effort should be made to contact the 
subject.  In any circumstance, every effort should be made to document subject outcome.   
Adverse events (AEs) and SAEs leading to the discontinuation of a subject will be followed until 
resolution, resolution to baseline or until the event is considered chronic. 
Subjects (including subjects that withdraw consent from study treatment but not overall study 
participation) must attend an End of Treatment Visit (EoT) (within 7 days following the decision 
to permanently discontinue study treatment) and a Safety Follow up Visit (30 +7 days from last 
dose of IPI-145) (Refer to Section 6.5.1 for further details).  Subjects who have not withdrawn 
consent from overall study participation will enter long-term follow-up phase of the trial (see 
Section 6.5.2). 
4.5 
STUDY DISCONTINUATION 
Subjects may voluntarily withdraw from the study at any time for any reason without prejudice.  
Subjects will be withdrawn from the study in case of any of the following reasons: 
• 
Subject death 
• 
Subject lost to follow-up  
• 
Completion of the follow-up period 
• 
Termination of the study by sponsor 
• 
Voluntary withdrawal from study participation (including follow-up) by subject 
If the subject withdraws consent from overall study participation (and not just study treatment), 
no further evaluations should be performed and no attempts should be made to collect additional 
data. 
 
 

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5 
STUDY POPULATION 
This study anticipates enrolling approximately 120 subjects with a diagnosis of iNHL whose 
disease is refractory to rituximab and to either chemotherapy or RIT.  This will include 
approximately 80 subjects with FL. Total enrollment may exceed 120 patients in order to enroll a 
sufficient number of FL subjects. 
5.1 
ENTRY CRITERIA 
5.1.1 
Inclusion Criteria 
Subjects must meet all of the following criteria: 
1. Age 18 years or older.  
2. Subjects who have been diagnosed with indolent NHL [defined as FL, MZL (splenic, 
nodal and extranodal), or SLL] that has progressed. 
a. For subjects for whom the most recent biopsy was performed >36 months before 
the first dose of IPI-145, a repeat biopsy to confirm histology should be 
performed, unless medically contraindicated. 
b. For subjects who progressed within 2 months of initiating last prior 
chemotherapy, a repeat biopsy to confirm histology should be performed, unless 
medically contraindicated. 
3. Subjects must have disease that is refractory to a chemotherapy regimen or RIT.  The 
chemotherapy regimen (with or without rituximab) must contain at least one alkylating 
agent or purine nucleoside antagonist.  See Appendix 5 for examples of suitable prior 
chemotherapy.   
Refractory is defined as either: 
a. Lack of a CR or PR while receiving the chemotherapy regimen or RIT  
or 
b. PD within 6 months of the last dose of the chemotherapy regimen or RIT 
documented by CT, PET/CT or MRI obtained within 6 months after the last dose  
Note:  Subjects exhibiting clinical progression within 6 months after the last dose of a 
chemotherapy regimen or RIT who are unable to undergo CT, PET/CT or MRI within 
the 6 month timeframe are allowed up to an additional 30 days to confirm radiologic 
progression. 
4. Subjects must have disease that is refractory to rituximab.  Refractory is defined as any of 
the following: 
a. Lack of a CR or PR during treatment with a full course of single-agent rituximab 
(≥4 doses of 375 mg/m2, weekly) or ≥2 doses of ≥375 mg/m2 of rituximab in 
combination with chemotherapy 
b. PD within 6 months of the last dose of a full course of single-agent rituximab or 
rituximab in combination with chemotherapy 

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c. PD during, or within 6 months of the last dose of a rituximab maintenance therapy 
5. Measurable disease with a lymph node or tumor mass ≥1.5 cm in at least one dimension 
by CT, PET/CT or MRI.  
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (corresponds to 
Karnofsky Performance Status [KPS] ≥60%). 
7. Adequate renal function, defined as serum creatinine ≤2 × upper limit of normal (ULN).  
8. Adequate hepatic function, defined as total bilirubin ≤1.5 × ULN (unless elevated due to 
Gilbert’s syndrome) and aspartate aminotransferase (AST) and alanine aminotransferase 
(ALT) levels ≤ 3× ULN. 
9. Negative serum or urine β human chorionic gonadotropin (βhCG) pregnancy test within 
1 week before first dose of study drug if the subject is a woman of childbearing potential 
(WCBP) (defined as a sexually mature woman who has not undergone surgical 
sterilization or who has not been naturally post-menopausal for at least 24 consecutive 
months for women ≤55 years or 12 consecutive months for women >55 years).   
10. Willingness of male and female subjects who are not surgically sterile or postmenopausal 
to use medically acceptable methods of birth control for the duration of the study, 
including 30 days after the last dose of IPI-145.  Sexually active men, and women using 
oral contraceptive pills, should also use barrier contraception. 
11. Ability to adhere to the study visit schedule and all protocol requirements. 
12. Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-
approved informed consent form before any study specific-screening procedures are 
performed. 
5.1.2 
Exclusion Criteria 
Subjects are to be excluded from the study if they meet any of the following criteria: 
1. Candidate for potentially curative therapies at the time of informed consent, in the 
opinion of the investigator. 
2. Prior treatment with any PI3K inhibitor or BTK inhibitor. 
3. Prior history of allogeneic hematopoietic stem cell transplant (HSCT). 
4. Major surgery within 28 days before the first dose of study drug.  
5. Prior chemotherapy, cancer immunosuppressive therapy, or other investigational agents 
within 4 weeks before first dose of study drug.  
6. Ongoing treatment with chronic immunosuppressants (e.g. cyclosporine) or systemic 
steroids >20 mg prednisone (or equivalent) once daily (QD) 
7. Grade 3B FL and/or clinical evidence of transformation to a more aggressive subtype of 
lymphoma.  
8. Symptomatic central nervous system (CNS) NHL; a lumbar puncture is not required 
unless CNS involvement with NHL is clinically suspected. 

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9. Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study 
treatment (defined as requiring therapeutic dosing of an antimicrobial, antifungal or 
antiviral agent) 
a. Subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically 
excluded if all other inclusion/exclusion criteria are met and there is no presence 
of active infection. 
10. Human immunodeficiency virus (HIV) infection 
11. Baseline QTcF >500 ms (average of triplicate readings). 
Note: This criterion does not apply to subjects with a right or left bundle branch block 
(BBB). 
12. Prior, current or chronic hepatitis B or hepatitis C infection, positive result for hepatitis C 
virus antibodies (HCV Ab) or hepatitis B surface antigen (HBsAg), or hepatitis B core 
antibody (HBcAb).  
13. Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV) 
or herpes zoster (VSV) at time of initiation of study treatment. 
14. History of chronic liver disease, such as cirrhosis or chronic hepatitis due to any cause, or 
who are suspected of alcohol abuse (iNHL in the liver is not an exclusion). 
15. Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function, 
unstable pulmonary condition).  Any important medical illness or abnormal laboratory 
finding that would, in the investigator’s judgment, increase the subject’s risk to 
participating in this study. 
16. Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ 
of the cervix; bladder cancer, or prostate cancer not requiring treatment.  Subjects with 
previous malignancies are eligible provided that they have been disease free for 2 years 
or more. 
17. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia 
requiring medication or mechanical control within the last 6 months prior to first dose of 
study drug. 
18. Prior surgery or gastrointestinal dysfunction that may affect absorption of study drug (e.g. 
gastric bypass, gastrectomy) 
19. Use of live or live attenuated vaccines within 30 days prior to signing informed consent.  
20. Administration of medications or foods that are strong inhibitors or inducers of 
CYP3Awithin 2 weeks prior to the first dose of study drug treatment. 
21. Female subjects who are pregnant or breastfeeding. 

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6 
STUDY PROCEDURES AND ASSESSMENTS 
The schedule of assessments are summarized in Table 1, Table 2, Table 3, and Table 4. 
6.1 
INFORMED CONSENT 
Subjects potentially eligible for participation must sign an informed consent form (ICF) prior to 
initiating any study specific procedures.  Results of standard of care assessments performed prior 
to the subject signing the informed consent form may be utilized. 
6.2 
SCREENING PERIOD 
6.2.1 
Medical History, Physical Examination, and Screening Assessments 
The Investigator at the site is responsible for maintaining a record of all subjects screened and 
those who are enrolled into the study. 
During the Screening visit, the following assessments will be performed:  
• Obtain signed ICF 
• Review of inclusion/exclusion criteria 
• Histologic confirmation of indolent B-cell lymphoma (FL, MZL or SLL) 
• A complete medical history will be obtained from each subject, including cancer history and 
documentation of all previous anticancer treatments and treatment results (e.g. best response 
to previous disease specific treatments) prior procedures, current medications, and all 
medications used within 30 days prior to informed consent. 
• Each subject will undergo a full physical examination including liver and spleen assessment, 
vital signs (temperature, blood pressure, pulse rate, and respiratory rate), height, and weight.   
• 12-lead ECG should be conducted following an approximate 10-minute rest period in a semi-
recumbent or supine position and obtained in triplicate within approximately a 5 minute time 
period. QTc measurements will use the Fridericia’s correction method (QTcF). 
• ECOG performance status.  
• Blood chemistry laboratory parameters including albumin, total protein, uric acid, sodium, 
potassium, calcium, phosphorous, chloride, bicarbonate (or CO2), blood urea nitrogen (BUN) 
or urea, creatinine, lipase, amylase, magnesium, and glucose. 
• Liver function tests including: lactate dehydrogenase (LDH), serum alanine aminotransferase 
(ALT), serum aspartate aminotransferase (AST), total and direct bilirubin, and alkaline 
phosphatase (ALP). 
• Hematology laboratory parameters including: hemoglobin, hematocrit, platelets, and white 
blood cell count with 5-part differential (manual or automated) [for an absolute neutrophil 
count (ANC), neutrophils, lymphocytes, monocytes, basophils and eosinophils].   
• Coagulation laboratory parameters including: prothrombin time (PT), International 
normalized ratio (INR) and activated partial thromboplastin time (aPTT). 

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• Complete urinalysis with qualitative analysis for protein (dipstick).  Subjects with positive 
result (urine protein >30 mg/dL by dipstick) will require quantitative analysis to be 
performed (assessment of urine protein to creatinine ratio). 
• Assessment of B symptoms [fever (i.e., temperature >38°C [>100.4°F]) for 3 consecutive 
days, weight loss exceeding 10% of body weight in 6 months, and/or drenching night sweats] 
• Follicular Lymphoma International Prognostic Index (FLIPI) score at Screening 
• Hepatitis Serology including anti-hepatitis C antibody (anti-HCV), hepatitis B surface 
antigen (HBsAg) and hepatitis B core antibody (HBcAb)  
• Assay for CMV and EBV (Ag and Ab) via serology or viral load detection via polymerase 
chain reaction (PCR) 
• Human Immunodeficiency virus (HIV) testing (if no previous documentation of a negative 
test) 
• Serum or urine βhCG pregnancy test for WCBP (must be performed within 7 days prior to 
first dose of study drug). 
• Baseline disease assessments, which include: 
• Bone marrow aspirate and/or bone marrow biopsy (for subjects where bone marrow 
biopsies and aspirates are a necessary part of the subject’s clinical staging or who have 
≥Grade 3 cytopenias at screening). 
• CT scans of chest, abdomen and pelvis are required for all subjects.  Other scans may 
be performed (e. g, head/neck CT) if clinically indicated or to evaluate a site of known 
disease.  Copies of all imaging/radiology films will be sent to a central laboratory for 
independent review.   
Note: 18-FDG-PET/CT or MRI may be substituted if clinically indicated, but the 
modality chosen to evaluate each individual subject should be the same throughout the 
duration of the study. 
• Quality of Life (QoL) questionnaire (EQ-5D) 
6.2.2 
Contraception 
The effects of IPI-145 on conception, pregnancy and lactation are unknown. 
At screening, all males and female subjects who are not surgically sterile or postmenopausal 
must agree to use medically acceptable methods of birth control for the duration of the study and 
for 30 days after the last dose of IPI-145. Acceptable forms of contraception for females are 
nonhormonal and hormonal intrauterine devices (IUD), hormonal birth control pills, hormonal 
birth control patches, hormonal birth control injections or hormonal birth control implants. 
Sexually active men, and women using contraceptive methods described above, should also use 
barrier contraception with spermicide. Acceptable barrier forms of contraception are condoms or 
diaphragm. 

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6.3 
TREATMENT PERIOD 
6.3.1 
Physical Examination and Vital signs 
A focused physical exam should be performed at all clinic visits indicated in Table 1 and is to 
include assessment of liver/spleen size, clinical assessment of tumor masses (if evaluable by 
physical exam), other clinically significant findings (new or previously noted at screening). Vital 
signs (including temperature, blood pressure, pulse rate, respiratory rate) and weight should also 
be assessed.  Results from the focused physical exams as outlined above will be utilized for 
disease response assessments at time points specific in Table 3.  Any new clinically significant 
abnormality, or worsening changes from Baseline should be recorded on the AE CRF.  If the 
Screening physical exam was performed within 7 days of the Cycle 1 Day 1 visit, then these 
results may be used in place of the Cycle 1 Day 1 physical exam results. 
6.3.2 
ECOG Performance Status 
If the Screening ECOG performance evaluation was performed within 7 days of Cycle 1, Day 1 
visit, these results can be used in place of the Cycle 1, Day 1 ECOG performance results.  ECOG 
performance status will be assessed on each Day 1 clinic visit as indicated in Table 1. 
6.3.3 
B symptoms 
B symptoms [fever (i.e., temperature >38°C [>100.4°F]) for 3 consecutive days, weight loss 
exceeding 10% of body weight in 6 months, and/or drenching night sweats] will be assessed on 
each Day 1 clinic visit indicated in Table 1.  
6.3.4 
12-Lead ECG 
Assessment of the QT interval via ECGs will be performed at visits as indicated in Table 1.  All 
ECGs should be conducted following an approximate 10-minute rest period in a semi-recumbent 
or supine position and obtained in triplicate within approximately a 5 minute time period. QTc 
measurements will use the Fridericia’s correction method (QTcF). 
Any clinically significant change from baseline in ECG parameters will be captured as an AE, 
per Section 8.2.1.   
6.3.5 
Clinical Laboratory Tests 
The following laboratory parameters will be evaluated according to Table 1: 
• Liver function tests including: lactate dehydrogenase (LDH), serum alanine 
aminotransferase (ALT), serum aspartate aminotransferase (AST), total and direct 
bilirubin, and alkaline phosphatase (ALP).  
• Hematology laboratory parameters including: hemoglobin, hematocrit, platelets, and 
white blood cell count with 5-part differential (manual or automated) [for an absolute 
neutrophil count (ANC), neutrophils, lymphocytes, monocytes, basophils and 
eosinophils].  

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• Blood chemistry laboratory parameters including: albumin, total protein, uric acid, 
sodium, potassium, calcium, phosphorous, chloride, bicarbonate (or CO2), BUN or urea, 
creatinine, lipase, amylase, magnesium, and glucose.   
• Coagulation laboratory parameters include: prothrombin time (PT), International 
normalized ratio (INR) and activated partial thromboplastin time (aPTT).  
• Complete urinalysis with qualitative analysis for protein (dipstick).Positive results (urine 
protein > 30 mg/dL by dipstick) will require quantitative analysis (assessment of urine 
protein to creatinine ratio) if not previously noted in medical history.   
• Serum or Urine Pregnancy test for WCBP  
• Serum quantitative immunoglobulin evaluation to include IgA, IgG, IgM, and where 
routinely performed, IgE, should be collected at visits as specified in Table 2. 
• Immunophenotyping evaluation to include T lymphocytes, B lymphocytes, natural killer 
cells, cytotoxic T cells and helper T cells will be performed at visits as specified in Table 
2. 
Additional (unscheduled) assessments should be done as clinically indicated. 
For Cycle 1, Day 1, routine hematology, liver function tests, blood chemistry, or coagulation 
evaluations and pregnancy test (if applicable) may be performed within 7 days prior to study 
treatment (Cycle 1, Day 1).  If the Screening hematology, liver function tests, blood chemistry, 
or coagulation evaluations or pregnancy test are performed within 7 days of Cycle 1, Day 1, then 
these Screening results can be used in place of the Cycle 1, Day 1 hematology, liver function 
tests, blood chemistry, or coagulation results. 
Clinically significant laboratory findings, including but not limited to those findings resulting in 
a drug interruption/reduction/discontinuation or medical requiring intervention should be 
reported as an AE (see protocol Section 8.1.1 for definition of an AE).   
6.3.6 
Study Drug Administration, Criteria for Treatment, and Drug Self-
administration Diary 
Beginning on Cycle 1, Day 1, IPI-145 will be administered daily in 28 day cycles BID.   
Doses should be taken every 12 hours within ±2 hours of the scheduled dose.  Missed doses 
outside this window or vomited doses should not be taken or repeated.  IPI-145 doses will be 
dispensed at a minimum monthly through Cycle 8 and every two months thereafter to the subject 
so that the subject has enough IPI-145 doses until at least the next dispensation visit, taking into 
account the dispensation visit window.  Additional details on study drug dosage and 
administration are described in Section 7.2.1 and 7.2.2, respectively.   
The date, time, and quantity of each capsule strength taken will be recorded in a Drug 
Self-administration Diary for Cycles 1 through 3, per Study Manual.  On Cycle 1, Day 15, the 
morning dose of study medication will be administered in the clinic to accommodate collection 
of PK samples.  When doses are taken outside of the clinic, subjects should also record any 
deviation from taking the full daily dose (e.g., vomited doses, missed doses, doses reduced due to 
missing or lost capsules).  An attempt should be made to enable each dose to be taken at 
approximately the same time of day.  Missed doses outside the windows defined above or 
vomited doses should not be taken or repeated.   
For dose modifications due to adverse events and laboratory abnormalities, see Section 4.2. 

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6.3.7 
Adverse Events 
Monitoring of AEs and SAEs will be performed from the signing of the informed consent form 
(after medical history is completed) for all subjects.  All AEs will be collected from the signing 
of the ICF through 30 days after the last dose from all subjects (excluding screen failures).  SAEs 
will be collected and immediately reported to the Sponsor or designee from the time of ICF (for 
all subjects including screen failures) through 30 days after the last dose of study drug for all 
subjects. See Section 8 for a full description of the collection and reporting of AEs during this 
study. 
6.3.8 
Concomitant Medication and Therapies 
On Day 1 of each Cycle (as well as Day 15 for Cycles 1, 2, and 3) through Cycle 8, every second 
Cycle thereafter, and the EoT visit, assessment of prior and concomitant medications and 
procedures will occur. 
Antimicrobial prophylaxis: 
Based on clinical experience with IPI-145 and the higher risk for infections in this study 
population for infections due to the refractory nature of their disease, the following are 
guidelines for the use of antimicrobial prophylaxis during study treatment: 
• Subjects are required to receive pneumocystis prophylaxis concomitant with treatment with 
IPI-145 per institutional guidelines.  Subjects who are found to be intolerant of pneumocystis 
prophylaxis may continue with study treatment at the discretion of the Investigator. 
• Subjects are required to receive prophylactic treatment for herpes simplex virus (HSV) and 
herpes zoster (VZV) concomitant with treatment with IPI-145 per institutional guidelines. 
• For subjects with history of CMV infection that required treatment, prophylactic treatment 
per institutional guidelines is recommended.  Subjects with history of CMV or EBV infection 
that required treatment, and/or who enter the study while receiving antiviral prophylaxis, 
should be monitored for reactivation via serology or viral load detection while on study 
treatment per institutional guidelines. 
• Investigators should consider prophylactic treatment for thrombocytopenia with platelets as 
clinically indicated.  Therapeutic treatments with platelets and /or other blood products to 
manage bleeding complications may be used at any time as clinically indicated.   
6.3.8.1 
Antiemetics and Antidiarrheals 
Antiemetic and antidiarrheal treatments may be used at the discretion of the Investigator and in 
accordance with the American Society of Clinical Oncology (ASCO) guidelines.  The choice of 
antiemetic or antidiarrheal treatment, if required, will be made at the discretion of the 
Investigator.  Subjects on stable doses of antiemetics and/or antidiarrheals to treat baseline 
conditions may continue on these therapies at the baseline dose. 
6.3.8.2 
Hematopoietic Growth Factors 
Hematopoietic growth factors may be used at the discretion of the Investigator and in accordance 
with the ASCO guidelines. Prophylactic use of growth factors such as granulocyte-colony 

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stimulating factor (G-CSF) and granulocyte macrophage-colony stimulating factor (GM-CSF) 
may be implemented if clinically indicated, in accordance with local guidelines and medical 
practice (e.g., if a subject has Grade 4 neutropenia for ≥7 days, Grade 4 febrile neutropenia, or 
according to the National Comprehensive Cancer Network [NCCN] practice guidelines for 
myeloid factors).  Subjects on a stable dose of erythropoietin to treat baseline anemia may 
continue on this therapy at this dose. 
6.3.8.3 
Use with caution: Medications that are Substrates of CYP3A or CYP2C8 
In vitro studies in human liver microsomes have demonstrated IPI-145 is an inhibitor of 
cytochrome P450 (CYP) enzyme CYP3A4.  Coadministration of IPI-145 with midazolam, a 
probe CYP3A substrate, resulted in an approximate 4-fold increase in midazolam systemic 
exposure (AUC). Systemic exposure to other medications that are substrates for CYP3A4 may be 
increased in subjects receiving IPI-145. Caution should be used if IPI-145 is used 
concomitantly with drugs or foods that are substrates of CYP3A4, particularly those with a 
narrow therapeutic index. Drugs that are substrates for CYP3A should be used only if 
medically necessary and therapeutic alternatives are not available. 
IPI-145 is an inhibitor of CYP2C8 in vitro. Physiologically based pharmacokinetic (PBPK) 
modelling indicates the inhibitory effect of IPI-145 on CYP2C8 substrates is not expected to be 
clinically meaningful at an IPI-145 dose of 25 mg BID. The predicted mean AUC ratio for 
rosiglitazone (a CYP2C8 substrate) with and without IPI-145 at 25 mg BID was 1.02.  Inhibition 
of CYP2C8 metabolism appears to be negligible and only minor changes in the systemic 
exposure to CYP2C8 substrates are anticipated in the presence of IPI-145.  Medications that 
are metabolized via CYP2C8 may be used as medically indicated but with caution. 
Appendix 1 provides a list of medications known to be substrates of CYP3A or CYP2C8.  Please 
note that Appendix 1 is not a comprehensive list of all medications which may be substrates of 
CYP3A or CYP2C8.  The Sponsor should be contacted with any questions regarding 
concomitant use of medications that are CYP3A or CYP2C8 substrates. 
6.3.8.4 
Prohibited: Medications or Food that Inhibit or Induce CYP3A  
In vitro data indicate that oxidative metabolism plays an important role in the elimination of 
IPI-145, with CYP3A4 identified as a primary contributor to drug metabolism.  Data from a 
drug-drug interaction study with ketoconazole (a potent CYP3A inhibitor) indicate exposure to a 
single dose of IPI-145 increased approximately 4- fold in the presence of ketoconazole.  
Similarly, exposure to IPI-145 was reduced approximately 80% when co-administered with 
rifampin, a recognized CYP3A inducer.  Based on these data, the concomitant use of drugs or 
foods that are strong inhibitors or inducers of CYP3A are not allowed during study treatment.  
Moderate or weak inhibitors or inducers may be used with caution. 
Subjects should avoid eating grapefruits or grapefruit-containing products.  In addition, subjects 
should avoid herbal supplements including, but not limited to, St. John’s wort throughout the 
study as this is known to be a strong inducer of CYP3A. 
Appendix 2 provides a list of medications known to be strong inhibitors or inducers of CYP3A. 
Please note that Appendix 2 is not a comprehensive list of all medications which may modulate 
CYP3A activity.   

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The Sponsor should be contacted with any questions regarding concomitant use of medications 
that are thought to modulate CYP3A activity.   
6.3.8.5 
Prohibited: Use of Vaccines 
For all subjects, the use of live or live attenuated vaccines is prohibited during the treatment.  
Note:  The use of inactivated (or killed) vaccines is allowed during the study, however subjects 
and their physicians should be aware that the effectiveness of any vaccine administered 
concomitantly with IPI-145 may be diminished. The ability to generate an immune response to 
any vaccine following the administration of IPI-145 has not been studied. 
6.3.8.6 
Prohibited:  Immunosuppressants 
Subjects are not to receive ongoing treatment with chronic immunosuppressants (e.g., 
cyclosporine) or systemic steroids for > 1 week at doses > the equivalent of 20 mg prednisone 
once daily (QD). 
Note: Acute treatment for underlying autoimmune disorders (e.g. reactive airway disease, 
rheumatoid arthritis etc) with corticosteroid doses > 20 mg prednisone or equivalent QD for ≤ 1 
week is permitted during the study. Corticosteroid doses of ≤ 20 mg prednisone or equivalent 
QD are permitted during the study for physiological replacement or chronic treatment for 
underlying autoimmune disorders (e.g. reactive airway disease, rheumatoid arthritis etc.).  
6.3.8.7 
Prohibited: PI3K and BTK Inhibitors 
Subjects are not to have any prior exposure to any PI3K inhibitor or BTK inhibitor and these 
medications are prohibited while on-study (excluding investigational agent IPI-145). 
6.3.8.8 
Prohibited:  Other Anticancer Therapies or Investigational Agents 
Subjects are not to receive any additional anticancer therapy or other investigational agents not 
outlined in the protocol, including chemotherapy, radiation, surgery or cancer immunotherapy, 
during the treatment period. 
6.3.8.9 
Use with caution:  Medications that are Substrates or Inhibitors of P-glycoprotein 
(P-gp) 
In vitro data indicate that IPI-145 is a substrate for P-glycoprotein (P-gp).  Concomitant 
medications that inhibit P-gp may cause the steady state concentration of IPI-145 to be reached 
more quickly than usual.  These medications may be used as medically indicated but with 
caution.  Additionally, in vitro studies demonstrated that IPI-145 has the potential to inhibit the 
active transport of other P-gp substrates. 
Appendix 3 provides a list of medications that are substrates or inhibitors of P-gp.  Please note 
that Appendix 3 is not a comprehensive list of all medications which may be substrates of P-gp 
or may modulate P-gp activity.  The Sponsor should be contacted with any questions regarding 
concomitant use of medications that are thought to modulate P-gp activity.  

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6.3.8.10 
Photosafety 
The effect of IPI-145 on the skin, especially when in direct sunlight or with artificial UV light 
(e.g. tanning booths) is not known. As a general precaution, subjects should be advised to use 
appropriate protective measures to minimize exposure to direct sunlight or UV light sources 
during the treatment period and for at least 30 days after the last dose of IPI-145. 
6.3.8.11 
Other Concomitant Therapies 
Any other medication which is considered necessary for the subject’s welfare, and which is not 
expected to interfere with the evaluation of IPI-145, or prohibited per protocol, may be given at 
the discretion of the Investigator. 
6.3.9 
Subject-reported Outcomes Assessment 
Subject self-reported health related quality of life will be assessed at Screening, on Day 1 of 
Cycle 3, Cycle 5, Cycle 7, and Cycle 10, and Day 1 of every 4th Cycle thereafter while on 
treatment (i.e., Cycle 14, 18, etc.), and, when possible, upon treatment discontinuation for any 
reason.  Subject-reported health-related quality of life will be assessed using the EQ-5D 
questionnaire.  An English–language example of this instrument is shown in Appendix 6. 
6.3.10 
Pharmacokinetic Sampling 
Peripheral blood will be collected in all study subjects to characterize the pharmacokinetics 
IPI-145 and, if applicable, its metabolite(s).  PK samples will be collected pre-dose and 
approximately 1 and 4 hours after administration of the morning dose of study medication on 
Cycle 1, Day 15.  The morning dose of study medication will be administered in the clinic on 
Cycle 1, Day 15.  Additional samples will be collected on Day 1 of Cycle 2 and Cycle 3 at any 
time during the clinic visit.  The exact date and time of the PK blood draws, along with the date 
and time of the previous 2 doses of study medication will be recorded.  Additionally, collection 
of a spot PK sample is requested when feasible at the time of the start and end of a drug 
interruption/hold for an adverse event.  
Subjects who have an unusual safety or efficacy event (i.e., an AE different in type or severity 
from that which is expected in the setting of IPI-145 use or an exceptional response to treatment) 
may be asked to have additional PK samples collected. These blood draws for pharmacokinetic 
analysis will only be performed after discussion between the Medical Monitor and the Principal 
Investigator.   
6.3.11 
Biomarker Assessments 
Serum and plasma will be collected pre-dose on Cycle 1, Day 1 and  Cycle 1, Day 15.On Day 1 
of Cycle 2, Cycle 3, Cycle 5, Cycle 7, Cycle 10, and Cycle 14, and the EoT visit, samples will be 
collected at any time during the clinic visit.  Pharmacodynamic biomarkers (e.g. signaling 
pathway markers, chemokines and cytokines) may be measured over time to explore changes 
that occur with IPI-145 treatment.  The time points are selected to enable characterization of 
early changes (first 3 Cycles) as well as potential changes that could occur with long-term dosing 
(Cycle 5 and thereafter).  Pre-treatment biomarker levels may also be correlated with clinical 
response to IPI-145 in order to identify biomarkers predictive of clinically responsive subject 

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populations and/or biomarkers predictive of safety.  Serum and plasma will be collected at EoT 
to enable the study of biomarkers with respect to disease progression or safety on IPI-145.  See 
the IPI-145-06 Laboratory Manual for predictive biomarker sample handling procedures.  
Blood will be collected periodically (see Table 2 for time points) to monitor immunoglobulins 
and immunophenotyping (e.g. B- and T-cell subsets, NK cells).  Additional studies may be 
performed to address B and T cell activation and function.  Immunophenotyping studies will be 
performed at a central laboratory site.  Immunophenotyping will also be performed if possible 
when subjects have drug held for toxicity and when drug is restarted after being held for toxicity.  
These results may be assessed for correlation to clinical response and/or safety as well as 
correlation to serum and plasma biomarkers (e.g. chemokines and cytokines). See the IPI-145-06 
Laboratory Manual for handling procedures. 
Archival tumor tissue will be collected at Screening for exploratory assessments of tumor 
characteristics that may predict clinical response to IPI-145.  Archival tumor tissue may be 
utilized for assessment of PI3K pathway and/or disease-specific biomarkers (e.g. PTEN, PI3K 
isoforms) by immunohistochemistry and/or in situ hybridization.  In addition, tumor genomic 
studies may be performed (e.g. DNA sequencing, DNA copy number analysis, RNA expression 
profiling) to explore whether specific genomic features correlate with response or resistance to 
IPI-145 in iNHL.  Archival tumor tissue is not required for enrollment, but should be submitted 
from all subjects (along with corresponding pathology report if available), where possible.  See 
the IPI-145-06 Laboratory Manual for archival tumor tissue sample handling procedures. 
In addition to archival tissue, optional tumor biopsies (e.g. of easily accessible lymph nodes or 
whole blood from subjects with measurable disease in the blood may be performed before 
treatment (prior to Cycle 1, Day1), during treatment at Cycle 1, Day 15, and on the day of last 
dose in cases where subjects are going off study due to disease progression.  Cycle 1, Day 1 
biopsy is pre-IPI-145 therapy and may be collected at any time during the screening period.  The 
Cycle 1 Day 15 on-treatment biopsy may be collected at any time during the clinic visit.  
Similarly, in cases where bone marrow biopsies and aspirates are a necessary part of the 
subject’s clinical care, leftover blocks or unstained slides are requested for biomarker studies.  
Optional serial tumor biopsies and tissue from serial bone marrow biopsies will be utilized to 
study tumor pharmacodynamics (e.g. phospho-PRAS40, phospho-S6 and/or other markers of 
PI3K pathway activity).  Comparisons will be made of pharmacodynamic biomarkers pre-dose, 
on-drug, and where available at the time of disease progression on drug with results ultimately 
being explored for correlation with pharmacokinetics and clinical outcome.  Exploratory 
genomic studies may also be performed with a goal of characterizing changes in tumor DNA 
sequence, DNA copy number and/or RNA expression that occur with treatment and at disease 
progression.  See the IPI-145-06 Laboratory Manual for handling procedures of optional tumor 
biopsies as well as tissue from on-study bone marrow biopsies and aspirates that are a part of the 
subject’s clinical care. 
6.3.12 
Pharmacogenomic Sample Collection (Optional) 
An optional whole blood sample for genetic research will be collected on a single occasion.  It is 
recommended that the blood sample be taken on Cycle 1 Day 1 from subjects who signed the 
informed consent form for the genetic research.  Subjects who do not wish to participate in the 
pharmacogenomic research may still participate in the clinical study. 

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DNA may be extracted from the pharmacogenomic samples and used to explore whether 
germline DNA sequence variations (e.g. in drug metabolizing enzymes, drug transporters, PI3K 
pathway members, and/or other signaling pathways involved in iNHL) correlate with 
pharmacokinetics, pharmacodynamics, safety and/or efficacy of IPI-145.  In addition, DNA may 
be used as matched normal control to determine whether a DNA sequence variation detected in 
the tumor sample is a somatic mutation versus a germline polymorphism. See the IPI-145-06 
Laboratory Manual for further instructions regarding the collection, handling, shipping, storage 
and destruction of pharmacogenomics samples. 
6.3.13 
Indolent NHL Response Assessments 
All disease specific assessments are to be completed (see Table 8) and as outlined in Table 3.  
The modality chosen to evaluate each individual subject should be the same throughout the 
duration of the study.  Copies of all scans will be sent for independent review of response 
assessment. 
CT scans of the chest, abdomen and pelvis are required for all subjects at Screening. These 
assessments may be performed within 7 days of initiating the next cycle of therapy ( Day -7 to 
Day 1) of Cycles 3, 5, 7, 10, 14 and every fourth Cycle thereafter (Cycle 18, 22, etc.) until 
disease progression or start of other anticancer therapy. Copies of all scans will be sent for 
independent review of response assessment.  Other scans may be performed (e. g, neck/head CT) 
if clinically indicated or if the area is a site of known disease. MRI may be substituted if 
clinically indicated, but the modality chosen to evaluate each individual subject should be the 
same throughout the duration of the study.  The frequency outlined is the minimum required for 
study participation.   
Scans will be performed at the EoT if the subject is discontinued for reasons other than 
radiological disease progression and a previous assessment has not been performed within 30 
days of the EoT visit.  If the subject has discontinued treatment for reasons other than disease 
progression, scans should be performed until disease progression or start of additional anticancer 
therapy (see Table 3 for scan frequency). 
Bone marrow biopsy and/or bone marrow aspirates are to be performed at Screening (where 
clinically indicated) and as required thereafter to confirm a complete response as per the revised 
IWG criteria.1  If the screening samples are performed within 60 days of Cycle 1, Day 1 and 
frozen aspirate sample and unstained slides or blocks are available, these results can be used in 
place of the Screening assessment.  If bone marrow aspirate and/or bone marrow biopsy is 
performed, the Screening and the post-Screening bone marrow biopsies and/or aspirate samples 
should be sent for biomarker analysis if available.  See the IPI-145-06 Laboratory Manual for 
further instructions regarding the handling, shipping, and storage of the samples.  
Table 8 shows the major criteria employed for disease response assessment. 

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Table 8: Disease Response Criteria 
Response 
Definition 
Nodal Masses 
Spleen Liver 
Bone Marrow 
CR 
Disappearance of all 
evidence of disease 
a) FDG-avid or PET positive prior to 
therapy: mass of any size permitted if 
PET negative 
b) Variable FDG-avid or PET negative 
prior to therapy: regression to normal 
size on CT 
Not palpable, 
nodules 
disappeared 
Infiltrate cleared on 
repeat biopsy; if 
indeterminate by 
morphology, 
immunochemistry 
should be negative 
PR 
Regression of 
measurable disease 
and no new sites 
≥50% decrease in SPD of up to 6 largest 
dominant masses; no increase in size of 
other nodes 
a) FDG-avid or PET positive prior to 
therapy: one or more PET positive at 
previously involved site  
b) Variable FDG-avid or PET negative: 
regression on CT 
 
≥50% decrease in 
SPD of nodules 
(for single nodule 
in greatest 
transverse 
diameter); no 
increase in size of 
liver and spleen 
Irrelevant if positive 
prior to therapy; cell 
type should be 
specified 
SD 
Failure to attain 
CR/PR or PD 
a)  FDG-avid or PET positive prior to 
therapy: PET positive at prior sites of 
disease and no new sites on CT or 
PET  
b) Variable FDG-avid or PET negative; 
no change in size of previous lesions 
on CT 
 
 
Relapsed 
disease or 
PD 
Any new lesion or 
increase by ≥50% of 
previously involved 
sites from nadir 
Appearance of new lesion(s) >1.5 cm in 
any axis, ≥50% increase in SPD from 
nadir of more than one node, or ≥50% 
increase in longest diameter of a 
previously identified node >1 cm in short 
axis 
Lesions PET positive if FDG-avid 
lymphoma or PET positive prior to 
therapy 
>50% increase 
from nadir in the 
SPD of any 
previous lesions 
New or recurrent 
involvement 
Abbreviations: CR, complete remission; FDG, [18F] fluorodeoxyglucose; PET, positron emission tomography, CT; computed 
tomography; PR, partial remission; SPD, sum of the product of the diameters; SD, Stable disease; PD progressive disease. 
Adverse events, including SAEs, associated with any disease assessment must be collected per 
Section 8.2.1.   
6.4 
END OF TREATMENT VISIT 
All subjects will have an end of treatment (EoT) visit within 7 days following the decision to 
permanently discontinue study treatment. Assessments to be performed at this visit are indicated 
in Table 1. 

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6.5 
POST-TREATMENT PERIOD 
6.5.1 
Safety Follow up Visit (30 Days Post-Treatment) 
A visit should occur for subjects approximately 30 days (+7 days) after discontinuation of 
IPI-145 administration.  If possible, this visit should be conducted prior to initiation of any 
subsequent therapy.  Assessments should include collection of AEs/SAEs and concomitant 
medication and procedures.  This can be performed by telephone call as long as the study subject 
does not require laboratory and/or other procedures related to any new or ongoing AEs, in which 
case a clinical visit will be required 
6.5.2 
Long-term Follow-up 
For subjects discontinuing treatment due to reasons other than radiologic disease progression, 
disease assessments should occur for 2 years after the first dose of IPI-145 (following the on-
treatment response assessment schedule, Table 3) or until documented disease progression or 
other anticancer therapy is initiated, whichever occurs first.  Disease response scans will be 
performed at the EoT, every 12 weeks within the first year of the start of dosing and then every 
16 weeks after a year since the start of dosing of study drug.   
All subjects who permanently discontinue treatment with IPI-145 for reasons other than 
withdrawal of consent from overall study participation will enter survival follow-up.  Survival 
follow-up will occur every 6 months (±4 weeks) from permanently discontinuing IPI-145 
treatment for up to 3 years after first dose of IPI-145 or until death.  The assessments shown in 
Table 4 can be conducted by telephone interview.  Information on initiation of other anticancer 
therapy will also be collected. 
Please see Table 4 for more details on the long-term follow-up assessments. 
6.6 
MISSED VISITS 
If a subject misses a scheduled visit, the subject will continue on the protocol and attend the next 
scheduled visit.  If a subject misses 2 scheduled visits, then the subject’s continued participation 
in the study must be re-evaluated (see Section 4.4).   
 
 

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7 
INVESTIGATIONAL MEDICINAL PRODUCT 
7.1 
DESCRIPTION OF INVESTIGATIONAL MEDICINAL PRODUCT 
IPI-145 drug substance is a white to off-white crystalline powder.  The IPI-145 drug product is 
formulated with excipients (Diluent/glidant, disintegrant, and lubricant) that are listed in FDA’s 
Inactive Ingredients Database for approved drug products and/or Generally Regarded as Safe 
(GRAS) in two different capsule strengths (5 mg and 25 mg) for oral delivery.  IPI-145 drug 
product will be supplied in capsule form as size 2, white opaque hard gelatin capsules (25 mg) 
and size 2, orange opaque hard gelatin capsules (5 mg).  
7.2 
DOSAGE AND ADMINISTRATION 
7.2.1 
Dosage 
IPI-145 will be administered daily in 28-day cycles.  IPI-145 is administered orally as a capsule 
formulation and will be supplied by the Sponsor.  IPI-145 will be administered as a fixed dose in 
mg/day and should be administered using the minimal number of capsules necessary.  Dose 
levels are listed in Table 7.  
For an individual subject, dose reductions and discontinuations may be based on the clinical 
judgment of the Investigator with notification to the Medical Monitor/Sponsor. 
7.2.2 
Administration 
Beginning on Cycle 1, Day 1, IPI-145 will be taken daily for 28 days BID (every 12±2 hours) in 
28-day cycles.  
The date, time, and quantity of each capsule strength taken will be recorded in a Drug 
Self-administration Diary for Cycles 1 through 3, per Study Manual.  On Cycle 1, Day 15, the 
morning dose of study medication will be administered in the clinic to accommodate PK sample 
collection. When doses are taken outside of the clinic, subjects should also record any deviation 
from taking the full daily dose (e.g., vomited doses, missed doses, doses reduced due to missing 
or lost capsules).  An attempt should be made to enable each dose to be taken at approximately 
the same time of day.  Missed doses outside the windows defined above or vomited doses should 
not be taken or repeated.   
IPI-145 doses will be dispensed at a minimum monthly through Cycle 8 and every 2 months 
thereafter to the subject so that the subject has enough IPI-145 doses until at least the next 
dispensation visit, taking into account the dispensation visit window.   
IPI-145 capsules should be swallowed whole with a glass of water (approximately 8 ounces or 
240 mL) at approximately the same time(s) each day.  Subjects must avoid grapefruit or 
grapefruit juice  
IPI-145 may be administered without regard to meals. 

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7.3 
PACKAGING AND LABELING 
IPI-145 drug product capsules will be provided in opaque bottles with induction sealed, child 
resistant cap.  IPI-145 will be supplied to the clinical trial site as open-label medication.  The 
label attached to each bottle will include, at a minimum, a statement limiting its use for 
investigational study only. 
7.4 
STORAGE AND HANDLING 
IPI-145 must be stored at room temperature (15 to 30°C). 
Caution is required when handling IPI-145.  Pharmacists should follow standard procedures for 
the handling of investigational drugs, including avoidance of eye or skin contact with the drug 
product.  If there is exposure to the drug product, provide treatment as necessary for physical 
exposure (skin washing) or inhalation (move to fresh air) and seek medical advice as necessary. 
When IPI-145 capsules are distributed for self-administration, they should only be handled by 
the study subject.  After handling capsules, the subject should wash their hands thoroughly.  If 
someone who is not enrolled in a clinical trial involving IPI-145 swallows a capsule or inhales 
drug powder from a broken capsule of IPI-145, they should contact the relevant Principal 
Investigator to determine whether safety monitoring is necessary.  Capsules should always be 
stored in the container provided to the study subject.  Refer to Section 8.2.3.2 for details on 
reporting any exposure. 
7.5 
INVESTIGATIONAL MEDICINAL PRODUCT ACCOUNTABILITY 
The Investigator or designee is responsible for taking an inventory of each shipment of IPI-145 
investigational supplies received, and comparing it with the accompanying drug accountability 
form. 
All unused IPI-145 will be retained at the site.  After full drug accountability and reconciliation, 
the Investigators will return all IPI-145 to the Sponsor, or its designee or, at the Sponsor’s 
request, will dispose of the study drug at the clinical trial site, according to site procedures.  If 
any study drug is lost or damaged, the disposition of the study drug should be documented.   
Subjects should be instructed to bring all unused IPI-145 to each study visit.  The study site 
should count all capsules that the subject returns, and should take account for taken doses, 
missed doses, doses reduced due to missing or lost capsules, etc., before dispensing new study 
drug to the subject.  Any subject who does not take the prescribed dose should be requested to 
return the remaining drug to the clinical trial site for accountability. 
7.6 
ASSIGNMENT TO TREATMENT 
Study IPI-145-06 is a Phase 2, open-label, safety and efficacy study.  A distinct subject identifier 
will be assigned by the clinical site’s IVRS system once the subject has met all entry criteria.  If 
a subject discontinues from the study, the subject identifier will not be reused and the subject 
will not be allowed to re-enter the study. 

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7.7 
ASSESSMENT OF COMPLIANCE 
At each applicable visit, doses will be dispensed to the subject so that the subject will have 
enough doses until the next applicable visit, taking into account the window for that subsequent 
visit.  Compliance for doses taken outside of the clinic will be assessed by a count of the 
capsules returned to the study trial site by the subject and will be reviewed with the subject by 
the Investigator/designee at each visit. 
7.8 
TREATMENT OF OVERDOSE 
In the case of overdose, clinic staff should be notified immediately and supportive care is to be 
given as indicated.  Subjects should be informed to contact their doctor immediately if they have 
taken an overdose and should stop taking IPI-145. 
Overdoses will be collected as part of the investigational medicinal product dosing information 
and/or as a protocol violation, as required.  AEs or SAEs associated with an IPI-145 overdose 
(intentional or unintentional) should be reported to the Sponsor or designee as outlined in 
Section 8.2.2.6 (Medication Errors).  
 
 
 
 

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8 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.1 
DEFINITIONS 
The definitions of AEs and SAEs are provided below. 
8.1.1 
Adverse Event 
Adverse event (AE) is any untoward medical occurrence associated with the use of a drug or 
with study participation, regardless of the relationship of the occurrence to IPI-145 or study 
protocol.  An AE can be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom or disease temporally associated with the use of the drug, whether or not 
considered related to the drug.  An adverse event can arise from any use of the drug, and from 
any route of administration, formulation or dose, including an overdose.  
Medical conditions present prior to the initiation of the study, as well as ongoing changes in 
laboratory values/conditions that are being treated at baseline, will be captured as an AE if the 
condition worsens.   
8.1.2 
Adverse Reactions and Suspected Adverse Reactions 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered adverse drug reactions.  Suspected adverse reactions are any adverse events for which 
there is a reasonable possibility that the drug caused the adverse event.  Adverse reactions also 
include medication errors and uses outside of what is foreseen in the protocol, which may 
include misuse, abuse and overdose (intentional and unintentional) of the product. 
8.1.3 
Serious Adverse Event 
An adverse event or suspected adverse reaction is considered serious if, in the view of either the 
investigator or Sponsor, it results in any of the following outcomes: 
• Results in death 
• Is immediately life-threatening 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
o Elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent form 
(as documented as medical history on the eCRF), or 
o Scheduled therapy for the target disease of the study, including admissions for 
transfusion support or convenience 
• Results in persistent or significant disability / incapacity 
• Results in congenital anomaly / birth defect. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization, may be considered a serious adverse drug experience when, based upon 

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appropriate medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition.  
Examples of such medical events include allergic bronchospasm requiring intensive treatment in 
an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse. 
8.2 
PROCEDURES FOR ELICITING, RECORDING, AND REPORTING 
ADVERSE EVENTS 
8.2.1 
Eliciting and Recording Adverse Events 
Subjects will be instructed to report all AEs and will be asked a general health status question at 
each study visit.  All AEs will be recorded in the eCRF from the time of informed consent until 
30 days after the last dose of study treatment for all subjects, excluding screen failures.  All 
SAEs occurring from time of informed consent (for all subjects including screen failures) 
through 30 days after the last dose of study treatment will be processed as outlined in 
Section 8.2.3.  An adverse event will be followed until it is either resolved, has returned to 
baseline, or is determined to be a stable or chronic condition.   
At each required visit during the trial, all AEs that have occurred since the previous visit must be 
recorded.  The Investigator or appropriate designee must determine if the adverse event is serious 
or non-serious.   
8.2.1.1 
Relationship to Study drug 
The Investigator is required to provide an assessment of relationship of AEs and SAEs to 
IPI-145.  A number of factors should be considered in making this assessment including:  1) the 
temporal relationship of the event to the administration of IPI-145; 2) whether an alternative 
etiology has been identified; and/or 3) biological plausibility.  The following guidelines should 
be used by Investigators to assess the relationship of an AE to the administration of the study 
drug.   
Relationship assessments that indicate the event is “Not Drug Related”: 
• None:  The event is related to an etiology other than the study product administration (the 
alternative etiology must be documented in the study subject’s medical record). 
• Remote:  The event is unlikely to be related to the study product and likely to be related 
to factors other than study product. 
Relationship assessments that indicate the event is “Drug Related”: 
• Possible:  There is an association between the event and the administration of IPI-145, 
and there is a plausible mechanism for the event to be related to the study product; but 
there may also be alternative etiology, such as characteristics of the subject’s clinical 
status or underlying disease. 
• Probable:  There is an association between the event and the administration of IPI-145, 
there is a plausible mechanism for the event to be related to the study product, and the 

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event could not be reasonably explained by known characteristics of the subject’s clinical 
status or an alternative etiology is not apparent. 
• Definite:  There is an association between the event and the administration of IPI-145, 
there is a plausible mechanism for the event to be related to the study product, and causes 
other than IPI-145 have been ruled out and/or the event re-appeared on re-exposure to 
IPI-145. 
8.2.1.2 
Adverse Event Severity 
The Grade of the AE will be assessed according to the NCI-CTCAE Version 4.03.  Toxicities 
that are not specified in NCI-CTCAE Version 4.03 will be defined as follows:  
• Grade 1:  Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
• Grade 2:  Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL). 
• Grade 3:  Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL. 
• Grade 4:  Life-threatening consequences; urgent intervention indicated. 
• Grade 5:  Death related to AE. 
  Note: it is important to distinguish between SAEs and severe AEs. Severity is a measure of 
intensity, whereas seriousness is classified by the criteria based on the regulatory definitions as 
described in Section 8.1.3 above.   
8.2.2 
Specific Instructions for Recording Adverse Events on the eCRF 
8.2.2.1 
Diagnosis versus Signs and Symptoms 
If a diagnosis is known at the time of reporting, this should be recorded in the eCRF and the SAE 
Report Form, if applicable, rather than the individual signs and symptoms (e.g., record only 
hepatitis rather than elevated transaminases, bilirubin, jaundice).  However, if a constellation of 
signs and/or symptoms cannot be medically characterized as a single diagnosis or syndrome at 
the time of reporting, each individual event should be recorded as an SAE or AE on the eCRF 
(and SAE Report Form, if applicable).  If a diagnosis is subsequently established, it should be 
reported as follow-up on the eCRF (and follow-up SAE Report Form, if applicable) and should 
replace the individual signs and/or symptoms as the event term on the eCRF (and SAE report 
Form, if applicable). 
8.2.2.2 
Adverse Events Occurring Secondary to Other Events 
In general, AEs occurring secondary to other events (e.g., clinical sequelae or a cascade of 
events) should be identified by their primary cause.  For example, if severe vomiting is known to 
result in dehydration, it is sufficient to record only vomiting as the SAE or AE on the eCRF (and 
SAE Report Form, if applicable).  However, medically significant AEs occurring secondary to an 

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initiating event that are separated in time should be recorded as independent events on the eCRF 
(and SAE Report Form, if applicable).  For example, if severe vomiting leads to acute renal 
failure, both events (i.e. vomiting and acute renal failure) should be recorded on the eCRF (and 
SAE Report form if applicable). 
8.2.2.3 
Persistent or Recurrent Adverse Events 
A persistent AE is one that extends continuously, without resolution, between subject evaluation 
time points.  Such events should only be recorded once on the AE eCRF (and SAE Report Form, 
if applicable).  If a persistent AE changes in grade, it should be recorded as a new AE on the 
eCRF. 
A recurrent AE is one that occurs and resolves between subject evaluation time points and 
subsequently recurs.  All recurrent AEs should be recorded on the eCRF (and SAE Report Form, 
if applicable). 
8.2.2.4 
Abnormal Laboratory Values 
If an abnormal laboratory value or vital sign is associated with clinical signs and/or symptoms, 
the sign or symptom should be reported as an AE or SAE and the associated laboratory value or 
vital sign should be considered additional information that is collected on the relevant eCRF.  
Abnormal laboratory values should be reported as an AE if the laboratory result: 
• requires an adjustment in the study drug or discontinuation of study treatment 
• require additional testing or surgical intervention 
• is associated with accompanying symptoms 
• is considered to be an AE by the Investigator 
Note:  If the laboratory abnormality is a sign of a disease or syndrome, only the diagnosis needs 
to be recorded on the eCRF (and SAE Report Form, if applicable). 
8.2.2.5 
New Cancers 
The development of a new primary cancer should be regarded as an AE and will generally meet 
at least one of the serious criteria (See Section 8.1.3).  New primary cancers are those that are not 
the primary reason for the administration of the trial treatment and have developed after the 
inclusion of the subject into the study.  They do not include metastases of the original cancer. 
Progression of the disease under study (i.e. disease progression) is not considered an AE/SAE 
unless it is fatal. 
8.2.2.6 
Medication Errors, Misuse and Abuse of Study Drug 
Overdose, medication error, misuse and abuse are defined as follows: 
• Overdose: refers to the administration of a quantity of study drug given per 
administration or cumulative, which is above the maximum dose according to the 
protocol.  Clinical judgment should always be applied. 
• Medication error: refers to an unintentional error in dispensing or administration of the 
study drug not in accordance with the protocol.   

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• Off-label use: relates to situations where the study drug is intentionally used for medical 
purpose not in accordance with the protocol. 
• Misuse: refers to situations where the study drug is intentionally and inappropriately used 
not in accordance with the protocol. 
• Abuse: corresponds to the persistent or sporadic, intentional excessive use of the study 
drug , which is accompanied by harmful physical or psychological effects. 
• Occupational exposure: refers to the exposure to the study drug as a result of one’s 
professional or non-professional occupation. 
Overdoses, medication errors, abuse or misuse will be collected as part of investigational 
medicinal product dosing information and/or as a protocol violation, as required.   
Any AE associated with an overdose, medication error, misuse or abuse of study drug should be 
recorded on the AE eCRF with the diagnosis of the AE.   
8.2.3 
Reporting of Serious Adverse Events 
8.2.3.1 
Immediate Reporting of Serious Adverse Events by Investigator to Sponsor 
All SAEs (including SAEs occurring in screen failures and treated subjects) from the time of 
informed consent will be reported to the Sponsor or designee within 24 hours of the 
Investigator’s first knowledge of the event, even if the experience does not appear to be related 
to IPI-145.   
Serious adverse events should be communicated on the Verastem SAE Report Form as follows:  
• Email: 
 
• Fax: 
 (USA & Canada)  
• Hotline (Phone): 
 (USA)  
• For International numbers, please refer to the SAE Form and supporting documentation. 
The initial SAE Report Form must be as complete as possible, including details of the current 
illness and (serious) AE, and an assessment of the causal relationship between the event and the 
investigational product(s).  Information not available at the time of the initial report (e.g., an 
outcome and end date for the AE, relevant laboratory values received after the report, or final 
diagnosis) must be documented on a follow-up SAE Report form.  All follow-up information 
must be reported in the same timelines as initial information (i.e. within 24 hours of the 
Investigator’s first knowledge of information). 
At any time after completion of the AE reporting period (i.e. 30 days post-treatment), if an 
Investigator becomes aware of an SAE that is suspected by the Investigator to be related to 
IPI-145, the event must be reported as described above. 
8.2.3.2 
Immediate Reporting of Medical Events of Interest 
Reports or laboratory results of AST or ALT >3x ULN in combination with bilirubin >2x 
ULN are medical events of interest, and therefore immediately reportable events, even if the 
events do not meet serious adverse event criteria.   

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Clinical findings of Grade 3 or higher rash are medical events of interest, and therefore 
immediately reportable events, even if the events do not meet serious adverse event criteria.  Pre-
existing skin conditions that recur would not meet this definition unless the recurrence is of a 
greater severity/frequency than previously experienced. 
All medical events of interest will be reported to the Sponsor or designee within 24 hours of the 
Investigator’s first knowledge of the event, even if the experience does not appear to be related 
to IPI-145.  Medical Events of Interest should be communicated on the Verastem SAE / MEOI 
report form as described above for SAEs.  
Any occupational exposure or exposure of an individual not enrolled in the study to the 
investigational medicinal product must be reported to the Sponsor or designee within 24 hours of 
the Investigator's first knowledge of the event, even if the exposure does not result in an AE.  
Unintentional exposures should be communicated on the SAE/MEOI report form, as described 
above for SAEs. 
8.2.3.3 
Reporting of Serious Adverse Events to the Institutional Review Board (IRB)/ 
Ethics Committee (EC) 
Verastem or designee shall notify the Investigator and/or the IRBs/ECs per institutional 
guidelines of potential serious risks from clinical trials or any other sources, including the 
following: 
• Suspected adverse reaction that is both serious and unexpected. 
• Any findings from other studies that suggest a significant risk in humans exposed to the 
drug. 
• Any finding from animal or in vitro testing that suggest a significant risk to humans 
exposed to the drug, such as mutagenicity, teratogenicity, or carcinogenicity; or report of 
significant organ toxicity at or near the expected human exposure. 
Verastem or designee shall notify the Central Ethics Committees (CEC) of new serious, related 
and unexpected AEs or significant risks to subjects, per local country requirements. 
The Investigator will also notify the IRB/ Local Ethics Committee (LEC), of serious, related and 
unexpected AE(s) or significant risks to subjects per local country requirements. 
The Investigator must keep copies of all AE information on file, including correspondence with 
Verastem and the IRB/LEC. 
8.2.3.4 
Reporting of Serious Adverse Events to Regulatory Authorities 
Verastem or designee shall notify Regulatory Authorities of serious, unexpected adverse 
reactions for IPI-145, as well as other adverse events, per local requirements.  Expectedness will 
be determined using the current IPI-145 Investigator Brochure.  
8.2.4 
Pregnancy and In Utero Drug Exposure 
Since IPI-145 has not been evaluated in pregnant or nursing women, the administration of IPI-
145 in pregnant women or women of childbearing potential who are not using effective 
contraception is contraindicated.   

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Pregnancies occurring in subjects or partners of male subjects during the study treatment period 
until 30 days after the subject’s last dose of study treatment are considered immediately 
reportable events.  If a pregnancy occurs in a subject, study treatment must be discontinued 
immediately.  The pregnant woman should be referred to an obstetrician/gynecologist 
experienced in reproductive toxicity for further evaluation and counseling. 
The pregnancy must be reported to Verastem or designee within 24 hours of the Investigator’s 
knowledge of the pregnancy using the Pregnancy Notification Form as follows: 
• Email: 
 
• Hotline (Phone): 
 (USA)  
• Fax: 
 (USA & Canada)  
• For International numbers, please refer to the Pregnancy Notification Form and 
supporting documentation. 
The Investigator will follow the pregnant woman until completion of the pregnancy, and must 
notify Verastem of the outcome within 24 hours of the Investigator’s knowledge of the 
pregnancy outcome.  The Investigator will provide this information on the Pregnancy Outcome 
Report Form.  This notification includes pregnancies resulting in live, “normal” births. 
If the pregnant subject experiences an SAE during pregnancy, or the outcome of the pregnancy 
meets the criteria for immediate classification as an SAE (i.e., spontaneous abortion [any 
congenital anomaly detected in an aborted fetus is to be documented], stillbirth, neonatal death, 
or congenital anomaly), the Investigator should follow the procedures for reporting SAEs (i.e., 
report the event to Verastem within 24 hours of the Investigator’s knowledge of the event). 
All neonatal deaths and congenital anomalies that occur within 30 days of birth (regardless of 
causality) should be reported as SAEs to Verastem.  In addition, any infant death or congenital 
anomaly occurring after 30 days that the Investigator suspects is related to the in utero exposure 
to the study drug should also be reported to Verastem. 
 
 
 
 

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9 
STATISTICAL METHODS 
Details of the statistical methods for this study will be documented in a Statistical Analysis Plan 
(SAP). The SAP may modify the statistical methods outlined in the protocol; however, any major 
modification will also be reflected in a protocol amendment. 
9.1 
SAMPLE SIZE DETERMINATION 
This study will test the null hypothesis that the ORR is ≤30% against the alternative that ORR is 
≥45%. Using a group sequential design with 1 interim analysis, 120 subjects will provide >90% 
power to achieve a one-sided overall significance level of 0.025.  The interim analysis will occur 
approximately 4 months after at least 30 subjects (25% of the total) have initiated treatment with 
IPI-145.  The cumulative Type II error to be spent at the interim and final analyses are 0.02 and 
0.1, respectively.  The interim analysis is intended for futility only and hence no Type I error will 
be spent.  
Among the 120 subjects to be enrolled, approximately 80 will be diagnosed with FL.  
9.2 
RANDOMIZATION AND STRATIFICATION 
Randomization and stratification are not applicable for this Phase 2, open-label single-arm study.   
9.3 
ANALYSIS SETS 
The Full Analysis Set (FAS) will include all subjects who were treated with at least one dose of 
IPI-145. The FAS will be the primary analysis set for all efficacy and safety analyses.  
The Evaluable Analysis Set (EAS) will include all subjects who had no major protocol violations 
and who remained in the treatment phase of the study for at least 8 weeks with an adequate 
baseline tumor assessment and at least 1 adequate post baseline tumor assessment.  Subjects with 
documented disease progression before 8 weeks of treatment should be considered as “early 
progression” subjects and, therefore, should be considered evaluable.  The EAS will be a 
secondary analysis set for selected efficacy analyses.  
Major protocol violations include failure to satisfy key entry criteria, or taking other anticancer 
therapies or other prohibited medications during the treatment phase of the study that could 
seriously confound the effects of the study treatment.  
For each of the above two analysis sets, subsets defined by disease subtypes will be identified so 
that efficacy analyses for disease subtypes can be performed. 
9.4 
EFFICACY ANALYSES 
Assessment of response and progression status will be evaluated locally (i.e. Investigator’s 
assessment) and by an independent, third party panel of radiologists and oncologists according to 
the revised IWG Response Criteria for Malignant Lymphoma1.  The independent response 
assessment will be used for the primary analyses of response and progression-based efficacy 
endpoints (i.e. ORR, PFS, TTR and DOR).  Data based on local assessment will also be 
presented for these endpoints.   

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The FAS will be the primary analysis set for all efficacy analyses.  The evaluable analysis set 
will also be used for some efficacy analyses, with details specified in the SAP.   
Analyses for primary and secondary efficacy endpoints will be performed for the overall study 
population (iNHL), the follicular lymphoma population and subsets defined by other disease 
subtypes.    
Analyses of the exploratory efficacy endpoint will be specified in the SAP. 
9.4.1 
Analysis of Primary Endpoint 
ORR will be tested against the null (≤30%) by 1-sided exact binomial test at 0.025 level.  The 
estimated ORR along with the 2-sided 95% exact confidence interval will be provided.  Missing 
data will be imputed by assuming that any subjects not exhibiting a response (CR or PR) are 
non-responders.   
ORR will also be presented for the follicular lymphoma population, as well as the other disease 
subtypes, with 2-sided 95% exact confidence intervals.   
9.4.2 
Analyses of Secondary Endpoints 
PFS will be presented using the Kaplan-Meier method.  A 2-sided 95% confidence interval for 
median PFS will be provided.  The details of PFS censoring will be specified in the SAP.  
TTR will be presented using the Kaplan-Meier method.  A 2-sided 95% confidence interval for 
median TTR will be provided.  TTR will only be analysed for responders (CR or PR).  
DOR will be presented using the Kaplan-Meier method.  A 2-sided 95% confidence interval for 
median DOR will be provided.  DOR will only be analysed for responders (CR or PR).  DOR 
will be censored in the same way as PFS with details provided in the SAP.  
OS will be presented using the Kaplan-Meier method.  A 2-sided 95% confidence interval for 
median OS will be provided.  
These analyses will also be performed similarly for the follicular lymphoma population, as well 
as the other disease subtypes. 
9.5 
SAFETY ANALYSES 
The FAS will be the primary analysis set for safety evaluation.  Safety will be assessed by AEs, 
ECG and laboratory test measurements.   
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
version 16.1 or higher and graded according to NCI-CTCAE Version 4.03.  If the AE is not 
included in the NCI-CTCAE Version 4.03, the Investigator will assign a grade according to 
Section 8.2.1.  
The focus of AE summaries will be on TEAEs. A TEAE is defined as any AE that emerges or 
worsens in the period from the first dose of study treatment to 30 days after the last dose of study 
treatment.  AEs will be summarized by the frequency of subjects experiencing TEAEs by 
MedDRA system organ classes (SOC) and preferred terms (PT). Separate tabulations will also be 

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produced for drug-related AEs, SAEs, AEs that led to treatment discontinuation, and AEs of at 
least Grade 3 severity. 
ECG measurements will be tabulated for changes over time on study. 
Laboratory parameters will be summarized for changes over time by descriptive statistics, and 
laboratory values that are of Grade 3 severity or greater will be tabulated and listed on an 
individual subject basis. 
9.6 
PHARMACOKINETIC ANALYSES 
Plasma samples will be analyzed for IPI-145 and potential metabolite concentrations using a 
validated high performance liquid chromatography-tandem mass spectrometry (LC/MS/MS) 
method.   
The PK data collected will be analyzed by standard population PK methods, using appropriate 
software. The intent of this analysis is to obtain exposure data in subjects with indolent 
lymphoma, to characterize the parameters of PK disposition, and to identify relevant covariates 
affecting drug exposure.  If there is only a limited amount of plasma concentration data from this 
study, the data may be pooled with the results of other studies to perform the population PK 
analysis. 
Additional details on the pharmacokinetic methods and analysis will be provided in the SAP. 
9.7 
ANALYSIS OF OTHER ENDPOINTS 
9.7.1 
Biomarker Analyses 
All biomarker analyses will be descriptive in nature.  Summary tabulations may be produced if 
data from a sufficient number of subjects are collected.  Additional details on the biomarker 
analysis methods will be provided in the SAP 
9.7.2 
Analyses of Health-Related QoL 
Details on the analysis methods of health-related QoL endpoints will be provided in the SAP.   
9.8 
INTERIM AND FINAL ANALYSES 
9.8.1 
Interim Analysis 
An interim futility analysis will be performed approximately 4 months after at least 30 subjects 
(25% of total) have initiated treatment with IPI-145.  The futility boundary is non-binding, 
meaning that the Type I error will be properly controlled if the study continues after the futility 
boundary is crossed at the interim analysis.  If the interim analysis occurs 4 months after exactly 
30 subjects have initiated treatment, the one-sided p-value for futility is 0.6552. This is 
equivalent to a response rate of 26.4% or 7 responders or less out of the 30 subjects.  Actual p-
value boundary for futility will be calculated based on the number of subjects at the interim 
analysis by linear interpolation. 
ORR based on the Investigator’s assessment will be used for the interim analysis. 

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If the required total number of subjects are accrued for the interim analysis but follow-up is not 
sufficiently mature to reasonably assess the ORR, accrual may proceed while the data on interim 
analysis subjects are being collated.   
An Independent Data Monitoring Committee (IDMC) will review ORR and other efficacy data 
at the planned interim analysis.  Safety analyses will also be performed at this interim analysis.  
Further details will be contained in the IDMC charter. 
9.8.2 
Final Analysis 
Final analyses will be conducted approximately 6 months after the final subject receives his / her 
first dose.     

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10 
STUDY ADMINISTRATION 
10.1 
GOOD CLINICAL PRACTICE STATEMENT 
This study is to be performed in accordance with the protocol, the Declaration of Helsinki, the 
ICH Harmonised Tripartite Guideline for GCP, and all applicable local regulatory requirements. 
10.2 
INFORMED CONSENT 
Verastem will provide a sample subject Informed Consent Form (ICF) for modification, as 
appropriate, by the Investigator.  The ICF must include all elements required by ICH, GCP, and 
must adhere to the IRB/IEC requirements and the ethical principles that have their origin in the 
Declaration of Helsinki. 
The Investigator or his/her staff will explain the nature of the study, its purpose and associated 
procedures, the expected duration, and the potential risks involved to the subject prior to 
enrollment.  The Investigator or designee will obtain written, informed consent.  The subject will 
have ample time and opportunity to ask questions and will be informed about the right to 
withdraw from the study at any time without any disadvantage and without having to provide a 
reason for this decision.  Following the discussion regarding the study, a subject will be asked if 
they are willing to sign and personally date a statement of informed consent.  Only if the subject 
voluntarily agrees to sign the informed consent statement and has done so, may he/she enter the 
study.  A copy of the signed and dated ICF will be provided to the subject.  The signed ICF is to 
remain in the Investigator’s file, per local requirements. 
The ICF and any other written information provided to the subjects will be revised whenever 
important new information becomes available that may be relevant to the subject’s consent, or if 
there is an amendment to the protocol which necessitates a change to the content of the subject’s 
informed consent.  The Investigator will inform the subject of changes in a timely manner and 
will ask the subject to confirm continuation of their participation in the study by their signature 
on the revised informed consent form (if applicable). Any written ICF and written information 
must receive the approval/favorable opinion of the IRB/IEC in advance of use.  Any additional 
approvals from the initial informed consent form should be forwarded to the Sponsor. 
10.3 
SUBJECT CONFIDENTIALITY 
The written ICF will explain that study data will be stored in a database, maintaining 
confidentiality in accordance with national data legislation.  All data processed by Verastem or 
its representative(s) will be identified by subject number and study code. 
The written ICF will also explain that for data verification purposes, authorized representatives 
of Verastem, a regulatory authority, and IRB/IEC may require direct access to parts of the 
hospital or clinic records relevant to the study that include the subject’s medical history. 
The Investigator must ensure that the subjects’ anonymity is maintained.  On the eCRFs or other 
documents submitted to the Sponsor, subjects should not be identified by their names, but by 
their assigned subject number and study code.  Documents not for submission to the Sponsor, 
such as signed Informed Consent Forms, should be maintained in strict confidence by the 
Investigator. 

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10.4 
INSTITUTIONAL REVIEW BOARD/ ETHICS COMMITTEE 
REQUIREMENTS 
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB/IEC at each clinical trial site.  The Principal Investigator 
must submit written approval to Verastem before he or she can enroll any subject into the study. 
The Principal Investigator is responsible for informing the IRB/IEC of any amendment to the 
protocol.  In addition, the IRB/IEC must approve all advertising used to recruit subjects for the 
study.  The protocol must be re-approved by the IRB/IEC annually. 
Progress reports and notifications of SAEs will be provided to the IRB/IEC according to 
regulations and guidelines. 
10.5 
CASE REPORT FORMS AND SOURCE DOCUMENTATION 
Electronic CRFs will be provided for the recording of all data.  The Principal Investigator / Sub-
Investigator or designee will record data on all observations, tests, and assessments specified in 
the protocol on the eCRFs provided by Verastem . 
10.6 
SPONSOR MONITORING 
Before the first subject is enrolled into the study, a representative of Verastem will visit the study 
site to: 
• Determine the adequacy of the facilities. 
• Discuss with the Investigator(s) (and other personnel involved with the study) their 
responsibilities with regard to the protocol, and the responsibilities of Verastem .   
During the conduct of the study, a representative of Verastem, Inc. will have regular contact with 
the clinical trial site, and have regular visits to the clinical trial site to: 
• Provide information and support the PI. 
• Confirm that the facilities remain acceptable. 
• Confirm that the study team is adhering to the protocol, data are being accurately 
recorded in the eCRFs, and the investigational product is being properly maintained and 
accountability records are current. 
• Perform source data verification with access to all original clinical records for each 
subject. 
10.7 
INDEPENDENT DATA MONITORING COMMITTEE 
An Independent Data Monitoring Committee (IDMC) will be assembled to periodically review 
all available safety information and recommend whether or not the trial should continue, or 
should continue with modifications, based on their review of this data.   In addition, the IDMC 
will review preliminary efficacy data at the time of the interim analysis and make a 
recommendation on futility of the study.  All final decisions regarding study conduct will reside 
with the Sponsor.  Membership and responsibilities of the IDMC will be documented in a 
separate IDMC Charter. 

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10.8 
QUALITY ASSURANCE 
In compliance with GCP and regulatory requirements, the Sponsor, a third party on behalf of the 
Sponsor, regulatory agencies or IRB/IECs may conduct quality assurance audits at any time 
during or following a study.  The Investigator must agree to allow auditors direct access to all 
study-related documents including source documents, and must agree to allocate his or her time 
and the time of his or her study staff to the auditors in order to discuss findings and issues. 
10.9 
STUDY OR CLINICAL SITE TERMINATION 
Verastem, or designee, reserves the right to terminate the study or a clinical trial site at any time.  
Conditions that may warrant termination of the study include, but are not limited to: 
• The discovery of an unexpected, serious, or unacceptable risk to subjects enrolled in the 
study. 
• The decision on the part of Verastem to suspend or discontinue testing or the treatment of 
the study drug. 
• Failure of the Investigator to comply with GCP. 
• Submission of knowingly false information from the clinical trial site to Verastem or 
regulatory authorities. 
• Insufficient adherence to protocol requirements. 
If terminating the study, Verastem and the Investigator(s) will assure that adequate consideration 
is given to the protection of the subjects’ interests. 
10.10 
DURATION OF THE STUDY, EXPECTED DURATION OF SUBJECT 
PARTICIPATION, AND END OF STUDY 
The study is estimated to complete enrollment within 30 months. Subjects will be followed for 
survival for up to 3 years after their first dose of IPI-145. The maximum number of months to 
complete the study is expected to be approximately 66 months.   
10.11 
RECORDS RETENTION 
All correspondence related to this clinical study should be kept in appropriate study files.  
Records of subjects, source documents, eCRFs, drug inventory, IRB, and Sponsor 
correspondence pertaining to the study must be kept on file.  All study documents must be kept 
secured for a period of 2 years after a marketing application is approved for IPI-145; or, until 
2 years after shipment and delivery of the drug for investigational use is discontinued or as long 
as required by local regulations, whichever is longer.  There may be other circumstances for 
which the Sponsor is required to maintain study records and, therefore, the Sponsor should be 
contacted prior to removing study records for any reason. 
10.12 
PUBLICATIONS 
Publication by the clinical trial site(s) of any data from this study must be carried out in 
accordance with the Clinical Trial Agreement. 

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11 
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31. Kim MS, Radinger M, Gilfillan AM. The multiple roles of phosphoinositide 3-kinase in 
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inflammation and hyperresponsiveness in murine asthma model. FASEB J. 2006 
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critical role in NK cell terminal maturation and cytokine/chemokine generation. J Exp Med. 
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34. Kim N, et al. The p110delta catalytic isoform of PI3K is a key player in NK-cell 
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35. Saudemont A, et al. p110gamma and p110delta isoforms of phosphoinositide 3-kinase 
differentially regulate natural killer cell migration in health and disease. Proc Natl Acad Sci 
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APPENDICES 
Appendix 1: Known CYP3A or CYP2C8 Substrates  
Note: Drugs or foods that are substrates for CYP3A should be used only if medically necessary 
and therapeutic alternatives are not available. Medications that are metabolized via CYP2C8 
may be used as medically indicated but with caution. 
The following lists provide known sensitive CYP3A substrates, CYP3A substrates with a narrow 
therapeutic range, and CYP2C8 substrates.  
Additional information can be found at 
http://www.medicine.iupui.edu/clinpharm/ddis/ClinicalTable.asp and 
http://www.pharmacytimes.com/issue/pharmacy/2008/2008-09/2008-09-8687. 
 
Sensitive CYP3A Substrates 
budesonide 
buspirone 
eplerenone 
eletriptan 
felodipine 
fluticasone 
lovastatin 
midazolam 
saquinavir 
sildenafil 
simvastatin 
triazolam 
vardenafil 
 
CYP3A Substrates with a Narrow Therapeutic Range 
alfentanil 
astemizole  
cisapride  
cyclosporine 
diergotamine 
ergotamine 
fentanyl 
pimozide 
quinidine  
sirolimus 
tacrolimus 
terfenadine 
CYP2C8 Substrates 
paclitaxel 
torsemide 
amodiaquine 
cervistatin 
repaglinide 
rosiglitazone 
pioglitazone 
 

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Appendix 2: Medications or Foods Known to Inhibit or Induce CYP3A 
Note: Subjects receiving IPI-145 are prohibited from concomitant use of medications or foods 
that are known to be strong inhibitors or inducers of CYP3A. 
The following list provides medications known to induce or inhibit CYP3A activity.  Note that 
this is not a comprehensive list of all medications which may modulate CYP3A activity.  
Additional information can be found at  
• http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugIn
teractionsLabeling/ucm080499.htm 
Classification of In Vivo Inhibitors of CYP3A  
Strong Inhibitors(1)   
Moderate inhibitors(2) 
Weak inhibitors(3)   
Boceprevir, 
clarithromycin, 
conivaptan, 
grapefruit juice,(5) 
indinavir, itraconazole, 
ketoconazole,  
lopinavir/ritonavir, 
mibefradil, (6) 
nefazodone, nelfinavir, 
posaconazole, ritonavir,  
saquinavir,  
telaprevir, 
telithromycin, 
voriconazole 
Amprenavir, aprepitant, 
atazanavir, ciprofloxacin, 
darunavir/ritonavir, 
diltiazem, erythromycin, 
fluconazole, 
fosamprenavir, grapefruit 
juice, (5) 
imatinib, verapamil 
Alprazolam, amiodarone, 
amlodipine, atorvastatin, 
bicalutamide, cilostazol, 
cimetidine, 
cyclosporine, fluoxetine, 
fluvoxamine, ginkgo, (4) 
goldenseal,(4) 
isoniazid, nilotinib, 
oral contraceptives, 
ranitidine, ranolazine, 
tipranavir/ritonavir, zileuton 
1. A strong inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a substrate for that 
CYP by equal or more than 5-fold or >80% decrease in CL. 
2. A moderate inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a sensitive 
substrate for that CYP by less than 5-fold but equal to or more than 2-fold or 50-80% decrease in CL.  
3. A weak inhibitor for a specific CYP is defined as an inhibitor that increases the AUC of a sensitive substrate for 
that CYP by less than 2-fold but equal to or more than 5-fold or 20-50% decrease in CL.  
4. Herbal product.  
5. The effect of grapefruit juice varies widely among brands and is concentration-, dose-, and preparation-
dependent.  Studies have shown that it can be classified as a “strong CYP3A inhibitor” when a certain 
preparation was used (e.g., high dose, double strength) or as a “moderate CYP3A inhibitor” when another 
preparation was used (e.g., low dose, single strength).  
6. Withdrawn from the United States market because of safety reasons.  
 
 

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Classification of In Vivo Inducers of CYP3A  
Strong Inducers 
≥ 80% decrease in 
AUC 
Moderate Inducers 
50-80% decrease in AUC 
Weak Inducers 
20-50% decrease in AUC 
Avasimibe,(1) 
carbamazepine, 
phenytoin, rifampin, St. 
John’s wort(2) 
Bosentan, efavirenz, 
etravirine, modafinil, 
nafcillin 
Amprenavir, aprepitant, 
armodafinil, echinacea,(3) 
pioglitazone, prednisone, 
rufinamide 
1. Not a marketed drug. 
2. The effect of St. John’s wort varies widely and is preparation-dependent. 
3. Herbal product. 
 

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Appendix 3: P-gp Substrates and Medications that are Inhibitors of P-gp 
Note: In subjects receiving IPI-145, caution should be used for the concomitant use of P-gp 
substrates or inhibitors 
The following list provides medications that are substrates or inhibitors of P-gp.  Note that this is 
not a comprehensive list of all medications which may be substrates of P-gp or may modulate 
P-gp activity. 
 
P-gp Substrates 
Amitriptyline 
Amiodarone 
Atorvastatin 
Cefoperazone 
Chlorpromazine 
Cimetidine 
Ciprofloxacin 
Clarithromycin 
Colchicine 
Cyclosporine 
Dexamethasone 
Digoxin 
Diltiazem 
Erythromycin 
Estradiol 
Fentanyl 
Fexofenadine 
Hydrocortisone 
Itraconazole 
Lansoprazole 
Levofloxacin 
Lidocaine 
 
Loperamide  
Losartan 
Lovastatin 
Methadone 
Methotrexate 
Methylprednisolone 
Morphine 
Nadolol 
Norfloxacin 
Nortriptyline 
Ondansetron 
Omeprazole 
Pantoprazole 
Phenytoin 
Pravastatin 
Propranolol 
Quinidine 
Ranitidine 
Sirolimus 
Tacrolimus 
Timolol 
Trimethoprim 
Verapamil 
 

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P-gp Inhibitors 
Amiodarone 
Amitriptyline 
Carvedilol 
Chlorpromazine 
Clarithromycin 
Cortisol 
Cyclosporine 
Desipramine 
Diltiazem 
Dipyridamole 
Doxepin 
Erythromycin 
Felodipine 
Fluphenazine 
Grapefruit juice 
Haloperidol 
Itraconazole 
Ketoconazole 
Lovastatin 
Mefloquine 
Nicardipine 
Nifedipine 
Ofloxacin 
Omeprazole 
Pantoprazole 
Progesterone 
Propafenone 
Propranolol 
Quinidine 
Rifampicin (Rifampin) 
Saquinavir 
Simvastatin 
Sirolimus 
Tacrolimus 
Testosterone 
Verapamil 
 
Source: Atkinson AJ et al. Principles of Clinical Pharmacology, 2nd ed. Academic 
Press, Massachusetts, 2007. 
 
 

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Appendix 4: ECOG Performance Status 
Grade 
ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry 
out work of a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work 
activities. Up and about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of 
waking hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed 
or chair 
5 
Dead 
Source : Eastern Cooperative Oncology Group : http://www.ecog.org/general/perf_stat.html 
As published in Am. J. Clin. Oncol.: 
Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: Toxicity And 
Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982 
 
 
 

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Appendix 5: Examples of Suitable Prior Chemotherapy 
 
1. Bendamustine 
2. Cyclophosphamide 
3. Ifosfamide 
4. Chlorambucil 
5. Melphalan 
6. Busulfan 
7. Nitrosoureas 
8. Fludarabine 
 
Please contact the Medical Monitor regarding the appropriateness of any prior chemotherapy not 
listed above prior to subject enrollment. 
 
 
 
 

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Appendix 6: QoL Instrument - EQ-5D Questionnaire 
 
(English version for the US) 
 
 
 
 
 

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