Clinical trial NCT03372057
Conditions: Peripheral T-cell Lymphoma
Keywords: Lymphoma T-cell Lymphoma Relapse Refractory PI3K-δ,γ
Sponsor: SecuraBio
Start date: 2018-02-22; Completion date: 2023-12-22
Enrollment: 156 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is a multi-center, parallel cohort, open-label, Phase 2 study of duvelisib, an oral dual inhibitor of phosphoinositide-3-kinase-delta, gamma (PI3K-δ,γ), in participants with relapsed/refractory peripheral T-cell lymphoma (PTCL).

Detailed description:
The study had 2 phases, a Dose Optimization Phase and an Expansion Phase.

In the Dose Optimization Phase, participants were randomly assigned to 1 of 2 study cohorts, as follows:

* Cohort 1: Duvelisib per oral (PO) twice daily (BID) at a starting dose of 25 milligrams (mg), with potential escalation on a per-participant basis to 50 mg and then 75 mg, based on the participant's response to and tolerance of therapy, in 28-day cycles.
* Cohort 2: Duvelisib 75 mg PO BID, administered in 28-day cycles.

A total of 20 participants were to be enrolled in the Dose Optimization Phase, with 10 participants per cohort. Based on the safety and activity data obtained in the Dose Optimization Phase of the study, the Expansion Phase dose of duvelisib was to be determined.

In the Expansion Phase, approximately 100-130 participants were to be enrolled and receive duvelisib dose in 28-day cycles as determined in Dose Optimization Phase.

Arms: arm 1: Duvelisib PO BID at a starting dose of 25 mg, with potential escalation on a per-participant basis to 50 mg and then 75 mg, based on the participant's response to and tolerance of therapy, in 28-day cycles. arm 2: Duvelisib 75 mg PO BID, administered in 28-day cycles. arm 3: Duvelisib PO BID at a starting dose of 75 mg for the first 2 cycles, followed by a mandatory reduction to 25 mg BID thereafter for those participants with complete response (CR), partial response (PR) or stable disease (SD), in 28-day cycles (dose determined in Optimization Phase).
Interventions: intervention 1: Duvelisib intervention 2: Duvelisib intervention 3: Duvelisib
Intervention descriptions: intervention 1: Duvelisib PO 25 mg BID or 50 mg BID or 75 mg BID in 28-day cycles. intervention 2: Duvelisib PO 75 mg BID in 28-day cycles. intervention 3: Duvelisib PO BID in 28-day cycles (dose determined in Optimization Phase).

Protocol documents:
Prot_000.pdf: 
Secura Bio, Inc. 
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Confidential Information 
Version 7.1, 24 November 2021 
CLINICAL STUDY PROTOCOL 
Protocol No. 
VS-0145-225 
Title: 
A Multi-Center, Phase 2, Open-label, Parallel Cohort Study of Efficacy and 
Safety of Duvelisib in Patients with Relapsed or Refractory Peripheral 
T-cell Lymphoma (PTCL)
IND Number(s): 
112,486 
EudraCT Number: 2019-001123-13 
Version: 
V 7.1 
V 7.0 
V 6.1 
V 6.0 
V 5.0 
V 4.0 
V 3.0 
V 2.0 
V 1.0 
24 November 2021 
20 July 2021 
08 December 2020 
16 September 2019 
09 August 2019 
16 April 2019 
14 March 2019 
01 November 2017 
31 July 2017 
Sponsor: 
Secura Bio, Inc. 
1995 Village Center Circle 
Suite 128 
Las Vegas, NV 89134 
Tel: 
 
CONFIDENTIAL 
This document is the sole property of Secura Bio, Inc. This document and any and all 
information contained herein has to be considered and treated as strictly confidential. This 
document shall be used only for the purpose of the disclosure herein provided. No disclosure or 
publication shall be made without the prior written consent of Secura Bio, Inc. 
NCT #: NCT03372057


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Sponsor Signatory: 
I have read this protocol for Study VS-0145-225, Version 7.1 and I approve the design of this 
study:  
 
Secura Bio, Inc. 
 
Date 
 
 
 
Medical Monitor Contact Information: 
 
 
Medical Monitor contact information will be provided separately in a study contact list. 
 
30-NOV-2021


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INVESTIGATOR AGREEMENT 
Secura Bio, Inc. 
Protocol No. VS-0145-225, Version No. 7.1 
I have read Protocol VS-0145-225, A Multi-Center, Phase 2, Open-label, Parallel Cohort Study 
of Efficacy and Safety of Duvelisib in Patients with Relapsed or Refractory Peripheral T-cell 
Lymphoma (PTCL). 
I will conduct the study as detailed herein and in compliance with International Conference on 
Harmonisation Guidelines for Good Clinical Practice and applicable regulatory requirements and 
to inform all who assist me in the conduct of this study of their responsibilities and obligations. 
 
 
 
Principal Investigator 
 
Date 
Printed Name:  
 
Institution: 
 
Address: 
 
 


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PROTOCOL SYNOPSIS 
Study Title: 
A Multi-Center, Phase 2, Open-label, Parallel Cohort Study of Efficacy and Safety 
of Duvelisib in Patients with Relapsed or Refractory Peripheral T-cell Lymphoma 
(PTCL) 
Protocol 
Number: 
VS-0145-225 
Study Phase: 
Phase 2 
Investigational 
Agent: 
Duvelisib (IPI-145, VS-0145) 
Study 
Objectives: 
Dose Optimization Phase 
Primary Objective:  
 
To determine the optimal duvelisib dose for utilization in the Expansion 
Phase by evaluating the overall response rate (ORR) of duvelisib supported 
by safety, additional efficacy, and pharmacokinetic (PK) parameters as well 
as any other available data in the population of patients receiving the optimal 
dose of duvelisib for at least one cycle in patients with relapsed or refractory 
PTCL 
Secondary Objectives: 
 
To evaluate additional efficacy parameters for duvelisib in the population of 
patients receiving duvelisib for at least one cycle in patients with relapsed or 
refractory PTCL 
 
To characterize the tolerability and safety of duvelisib in patients with 
relapsed or refractory PTCL 
 
To evaluate pharmacokinetics (PK) of duvelisib and if applicable, its 
metabolite(s) 
Exploratory Objective: 
 
To evaluate pharmacodynamic and prognostic biomarkers 
Expansion Phase 
Primary Objective: 
 
To determine the efficacy of duvelisib at an optimal dose in patients with 
relapsed or refractory PTCL 
Secondary Objectives: 
 
To evaluate additional efficacy parameters for duvelisib 
 
To characterize the tolerability and safety of duvelisib in patients with 
relapsed or refractory PTCL 
 
To evaluate PK of duvelisib and if applicable, its metabolite(s) 
Exploratory Objective: 


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 
To evaluate pharmacodynamic and prognostic biomarkers 
Study 
Treatment: 
All patients will receive duvelisib orally (PO) twice daily (BID) continuously in 28-
day cycles. In the Dose Optimization phase, duvelisib will be administered at doses 
of 25 mg, 50 mg, and 75 mg BID; the duvelisib dose administered to individual 
patients is dependent on the cohort allocation as well as the patient’s response to and 
tolerance of therapy (see Study Design).  
Study Design: 
This is a multi-center, parallel cohort, open-label, Phase 2 study of duvelisib, an oral 
dual inhibitor of PI3K-δ,γ, in patients with relapsed/refractory PTCL. 
The study has 2 phases, a Dose Optimization Phase and an Expansion Phase. 
Regardless of study phase, all patients will undergo screening assessments up to 
30 days before the first study drug dose (Cycle 1, Day 1 [C1D1]). Patients meeting 
all of the entrance criteria, based on Screening assessments, will be enrolled in the 
study and receive the first study drug dose on C1D1. Thereafter, patients will attend 
study center visits as per the Schedule of Events (Table 1 or Table 2). 
At screening, disease will be measured using 18F-fluorodeoxyglucose-positron 
emission tomography (18FDG-PET)-computed tomography (CT) scanning (PET-CT) 
(CT images along with PET should be diagnostic with contrast unless 
contraindicated). Where PET-CT is not feasible, CT with contrast or magnetic 
resonance imaging (MRI) may be used after discussion with the Medical Monitor. 
Subsequently, for FDG-avid PTCL, PET-CT will be used to assess disease status, 
and for FDG-non-avid PTCL, CT with contrast or MRI will be appropriate 
substitutes. The modality chosen to evaluate response in each individual patient 
should be the same throughout the duration of the study. 
For the purposes of patient management during the conduct of the study, the 
Investigator’s assessment of disease response will be used. Images also will be 
centrally stored, and disease response will be determined by an Independent Review 
Committee (IRC) for futility and at the end of the study.  
Dose Optimization Phase 
In the Dose Optimization Phase, patients will be randomly assigned to 1 of 2 study 
cohorts, as follows: 
 
Cohort 1: Duvelisib PO BID at a starting dose of 25 mg, with potential 
escalation on a per-patient basis to 50 mg BID and then 75 mg BID, based 
on the patient’s response to and tolerance of therapy, in 28-day cycles 
 
Cohort 2: Duvelisib 75 mg PO BID, administered in 28-day cycles 
Approximately10 patients each will be enrolled in Cohorts 1 and 2. Patients in the 
Dose Optimization Phase who discontinue before receiving at least 1 cycle of study 
drug may be replaced. Enrollment into the Dose Optimization Phase may continue 
until the initiation of the Expansion Phase. 


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For both cohorts, dose modification criteria for duvelisib will be applied if the 
starting dose or a subsequent dose of duvelisib is deemed intolerable. 
Dose Optimization patients will complete treatment as defined for their cohort. 
Cohort 1 
All patients will receive duvelisib at a starting dose of 25 mg PO BID (Level 1), with 
potential sequential escalation to 50 mg PO BID (Level 2), and then to 75 mg PO 
BID (Level 3). Intra-patient dosing decisions will occur as follows: 
After completion of Cycle 1 and every 2 cycles thereafter: 
 
Patients with complete response (CR) or partial response (PR) will have 
their duvelisib dose maintained at the current dose level 
 
Patients with stable disease (SD) who are, in the Investigator’s opinion, 
tolerating and otherwise suitable to continue receiving therapy, will have the 
duvelisib dose increased to the next level until the next response assessment 
or development of progressive disease (PD) or intolerance, as determined by 
the Investigator 
Patients with PD, who are not tolerating therapy, or otherwise not suitable to 
continue receiving therapy, will discontinue duvelisib 
In no case will the duvelisib dose be increased to a level > 75 mg BID (total daily 
dose 150 mg). All patients in Cohort 1 will receive duvelisib until development of 
PD or unacceptable toxicity, as determined by the Investigator. 
Cohort 2 
All patients in Cohort 2 will receive duvelisib 75 mg PO BID in 28-day cycles until 
development of PD or unacceptable toxicity, as determined by the Investigator.  
Expansion Phase 
After a sufficient number of patients from the Dose Optimization Phase are 
evaluable, all available data will be reviewed and an optimal dose for the Expansion 
Phase will be selected. (Note: the optimal dose for the Expansion Phase has been 
selected and documented in Protocol Amendment 2 V3, 14 March 2019 – see 
Expansion Phase Dose Selection below and Section 1.3). The interim results of the 
Dose Optimization Phase may also drive changes to the Expansion Phase of the 
study, such as modification to the study patient population, other aspects of entry 
criteria, and the inclusion of patients from geographic regions outside the United 
States (US); any such changes will be documented in an amendment to the protocol. 
The Secura Bio study team, in collaboration with the Investigators, will make the 
determination of duvelisib dose for the Expansion Phase of the study based on the 
safety and activity data (see Section 1.3). Patients will have disease assessment after 
Cycle 2 and every 2 cycles thereafter until the follow-up stage is reached. All 
patients in the Expansion Phase will receive duvelisib until development of PD or 
unacceptable toxicity, as determined by the Investigator. 
Expansion Phase Dose Selection: 


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As of 02 January 2019, 20 patients met the criteria for the Dose Optimization 
efficacy population and available data as of 11 February 2019 were reviewed. A 
dosage of 75 mg BID for the first 2 cycles, followed by a mandatory reduction to 
25 mg BID thereafter for those patients with CR, PR or SD, will be used for the 
Expansion Phase. The dose may be re-escalated to 75 mg BID based on response 
assessment and safety (see Sections 1.3 and 9.1.2). 
Number of 
Patients: 
Dose Optimization Phase 
Approximately 20 patients with relapsed/refractory PTCL will be enrolled in the 
Dose Optimization Phase, with approximately 10 evaluable patients per cohort. 
Patients in the Dose Optimization Phase who discontinue before receiving at least 1 
cycle of study drug may be replaced. Enrollment into the Dose Optimization Phase 
may continue until the initiation of the Expansion Phase.  
Expansion Phase 
Approximately 100-130 patients may be enrolled, for a total of approximately 130-
160 patients across both phases.  
After the first 100 patients are enrolled in the expansion phase an additional 20-30 
patients may be enrolled with a target of 8-10 patients having an ALCL or NK cell 
subtype. 
Duration of 
Study: 
The total duration of this study is anticipated to be 3.2 years. 
Study Centers: 
The Dose Optimization Phase will be conducted at up to approximately 15 centers in 
the US. 
The Expansion Phase will be conducted at approximately 40-50 centers globally. 
Inclusion 
Criteria: 
Inclusion Criteria: 
Patients meeting all of the following criteria are eligible for study participation: 
1. ≥ 18 years of age 
2. Pathologically-confirmed PTCL, as defined by the World Health 
Organization. Slides must be submitted for central pathology review. Results 
of central pathology review are not required prior to initiation of treatment. 
3. Received at least 2 cycles of one standard regimen for newly diagnosed 
advanced PTCL, and one of the following:  
(a) failed to achieve at least a partial response after 2 or more cycles of 
standard therapy; 
(b) failed to achieve a complete response after completion of standard 
therapy; and/or 
(c) persistent or progressive disease after an initial response 
4. For patients with CD30+ anaplastic large cell lymphoma (ALCL), failed or 
are ineligible or intolerant to brentuximab vedotin 


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5. Measurable disease as defined by Lugano (Cheson et al, 2014) for PTCL, 
i.e., at least 1 measurable disease lesion > 1.5 cm in at least one dimension 
by conventional techniques (18FDG-PET-CT, CT with contrast, MRI) 
6. Must have the following laboratory parameters: 
 
Hemoglobin ≥ 8.0 g/dL with or without transfusion support 
 
Platelet count ≥ 25 × 109/L 
 
Serum creatinine ≤ 2.0 × the upper limit of normal (ULN) 
 
Total bilirubin ≤ 1.5 × ULN (in patients with Gilbert's Syndrome a 
bilirubin > 1.5 × ULN may be allowed) 
 
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
≤ 3.0 × ULN 
 
Expansion Phase Only: CD4 lymphocyte count ≥ 50/mm3 (0.05 x 109/L) 
7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 
8. Recovery to ≤ Grade 1 or baseline for any toxicities due to prior treatments, 
with the exception of peripheral neuropathy (recovery to ≤ Grade 2) or 
alopecia 
9. Washout of at least 14 days or 5 half-lives, whichever is longer, from PTCL-
directed therapy. If previously treated with lenalidomide, must have 
completed treatment 4 weeks prior to C1D1. 
10. For women of childbearing potential (WCBP): negative serum β-human 
chorionic gonadotropin (β-hCG) pregnancy test within 1 week before first 
treatment (WCBP defined as a sexually mature woman who has not 
undergone surgical sterilization or who has not been naturally post-
menopausal for at least 12 consecutive months for women > 55 years of age) 
11. Male and female patients of reproductive potential (i.e., not surgically sterile 
or female patients who are not postmenopausal) must be willing to use a 
highly effective method of contraception for the duration of study treatment 
and for at least 3 months after the last dose of duvelisib 
12. Signed and dated institutional review board (IRB)/independent ethics 
committee (IEC)/central ethics committee (CEC)-approved informed 
consent form before any Screening procedures are performed 


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Exclusion 
Criteria: 
Exclusion Criteria: 
Patients meeting any of the following criteria are not eligible for study participation:  
1. Primary leukemic PTCL subtypes (i.e., T-cell prolymphocytic leukemia, T-
cell large granular lymphocytic leukemia, adult T-cell leukemia/lymphoma 
and aggressive NK-cell leukemia) or transformed mycosis fungoides  
2. Received prior allogeneic transplant  
3. Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor 
4. Major surgery within 4 weeks prior to Screening 
5. Known central nervous system involvement by PTCL 
6. Infection with hepatitis B, hepatitis C, human immunodeficiency virus 
(HIV) or human T-lymphotropic virus type 1. (Patients with a positive 
hepatitis B surface antigen [HBsAg] or hepatitis C antibody [HCVAb] will 
be excluded. Patients with a positive hepatitis B core antibody [HBcAb] 
must have negative hepatitis B virus [HBV] deoxyribonucleic acid (DNA) to 
be eligible, must receive prophylaxis with entecavir [or equivalent] 
concomitant with duvelisib treatment, and must be periodically monitored 
for HBV reactivation by institutional guidelines. Investigators who strongly 
believe that a positive HBcAb is false due to passive immunization from 
previous immunoglobulin infusion therapy should discuss the potential to 
defer HBV prophylaxis with the Medical Monitor.) 
7. Active cytomegalovirus (CMV) infection (patients with detectable viral 
load) 
8. History of tuberculosis treatment within 2 years prior to C1D1 
9. History of chronic liver disease, veno-occlusive disease, or alcohol abuse 
10. Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or 
systemic steroids > 20 mg of prednisone (or equivalent) once daily (QD) 
11. Ongoing treatment for systemic bacterial, fungal, or viral infection at 
Screening  
NOTE: Patients on antimicrobial, antifungal, or antiviral prophylaxis are not 
specifically excluded if all other inclusion/exclusion criteria are met 
12. Administration of a live vaccine within 6 weeks of C1D1 
13. Concurrent administration of medications or foods that are strong inhibitors 
or inducers of cytochrome P450 3A (CYP3A) 
14. Unable to receive prophylactic treatment for pneumocystis at Screening 
15. Baseline left ventricular ejection fraction (LVEF) < 50% (or below 
institution’s normal limit) 
16. Baseline QT interval corrected with Fridericia’s method (QTcF) >480 ms  


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NOTE: criterion does not apply to patients with a right or left bundle branch 
block 
17. Prior surgery or condition with gastrointestinal dysfunction that may 
significantly affect drug absorption (e.g., gastric bypass surgery, 
gastrectomy, etc., see Section 5.2) 
18. If female, pregnant or breastfeeding 
19. Concurrent active malignancy other than nonmelanoma skin cancer, 
carcinoma in situ of the cervix 
NOTE: Patients with previous malignancies are eligible if disease-free for >2 
years. 
20. History of stroke, unstable angina, myocardial infarction, or ventricular 
arrhythmia requiring medication or a pacemaker within the last 6 months 
prior to Screening 
21. Unstable or severe uncontrolled medical condition (e.g., unstable cardiac 
function, unstable pulmonary condition, uncontrolled diabetes) or any 
important medical illness or abnormal laboratory finding that would, in the 
Investigator’s judgment, increase the risk to the patient associated with his 
or her participation in the study 
22. Known hypersensitivity to duvelisib and/or its excipients 
Study 
Endpoints: 
Primary Endpoint(s): 
Dose Optimization Phase 
 
Objective response rate (ORR [CR + PR]), as assessed by the Investigator, 
as determined using the Lugano criteria (Cheson et al, 2014) supported by 
secondary efficacy, safety and PK parameters 
Expansion Phase 
 
ORR (CR + PR), according to Lugano criteria (Cheson et al, 2014) as 
assessed by IRC 
Secondary Endpoints 
Dose Optimization Phase and Expansion Phase 
 
DOR, for those patients with CR or PR, defined as the time from the first 
documentation of response to the first documentation of PD, or death due to 
any cause 
 
Treatment-emergent adverse events (TEAEs) and changes in laboratory 
values 
 
PFS, defined as the time from the first study drug dose to the first 
documentation of PD, or death from any cause 
 
Disease control rate (DCR), defined as CR + PR + stable disease ≥ 8 weeks 
 
Overall survival (OS) 


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 
PK parameters derived from blood concentrations of duvelisib and its 
metabolites 
Exploratory Endpoints: 
Dose Optimization and Expansion Phases 
 
Analysis of PTCL tumor pharmacodynamic markers 
 
Analysis of PTCL tumor prognostic markers 
 
Analysis of cytokines and non-tumor immune populations 
NOTE: Additional exploratory analyses identified by the Sponsor may be 
performed on study samples 
Statistical 
Methodology: 
Dose Optimization Phase:  
Sample Size Considerations: 
This phase of the study will enroll approximately 20 evaluable patients. However, 
enrollment may discontinue in either cohort if no CR/PR is noted in the first 5 
evaluable patients per cohort. This stopping rule is based on the first stage decision 
rule of a Simon 2-stage design, with assumptions of a hypothesized ORR of 50% 
and a null rate of 15% with a one-sided alpha of 0.05 and a power of 85%. 
Response Assessment: 
The Investigator’s determination of response to study treatment will be used in 
primary and secondary efficacy analyses. The IRC’s determination of disease 
response will be used in supportive efficacy analyses. For both the IRC and 
Investigator response determinations, response will not require confirmation by 
second assessment. 
Analysis Sets: 
The Dose Optimization Efficacy Set will include patients who 1) receive at least one 
dose of study drug and 2) complete at least one cycle of treatment and 3) have at 
least one scan to assess disease response after completion of one cycle of treatment. 
The Modified Intent-to-Treat (mITT) Set will include patients who receive at least 
one dose of study drug. 
Efficacy Analyses: 
The Dose Optimization Efficacy Set will be used for all primary and secondary 
efficacy analyses. 
Statistical analyses of safety and response will be primarily descriptive in nature. 
Summary statistics will be produced by dose level, patients with dose changes and 
for the overall study population for both safety and biological effect parameters. At 
the conclusion of the Dose Optimization Phase, activity, PK, and safety data as well 
as any other available data will be taken into consideration to recommend the 
optimal dose for the Expansion Phase. 
Expansion Phase:  


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Sample Size Considerations: One-hundred patients at the optimal duvelisib dose will 
provide 99.2% power to distinguish between a null ORR of 20% and an alternative 
ORR of 40% with a two-sided alpha of 0.05. The obtained ORR will have 95% 
confidence bounds of no greater than ± 10% when the normal approximation method 
is employed (assumes 50% ORR). If the observed ORR is greater or less than 50%, 
the confidence bounds will be less than ± 10%. These bounds around the obtained 
ORR are thought to adequately characterize the effect of the optimal dose of 
duvelisib in this PTCL population. 
With protocol amendment 7.0, 20-30 additional patients will be enrolled in the 
Expansion Phase.  Assuming a total of 120 or 130 patients the power to distinguish 
between a null hypothesis of ORR of 20% and an alternative ORR of 40% will be 
99.4% or 99.6% respectively.   
The primary analysis for the Expansion Phase will be performed once approximately 
100 patients with a centrally confirmed diagnosis of PTCL have been enrolled and 
evaluated for the primary endpoint. In the event that enrollment in the expansion 
phase exceeds 110% of the planned sample size, a sensitivity analysis will be 
performed on the first 100 patients enrolled in the Expansion Phase. 
The final analysis for the Expansion phase will be performed once all patients 
with a centrally confirmed diagnosis of PTCL have been enrolled and 
evaluated for the primary endpoint. The total number of patients (up to 130) 
will be determined by the Sponsor. An important driver of the final sample 
size may be the number of additional patients needed to add an additional 8-
10 patients having PTCL subtype of either ALCL or NK cell. 
Response Assessment: 
The IRC’s determination of response to study treatment will be used in primary and 
secondary efficacy analyses. Investigator’s determination of disease response will be 
used in supportive efficacy analyses. For both the IRC and Investigator response 
determinations, response will not require confirmation by second assessment. 
Analysis Set: 
The mITT Set will include patients who receive at least one dose of study drug. 
Efficacy Analysis:  
Efficacy analyses will be performed using the mITT population for all primary and 
secondary efficacy analyses using the response determined by the IRC.  
An assessment of ORR will be conducted after 40 patients from the Expansion Phase 
have been followed for a minimum of 4 months from the last patient’s first dose. 
Enrollment in the Expansion Phase may be held if ORR as assessed by IRC, is less 
than 20%. At that time, the efficacy data (including durability of response) will be 
reviewed in combination with safety and PK and upon review, the study may be 
fully stopped for futility.  


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Figure 1 
Study Overview 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: BID: twice daily; CR: complete response; DLT: dose-limiting toxicity; DOR: duration of response; DCR: disease control rate; N: number; ORR: 
overall response rate; OS: overall survival; PD: progressive disease; PFS: progression-free survival; PK: pharmacokinetic; PR: partial response; SD: stable 
disease 
The study is being conducted in two phases, with the Dose Optimization Phase (DOP) used to identify a dose for further evaluation in the Expansion Phase. The 
DOP has been completed and 75 mg BID with a mandatory dose reduction after 2 cycles to 25 mg BID was selected for the Expansion Phase. The primary 
overall response rate (ORR) endpoint will be assessed according to the Lugano criteria (Cheson et al, 2014). ORR in the DOP was based on investigator 
assessment, while ORR in the Expansion Phase will be determined by an Independent Review Committee. 
 


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Table 1: 
Dose Optimization Phase Schedule of Events 
Procedure1 
Screen-
ing 
D-30 
to -12 
Cycle / Day 
End of 
Treat-
ment 
(EOT)5 
Safety 
Follow-
up 
PD 
Follow-
Up6 
Survival 
Follow-
up7 
Cycle 1 
Cycle 2 
Cycle 4 
and then 
every 2 
cycles4 
D12,3 
D8 ± 3 
D15 ± 3 
D1 ± 3 
D15 ± 3 
D1 ± 4 
≤ 7 d 
from last 
dose 
30 + 7 d 
from last 
dose 
Q2M 
(± 1M) 
Q3M 
(± 1M) 
Provision of written informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical History, including 
cancer history 
X 
 
 
 
 
 
 
 
 
 
 
12-lead electrocardiogram 
X 
 
 
 
 
 
 
 
 
 
 
Echocardiogram 
X 
 
 
 
 
 
 
 
 
 
 
Complete physical examination 
X 
 
 
 
 
 
 
X 
 
 
 
Targeted physical examination 
 
X 
 
 
X 
 
X 
 
X 
See  
Table 3  
 
Vital signs8 
X 
X 
 
 
X 
 
X 
X 
X 
 
 
Screening serology9 
X 
 
 
 
 
 
 
 
 
 
 
Blood chemistry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Hematology 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
β-hCG pregnancy test10 
X 
X 
 
 
X 
 
X 
X 
X 
 
 
Serum Immunoglobulins  
X 
X 
 
 
 
 
X 
X 
 
 
 
Tumor tissue 
X11 
 
 
 
 
 
 
 
 
 
 
Blood for pharmacodynamic 
assessment 
 
X12 
 
 
X12 
X12 
 
 
 
 
 


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Procedure1 
Screen-
ing 
D-30 
to -12 
Cycle / Day 
End of 
Treat-
ment 
(EOT)5 
Safety 
Follow-
up 
PD 
Follow-
Up6 
Survival 
Follow-
up7 
Cycle 1 
Cycle 2 
Cycle 4 
and then 
every 2 
cycles4 
D12,3 
D8 ± 3 
D15 ± 3 
D1 ± 3 
D15 ± 3 
D1 ± 4 
≤ 7 d 
from last 
dose 
30 + 7 d 
from last 
dose 
Q2M 
(± 1M) 
Q3M 
(± 1M) 
Blood for pharmacokinetic 
assessment 
See Table 5 
Blood for exploratory 
biomarkers13 
X 
X 
 
 
X 
 
X 
 
 
X 
 
Response Assessments  
See Table 3 
ECOG Performance Status 
Concomitant medications & 
Procedures  
All concomitant medications and procedures are to be documented from 30 days before the Screening visit 
through 30 days after the last study drug dose 
X 
 
AE/SAE assessment 
All AEs are to be documented the time written informed consent is provided through 30 days after the last study 
drug dose  
 
 
Study Drug Administration 
 
Duvelisib is to be administered PO BID continuously in 28-day cycles 
 
 
 
 
Survival status 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviations: AE = adverse event; BID = twice daily; CMV = cytomegalovirus; d = day; D = Study Day; ECOG = Eastern Cooperative Oncology Group; EOT = End-of-
Treatment; HIV = human immunodeficiency virus; HTLV-1 = human T-lymphotropic virus type 1; M = month; PD = progressive disease; PO = orally; Q2M = every 2 months; 
SAE = serious adverse event; β-hCG = β-human chorionic gonadotropin. 
1. See Section 6 for additional information on each assessment. 
2. Screening evaluations other than clinical laboratory tests performed within 7 days of C1D1 do not need to be repeated at C1D1 (predose). C1D1 laboratory 
tests do not need to be repeated if performed within 72 hours prior to Screening. 
3. All laboratory samples on C1D1 should be collected predose. 
4. Additional visits may be scheduled / procedures may be performed at the Investigator’s discretion, as clinically indicated. 
5. The End-of-Treatment (EOT) visit is to be performed within 7 days after the last study drug dose. If safety assessments were performed within the previous 
2 weeks, they need not be performed at the EOT visit. If disease response assessments were performed within the previous 4 weeks, they need not be 
performed at the EOT visit. 
6. Patients who discontinue treatment from duvelisib for reasons other than PD are to have disease response assessments performed Q2M per Table 3 until the 
development of PD, as determined by the Investigator, death, or initiation of alternate anti-cancer therapy.  
7. After development of PD, as determined by the Investigator, patients are to be followed Q3M for survival; this follow-up may be conducted via telephone. 
8. Vital signs, including temperature, blood pressure, and heart rate, are to be measured only if clinically indicated. 


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9. Screening serology includes assessment of CMV serologies and a liver serology panel. HIV and HTLV-1 tests are to be performed during Screening for all 
patients without documentation of prior negative results (see Section 6.10.1 for details). 
10. Urine or serum β-human chorionic gonadotropin pregnancy testing is to be performed for women of childbearing potential. Pregnancy testing is to be 
repeated as deemed necessary by the Investigator. 
11. Tumor biopsy from Screening or archival tumor tissue will be collected to evaluate prognostic markers. In the event a bone marrow biopsy is collected at 
Screening please provide a sample. 
12. Blood collected at C1D1 (predose), C1D1 (1 hour postdose), C1D1 (4 hour postdose), C2D1 (predose), C2D15 (1 hour), C2D15 (4 hour) (Cohort 1, for 
patients receiving 50 mg on C2D15) and sent to the central laboratory.  
13. To be sent to the central laboratory. Blood collected at predose on C1D1, C2D1, C4D1, and predose every 2 cycles thereafter. 
 
 
 


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Table 2: 
Expansion Phase Schedule of Events 
Procedure1 
Screen-
ing 
D-30 
to -12 
 
Cycle / Day 
End of 
Treat-
ment 
(EOT)5 
Safety 
Follow-
up 
PD 
Follow-
Up6 
Survival 
Follow-
up7 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
and then 
every 2 
cycles 
(WCBP only)13 
Cycle 5 
and then 
every 2 
cycles4 
D12,3 
D8 ± 3 
D15 ± 3 
D1 ± 3 
D15 ± 3 
D1 ± 3 
 
D1 ± 4 
≤ 7 d 
from 
last dose 
30 + 7 d 
from 
last dose 
Q2M 
(± 1M) 
Q3M 
(± 1M) 
Provision of written informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History, including 
cancer history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Archival Slides, initial 
pathological diagnosis 
X8 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead electrocardiogram9 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Echocardiogram10 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
examination 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
Targeted physical examination 
 
X 
 
 
X 
 
X 
 
X 
 
X 
See 
Table 4 
 
Vital signs11 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
Screening serology12 
X 
 
 
 
 
 
 
 
 
 
 
 
 
CD4 lymphocyte cell count 
(local laboratory) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Blood chemistry 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
Hematology 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
β-hCG pregnancy test13 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
 
 


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Procedure1 
Screen-
ing 
D-30 
to -12 
 
Cycle / Day 
End of 
Treat-
ment 
(EOT)5 
Safety 
Follow-
up 
PD 
Follow-
Up6 
Survival 
Follow-
up7 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
and then 
every 2 
cycles 
(WCBP only)13 
Cycle 5 
and then 
every 2 
cycles4 
D12,3 
D8 ± 3 
D15 ± 3 
D1 ± 3 
D15 ± 3 
D1 ± 3 
 
D1 ± 4 
≤ 7 d 
from 
last dose 
30 + 7 d 
from 
last dose 
Q2M 
(± 1M) 
Q3M 
(± 1M) 
Serum Immunoglobulins  
X 
X 
 
 
 
 
X 
 
X 
X 
 
 
 
Tumor tissue 
X14 
 
 
 
 
 
 
 
 
 
 
 
 
Blood for pharmacodynamic 
assessment 
 
X15 
 
 
 
X15 
 
 
 
 
 
 
 
Blood for pharmacokinetic 
assessment 
 
 
See Table 5 
Blood for exploratory 
biomarkers16 
X 
X 
 
 
X 
 
X 
 
X 
 
 
X 
 
Response Assessments  
 
 
See Table 4 
ECOG Performance Status 
 
 
Concomitant medications & 
Procedures  
 
 
All concomitant medications and procedures are to be documented from 30 days before the Screening 
visit through 30 days after the last study drug dose 
X 
 
AE/SAE assessment 
 
 
All AEs are to be documented at the time written informed consent is provided through 30 days after the 
last study drug dose  
 
 
Study Drug Administration 
 
 
 
Duvelisib is to be administered PO BID continuously in 28-day cycles 
 
 
 
 
Survival status 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviations: AE = adverse event; BID = twice daily; CMV = cytomegalovirus; d = day; D = Study Day; ECOG = Eastern Cooperative Oncology Group; EOT = End-of-
Treatment; HIV = human immunodeficiency virus; HTLV-1 = human T-lymphotropic virus type 1; M = month; PD = progressive disease; PO = orally; Q2M = every 2 months; 
SAE = serious adverse event; β-hCG = β-human chorionic gonadotropin.  
1. See Section 6 for additional information on each assessment.  
2. Screening evaluations other than clinical laboratory tests performed within 7 days of C1D1 do not need to be repeated at C1D1 (predose). C1D1 laboratory 
tests do not need to be repeated if performed within 72 hours prior to Screening. 
3. All laboratory samples on C1D1 should be collected predose. 
4. Additional visits may be scheduled / procedures may be performed at the Investigator’s discretion, as clinically indicated. 


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5. The End-of-Treatment (EOT) visit is to be performed within 7 days after the last study drug dose. If safety assessments were performed within the previous 
2 weeks, they need not be performed at the EOT visit. If disease response assessments were performed within the previous 4 weeks, they need not be 
performed at the EOT visit. 
6. Patients who discontinue treatment from duvelisib for reasons other than PD are to have disease response assessments performed Q2M per Table 4 until the 
development of PD, as determined by the Investigator, death, or initiation of alternate anti-cancer therapy. 
7. After development of PD, as determined by the Investigator, patients are to be followed Q3M for survival; this follow-up may be conducted via telephone. 
8. Stained Formalin-fixed, paraffin-embedded (FFPE) slides used for PTCL diagnosis must be collected for all patients enrolled and submitted for central 
pathology review. See lab manual for details. 
9. Additional on-treatment or follow-up electrocardiograms should be performed at the Investigator’s discretion as clinically indicated. 
10. Additional on-treatment or follow-up echocardiograms should be performed at the Investigator’s discretion as clinically indicated. 
11. Vital signs, including temperature, blood pressure, pulse, and respiration rate, and weight (kg) are to be measured. Height (cm) to be measured only at 
Screening.  
12. Screening serology includes assessment of CMV serologies and a liver serology panel. HIV and HTLV-1 tests are to be performed during Screening for all 
patients without documentation of prior negative results (see Section 6.10.1 for details). 
13. Urine or serum β-human chorionic gonadotropin pregnancy testing is to be performed for women of childbearing potential. Pregnancy testing is to 
performed monthly and may be repeated as deemed necessary by the Investigator. For cycles where pregnancy testing is the only requirement, the patient 
may have this done locally. 
14. Tumor biopsy from Screening or archival tumor tissue will be collected to evaluate prognostic markers. In the event a bone marrow biopsy is collected at 
Screening please provide a sample. 
15. Blood collected at C1D1 (predose), C1D1 (1 hour postdose), C1D1 (4 hour postdose), C2D15 (predose), C2D15 (1 hour), C2D15 (4 hour) and sent to the 
central laboratory. The collection of PD samples will occur for patients in the US only. 
16. To be sent to the central laboratory. Blood collected at predose on C1D1, C2D1, C3D1, and predose every 2 cycles thereafter up to Cycle 11. 
 


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Table 3: 
Dose Optimization Phase Disease Response and Follow-up Assessments 
Procedure1 
Screening
D-30 to -1 
Cycle / Day 
End of 
Treatment 
(EOT)3 
PD 
Follow-
up4 
Survival 
Follow-
up5 
Cycle 1 
Cycle 2 
Cycle 4 
and then 
every 2 
cycles 2 
D1 
D8 ± 3 
D15 ± 3 
D1 ± 3 
D15 ± 3 
D1 ± 4 
≤ 7 d from 
last dose 
Q2M 
(± 1M) 
Q3M 
(± 1M) 
PET-CT or CT or MRI6 
X7 
 
 
 
X8 
 
X 
X 
X 
 
ECOG performance status 
X 
 
 
 
 
 
X 
X 
X 
 
Survival status 
 
 
 
 
 
 
 
 
 
X 
Abbreviations: C = cycle; CT = d = day; D = Study Day; ECOG = Eastern Cooperative Oncology Group; EOT = End-of-Treatment; FDG = fluorodeoxyglucose ; IRC = 
independent review committee; M = month; MRI = magnetic resonance imaging; PD = progressive disease; PET = positron emission tomography; PTCL = peripheral T-cell 
lymphoma; Q2M = every 2 months.  
1. See Section 6.11 for additional information on disease response assessments.  
2. Additional visits may be scheduled / procedures may be performed at the Investigator’s discretion, as clinically indicated. 
3. The EOT visit is to be performed within 7 days after the last study drug dose.  
4. Patients who discontinue treatment from duvelisib for reasons other than PD are to have disease response assessments performed Q2M until the development 
of PD, as determined by the Investigator, death, or initiation of alternate anti-cancer therapy.  
5. After development of PD, as determined by the Investigator, patients are to be followed Q3M for survival until closure of the study by the Sponsor; this 
follow-up may be conducted via telephone. 
6. PET-CT is the preferred method of assessment. The modality chosen to evaluate response in each individual patient should be the same throughout the 
duration of the study. PET images are to be assessed using the 5-point scale (5PS). At each scheduled timepoint, the Investigator will be asked to provide a 
PET-CT-based response, based on the Lugano (Cheson et al, 2014) response criteria. Images will be centrally stored and read, with disease response 
determined by the IRC using the central image assessments. 
7. To be performed within 14 days before C1D1. At Screening, disease will be assessed with PET-CT. Where PET-CT is not feasible, CT with contrast or MRI 
may be used after discussion with the Medical Monitor. Subsequently, for FDG-avid PTCL, PET-CT will be used to assess disease status and for FDG-non-
avid PTCL, CT with contrast or MRI will be appropriate substitutes. 
8. To be performed within 7 days prior to starting Cycle 2. 
 


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Table 4: 
Expansion Phase Disease Response and Follow-up Assessments 
Procedure1 
Screening
D-30 to -1 
Cycle / Day 
End of 
Treatment 
(EOT)3 
PD 
Follow-
up4 
Survival 
Follow-
up5 
Cycle 1 
Cycle 3 
Cycle 5 
and then 
every 2 
cycles 2 
D1 
D8 ± 3 
D15 ± 3 
D1 ± 3 
D15 ± 3 
D1 ± 4 
≤ 7 d from 
last dose 
Q2M 
(± 1M) 
Q3M 
(± 1M) 
PET-CT or CT or MRI6 
X7 
 
 
 
X8 
 
X 
X 
X 
 
ECOG performance status 
X 
 
 
 
 
 
X 
X 
X 
 
Survival status 
 
 
 
 
 
 
 
 
 
X 
Abbreviations: C = cycle; CT = d = day; D = Study Day; ECOG = Eastern Cooperative Oncology Group; EOT = End-of-Treatment; FDG = fluorodeoxyglucose ; IRC = 
independent review committee; M = month; MRI = magnetic resonance imaging; PD = progressive disease; PET = positron emission tomography; PTCL = peripheral T-cell 
lymphoma; Q2M = every 2 months.  
1. See Section 6.11 for additional information on disease response assessments. 
2. Additional visits may be scheduled / procedures may be performed at the Investigator’s discretion, as clinically indicated. 
3. The EOT visit is to be performed within 7 days after the last study drug dose. 
4. Patients who discontinue treatment from duvelisib for reasons other than PD are to have disease response assessments performed Q2M until the development 
of PD, as determined by the Investigator, death, or initiation of alternate anti-cancer therapy. 
5. After development of PD, as determined by the Investigator, patients are to be followed Q3M for survival until closure of the study by the Sponsor; this 
follow-up may be conducted via telephone. 
6. PET-CT is the preferred method of assessment. The modality chosen to evaluate response in each individual patient should be the same throughout the 
duration of the study. PET images are to be assessed using the 5-point scale (5PS). At each scheduled timepoint, the Investigator will be asked to provide a 
PET-CT-based response, based on the Lugano (Cheson et al, 2014) response criteria. Images will be centrally stored and read, with disease response 
determined by the IRC using the central image assessments. 
7. To be performed within 14 days before C1D1. At Screening, disease will be assessed with PET-CT. Where PET-CT is not feasible, CT with contrast or MRI 
may be used after discussion with the Medical Monitor. Subsequently, for FDG-avid PTCL, PET-CT will be used to assess disease status and for FDG-non-
avid PTCL, CT with contrast or MRI will be appropriate substitutes. 
8. To be performed within 7 days prior to starting Cycle 3.  
 


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Table 5: 
Dose Optimization and Expansion Phase Pharmacokinetic Assessment 
Procedure1 
Cycle / Day 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 5 
D1 
D8 ± 3 
D15 ± 3 
D1 ± 3 
D15 ± 3 
D1 ± 3 
D1 ± 4 
Dose Optimization Phase2 
X3 
X4 
X3 
X4 
X5 
Expansion Phase2 
X6 
X6 
X4
X4 
Abbreviations: AE = adverse event; BID = twice daily; PK = pharmacokinetic. 
1.
On the PK sampling days, duvelisib will be administered in clinic in the morning after predose PK sampling.
2.
An additional blood sample(s) for PK is requested at the start and end of any drug interruptions for an AE, when feasible.
3.
PK blood samples will be collected from all patients on C1D1 and C1D15 at predose (within 30 minutes prior to the morning dosing) and 0.5, 1, 1.5, 2, 3, 4,
and 6 hours postdose.
4.
Predose sample is drawn within 30-minutes prior to the morning dosing.
5.
PK blood samples will be collected only from patients receiving 50 mg BID on C2D15 at predose (within 30 minutes prior to the morning dosing) and 0.5, 1,
1.5, 2, 3, 4, and 6 hours postdose.
6.
PK blood samples will be collected from all patients on C1D15 and C2D15 at predose (within 30 minutes prior to the morning dosing) and 1, 2, and 4 hours
postdose.


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TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ..................................................................................................1 
INVESTIGATOR AGREEMENT...................................................................................................3 
PROTOCOL SYNOPSIS ................................................................................................................4 
TABLE OF CONTENTS ...............................................................................................................23 
LIST OF TABLES .........................................................................................................................27 
LIST OF FIGURES .......................................................................................................................28 
LIST OF ABBREVIATIONS ........................................................................................................29 
1. 
BACKGROUND AND STUDY RATIONALE ........................................................32 
1.1. 
Peripheral T-cell Lymphoma ......................................................................................32 
1.2. 
Duvelisib (IPI-145; VS-0145) ....................................................................................32 
1.3. 
Study Rationale ...........................................................................................................33 
1.4. 
Benefit/Risk Assessment ............................................................................................35 
2. 
STUDY OBJECTIVES ..............................................................................................36 
2.1. 
Dose Optimization Phase ............................................................................................36 
2.1.1. 
Primary Objective .......................................................................................................36 
2.1.2. 
Secondary Objectives .................................................................................................36 
2.1.3. 
Exploratory Objective .................................................................................................36 
2.2. 
Expansion Phase .........................................................................................................36 
2.2.1. 
Primary Objective .......................................................................................................36 
2.2.2. 
Secondary Objectives .................................................................................................37 
2.2.3. 
Exploratory Objective .................................................................................................37 
3. 
STUDY ENDPOINTS ................................................................................................38 
3.1. 
Dose Optimization Phase ............................................................................................38 
3.1.1. 
Primary Endpoint ........................................................................................................38 
3.1.2. 
Secondary Endpoints ..................................................................................................38 
3.1.3. 
Exploratory Endpoints ................................................................................................38 
3.2. 
Expansion Phase .........................................................................................................39 
3.2.1. 
Primary Endpoint ........................................................................................................39 
3.2.2. 
Secondary Endpoints ..................................................................................................39 
3.2.3. 
Exploratory Endpoints ................................................................................................39 
4. 
STUDY DESIGN .......................................................................................................40 


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4.1. 
Overview of Study Design ..........................................................................................40 
4.1.1. 
Dose Optimization Phase ............................................................................................40 
4.1.2. 
Expansion Phase .........................................................................................................41 
4.1.3. 
Independent Review Committee .................................................................................42 
4.2. 
Number of Patients .....................................................................................................42 
4.3. 
Duration of Patient Participation ................................................................................42 
5. 
STUDY POPULATION .............................................................................................44 
5.1. 
Inclusion Criteria ........................................................................................................44 
5.2. 
Exclusion Criteria .......................................................................................................45 
6. 
STUDY CONDUCT ...................................................................................................48 
6.1. 
Study Procedures ........................................................................................................48 
6.2. 
Informed Consent .......................................................................................................48 
6.3. 
Inclusion and Exclusion Criteria ................................................................................48 
6.4. 
Medical and Medication History ................................................................................48 
6.4.1. 
Disease Confirmation by Central Pathology Review .................................................48 
6.5. 
Demography ...............................................................................................................48 
6.6. 
Physical Examination .................................................................................................49 
6.7. 
Electrocardiogram .......................................................................................................49 
6.8. 
Echocardiogram ..........................................................................................................49 
6.9. 
Vital Signs, Height and Weight ..................................................................................49 
6.10. 
Clinical Laboratory Tests ...........................................................................................49 
6.10.1. 
Screening Serology .....................................................................................................49 
6.10.2. 
Pregnancy Test ............................................................................................................50 
6.10.3. 
Clinical Laboratory Tests ...........................................................................................50 
6.11. 
Disease and Response Assessment .............................................................................51 
6.11.1. 
ECOG Performance Status .........................................................................................54 
6.12. 
Pharmacokinetic Assessment ......................................................................................54 
6.13. 
Exploratory Biomarkers ..............................................................................................54 
6.14. 
Unscheduled Visits .....................................................................................................55 
7. 
COMPLETION OF TREATMENT ...........................................................................56 
7.1. 
Completion of Study ...................................................................................................56 
7.2. 
Concomitant Medications ...........................................................................................56 
7.3. 
Adverse Events ...........................................................................................................56 


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8. 
DISCONTINUATION CRITERIA ............................................................................57 
8.1. 
Withdrawal of Individual Patients from Study Drug ..................................................57 
8.2. 
Withdrawal of Individual Patients from the Study .....................................................57 
8.3. 
Early Discontinuation of the Study.............................................................................58 
8.4. 
End of Study Definition ..............................................................................................58 
9. 
STUDY DRUG REGIMEN .......................................................................................59 
9.1. 
Dosing and Administration of Study Drug .................................................................59 
9.1.1. 
Dose Optimization Phase ............................................................................................59 
9.1.2. 
Expansion Phase .........................................................................................................60 
9.2. 
Description ..................................................................................................................60 
9.3. 
Packaging and Labeling ..............................................................................................60 
9.3.1. 
Dispensing and Storage Instructions ..........................................................................61 
9.3.2. 
Drug Accountability ...................................................................................................61 
9.4. 
Toxicity Management .................................................................................................61 
9.4.1. 
Toxicity Grading Criteria ...........................................................................................61 
9.4.2. 
Dose Modifications and Discontinuation ...................................................................61 
9.5. 
Permitted Concomitant Medications and Procedures .................................................65 
9.5.1. 
Antimicrobial Prophylaxis ..........................................................................................65 
9.5.2. 
Transfusion and Growth Factor Support (Prophylaxis or Supportive Care) ..............66 
9.5.3. 
Contraception and Pregnancy .....................................................................................66 
9.6. 
Excluded Concomitant Medications and Procedures .................................................66 
9.6.1. 
Vaccines ......................................................................................................................66 
9.6.2. 
Immunosuppressants ...................................................................................................67 
9.6.3. 
Other Anticancer Therapy or Investigational Agents .................................................67 
9.6.4. 
Medications or Food that Inhibit or Induce CYP3A ..................................................67 
9.7. 
Concomitant Medications to be Used with Caution ...................................................67 
9.7.1. 
Medications that are Substrates of CYP3A or CYP2C8 ............................................67 
9.7.2. 
Medications that are Substrates or Inhibitors of P-glycoprotein ................................68 
9.8. 
Other Concomitant Therapies .....................................................................................68 
9.8.1. 
Photo Safety ................................................................................................................68 
9.9. 
Blinding and Unblinding ............................................................................................68 
9.10. 
Treatment Compliance ................................................................................................69 
10. 
ADVERSE EVENT MANAGEMENT ......................................................................70 


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10.1. 
Definition of an Adverse Event ..................................................................................70 
10.2. 
Definition of a Serious Adverse Event .......................................................................70 
10.3. 
Reporting of Adverse Events and Serious Adverse Events ........................................71 
10.4. 
Severity of Adverse Events ........................................................................................72 
10.5. 
Relationship of Adverse Events to Study Drug ..........................................................73 
10.6. 
Clinical Laboratory Adverse Events ...........................................................................73 
10.7. 
Regulatory Aspects of Adverse Event Reporting .......................................................74 
10.8. 
Overdose .....................................................................................................................74 
10.9. 
Pregnancy ...................................................................................................................74 
11. 
STATISTICAL METHODS .......................................................................................76 
11.1. 
Statistical Analysis Plan .............................................................................................76 
11.2. 
Determination of Sample Size ....................................................................................76 
11.3. 
Randomization and Stratification ...............................................................................77 
11.4. 
Populations for Analysis .............................................................................................77 
11.5. 
Procedures for Handling Missing, Unused, and Spurious Data .................................78 
11.6. 
Patient Disposition ......................................................................................................78 
11.7. 
Demographic and Baseline Characteristics ................................................................78 
11.8. 
Exposure .....................................................................................................................78 
11.9. 
Efficacy Analyses .......................................................................................................78 
11.10. 
Safety Analyses ..........................................................................................................79 
11.11. 
Pharmacodynamic and Biomarker Data .....................................................................80 
11.12. 
Pharmacokinetic Data .................................................................................................80 
11.13. 
Interim Analyses .........................................................................................................80 
12. 
ADMINISTRATIVE REQUIREMENTS ..................................................................82 
12.1. 
Good Clinical Practice ................................................................................................82 
12.2. 
Ethical Considerations ................................................................................................82 
12.3. 
Informed Consent .......................................................................................................82 
12.4. 
Patient Confidentiality and Disclosure .......................................................................82 
12.5. 
Data Collection ...........................................................................................................82 
12.6. 
Patient Data Protection ...............................................................................................83 
12.7. 
Data Quality Assurance and Monitoring ....................................................................83 
12.8. 
Auditing Procedures ...................................................................................................84 
12.9. 
Investigator Compliance .............................................................................................84 


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12.10. 
Product Complaints ....................................................................................................84 
12.11. 
Study Closure..............................................................................................................84 
12.12. 
Retention of Documents .............................................................................................85 
12.13. 
Disclosure of Information ...........................................................................................85 
13. 
REFERENCES ...........................................................................................................87 
14. 
APPENDICES ............................................................................................................89 
APPENDIX 1: CONTRACEPTION GUIDANCE .....................................................................89 
APPENDIX 2: EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) SCALE 
FOR PERFORMANCE STATUS ..............................................................................91 
APPENDIX 3: MEDICATIONS OR FOODS KNOWN TO INHIBIT OR INDUCE 
CYP3A ........................................................................................................................92 
APPENDIX 4: CYP3A OR CYP2C8 SUBSTRATES ...............................................................94 
APPENDIX 5: P-GP SUBSTRATES AND MEDICATIONS THAT ARE 
INHIBITORS OF P-GP ..............................................................................................95 
APPENDIX 6: SUMMARY OF CHANGES .............................................................................97 
Protocol Version 7.0 (Amendment 7), 20 July 2021 .....................................................................97 
Protocol Version 6.1 (Amendment 6), 08 December 2020 ...........................................................97 
Protocol Version 6.0 (Amendment 5), 16 September 2019 ...........................................................98 
Protocol Version 5.0 (Amendment 4), 09 August 2019 ..............................................................100 
Version History ............................................................................................................................102 
 
 
LIST OF TABLES 
Table 1: 
Dose Optimization Phase Schedule of Events ............................................................14 
Table 2: 
Expansion Phase Schedule of Events .........................................................................17 
Table 3: 
Dose Optimization Phase Disease Response and Follow-up Assessments ................20 
Table 4: 
Expansion Phase Disease Response and Follow-up Assessments .............................21 
Table 5: 
Dose Optimization and Expansion Phase Pharmacokinetic Assessment ...................22 
Table 6: 
5-Point Scale (Lugano Classification) ........................................................................51 
Table 7: 
Response Criteria for Malignant Lymphoma .............................................................51 
Table 8: 
Duvelisib Dose Modification and Toxicity Management ..........................................62 
Table 9: 
Duvelisib Dose Reduction Levels for Patients Receiving 25 mg or 75 mg 
BID .............................................................................................................................64 


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Table 10: Duvelisib Dose Reduction Levels for Patients Receiving 50 mg BID .......................65 
Table 11: CTCAE Grading .........................................................................................................72 
Table 12: Confidence Bounds for Potential ORR Scenarios ......................................................77 
Table 13 
Summary of Changes for Version 6.0 ........................................................................98 
Table 14: Summary of Changes for Version 5.0 ......................................................................100 
Table 15: Primary Reason for Each Version ............................................................................102 
 
LIST OF FIGURES 
Figure 1 
Study Overview ..........................................................................................................13 
 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
18FDG-PET 
[18F] Fluorodeoxyglucose-positron emission tomography 
5PS 
5-point scale 
AE 
Adverse event 
ALC 
Absolute lymphocyte count 
ALCL 
Anaplastic large cell lymphoma 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BID 
Twice daily 
CEC 
Central ethics committee 
CMV 
Cytomegalovirus 
CR 
Complete response 
CRO 
Contract Research Organization 
CT 
Computed tomography 
CX 
Cycle X 
CYP3A 
Cytochrome P450 3A 
DCR 
Disease control rate 
DNA 
Deoxyribonucleic acid 
DOR 
Duration of response 
DX 
Day X 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EOT 
End-of-Treatment 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
G-CSF 
Granulocyte-colony stimulating factor 
Gi 
Giga (1 x 109) or 1 billion 
GI 
Gastrointestinal 
HBcAb 
Hepatitis B core antibody  
HBsAg 
Hepatitis B surface antigen 
HCV Ab 
Hepatitis C Ab 
HIV 
Human immunodeficiency virus 


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Abbreviation 
Definition 
HSV 
Herpes simplex virus 
HTLV-1 
Human T-lymphotropic virus type 1 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent ethics committee 
Ig 
Immunoglobulin 
IHC 
Immunohistochemistry 
IRB 
Institutional review board 
IRC 
Independent Review Committee 
ITT 
Intent-to-treat 
IV 
Intravenous(ly) 
IWG 
International Working Group 
LDi 
Longest transverse diameter of a lesion 
LVEF 
Left ventricular ejection fraction 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic resonance imaging 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NKTL 
Natural-killer/T-cell lymphoma 
NOS 
Not otherwise specified 
ORR 
Objective response rate 
OS 
Overall survival 
PD 
Progressive disease 
PFS 
Progression-free survival 
P-gp 
P-glycoprotein 
PI3K 
Phosphoinositide-3-kinase 
PO 
Oral(ly) 
PPD 
Cross product of the LDi and perpendicular diameter 
PR 
Partial response 
PTCL 
Peripheral T-cell lymphoma 
QD 
Once daily 
QTcF 
QT interval corrected with Fridericia’s method 
SAE 
Serious adverse event 


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Abbreviation 
Definition 
sALCL 
Systemic anaplastic large cell lymphoma 
SAP 
Statistical Analysis Plan 
SCT 
Stem cell transplantation 
SD 
Stable disease 
SDi 
Shortest axis perpendicular to the LDi 
SPD 
Sum of the product of the perpendicular diameters for multiple lesions 
SPTCL 
Subcutaneous panniculitis-like T-cell lymphoma  
SUV 
Standardized uptake value 
TEAE 
Treatment-emergent adverse event 
ULN 
Upper limit of normal 
US 
United States 
UV 
Ultraviolet 
VZV 
Herpes zoster virus 
WBC 
White blood cell count 
WCBP 
Women/woman of childbearing potential 
β-hCG 
β-human chorionic gonadotropin 
 
 
 


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1. 
BACKGROUND AND STUDY RATIONALE 
1.1. 
Peripheral T-cell Lymphoma 
Peripheral T-cell lymphoma (PTCL) is a rare, aggressive type of non-Hodgkin lymphoma with 
an incidence of < 1 in 100,000 in the United States (US). The incidence varies geographically, 
with higher incidences in Asian countries than in Western countries (Park et al, 2014). PTCL 
generally affects people aged 60 years and older and is diagnosed slightly more often in men 
than in women. In addition to the incidence, there is a geographic difference in the PTCL 
subtypes. For example, PTCL-not otherwise specified (NOS) is the most common subtype in 
North American and Europe, while adult T-cell leukemia/lymphoma (ATLL) is most common in 
Asia (Vose et al, 2008). 
Patients with newly diagnosed PTCL are most commonly treated with combination 
chemotherapy regimens, often followed by consolidation with high-dose chemotherapy and stem 
cell transplantation (SCT). However, the majority of patients develop relapsed or refractory 
disease (Zinzani et al, 2016). In addition, co-existing co-morbidities often preclude SCT 
consolidation in older PTCL patients. 
Historically, patients with relapsed disease have had a dismal prognosis, with a median overall 
survival (OS) of less than 6 months. Pralatrexate, a folate analog, and belinostat and romidepsin, 
both intravenously (IV)-administered histone deacetylase inhibitors, were approved by the US 
Food and Drug Administration (FDA) for the treatment of relapsed or refractory PTCL patients 
based on objective response rates (ORR) ranging from 25% to 27% in single-arm studies. 
Brentuximab vedotin, a CD30-directed antibody-drug conjugate, also administered IV, is 
indicated for systemic anaplastic large cell lymphoma (sALCL), a sub-type of PTCL, also on the 
basis of a single-arm study. To date, no agent has been shown to improve OS. However, these 
treatments are associated with toxicities and only one to date is globally available (Laribi et al, 
2018). Apart from a few patients who achieve complete response (CR), response durations 
remain brief. Therefore, PTCL remains a condition of high unmet medical need. 
1.2. 
Duvelisib (IPI-145; VS-0145) 
Phosphoinositide-3-kinase (PI3K) is a lipid kinase involved in intracellular signal transduction in 
many cells. The isoforms of PI3K’s catalytic subunit (p110) exist as α, β, δ, and γ, the δ and γ 
isoforms being preferentially expressed in leukocytes and involved in innate and adaptive 
immune function (Clayton et al, 2002; Okkenhaug et al, 2002; Vanhaesebroeck et al, 2010; 
Fung-Leung et al, 2011). For patients with advanced hematologic malignancies, including T-cell 
lymphomas, the pathways mediated by PI3K-δ,γ contribute to survival, proliferation, and 
differentiation of cancer cells. It is well recognized that 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 that promote angiogenesis 
and augment tumor growth (Lewis et al, 2006). PI3K-δ and PI3K-γ also have roles in the 
establishment and maintenance of the tumor microenvironment that plays an important role in 


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the development and maintenance of cancer cells (Hanahan et al, 2011). Accordingly, PI3K-δ,γ 
inhibition would be expected to disrupt tumor maintenance and progression (Schmid et al, 2011). 
Duvelisib is a potent PI3K-δ,γ inhibitor being developed by Secura Bio, Inc. (Secura Bio) as an 
orally administered therapeutic in hematologic malignancies, including PTCL. Duvelisib is 
mechanistically distinct from other agents either currently available or being developed for 
PTCL and has demonstrated encouraging clinical activity in heavily pre-treated PTCL patients 
treated at doses of 60 mg twice daily (BID) (n = 2), 75 mg BID (n = 13), or 100 mg BID (n = 1). 
Among these 16 patients, the Investigator-assessed ORR per International Working Group 
(IWG) criteria was 50% (8/16), which included 2 CRs and 5 partial responses (PRs) in the 75 mg 
BID dose group and 1 CR in the 60 mg BID dose group. Responses were seen across the 
spectrum of PTCL subtypes, with CRs in patients with enteropathy-associated T-cell lymphoma 
(EATL), angioimmunoblastic T-cell lymphoma (AITL), and PTCL-NOS, and PRs in those with 
subcutaneous panniculitis-like T-cell lymphoma (SPTCL), ALCL, AITL and PTCL-NOS. 
Responses were observed in patients who had relapsed from prior treatment with approved 
therapies for PTCL. The median time to response was 1.9 months and the median duration of 
response was not estimable, as only 1 patient had progression or death after response. The 
median OS was 8.4 months, and the estimated probability of survival at 24 months was 34.4%. 
Furthermore, duvelisib demonstrated an acceptable safety profile in this relapsed and refractory 
patient population. In the combined population of patients with PTCL or cutaneous T-cell 
lymphoma (n = 35), the most frequently observed ≥ Grade 3 adverse events (AEs) were elevated 
transaminase (11 patients; 31% alanine aminotransferase [ALT]/aspartate aminotransferase 
[AST]), maculopapular rash (6 patients;17%), neutropenia (3 patients; 9%) pneumonia 
(5 patients;14%), and lung infection (3 patients; 9%), which were generally manageable with 
dose modifications and standard of care interventions (Horwitz et al, 2018). 
For additional preclinical information on the antitumor activity of duvelisib, please see the 
Investigator’s Brochure (IB).  
1.3. 
Study Rationale 
The activity and evidence of response durability in 16 patients with heavily pre-treated PTCL 
observed in the Phase 1 study suggest that duvelisib is an active single agent for relapsed or 
refractory PTCL, an indication with a high unmet therapeutic need. 
The Phase 2/3 clinical dose of duvelisib has been identified as 25 mg BID for patients with 
indolent non-Hodgkin lymphoma and chronic lymphocytic leukemia. Duvelisib (COPIKTRA™) 
was approved in the US in September 2018 with a dosage of 25 mg orally BID and is indicated 
for the treatment of adult patients with relapsed or refractory CLL or SLL after at least two prior 
therapies and accelerated approval for the treatment of adult patients with relapsed or refractory 
FL after at least two prior systemic therapies. In the Phase 1, dose-escalation study in patients 
with hematologic malignancies, including PTCL, duvelisib was administered BID at escalating 
doses of 8 mg, 15 mg, 25 mg, 35 mg, 50 mg, 60 mg, 75 mg, and 100 mg, with the maximum 


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tolerated dose identified as 75 mg BID. Patients with PTCL received dose levels ≥ 60 mg; 
therefore, the activity of duvelisib in patients with PTCL at lower dose levels has not been 
evaluated. Accordingly, the current study will employ a Dose Optimization Phase, in which 
patients will initially start treatment with duvelisib 25 mg BID, with potential sequential 
escalation on a per-patient basis to 50 mg BID and then 75 mg BID, based on disease response 
and tolerability. The optimal dose, as identified in the Dose Optimization Phase will then be 
selected for use in the subsequent Expansion Phase. 
As described in Section 11.13 a review of preliminary indications of response in each cohort was 
conducted when 5 patients had completed the first cycle in each cohort of the Dose Optimization 
Phase. Responses had been reported by the investigators for at least one patient in each cohort 
and enrollment was allowed to continue. 
The interim analysis from the Dose Optimization Phase demonstrated the following: 
 Sixteen patients on Cohort 1 and 11 patients on Cohort 2 received at least one dose of 
duvelisib. Ten patients from each cohort were evaluable for response. Six patients 
discontinued treatment prior to reaching the first assessment, all of whom were on Cohort 
1. Premature discontinuations were due primarily to disease progression and/or toxicities. 
 Five patients per cohort demonstrated radiographic responses, including 4 CRs on Cohort 
1 and 2 CRs on Cohort 2. Not all responses have been confirmed. Responses were not 
limited to a particular subtype of PTCL. 
 With a mean follow-up time of 4 weeks for Cohort 1 and 8 weeks for Cohort 2, there 
appeared to be a numerically greater number of adverse events in Cohort 1. Among the 
16 patients in Cohort 1 and 11 in Cohort 2, 68.8% and 36.4%, respectively, had ≥ Grade 
3 AE’s. Similarly, the incidence of serious adverse events in Cohort 1 and Cohort 2 was 
43.8% and 18.2%, respectively. However, 2 patients in Cohort 1 had more than 1 AE. No 
new safety signals were identified. Infections and neutropenia appeared to account for the 
majority of the differences in the incidence of AEs between the two cohorts. 
 Area Under the Curve (AUC) increased with dose, and the mean steady state AUC at 75 
mg BID was approximately 2 times that at 25 mg BID. 
 Exploratory biomarker analysis revealed a difference in the baseline CD4 lymphocyte 
counts between evaluable patients (mean CD4 count of 398/mm3) and non-evaluable 
patients (mean CD4 count of 230/mm3). CD8 lymphocyte counts also showed a similar 
difference. The reasons for these differences are unclear. 
In summary, the preliminary data from the Dose Optimization Phase support continuation to the 
Expansion Phase (see Section 4.1.2 and Section 11). While both starting doses are active, it 
appears that more patients discontinued prematurely on Cohort 1 because of more rapid disease 
progression and toxicity. This observation suggests that the higher starting dosage of 75 mg BID 
may result in a more rapid debulking of tumor and more rapid disease control. However, the 


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longer-term toxicities with the 75 mg BID dosage have not yet been assessed during this phase of 
the study. It is likely that toxicities with longer times of onset, such as colitis, may be 
disproportionately greater with the 75 mg BID starting dosage. Therefore, to achieve both a rapid 
remission and ameliorate longer-term toxicities, the dosage will be 75 mg BID until the first 
response assessment (2 cycles) at which the dose will be reduced to 25 mg BID. As it is now 
known that the 25 mg BID dosage can be active in PTCL, and later-onset toxicities may be 
prevented, a proactive decrease in the dose is justified. 
Response assessments will continue at approximately 8-week intervals. If a subsequent 
assessment demonstrates progression and the patient did not require a dose modification due to 
toxicity, the dose can be re-escalated to 75 mg BID with a confirmatory scan after approximately 
4 weeks of therapy. Patients that re-escalate to 75 mg BID may remain at this dose level until the 
need for dose modification or the criteria for discontinuation is met. The rationale for re-
escalation in the absence of clinically significant toxicities is justified by the prior clinical benefit 
on the higher dose. 
Responses in the Phase 1 were seen in SPTCL (n=2 of 3 patients; PRs) and EATL (n=1 of 
1 patient; CR) which were additional subtypes of PTCL not included initially in this study. 
Therefore, the inclusion criterion number 1 was broadened.  
Lastly, the rationale for the requirement of CD4 lymphocyte count of ≥ 50/mm3 (0.05 x 109/L) is 
based on the emerging data from the Dose Optimization Phase that non-evaluable patients were 
more likely to be immunodeficient with respect to CD4 lymphocyte cell count. By using the 
Grade 4 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI 
CTCAE) definition for decreased CD4+ lymphocytes as the cut off, the patient population could 
be enriched for patients who are more likely to stay on treatment to allow sufficient time to 
achieve a response. This cut-off was chosen on the basis of above data, input from investigators, 
and aligned with the NCI CTCAE definition of life-threatening lymphopenia. 
1.4. 
Benefit/Risk Assessment 
Clinical study results to date support a favorable benefit-risk of duvelisib for patients with 
hematologic malignancies. The risks are consistent with the AE profile for the PI3K inhibitor 
drug class and AEs experienced by patients undergoing treatment for advanced 
cancers. Important identified risks include infections, diarrhea/colitis, cutaneous reactions, 
pneumonitis, neutropenia, and ALT/AST elevation. Potential risks include hepatotoxicity, drug-
drug interaction (DDI) and reproductive toxicity. These toxicities are managed using a 
combination of prophylaxis, supportive care and dose modifications. Duvelisib monotherapy has 
demonstrated encouraging activity in relapsed and refractory PTCL seen in this study and the 
Phase 1 study in hematologic malignancies. The starting dosage will be 75 mg BID until the first 
response assessment (2 cycles) in an attempt to debulk the tumor more efficiently. Subsequently, 
the dose will be reduced to 25 mg BID to anticipate and reduce toxicities of later times of onset. 
As both dose levels have demonstrated preliminary responses, this strategy is designed to reduce 
the risk of toxicity while maintaining clinical benefit. Overall, the potential benefit to a patient 


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with relapsed/refractory PTCL with few treatment options and historically a dismal prognosis, 
appears at this time, to outweigh any potential risks. 
2. 
STUDY OBJECTIVES 
2.1. 
Dose Optimization Phase 
2.1.1. 
Primary Objective 
The primary objective of the Dose Optimization Phase is: 
 To determine the optimal duvelisib dose for utilization in the Expansion Phase by 
evaluating the ORR supported by safety, additional efficacy, and pharmacokinetics (PK) 
parameters as well as any other available data in the population of patients receiving the 
optimal dose of duvelisib for at least one cycle in patients with relapsed or refractory 
PTCL 
2.1.2. 
Secondary Objectives 
The secondary objectives of the Dose Optimization Phase are: 
 To evaluate additional efficacy parameters for duvelisib in the population of patients 
receiving duvelisib for at least one cycle in patients with relapsed or refractory PTCL 
 To characterize the tolerability and safety of duvelisib in patients with relapsed or 
refractory PTCL 
 To evaluate the PK of duvelisib and if applicable, its metabolite(s) 
2.1.3. 
Exploratory Objective 
The exploratory objective of the Dose Optimization Phase is: 
 To evaluate pharmacodynamic and prognostic biomarkers 
2.2. 
Expansion Phase 
2.2.1. 
Primary Objective 
The primary objective of the Expansion Phase is: 
 To determine the efficacy of the optimal dose of duvelisib in patients with relapsed or 
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2.2.2. 
Secondary Objectives 
The secondary objectives of the Expansion Phase are: 
 To evaluate additional efficacy parameters for duvelisib 
 To characterize the tolerability and safety of duvelisib in patients with relapsed or 
refractory PTCL 
 To evaluate the PK of duvelisib and if applicable, its metabolite(s) 
2.2.3. 
Exploratory Objective 
The exploratory objective of the Expansion Phase is: 
 To evaluate pharmacodynamic and prognostic biomarkers 


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3. 
STUDY ENDPOINTS 
3.1. 
Dose Optimization Phase 
The evaluation of the primary and secondary efficacy endpoints based upon Lugano criteria 
(Cheson et al, 2014), will be performed using Investigator assessments unless otherwise noted, 
with results from Independent Review Committee (IRC) assessments used as supportive 
analyses. 
3.1.1. 
Primary Endpoint 
The primary endpoint is: 
 ORR (CR + PR), as assessed by the Investigator, as determined using the Lugano criteria 
(Cheson et al, 2014), supported by secondary efficacy, safety and PK in the population of 
patients receiving the optimal dose of duvelisib for at least one cycle of study therapy 
3.1.2. 
Secondary Endpoints 
The secondary endpoints are: 
 Duration of response (DOR), for those patients with CR or PR, defined as the time from 
the first documentation of response to the first documentation of progressive disease 
(PD), or death due to any cause 
 Treatment-emergent adverse events (TEAEs) and changes in laboratory values 
 Progression-free survival (PFS), defined as the time from the first study drug dose to the 
first documentation of PD, or death from any cause 
 Disease control rate (DCR), defined as CR + PR + stable disease ≥ 8 weeks 
 Overall survival (OS) 
 PK parameters derived from blood concentrations of duvelisib and its metabolites 
3.1.3. 
Exploratory Endpoints 
The exploratory endpoints are: 
 Analysis of PTCL tumor pharmacodynamic markers 
 Analysis of PTCL tumor prognostic markers 
 Analysis of cytokines and non-tumor immune populations 


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NOTE: Additional exploratory analyses identified by the Sponsor may be performed on study 
samples 
3.2. 
Expansion Phase 
The evaluation of the primary and secondary efficacy endpoints based upon Lugano criteria 
(Cheson et al, 2014) will be performed using IRC assessments, with results from Investigator-
assessed response used as supportive analyses. 
3.2.1. 
Primary Endpoint 
The primary endpoint is: 
 ORR (CR+PR), as assessed by the IRC, according to Lugano criteria (Cheson et al, 2014) 
3.2.2. 
Secondary Endpoints 
The secondary endpoints are: 
 TEAEs and changes in laboratory values 
 DOR, for those patients with CR or PR, defined as the time from the first documentation 
of response to the first documentation of PD, or death due to any cause 
 PFS, defined as the time from the first dose of study treatment to the first documentation 
of PD, or death from any cause 
 DCR, defined as CR + PR + SD ≥ 8 weeks 
 OS 
 PK parameters derived from blood concentrations of duvelisib and its metabolites 
3.2.3. 
Exploratory Endpoints 
The exploratory endpoints are: 
 Analysis of PTCL tumor pharmacodynamic markers 
 Analysis of PTCL tumor prognostic markers 
 Analysis of cytokines and non-tumor immune populations 
NOTE: Additional exploratory analyses identified by the Sponsor may be performed on study 
samples 


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4. 
STUDY DESIGN 
4.1. 
Overview of Study Design 
This is a multi-center, parallel cohort, open-label, Phase 2 study of duvelisib, an oral dual 
inhibitor of PI3K-δ,γ, in patients with relapsed/refractory PTCL. The study has 2 phases, a Dose 
Optimization Phase and an Expansion Phase. 
Regardless of study phase, all patients will undergo screening assessments up to 30 days before 
the first study drug dose (Cycle 1, Day 1 [C1D1]). Patients meeting all of the entrance criteria, 
based on Screening assessments, will be enrolled in the study and receive the first study drug 
dose on C1D1. Thereafter, patients will attend study center visits as per the applicable Phase 
Schedule of Events (Dose Optimization: Table 1, Expansion Phase: Table 2). At screening, 
disease will be measured using 18F-fluorodeoxyglucose-positron emission tomography (18FDG-
PET)-computed tomography (CT) scanning (PET-CT) (CT images along with PET should be 
diagnostic with contrast unless contraindicated). Where PET-CT is not feasible, CT with contrast 
or magnetic resonance imaging (MRI) may be used after discussion with the Medical Monitor. 
Subsequently, for FDG-avid PTCL, PET-CT will be used to assess disease status and for FDG-
non-avid PTCL, CT with contrast or MRI will be appropriate substitutes. The modality chosen to 
evaluate response in each individual patient should be the same throughout the duration of the 
study. For the purposes of patient management during the conduct of the study, the Investigator’s 
assessment of disease response will be used. Images also will be centrally stored, and disease 
response will be determined by an IRC for futility and at the end of the study. 
4.1.1. 
Dose Optimization Phase 
The Dose Optimization Phase will be conducted at up to approximately 15 centers in the US. 
In the Dose Optimization Phase, patients will be randomly assigned at a 1:1 ratio to 1 of 2 study 
cohorts, as follows: 
 Cohort 1: Duvelisib orally (PO) BID at a starting dose of 25 mg, with potential escalation 
on a per-patient basis to 50 mg BID and then to 75 mg BID, based on the patient’s 
response to and tolerance of therapy, in 28-day cycles 
 Cohort 2: Duvelisib 75 mg PO BID, administered in 28-day cycles 
Approximately 10 patients each will be enrolled in Cohorts 1 and 2. Patients in the Dose 
Optimization Phase who discontinue before receiving at least 1 cycle of study drug may be 
replaced. Enrollment into the Dose Optimization Phase may continue until the initiation of the 
Expansion Phase. 
For both cohorts, dose modification criteria for duvelisib will be applied if the starting dose or a 
subsequent dose of duvelisib is deemed intolerable (see Section 9.4.2). Dose Optimization Phase 
patients will complete treatment as defined for their cohort. 


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Cohort 1 
All patients will receive duvelisib at a starting dose of 25 mg PO BID (Level 1), with potential 
sequential escalation to 50 mg PO BID (Level 2), and then to 75 mg PO BID (Level 3). Intra-
patient dosing decisions will occur as follows: 
After completion of Cycle 1 and every 2 cycles thereafter: 
 Patients with complete response (CR) or partial response (PR) will have their duvelisib 
dose maintained at the current dose level 
 Patients with stable disease (SD) who are, in the Investigator’s opinion, tolerating and 
otherwise suitable to continue receiving therapy, will have the duvelisib dose increased to 
the next level until the next response assessment or development of PD or intolerance, as 
determined by the Investigator 
Patients with PD, who are not tolerating therapy, or otherwise not suitable to continue receiving 
therapy will discontinue duvelisib 
In no case will the duvelisib dose be increased to a level > 75 mg BID (total daily dose 150 mg). 
All patients in Cohort 1 will receive duvelisib until development of PD or unacceptable toxicity, 
as determined by the Investigator. 
Cohort 2 
All patients in Cohort 2 will receive duvelisib 75 mg PO BID in 28-day cycles until development 
of PD or unacceptable toxicity, as determined by the Investigator. 
4.1.2. 
Expansion Phase 
The Expansion Phase will be conducted at approximately 40-50 centers globally. 
After a sufficient number of patients from the Dose Optimization Phase are evaluable, efficacy, 
PK, and safety data as well as any other available data will be taken into consideration to 
recommend the optimal dose for the Expansion Phase (Note: the optimal dose for the Expansion 
Phase has been selected and documented in Protocol Amendment 2 V3, 14 March 2019 –see 
Expansion Phase Dose Selection below and Section 1.3). The interim results of the Optimization 
Phase may also drive changes to the Expansion Phase of the study such as modification to the 
study patient population, other aspects of entry criteria, and the inclusion of patients from 
geographic regions outside the US; any such changes will be documented in an amendment to 
the protocol. Patients will have disease assessment after Cycle 2 and every 2 cycles thereafter 
until the follow-up stage is reached and assessment will occur according to Table 4. 
Expansion Phase Dose Selection: 


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As of 02 January 2019, 20 patients met the criteria for the Dose Optimization efficacy population 
and available data as of 11 February 2019 were reviewed. A dosage of 75 mg BID for the first 
2 cycles, followed by a mandatory reduction to 25 mg BID thereafter for those patients with CR, 
PR or SD, will be used for the Expansion Phase. The dose may be re-escalated to 75 mg BID 
based on response assessment and safety (see Sections 1.3 and 9.1.2). 
4.1.3. 
Independent Review Committee 
An IRC will be established to provide a blinded review of imaging and pertinent clinical data in 
order to provide expert interpretation of treatment response. The IRC will be composed of 
independent clinicians not otherwise involved in the study. The specifics of the IRC composition 
and processes will be described in a separate IRC charter. 
4.2. 
Number of Patients 
Approximately 20 patients with relapsed/refractory PTCL will be enrolled in the Dose 
Optimization Phase, with approximately 10 evaluable patients each in Cohorts 1 and 2. Patients 
in the Dose Optimization Phase who discontinue before receiving at least 1 cycle of study drug 
may be replaced. 
Approximately 100-130 patients are anticipated to participate in the Expansion Phase, for a total 
of 130-160 patients across both phases.  
After the first 100 patients are enrolled in the expansion phase an additional 20-30 patients may 
be enrolled with a target of 8-10 patients have an ALCL or NK cell subtype. 
4.3. 
Duration of Patient Participation 
The duration of patient participation is dependent on the patient’s tolerance of and response to 
duvelisib; it is anticipated that patients will participate in the study for a minimum of ~3 months. 
All patients will be screened for study eligibility within 30 days before the first study drug dose 
(i.e., Baseline, C1D1). Patients who are determined to be eligible will be enrolled in the study at 
Baseline and will receive duvelisib continuously in 28-day cycles. For the Dose Optimization 
Phase, it is anticipated that patients will receive at least 1 cycle of therapy. For the Expansion 
Phase, it is anticipated that patients will receive at least 2 cycles of therapy. Unlike the Dose 
Optimization Phase if the patient demonstrates progression and no dose modification was 
required for toxicity, the patient may re-escalate to 75 mg BID with a confirmatory scan after 
approximately 4 weeks of therapy. Patients will continue duvelisib until development of PD or 
intolerance or another discontinuation criterion is met, as determined by the Investigator; no 
maximum duration of therapy has been set. After discontinuation of duvelisib, all patients are to 
attend an End-of-Treatment (EOT) visit within 7 days after the last study drug dose and then a 
Safety Follow-up visit 30 days after the last study drug dose. Patients who have not experienced 
PD will continue to be followed for disease response as per Table 3 or Table 4 until development 


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of PD, as determined by the Investigator. Patients with documented PD, as determined by the 
Investigator, will be followed on an every 3-month basis for survival until closure of the study by 
the Sponsor; follow-up for survival may be conducted via telephone.  


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5. 
STUDY POPULATION 
5.1. 
Inclusion Criteria 
Patients eligible for inclusion in this study must fulfill all of the following criteria: 
1. ≥ 18 years of age 
2. Pathologically-confirmed PTCL, as defined by the World Health Organization. Slides 
must be submitted for central pathology review. Results of central pathology review are 
not required prior to initiation of treatment. 
3. Received at least 2 cycles of one standard regimen for newly diagnosed advanced PTCL, 
and one of the following: 
(a) failed to achieve at least a PR after 2 or more cycles of standard therapy; 
(b) failed to achieve a CR after completion of standard therapy; and/or 
(c) persistent or progressive disease after an initial response 
4. For patients with CD30+ ALCL, failed or are ineligible or intolerant to brentuximab 
vedotin 
5. Measurable disease as defined by Lugano for PTCL, i.e., at least 1 measurable disease 
lesion > 1.5 cm in at least one dimension by conventional techniques (18FDG-PET-CT, 
CT with contrast, MRI) 
6. Must have the following laboratory parameters: 
 
Hemoglobin ≥ 8.0 g/dL with or without transfusion support  
 
Platelet count ≥ 25 × 109/L 
 
Serum creatinine ≤ 2.0 × the upper limit of normal (ULN) 
 
Total bilirubin ≤ 1.5 × ULN (in patients with Gilbert's Syndrome a bilirubin > 1.5 × 
ULN may be allowed) 
 
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN 
 CD4 lymphocyte count ≥ 50/mm3 (0.05 x 109/L) (Expansion Phase) 
7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 
8. Recovery to ≤ Grade 1 or baseline for any toxicities due to prior treatments, with the 
exception of peripheral neuropathy (recovery to ≤ Grade 2) or alopecia 


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9. Washout of at least 14 days or 5 half-lives, whichever is longer, from PTCL-directed 
therapy. If previously treated with lenalidomide, must have completed treatment 4 weeks 
prior to C1D1 
10. For women of childbearing potential (WCBP): negative serum β-human chorionic 
gonadotropin (β-hCG) pregnancy test within 1 week before first treatment (WCBP 
defined as a sexually mature woman who has not undergone surgical sterilization or who 
has not been naturally post-menopausal for at least 12 consecutive months for women 
> 55 years of age) 
11. Male and female patients of reproductive potential (i.e., not surgically sterile or female 
patients who are not postmenopausal) must be willing to use a highly effective method of 
contraception for the duration of study treatment and for at least 3 months after the last 
dose of duvelisib 
12. Signed and dated institutional review board (IRB)/independent ethics committee 
(IEC)/central ethics committee (CEC)-approved informed consent form before any 
Screening procedures are performed 
5.2. 
Exclusion Criteria 
Patients who fulfill 1 or more of the following criteria will not be eligible for inclusion in this 
study: 
1. Primary leukemic PTCL subtypes (i.e., T-cell prolymphocytic leukemia, T-cell large 
granular lymphocytic leukemia, adult T-cell leukemia/lymphoma and aggressive NK-cell 
leukemia) or transformed mycosis fungoides  
2. Received prior allogeneic transplant 
3. Received prior treatment with a PI3K inhibitor 
4. Major surgery within 4 weeks prior to Screening 
5. Known central nervous system involvement by PTCL 
6. Infection with hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or Human 
T-lymphotropic virus type 1 (HTLV-1). (Patients with a positive hepatitis B surface 
antigen [HBsAg] or hepatitis C antibody [HCV Ab] will be excluded. Patients with a 
positive hepatitis B core antibody [HBcAb] must have negative hepatitis B virus [HBV] 
deoxyribonucleic acid (DNA) to be eligible, must receive prophylaxis with entecavir [or 
equivalent] concomitant with duvelisib treatment, and must be periodically monitored for 
HBV reactivation by institutional guidelines. Investigators who strongly believe that that 
a positive HBcAb is false due to passive immunization from previous immunoglobulin 


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infusion therapy should discuss the potential to defer HBV prophylaxis with the Medical 
Monitor.) 
7. Active cytomegalovirus (CMV) infection (patients with detectable viral load) 
8. History of tuberculosis treatment within 2 years prior to C1D1 
9. History of chronic liver disease, veno-occlusive disease, or alcohol abuse 
10. Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic 
steroids > 20 mg of prednisone (or equivalent) once daily (QD) 
11. Ongoing treatment for systemic bacterial, fungal, or viral infection at Screening 
NOTE: Patients on antimicrobial, antifungal, or antiviral prophylaxis are not specifically 
excluded if all other inclusion/exclusion criteria are met 
12. Administration of a live vaccine within 6 weeks of C1D1 
13. Concurrent administration of medications or foods that are strong inhibitors or inducers 
of cytochrome P450 3A (CYP3A) 
14. Unable to receive prophylactic treatment for pneumocystis at Screening 
15. Baseline left ventricular ejection fraction (LVEF) < 50% (or below institution’s normal 
limit) 
16. Baseline QT interval corrected with Fridericia’s method (QTcF) > 480 ms 
NOTE: criterion does not apply to patients with a right or left bundle branch block 
17. Prior surgery or condition with gastrointestinal dysfunction that may significantly affect 
drug absorption (e.g., gastric bypass surgery, gastrectomy, clinically significant medical 
condition of malabsorption, inflammatory bowel disease, chronic conditions which 
manifest with diarrhea, refractory nausea, vomiting) 
18. If female, pregnant or breastfeeding 
19. Concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of 
the cervix 
NOTE: Patients with previous malignancies are eligible if disease-free for > 2 years 
20. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia 
requiring medication or a pacemaker within the last 6 months prior to Screening 


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21. Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function, 
unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or 
abnormal laboratory finding that would, in the Investigator’s judgment, increase the risk 
to the patient associated with his or her participation in the study 
22. Known hypersensitivity to duvelisib and/or its excipients 


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6. 
STUDY CONDUCT 
This study will be conducted in compliance with the protocol, good clinical practice (GCP), 
applicable regulatory requirements, and International Council for Harmonisation (ICH) 
guidelines. 
6.1. 
Study Procedures 
Patients will be evaluated at scheduled visits over 6 study periods: Screening, Treatment, End of 
Treatment, Safety Follow-up, PD Follow-up, and Survival Follow-Up. Tests and procedures 
should be performed in accordance with the Schedule of Events provided in Table 1 and Table 2. 
Additional details are provided in the sections that follow. 
6.2. 
Informed Consent 
Each patient must sign a written informed consent form (ICF) prior to performing any study-
specific procedure unless the procedure is performed as part of standard of care. 
6.3. 
Inclusion and Exclusion Criteria 
All patients must meet the inclusion and exclusion criteria prior to being enrolled in the study. 
Eligibility criteria will be reviewed during Screening and again prior to dosing on C1D1. 
6.4. 
Medical and Medication History 
During Screening, a complete medical history will be obtained from each patient including 
relevant medical history, current medications, current primary cancer diagnosis, prior cancer 
treatments (chemo and immunotherapies, radiation therapy, surgeries) including duration of prior 
response, and disease-specific characteristics such as tumor stage and histology. Current 
medications and all medications used within 30 days prior to Screening will be documented. 
6.4.1. 
Disease Confirmation by Central Pathology Review 
As part of the patient’s medical history, pathology reports from the time of diagnosis are to be 
collected. In addition, stained formalin-fixed, paraffin-embedded (FFPE) slides used for PTCL 
diagnosis must be collected for all patients enrolled and submitted for central pathology review. 
Refer to lab manual for more details. 
6.5. 
Demography 
At Screening, patient demographic data will be collected, including date of birth, gender, race, 
and ethnicity, as allowable according to local law. 


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6.6. 
Physical Examination 
A complete physical examination per standard of care will be conducted at the Screening and 
EOT visits. Targeted physical examinations should be performed at time points specified in the 
Schedule of Events (Table 1 and Table 2). 
Any physical examination abnormality deemed clinically significant by the Investigator during 
Screening will be reported as medical history. Any physical examination abnormality that 
emerges or has worsened after signing of the ICF and that is assessed as clinically significant by 
the Investigator will be reported as an AE. 
6.7. 
Electrocardiogram 
A twelve-lead electrocardiogram (ECG) will be conducted during Screening and assessed by the 
Investigator to confirm eligibility. A single ECG tracing is sufficient unless there is an 
abnormality, such as prolonged QTcF ≥ 480 msec, new arrhythmia, or other clinically significant 
finding. If an abnormality is observed, the ECG is to be performed in triplicate at least 2 minutes 
apart. Additional on-treatment or follow-up ECGs should be performed at the Investigator’s 
discretion as clinically indicated. 
6.8. 
Echocardiogram 
An echocardiogram will be conducted during Screening and assessed by the Investigator to 
confirm eligibility (patients with baseline LVEF < 50% [or below institution’s normal limit] are 
excluded). Additional on-treatment or follow-up echocardiograms should be performed at the 
Investigator’s discretion as clinically indicated. 
6.9. 
Vital Signs, Height and Weight 
Vital signs, including temperature (°C), blood pressure, pulse, and respiration rate, as well as 
weight (kg) will be measured at the time points specified in the Schedule of Events (Table 1 and 
Table 2). Height (cm) will be measured during Screening only. 
Systolic and diastolic blood pressure and pulse will be measured with the patient in a supine or 
sitting position; the same position will be used for a patient throughout the study. Blood pressure 
should be assessed on the same arm throughout the study. 
6.10. 
Clinical Laboratory Tests 
6.10.1. 
Screening Serology 
Laboratory studies to assess the status of prior or current CMV infection include CMV 
serologies, CMV immunoglobulin (Ig) G and IgM, and viral load, are to be conducted during 
Screening. Patients with a detectable viral load will not be eligible for enrollment. During 


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duvelisib treatment, periodic CMV viral load monitoring is recommended in patients with a 
history of CMV reactivation or other opportunistic infections. 
Furthermore, a liver serology panel, including HBsAg, HBcAb, and HCV Ab, is to be performed 
during Screening. Patients with a positive HBsAg or HCV Ab will be excluded. Patients with a 
positive HBcAb must have negative HBV DNA to be eligible, must receive prophylaxis with 
entecavir (or equivalent) concomitant with duvelisib treatment, and must be periodically 
monitored for HBV reactivation by institutional guidelines. Investigators who strongly believe 
that that a positive HBcAb is false due to passive immunization from previous immunoglobulin 
infusion therapy should discuss the potential to defer HBV prophylaxis with the Medical 
Monitor. 
HIV and HTLV-1 tests are to be performed during Screening for all patients without 
documentation of prior negative results. 
6.10.2. 
Pregnancy Test 
A serum or urine pregnancy test will be done during Screening and repeated predose on C1D1 
for WCBP; results must be available and confirmed to be negative before administration of the 
first study drug dose. If the Screening pregnancy test is performed within 1 week before C1D1, it 
need not be repeated on C1D1. 
For the Dose Optimization Phase, pregnancy tests are to be repeated during the Treatment Period 
at the time points designated in the Schedule of Events (Table 1). For the Expansion Phase, 
pregnancy tests are to be repeated monthly (see Table 2). For cycles where pregnancy testing is 
the only requirement in the Schedule of Events, the patient may have this done locally. For both 
phases, the pregnancy test may be repeated as deemed necessary by the Investigator. 
6.10.3. 
Clinical Laboratory Tests 
Clinical laboratory tests will be performed by the investigative site's local laboratory. Samples 
will be collected from patients at scheduled study visits before the administration of study drug 
unless otherwise noted. 
Blood samples for evaluation of the following clinical laboratory tests will be collected at the 
time points specified in the Schedule of Events (Table 1 and Table 2). Samples may be collected 
up to 24 hours from the visit. C1D1 laboratory tests do not need to be repeated if performed 
within 72 hours prior to Screening. All safety Screening/C1D1 laboratory results will be 
reviewed prior to dosing to ensure patient is eligible. 
 Hematology: Hemoglobin, hematocrit, platelets, white blood cell count (WBC) with 
5-part differential (neutrophils, lymphocytes, monocytes, eosinophils, basophils), such 
that an absolute neutrophil count and an absolute lymphocyte count (ALC) can be 
derived, if it is not already provided as part of the laboratory analysis. 


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 Clinical Chemistries: Sodium, potassium, chloride, bicarbonate, albumin, total protein, 
creatinine, blood urea nitrogen or urea, lipase, amylase, uric acid, calcium, phosphorus, 
magnesium, glucose, lactic dehydrogenase, serum ALT, serum AST, total and direct 
bilirubin, and alkaline phosphatase. 
 Serum Quantitative Immunoglobulins (Ig): IgA, IgM, and IgG. 
 CD4 Lymphocyte Cell Count (at Screening) 
6.11. 
Disease and Response Assessment 
At Screening, disease will be measured using PET-CT (CT images with PET should be 
diagnostic with contrast unless contraindicated). Where PET-CT is not feasible, CT with contrast 
or magnetic resonance imaging (MRI) may be used after discussion with the Medical Monitor. 
Subsequently, for FDG-avid PTCL, PET-CT will be used to assess disease status and for FDG-
non-avid PTCL, CT with contrast or MRI will be appropriate substitutes. In all cases, disease 
status will be assessed using the Lugano criteria (Cheson et al, 2014). The modality chosen to 
evaluate each individual patient should be the same throughout the duration of the study, if 
feasible. Response and progression will be assessed as indicated in Table 7. 
PET images are to be assessed using the 5-point scale (5PS), a semi-quantitative analysis that is a 
pragmatic yet robust predictor of patient outcome (Table 6). 
Table 6: 
5-Point Scale (Lugano Classification) 
Score 
Criterion 
1 
No uptake above background 
2 
Uptake ≤ mediastinum 
3 
Uptake > mediastinum, but ≤ liver 
4 
Uptake moderately > liver* 
5 
Uptake markedly higher than liver and/or new lesions* 
X 
(New) areas of uptake unlikely to be related to lymphoma 
*It is suggested according to published data that score 4 be applied to uptake greater than the maximum standardized uptake 
value (SUV) in a large region of normal liver and score 5 to uptake 2× to 3× greater than the maximum SUV in the liver. 
Source: Barrington et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the 
International Conference on Malignant Lymphomas Imaging Working Group Clin Oncol. 2014 Sep 20; 32(27): 
3048–3058. 
At each scheduled disease response assessment (Table 3 or Table 4), a PET-CT- or CT-based 
response will be determined, based on the Lugano response criteria for patients with malignant 
lymphoma (Table 7). 
Table 7: 
Response Criteria for Malignant Lymphoma 
Response and Site 
PET-CT-based Response 
CT-Based Response 
Complete Response 
Complete metabolic response 
Complete radiologic response  
(requires all of the following) 


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Response and Site 
PET-CT-based Response 
CT-Based Response 
Lymph nodes and extralymphatic 
sites 
Score of 1, 2, or 3* with or without 
a residual mass on 5PS†  
It is recognized that in Waldeyer’s 
ring or extranodal sites with high 
physiologic uptake or with 
activation within spleen or marrow 
(e.g., with chemotherapy or 
myeloid colony-stimulating 
factors), uptake may be greater than 
normal mediastinum and/or liver. In 
this circumstance, complete 
metabolic response may be inferred 
if uptake at sites of initial 
involvement is no greater than 
surrounding normal tissue even if 
the tissue has high physiologic 
uptake 
Target nodes/nodal masses must 
regress to ≤ 1.5 cm in LDi 
No extralymphatic sites of disease 
Non-measured lesions 
Not applicable 
Absent 
Organ enlargement 
Not applicable 
Regress to normal 
New lesions 
None 
None 
Bone marrow 
No evidence of FDG-avid disease 
in bone marrow 
Normal by morphology; if 
indeterminate, IHC negative 
Partial Response 
Partial metabolic response 
Partial remission  
(all of the following) 
Lymph nodes and extralymphatic 
sites 
5PS score 4 or 5 with reduced 
uptake compared with baseline and 
residual mass(es) of any size 
During treatment, these findings 
suggest responding disease 
At end of treatment, these findings 
indicate residual disease 
≥ 50% decrease in SPD of up to 
6 target measurable nodes and 
extranodal sites 
When a lesion is too small to 
measure on CT, assign 5 mm × 
5 mm as the default value 
When no longer visible, 0 × 0 mm 
For a node > 5 mm × 5 mm, but 
smaller than normal, use actual 
measurement for calculation 
Nonmeasured lesions 
Not applicable 
Absent/normal, regressed, but no 
increase 
Organ enlargement 
Not applicable 
Spleen must have regressed by 
≥ 50% in length beyond normal 
New lesions 
None 
None 
Bone marrow 
Residual uptake higher than uptake 
in normal marrow but reduced 
compared with baseline (diffuse 
uptake compatible with reactive 
changes from chemotherapy 
allowed). If there are persistent 
focal changes in the marrow in the 
context of a nodal response, 
consideration should be given to 
Not applicable 


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Response and Site 
PET-CT-based Response 
CT-Based Response 
further evaluation with MRI or 
biopsy or an interval scan 
Stable disease (no response) 
No metabolic response 
Stable disease 
Target nodes/nodal masses, 
extranodal lesions 
5PS score 4 or 5 with no significant 
change in FDG uptake from 
baseline at interim or end of 
treatment 
< 50% decrease from baseline in 
SPD of up to 6 dominant, 
measurable nodes and extranodal 
sites; no criteria for progressive 
disease are met 
Non-measured lesions 
Not applicable 
No increase consistent with 
progression 
Organ enlargement 
Not applicable 
No increase consistent with 
progression 
New lesions 
None 
None 
Bone marrow 
No change from baseline 
Not applicable 
Progressive Disease 
Progressive metabolic disease 
Progressive disease requires at 
least 1 of the following: 
Individual target nodes/nodal 
masses 
5PS score 4 or 5 with an increase in 
intensity of uptake from baseline 
and/or 
PPD progression 
Extranodal lesions 
New FDG-avid foci consistent with 
lymphoma at interim or end-of-
treatment assessment 
An individual node/lesion must be 
abnormal with: 
LDi > 1.5 cm and 
Increase by ≥ 50% from PPD nadir 
and 
An increase in LDi or SDi from 
nadir 
0.5 cm for lesions ≤ 2 cm 
1.0 cm for lesions > 2 cm 
In the setting of splenomegaly, the 
splenic length must increase by > 
50% of the extent of its prior 
increase beyond baseline (e.g., a 
15-cm spleen must increase to > 
16 cm). If no prior splenomegaly, 
must increase by at least 2 cm from 
baseline 
New or recurrent splenomegaly 
Non-measured lesions 
None 
New or clear progression of 
preexisting nonmeasured lesions 
New lesions 
New FDG-avid foci consistent with 
lymphoma rather than another 
etiology (e.g., infection, 
inflammation). If uncertain 
regarding etiology of new lesions, 
biopsy or interval scan may be 
considered 
Regrowth of previously resolved 
lesions 
A new node > 1.5 cm in any axis 
A new extranodal site > 1.0 cm in 
any axis; if < 1.0 cm in any axis, its 
presence must be unequivocal and 
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Response and Site 
PET-CT-based Response 
CT-Based Response 
Assessable disease of any size 
unequivocally attributable to 
lymphoma 
Bone marrow 
New or recurrent FDG-avid foci 
New or recurrent involvement 
Abbreviations: 5PS=5-point scale; CT=computed tomography; FDG=fluorodeoxyglucose; IHC=immunohistochemistry; 
LDi=longest transverse diameter of a lesion; MRI=magnetic resonance imaging; PET=positron emission tomography; PPD=cross 
product of the LDi and perpendicular diameter; SDi=shortest axis perpendicular to the LDi; SPD=sum of the product of the 
perpendicular diameters for multiple lesions. 
*A score of 3 in many patients indicates a good prognosis with standard treatment, especially if at the time of an 
interim scan. However, in studies involving PET where de-escalation is investigated, it may be preferable to 
consider a score of 3 as inadequate response (to avoid undertreatment). Measured dominant lesions: Up to 6 of the 
largest dominant nodes, nodal masses, and extranodal lesions selected to be clearly measurable in 2 diameters. 
Nodes should preferably be from disparate regions of the body and should include, where applicable, mediastinal 
and retroperitoneal areas. Non-nodal lesions include those in solid organs (e.g., liver, spleen, kidneys, lungs), 
gastrointestinal (GI) involvement, cutaneous lesions, or those noted on palpation. Nonmeasured lesions: Any disease 
not selected as measured, dominant disease and truly assessable disease should be considered not measured. These 
sites include any nodes, nodal masses, and extranodal sites not selected as dominant or measurable or that do not 
meet the requirements for measurability but are still considered abnormal, as well as truly assessable disease, which 
is any site of suspected disease that would be difficult to follow quantitatively with measurement, including pleural 
effusions, ascites, bone lesions, leptomeningeal disease, abdominal masses, and other lesions that cannot be 
confirmed and followed by imaging. In Waldeyer’s ring or in extranodal sites (e.g., GI tract, liver, bone marrow), 
FDG uptake may be greater than in the mediastinum with complete metabolic response but should be no higher than 
surrounding normal physiologic uptake (e.g., with marrow activation as a result of chemotherapy or myeloid growth 
factors). 
Source: Cheson, BD, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-
Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014;32(27):3059-3067. 
6.11.1. 
ECOG Performance Status  
Performance status will be assessed using the ECOG Scale (see Appendix 2) at the time points 
specified in the Schedule of Events (Table 1 and Table 2). 
6.12. 
Pharmacokinetic Assessment 
Blood samples for PK analyses will be collected in both the Dose Optimization (Cohort 1 and 
Cohort 2) and Expansion Phases, as described in Table 5. 
6.13. 
Exploratory Biomarkers 
Blood and tissue specimens are to be collected at the times designated in the Schedule of Events 
for exploratory biomarker analysis (Table 1 and Table 2). In addition, whenever a bone marrow 
specimen is collected during Screening, an aliquot is to be reserved for exploratory biomarker 
assessments. Each of the specimens listed may be analyzed at a central laboratory or at a 
specialized laboratory vendor as determined by the Sponsor, for the various biomarkers outlined 
below: 
 Pharmacodynamic markers of target inhibition in PTCL and immune populations (only 
for the US) 


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 Immunophenotypes and functional tests of major immune populations in the blood (only 
for the US) 
 Cytokines and other circulating biomarkers  
 Prognostic markers assessed by DNA, ribonucleic acid, and protein analysis from tissue 
and blood specimens 
6.14. 
Unscheduled Visits 
Unscheduled visits and assessments may occur at the Investigator’s discretion, as clinically 
warranted. 


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7. 
COMPLETION OF TREATMENT 
Patients will be considered to have completed study treatment if they receive the study drug until 
PD or until discontinuation for unacceptable toxicity, withdrawal of consent, or death. Patients 
will attend an EOT visit within 7 days after receiving the last dose of study drug and will 
continue to be followed for other follow-up assessments specified in the Schedule of Events 
(Table 3 or Table 4). 
7.1. 
Completion of Study 
Patients will be considered to have completed the study at the time of documented PD or death 
or closure of the study by the Sponsor. 
7.2. 
Concomitant Medications 
Medications received on or after the start of duvelisib therapy through the Safety Follow-up visit 
will be documented. 
7.3. 
Adverse Events 
AEs, including serious adverse events (SAEs) will be reported from the time the patient signs the 
ICF through 30 calendar days after last administration of study drug. The severity of AE will be 
assessed using the NCI CTCAE version 5.0 (see web page at http://ctep.cancer.gov for details). 
Study treatment related AE/SAE should continue to be followed until resolution or stabilization. 
See Section 10, Adverse Event Management, for additional details regarding AE reporting and 
recording. 


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8. 
DISCONTINUATION CRITERIA 
8.1. 
Withdrawal of Individual Patients from Study Drug 
Duvelisib will be discontinued for any of the following reasons: 
 Patient withdrawal of informed consent 
 Disease progression (NOTE: In the Expansion Phase, patients may stay on therapy if PD 
occurs following mandatory dose reduction if criteria are met. See Sections 1.3 and 9.1.2) 
 Clinical deterioration due to PD (at the discretion of the Investigator) 
 Study drug interruption for > 42 days due to duvelisib-related toxicity (unless approved 
by study Medical Monitor). 
 AE, such as unacceptable toxicity 
 Pregnancy 
 Termination of the study by the Sponsor 
 Death 
 Other reasons, including major protocol violation, noncompliance 
The Investigator must determine the primary reason for a duvelisib withdrawal and record this 
information on the electronic case report form (eCRF). The patient will be observed after 
discontinuation according to the Schedule of Assessments and Events. 
8.2. 
Withdrawal of Individual Patients from the Study 
A patient may be discontinued from the study at any time. Patients will be withdrawn from the 
study for any of the following reasons: 
 Patient withdrawal of informed consent 
 Termination of the study by the Sponsor 
 Death 
 Lost to follow-up 
 Other reasons, including major protocol violation and noncompliance with study 
procedures, as specified by the Investigator 


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The Investigator must determine the primary reason for a patient’s withdrawal from the study 
and record this information on the eCRF.  
8.3. 
Early Discontinuation of the Study 
The Sponsor may terminate this study at any time, provided a written notice is submitted at a 
reasonable time in advance of the intended termination. 
8.4. 
End of Study Definition 
The end of the study is defined as the date of the last scheduled procedure shown in the Schedule 
of Events (Table 2, Table 4 and Table 5) for the last patient in the study or closure of the study 
by the Sponsor. 


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9. 
STUDY DRUG REGIMEN 
9.1. 
Dosing and Administration of Study Drug 
All eligibility criteria must be met and documented prior to study drug administration. The study 
drug will be administered only to eligible patients under the supervision of the Investigator or 
identified Sub-Investigator(s). 
Duvelisib is to be self-administered by patients as an oral capsule supplied by the Sponsor. 
Patients will receive duvelisib PO BID continuously in 28-day cycles. 
On C1D1, the morning dose will be administered in the clinic. Duvelisib also will be 
administered in the clinic on PK sample collection days (see Table 5). 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. 
Duvelisib should be swallowed whole with a glass of water (approximately 8 ounces or 240 mL). 
Duvelisib may be administered without regard to meals, however, patients must avoid grapefruit 
and grapefruit juice while on duvelisib. 
Dose reductions and interruptions for individual patients because of toxicity may be made based 
on the clinical judgment of the Investigator (see Section 9.4). In the event of a dose reduction, 
doses of less than 25 mg will utilize the 5 mg capsules. 
Refer to the Pharmacy Manual for additional instructions regarding study drug administration. 
9.1.1. 
Dose Optimization Phase 
In the Dose Optimization Phase, the duvelisib dose schedule is dependent on the cohort 
allocation, as follows: 
 Cohort 1: Duvelisib PO BID at a starting dose of 25 mg, with potential escalation on a 
per-patient basis to 50 mg and then 75 mg, based on the patient’s response to and 
tolerance of therapy, in 28-day cycles 
 Cohort 2: Duvelisib 75 mg PO BID, administered in 28-day cycles 
In Cohort 1, all patients will receive duvelisib at a starting dose of 25 mg PO BID (Level 1), with 
potential sequential escalation to 50 mg PO BID (Level 2), and then to 75 mg PO BID (Level 3). 
The duvelisib dose will be escalated on a per-patient basis in 25-mg increments as follows. 


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After completion of Cycle 1 and every 2 cycles thereafter: 
 Patients with CR or PR will have their duvelisib dose maintained at the current dose level 
 Patients with SD will have the duvelisib dose increased to the next level until the next 
response assessment or development of PD or intolerance 
Patients with PD, who are not tolerating therapy, or not otherwise suitable to continue receiving 
therapy, will have duvelisib discontinued 
In no case will the duvelisib dose be increased to a level > 75 mg BID (total daily dose 150 mg). 
All patients in the Dose Optimization Phase will receive duvelisib until development of PD or 
unacceptable toxicity, as determined by the Investigator. Note that for the purposes of patient 
management during the conduct of the study, the Investigator’s assessment of disease response 
will be used. Dose Optimization Phase patients will complete treatment as defined for their 
cohort. 
9.1.2. 
Expansion Phase 
The duvelisib dose in the Expansion Phase will be: 
Duvelisib PO at 75 mg BID for the first 2 cycles (cycle = 28 days) until the first response 
assessment (See Table 4). Then, dose will be reduced to 25 mg BID and administered in 28-day 
cycles. 
If a subsequent assessment demonstrates progression and the patient did not require a dose 
modification due to toxicity, the dose can be re-escalated to 75 mg BID with a confirmatory scan 
after approximately 4 weeks of therapy. If the patient has progressive disease at the confirmatory 
scan, then the patient should be discontinued. Patients that re-escalate to 75 mg BID may remain 
at this dose level until the need for dose modification or the criteria for discontinuation is met. 
9.2. 
Description 
Duvelisib drug substance is a white to off-white crystalline powder. The duvelisib drug product 
is formulated in 2 different capsule strengths (5 mg and 25 mg; percent active drug in capsules 
are identical) for oral delivery with excipients (diluent, glidant, disintegrant, and lubricant) that 
are listed in the US FDA Inactive Ingredients Database for approved drug products and/or 
Generally Recognized as Safe. 
Additional information is provided in the Pharmacy Manual. 
9.3. 
Packaging and Labeling 
Duvelisib packaging and labeling will be prepared to meet all regulatory requirements. 


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9.3.1. 
Dispensing and Storage Instructions 
Dispensing and storage instructions for duvelisib will be provided in the Pharmacy Manual. 
On receipt at the investigative site, duvelisib should remain in the blister cards provided until use 
or dispensation. The blister cards should be stored at the investigative site at room temperature 
(15 to 30C or 59 to 86F). All excursions should be brought to Secura Bio's attention for 
assessment and authorization for continued use. Expired drug is not to be dispensed. 
9.3.2. 
Drug Accountability 
Accountability for study drug at the site is the responsibility of the Investigator. The Investigator 
or delegated study staff will verify the integrity of the clinical study supplies (storage conditions, 
correct amount received, condition of shipment, kit numbers, etc.). 
Records of duvelisib (used, lost, destroyed, and returned blister cards) must be maintained. Drug 
accountability records will indicate the drug’s delivery to and receipt by the site, inventory at the 
site, dispensing to patients, use by each patient, and amount returned and/or disposed. Drug 
accountability records will be checked routinely by the study monitor. 
Unused duvelisib will be destroyed locally per site standard operation procedures or returned to a 
location designated by Secura Bio. Destruction of duvelisib should not occur until the end of the 
study, unless otherwise authorized by Secura Bio. 
9.4. 
Toxicity Management 
9.4.1. 
Toxicity Grading Criteria 
Toxicity grading will be assessed by the Investigator using the NCI CTCAE version 5.0: 
http://evs.nci.nih.gov/ftp1/CTCAE/About.html. 
9.4.2. 
Dose Modifications and Discontinuation 
If a patient has an AE at least possibly related to duvelisib, then dose interruptions with possible 
modifications and toxicity management may be implemented as noted in Table 8. Adjustments to 
these guidelines may occur based on the clinical judgment of the Investigator with notification to 
the Medical Monitor/Sponsor. Additional information on the management of toxicities can be 
found in the Summary of Data and Guidance to the Investigator section of the Investigator’s 
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Table 8: 
Duvelisib Dose Modification and Toxicity Management 
Treatment Related 
Toxicity1,2 
Adverse Reaction Grade 
Duvelisib Dose Modification and Toxicity 
Management 
Nonhematologic Adverse Reactions 
Infections 
 Grade 3 or higher infection 
 
Withhold until resolved  
 
Resume at the same or reduced dose (see Table 9) 
Clinical CMV infection or 
viremia (positive PCR or 
antigen test) 
 
Withhold until resolved  
 
Resume at the same or reduced dose (see Table 9)  
 
If duvelisib is resumed, monitor patients for CMV 
reactivation (by PCR or antigen test) at least monthly 
PJP 
 
For suspected PJP, withhold duvelisib until evaluated 
 
For confirmed PJP, discontinue duvelisib 
Non-infectious 
Diarrhea or colitis  
Mild/moderate diarrhea 
(Grade 1-2, up to 6 stools per 
day over baseline) and 
responsive to antidiarrheal 
agents, 
OR 
Asymptomatic (Grade 1) 
colitis 
 
No change in dose  
 
Initiate supportive therapy with antidiarrheal agents 
as appropriate 
 
Monitor at least weekly until resolved 
Mild/moderate diarrhea 
(Grade 1-2, up to 6 stools per 
day over baseline) and 
unresponsive to antidiarrheal 
agents 
Withhold until resolved 
 
Initiate supportive therapy with enteric acting 
steroids (e.g., budesonide)  
 
Monitor at least weekly until resolved 
 
Resume at a reduced dose (see Table 9)  
 
Abdominal pain, stool with 
mucus or blood, change in 
bowel habits, peritoneal 
signs, 
 
OR 
 
Severe diarrhea (Grade 3, 
> 6 stools per day over 
baseline) 
 
Withhold until resolved 
 
Initiate supportive therapy with enteric acting 
steroids (e.g., budesonide) or systemic steroids 
 
Monitor at least weekly until resolved 
 
Resume at a reduced dose (see Table 9) 
 
For recurrent Grade 3 diarrhea or recurrent colitis of 
any grade, discontinue  
Life-threatening 
 
Discontinue  


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Treatment Related 
Toxicity1,2 
Adverse Reaction Grade 
Duvelisib Dose Modification and Toxicity 
Management 
Cutaneous reactions 
Grade 1-2 
 
No change in dose 
 
Initiate supportive care with emollients, anti-
histamines (for pruritus), or topical steroids 
 
Monitor closely 
Grade 3 
 
Withhold until resolved 
 
Initiate supportive care with emollients, anti-
histamines (for pruritus), or topical steroids 
 
Monitor at least weekly until resolved 
 
Resume at reduced dose (see Table 9) 
 
If severe cutaneous reaction does not improve, 
worsens, or recurs, discontinue 
Life-threatening 
 
Discontinue 
SJS, TEN, DRESS (any 
grade) 
 
Discontinue 
Pneumonitis without 
suspected infectious 
cause 
Moderate (Grade 2) 
symptomatic pneumonitis 
 
Withhold 
 
Treat with systemic steroid therapy 
 
If pneumonitis recovers to Grade 0 or 1, duvelisib 
may be resumed at reduced dose (see Table 9) 
 
If non-infectious pneumonitis recurs or patient does 
not respond to steroid therapy, discontinue 
Severe (Grade 3) or life-
threatening pneumonitis 
 
Discontinue 
 
Treat with systemic steroid therapy 
ALT/AST elevation 
3 to 5 × upper limit of 
normal (ULN) (Grade 2) 
 
Maintain duvelisib dose  
 
Monitor at least weekly until return to  
< 3 × ULN 
> 5 to 20 × ULN (Grade 3) 
 
Withhold duvelisib and monitor at least weekly until 
return to < 3 × ULN  
 
Resume duvelisib at same dose (first occurrence) or 
at a reduced dose for subsequent occurrence (see 
Table 9) 
> 20 × ULN (Grade 4) 
 
Discontinue duvelisib 
Hematologic Adverse Reactions 
Febrile neutropenia 
Grade 3-4 
 
Withhold duvelisib until afebrile and resolution of 
Grade 3 or Grade 4 neutropenia to Grade ≤ 2 (ANC 
> 1.0 Gi/L) 
 
Monitor ANC at least weekly until > 1.0 Gi/L 
 
Resume at same dose (first occurrence) or at a 
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Treatment Related 
Toxicity1,2 
Adverse Reaction Grade 
Duvelisib Dose Modification and Toxicity 
Management 
Neutropenia 
Absolute neutrophil count 
(ANC) 0.5 to 1.0 Gi/L 
 
Maintain duvelisib dose 
 
Monitor ANC at least weekly 
ANC less than 0.5 Gi/L 
 
Withhold duvelisib 
 
Monitor ANC until > 0.5 Gi/L 
 
Resume at same dose (first occurrence) or at a 
reduced dose for subsequent occurrence (see 
Table 9) 
Thrombocytopenia 
Platelet count 25 to < 50 
Gi/L (Grade 3) with Grade 1 
bleeding 
 
No change in dose 
 
Monitor platelet counts at least weekly 
Platelet count 25 to < 50 
Gi/L (Grade 3) with Grade 2 
bleeding  
or  
Platelet count < 25 Gi/L 
(Grade 4) 
 
Withhold duvelisib 
 
Monitor platelet counts until ≥ 25 Gi/L and 
resolution of bleeding (if applicable) 
 
Resume at same dose (first occurrence) or resume at 
a reduced dose for subsequent occurrence (see 
Table 9) 
Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate 
aminotransferase; CMV = cytomegalovirus; DRESS = drug reaction with eosinophilia and systemic systems; Gi = 
1 x 109; PCR = polymerase chain reaction; PJP = Pneumocystis jirovecii; pneumonia; SJS = Stevens-Johnson 
syndrome; TEN = toxic epidermal necrolysis; ULN = upper limit of normal 
1. 
Treatment-related toxicity: possible, probable, or definite relationship to study treatment  
2. Toxicity grades are defined per CTCAE version 5.0. Note if parameter is not defined by CTCAE, then AE 
grading criteria (Section 10.4) should be utilized. 
Duvelisib may be held up to 42 days for toxicity. Doses held for > 42 days due to treatment-
related toxicity will result in permanent discontinuation from duvelisib unless Sponsor Medical 
Monitor approves resuming treatment after Investigator confirmation of acceptable benefit-risk 
assessment. Any patient who requires a dose-level reduction to below dose level -3 (see Table 9) 
due to treatment-related toxicities will be permanently discontinued from duvelisib treatment. 
In the event that study drug is discontinued due to any reason other than PD (e.g., AE), patients 
should continue disease response assessments until documentation of PD, as determined by the 
Investigator, death, or new anticancer treatment as outlined in Table 3 or Table 5. 
Dose reduction levels, based on the patient’s initial assigned dose optimization dose level, are 
shown in Table 9. 
Table 9: 
Duvelisib Dose Reduction Levels for Patients Receiving 25 mg or 75 mg BID 
Dose Level 
Duvelisib (mg) 
Starting Dose 
25 BID 
75 BID 


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-1 
15 BID 
50 BID 
-2 
10 BID 
25 BID 
-3 
5 BID 
15 BID 
Abbreviations: BID = twice daily 
In the Dose Optimization Phase, patients in Cohort 1 will start treatment with duvelisib 25 mg 
BID; however, by design, a patient’s assigned dose may be increased to 50 mg BID, based on the 
dose escalation scheme; dose reduction levels for such patients are shown in Table 10. 
Table 10: 
Duvelisib Dose Reduction Levels for Patients Receiving 50 mg BID 
Dose Level 
Duvelisib (mg) 
Starting Dose 
50 BID 
-1 
25 BID 
-2 
15 BID 
-3 
10 BID 
Abbreviations: BID = twice daily 
For dosing requirements in the Expansion Phase, please refer to Section 9.1.2. 
9.5. 
Permitted Concomitant Medications and Procedures 
Patients should receive full supportive care (including transfusion of blood and blood products 
and antibiotics, etc.) according to local standards and guidelines. Treatment for nausea, vomiting, 
and diarrhea is permitted according to institutional guidelines. Concomitant medications received 
from 30 days before the Screening visit through the Safety Follow-up visit will be recorded in 
the eCRF. 
9.5.1. 
Antimicrobial Prophylaxis 
Based on the duvelisib clinical experience to date, the following are recommended: 
 Patients are required to receive pneumocystis prophylaxis concomitant with study drug 
treatment. Selection of pneumocystis prophylaxis agent is per Investigator discretion. 
Patients who are found to be intolerant of all available pneumocystis prophylaxis may 
continue with study treatment at the discretion of the Investigator 
 Herpes simplex virus (HSV) and varicella zoster virus (VZV) infections have been 
observed with duvelisib; therefore, herpes (HSV/VZV) prophylaxis concomitant with 
treatment is recommended, per Investigator discretion according to institutional 
guidelines 
 Patients with a history of CMV infection or reactivation that required treatment, or 
history of other opportunistic infections, should be monitored for reactivation per 


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Investigator standard practice. Prophylactic treatment per institutional guidelines is 
recommended for patients considered by Investigator to be at high risk for CMV 
reactivation 
 Antimicrobial prophylaxis is recommended for patients with history of or considered at 
high risk for opportunistic infections and during periods of severe neutropenia. Choice of 
antimicrobial agent (antifungal, antibiotic, antiviral) is per the Investigator’s discretion 
 Investigators may consider administration of pneumococcal pneumonia vaccine prior to 
C1D1 
9.5.2. 
Transfusion and Growth Factor Support (Prophylaxis or Supportive Care) 
During any time on treatment, blood cell transfusion (packed red blood cells or platelets) to 
maintain a patient’s hemoglobin ≥ 8.0 mg/dL or platelets ≥ 10,000 per µL is recommended. 
Transfusions may be used at any time, as clinically indicated.  
Prophylactic use of growth factors such as granulocyte-colony stimulating factor (G-CSF) or 
pegylated G-CSF may be implemented if clinically indicated, in accordance with institutional 
guidelines and/or according to the National Comprehensive Cancer Network or ASCO practice 
guidelines for myeloid factors). Patients on a stable dose of erythropoietin to treat baseline 
anemia may continue on this therapy at this dose. 
9.5.3. 
Contraception and Pregnancy 
The effects of duvelisib on conception, pregnancy, and lactation are unknown. 
At Screening, male and female patients of reproductive potential (i.e., not surgically sterile or 
female patients who are not postmenopausal) must be willing to use a highly effective method of 
contraception for the duration of study treatment and for at least 3 months after the last dose of 
duvelisib. See Appendix 1 for Contraceptive Guidance including examples of highly effective 
contraceptive methods. Pregnancy testing will be performed throughout the study as shown in 
the Schedule of Events (Table 1 and Table 2). 
9.6. 
Excluded Concomitant Medications and Procedures 
9.6.1. 
Vaccines 
For all patients, the use of live or live attenuated vaccines is prohibited within 6 weeks prior to 
C1D1during the treatment with duvelisib, and for 3 months after the last dose of study drug. 
Investigators may consider administration of pneumococcal pneumonia vaccine prior to C1D1 
The use of inactivated (or killed) vaccines is allowed during the study, however patients and their 
physicians should be aware that the effectiveness of any vaccine administered concomitantly 


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with duvelisib may be diminished. The ability to generate an immune response to any vaccine 
following the administration of duvelisib has not been studied. 
9.6.2. 
Immunosuppressants 
Patients 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 
QD, unless being used to treat treatment-emergent toxicity. 
NOTE: Acute treatment for underlying autoimmune disorders (e.g., reactive airway disease, 
rheumatoid arthritis) 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). 
9.6.3. 
Other Anticancer Therapy or Investigational Agents 
During study treatment period, additional anticancer therapy or other investigational agents are 
prohibited during the study treatment period. 
9.6.4. 
Medications or Food that Inhibit or Induce CYP3A 
In vitro data indicate that duvelisib is mostly metabolized by CYP3A4. Therefore, concomitant 
use of drugs or foods that are strong inhibitors or inducers of CYP3A are not allowed during 
study treatment with duvelisib. 
Appendix 3 provides a list of medications known to be strong inhibitors or inducers of CYP3A. 
Please note that Appendix 3 is not a comprehensive list of all medications that may modulate 
CYP3A activity. 
Patients should avoid eating grapefruits or grapefruit-containing products. In addition, patients 
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. 
The Sponsor should be contacted with any questions regarding concomitant use of medications 
that are thought to modulate CYP3A activity. The concomitant use of moderate or weak 
inhibitors may be allowed in selected circumstances after consultation with the medical monitor. 
9.7. 
Concomitant Medications to be Used with Caution 
9.7.1. 
Medications that are Substrates of CYP3A or CYP2C8 
In vitro studies have demonstrated duvelisib is an inhibitor of CYP3A4. Coadministration of 
duvelisib with midazolam, a sensitive CYP3A substrate, resulted in an approximate 4-fold 
increase in the midazolam AUC. Systemic exposure to other medications that are substrates for 
CYP3A may be increased in patients receiving duvelisib. Caution should be used if duvelisib is 


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administered concomitantly with drugs that are substrates for CYP3A, particularly those with a 
narrow therapeutic range. Drugs that are substrates for CYP3A should be used only if medically 
necessary and therapeutic alternatives are not available. 
Duvelisib is an inhibitor of CYP2C8 in vitro. Physiologically based pharmacokinetic modeling 
indicates the inhibitory effect of duvelisib on CYP2C8 substrates is not expected to be clinically 
meaningful at a duvelisib dose of 25 mg BID. The predicted mean area under the curve ratio for 
rosiglitazone (a CYP2C8 substrate) with and without duvelisib 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 duvelisib. 
Medications that are metabolized via CYP2C8 may be used as medically indicated but with 
caution. 
Appendix 4 provides a list of medications known to be substrates of CYP3A or CYP2C8. Please 
note that Appendix 4 is not an exhaustive 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. 
9.7.2. 
Medications that are Substrates or Inhibitors of P-glycoprotein 
In vitro data indicate duvelisib is a substrate for P-glycoprotein (P-gp) and may have the 
potential to inhibit the activity of P-gp. P-gp substrates or inhibitors may be used as medically 
indicated but with caution. 
Appendix 5 provides a list of medications that are substrates or inhibitors of P-gp. Please note 
that Appendix 5 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. 
9.8. 
Other Concomitant Therapies 
Any other medication which is considered necessary for the patient’s welfare, and which is not 
expected to interfere with the evaluation of duvelisib may be given at the discretion of the 
Investigator. 
9.8.1. 
Photo Safety 
Duvelisib was determined to have the potential for phototoxicity in an in vitro phototoxicity 
assay and in a follow-up in vivo phototoxicity study. Patients should be advised to use 
appropriate protective measures to minimize exposure to direct sunlight or ultraviolet light 
sources during the treatment period and for at least 30 days after the last dose of duvelisib. 
9.9. 
Blinding and Unblinding 
Treatment assignment is not blinded. 


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9.10. 
Treatment Compliance 
The Investigator will dispense the study drug only for use by patients enrolled in the study as 
described in this protocol. The study drug is not to be used for reasons other than those described 
in this protocol. 
The Investigator or other study staff will supervise study drug given in the clinic and instruct the 
patient on duvelisib self-administration. Patients will be asked to bring their duvelisib blister 
cards with them at each visit. Compliance with protocol-defined duvelisib intake will be checked 
by pill count. 


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10. 
ADVERSE EVENT MANAGEMENT 
10.1. 
Definition of an Adverse Event 
An AE is defined as any untoward medical occurrence in a patient administered a medicinal 
product that does not necessarily have a causal relationship with this treatment. An AE can, 
therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not related to the study (investigational) product. This includes an exacerbation of 
pre-existing conditions or events, concurrent illnesses, drug interaction, or the significant 
worsening of the indication under investigation. Anticipated fluctuations of pre-existing 
conditions, including the disease under study that does not represent a clinically significant 
exacerbation or worsening, need not be considered AEs. 
Symptoms of the disease under study / lack of efficacy / disease progression should not be 
classified as an AE as long as they are within the normal day-to-day fluctuation or expected 
progression of the disease. 
It is the responsibility of the Investigator to document all AEs that occur during the study. AEs 
should be reported on the appropriate page of the eCRF. 
10.2. 
Definition of a Serious Adverse Event 
An SAE is any untoward medical occurrence at any dose (including after the ICF is signed and 
prior to dosing) that: 
 Results in death 
 Is life-threatening (patient is at immediate risk of death from the event as it occurred) 
 Requires inpatient hospitalization (formal admission to a hospital for medical reasons) or 
prolongation of existing hospitalization 
 Results in persistent or significant disability/incapacity 
 Results in a congenital anomaly/birth defect 
Important medical events that may not result in death, are not immediately life-threatening, or do 
not require hospitalization may be considered SAEs when, based on appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. Examples of such 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 
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For SAE reporting purposes, hospitalization is defined as an inpatient hospital stay ≥ 24 hours. 
Hospitalizations for elective surgery or other medical procedures that are not related to a TEAE 
are not considered SAEs. Hospitalization, which in the opinion of the Investigator, is unrelated to 
the study drug, and due to purely non-medical circumstances (e.g., respite care, lack of a 
caretaker at home, lack of transportation home) are also not considered to be SAEs. PD under 
study (including signs and symptoms of progression) if documented by use of appropriate 
methods, should not be reported as an SAE unless the outcome is fatal during the study or within 
the safety reporting period (see Section 10.3, Reporting of Adverse Events and Serious Adverse 
Events). If the malignancy has a fatal outcome during the study or within the safety reporting 
period, then the event should be reported using the term "disease progression" with a CTCAE 
severity of Grade 5. 
Death is an outcome. The primary reason for patients' death should be reported as an SAE. 
10.3. 
Reporting of Adverse Events and Serious Adverse Events 
The AE reporting period begins from the time that the patient signs the ICF through and 
including 30 calendar days after the last study drug dose. All treatment-related AEs/SAEs should 
be followed until resolution or stabilization. Any SAE occurring after the reporting period must 
be promptly reported if a causal relationship to the investigational drug is suspected. If the 
patient begins a new anticancer therapy, the safety reporting period ends at the time the new 
treatment is started, however, death must always be reported if it occurs during the AE reporting 
period irrespective of intervening treatment. 
Elective or previously scheduled hospitalizations for pre-existing conditions that have not 
worsened after initiation of treatment should not be classified as SAEs. For example, an 
admission for a previously scheduled ventral hernia repair would not be classified as an SAE. 
All AEs should be recorded individually unless, in the opinion of the Investigator or designated 
physician, the AEs constitute components of a recognized condition, disease, or syndrome. In the 
latter case, the condition, disease, or syndrome should be reported rather than each individual 
sign or symptom. 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 AE or SAE as appropriate on the relevant form(s) (SAE Report Form and/or AE 
eCRF). If a diagnosis is subsequently established, it should be reported as follow-up information 
is available. If a diagnosis is determined subsequent to the reporting of the constellation of 
symptoms, the signs/symptoms should be updated to reflect the diagnosis. 
Each AE is to be evaluated for duration, severity, seriousness, and causal relationship to the 
investigational drug. The action taken with study drug and the outcome must also be recorded. 
All SAEs, regardless of relationship to the study treatment, must be reported immediately to the 
Sponsor and Contract Research Organization (CRO) pharmacovigilance group, with the 
timeframe not to exceed 24 hours of the Investigator becoming aware of the event. Initial SAE 


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notification should be made by e-mailing or faxing the SAE report form to the e-mail or fax 
number provided on the SAE report form. 
An initial SAE Report may be sent without the Investigator’s signature but must be followed by 
a report signed by the Investigator within 48 hours of becoming aware of the event. Follow-up 
SAE reports must be submitted by the Investigator as new information becomes available. 
The Medical Monitors for this study may be contacted in case of need for advice or assistance. 
Contact details will be provided in the Study Manual. 
10.4. 
Severity of Adverse Events 
The severity of the AE will be graded according to the NCI CTCAE, version 5.0 (see web page 
at http://ctep.cancer.gov for details). AEs not listed in the CTCAE should be graded as 
summarized in Table 11. 
Table 11: 
CTCAE Grading 
CTC Grade Equivalent To: 
Definition 
Grade 1 
Mild 
Discomfort noticed but no disruption of normal 
daily activity  
Grade 2 
Moderate 
Discomfort sufficient to reduce or affect daily 
activity; no treatment or medical intervention is 
indicated although this could improve the overall 
well-being or symptoms of the patient 
Grade 3 
Severe 
Inability to work or perform normal daily activity; 
treatment or medical intervention is indicated in 
order to improve the overall well-being or 
symptoms; delaying the onset of treatment is not 
putting the survival of the patient at direct risk 
Grade 4 
Life-threatening/ 
disabling 
An immediate threat to life or leading to a 
permanent mental or physical conditions that 
prevents work or performing normal daily 
activities; treatment or medical intervention is 
required in order to maintain survival 
Grade 5 
Death 
AE resulting in death  
 


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10.5. 
Relationship of Adverse Events to Study Drug 
The Investigator will make a judgment regarding whether or not the AE was related to study 
drug, as outlined below: 
 Definitely related: This category applies when, after careful medical consideration, there 
is almost no consideration of other causation. 
 Probably related: There is a clinically plausible time sequence between onset of the AE 
and study drug administration. The AE is unlikely to be caused by a concurrent or 
underlying illness, other drugs, or procedures. If applicable, the AE follows a clinically 
consistent resolution pattern upon withdrawal of study drug. 
 Possibly related: There is a clinically plausible time sequence between onset of the AE 
and study drug administration, but the AE could also have been caused by the concurrent 
or underlying illness, other drugs, or procedures. Information regarding study drug 
withdrawal may be lacking or unclear. "Possible" should be used when study drug 
administration is one of several biologically plausible causes of the AE. 
 Unlikely related: The AE is most likely due to a cause not related to study drug 
administration. However, association with the study drug cannot be completely ruled out. 
 Unrelated: Another cause of the AE is most plausible and a clinically plausible temporal 
sequence is inconsistent with the onset of the AE and study drug administration and/or a 
causal relationship is considered biologically implausible. 
For the purpose of regulatory reporting requirements, causal relationships of definite, probable, 
and possible will be considered treatment-related, while unlikely and unrelated will be 
considered not treatment-related. 
10.6. 
Clinical Laboratory Adverse Events 
A clinical laboratory AE is any laboratory value that is deemed clinically significant by the 
Investigator, is greater than Grade 2 in severity, and is accompanied by one of the following: 
 requires a medical intervention 
 requires a change or suspension of study drug 
 is accompanied by clinical symptoms 
Laboratory abnormalities that have not required medical intervention should not be recorded as 
AEs and will be captured and reported in the Laboratory section of the clinical study report. If a 
medical intervention occurs, it should be recorded as a treatment with the abnormal laboratory 
finding as the AE (e.g., anemia with treatment required and blood transfusion recorded as a 


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procedure, hyperglycemia with treatment required and change in insulin dose recorded on 
concomitant medications). 
The Investigator should decide, based upon the AE criteria and the clinical condition of the 
patient, whether a change in a laboratory parameter is clinically significant and therefore 
represents an AE. 
If, at the end of the treatment phase with the study drug, there are pathological laboratory values 
which were not present at Baseline, further clinical or laboratory investigations should be 
performed until the values return to within reference range or until a plausible explanation (i.e., 
concomitant disease) is found for the pathological laboratory values. 
10.7. 
Regulatory Aspects of Adverse Event Reporting 
The Sponsor is responsible for submitting reports of SAEs associated with the use of the study 
drug to the appropriate Regulatory Authority (e.g., the US Food and Drug Administration), 
Investigators, and IRB/IEC/central ethics committee (CEC) in accordance with all applicable 
regulations and guidelines. 
It is the responsibility of the Investigator to notify the IRB of all SAEs that occur at his or her 
site. Investigators will be notified of all suspected unexpected serious adverse reactions 
(SUSARs; 7 / 15 Day Safety Reports) that occur during any clinical studies that are using the 
investigative compound. Each site is responsible for notifying their IRB/IEC/CEC of these 
additional SUSARs in accordance with local regulations. 
10.8. 
Overdose 
In the case of overdose, clinic staff should be notified immediately, and supportive care is to be 
given as indicated. Patients should be informed to contact their doctor immediately if they have 
taken an overdose and should stop taking duvelisib. 
For this study, overdose is defined as a daily dose of duvelisib higher than the prescribed daily 
dose. Overdoses will not be considered SAEs unless the outcome of the overdose meets 
seriousness criteria as defined in Section 10.2, Definition of a Serious Adverse Event. In the 
event of an overdose, the Sponsor should be immediately notified. The patient should be 
carefully monitored for potential adverse reactions and symptomatic treatment instituted as per 
institutional standards of care. 
10.9. 
Pregnancy 
Pregnancy per se is not considered an AE unless there is cause to believe that the study drug may 
have interfered with the effectiveness of a contraceptive medication or if the outcome of the 
pregnancy meets SAE criteria (miscarriage or congenital anomaly/birth defect, etc.), in which 
case it should be reported in the same manner and timelines as an SAE. In addition, any infant 
death or congenital anomaly occurring after 30 days that the Investigator suspects is related to 


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the in-utero exposure to the study drug should also be reported as an SAE. Hospitalization for 
normal delivery of a healthy newborn is not an SAE. 
Since duvelisib has not been evaluated in pregnant or nursing women, the treatment of pregnant 
women or WCBP who are not using effective contraception is contraindicated (see 
Section 6.10.2 and Section 9.5.3 for instructions on pregnancy testing and birth control). 
Pregnancies occurring in patients or partners of male patients during the study treatment period 
until 30 days after the patient’s last dose of study treatment are considered immediately 
reportable events. If a pregnancy occurs in a patient, 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 the Sponsor or designee within 24 hours of the Investigator’s 
knowledge of the pregnancy using a Pregnancy Report Form. 
The Investigator will follow the pregnant woman until completion of the pregnancy and must 
notify the Sponsor of the outcome within 24 hours of the Investigator’s knowledge of the 
pregnancy outcome using a Pregnancy Outcome Form. This notification includes pregnancies 
resulting in live, “normal” births. 


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11. 
STATISTICAL METHODS 
11.1. 
Statistical Analysis Plan 
A formal detailed Statistical Analysis Plan (SAP) will be used for the evaluation of the Dose 
Optimization Phase and Expansion Phase. The SAP will be finalized prior to database lock. 
Deviations from the statistical analyses outlined in this protocol will be indicated in the SAP; any 
further modifications will be noted in the final clinical study report. 
11.2. 
Determination of Sample Size 
Approximately 20 patients will be enrolled in the Dose Optimization Phase, with approximately 
10 evaluable patients per cohort. However, enrollment may discontinue in either cohort if no 
CR/PR is noted in the first 5 evaluable patients per cohort. This stopping rule is based on the first 
stage decision rule of a Simon 2-stage design, with assumptions of a hypothesized ORR of 50% 
and a null rate of 15% with a one-sided alpha of 0.05 and a power of 85%. 
Patients in the Dose Optimization Phase who discontinue before receiving at least 1 cycle of 
study drug may be replaced. 
In the Expansion Phase, the target enrollment is approximately 100 patients with a centrally 
confirmed diagnosis of PTCL. It is anticipated up to 5% of patients may have a diagnosis that is 
not confirmed upon central pathology review. One-hundred patients will provide 99.2% power to 
distinguish between a null ORR of 20% and an alternative ORR of 40% with a two-sided alpha 
of 0.05. Further, with approximately 100 patients treated at the optimal duvelisib dose, the 
obtained ORR will have 95% confidence bounds of no greater than ± 10% when the normal 
approximation method is employed (assumes 50% ORR). If the observed ORR is greater or less 
than 50%, the confidence bounds will be less than ± 10%. These bounds around the obtained 
ORR are thought to adequately characterize the effect of the optimal dose of duvelisib in this 
PTCL population.  
With protocol amendment 7.0, 20-30 additional patients will be enrolled in the expansion phase. 
Assuming a total of 120 or 130 patients the power to distinguish between a null hypothesis of 
ORR of 20% and an alternative ORR of 40% will be 99.4% or 99.6%, respectively. Table 12 has 
been updated with the 95% confidence bounds using the normal approximation method under the 
assumption of 120 and 130 total patients.  
 
Table 12 below shows the 95% confidence bounds that would be observed under different ORRs 
by total number of patients: 


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Table 12: 
Confidence Bounds for Potential ORR Scenarios 
ORR % 
95% CI Bound 
95% CI Bound 
95% CI Bound 
 
(N=100) 
(N=120) 
(N=130) 
30% 
21%-39% 
22%-38% 
22%-38% 
35% 
26%-44% 
26%-44% 
27%-44% 
40% 
30%-50% 
31%-49% 
32%-48% 
45% 
35%-55% 
36%-54% 
37%-54% 
50% 
40%-60% 
41%-59% 
41%-59% 
Abbreviations: CI = confidence interval; ORR = overall response rate 
 
The primary analysis for the Expansion Phase will be performed once approximately 
100 patients with a centrally confirmed diagnosis of PTCL have been enrolled and evaluated for 
the primary endpoint. In the event that enrollment in the expansion phase exceeds 110% of the 
planned sample size, a sensitivity analysis will be performed on the first 100 patients enrolled in 
the Expansion Phase. 
 
The final analysis for the Expansion phase will be performed once all patients with a centrally 
confirmed diagnosis of PTCL have been enrolled and evaluated for the primary endpoint. The 
total number of patients (up to 130) will be determined by the Sponsor. An important driver of 
the final sample size may be the number of additional patients needed to add an additional 8-10 
patients having PTCL subtype of either ALCL or NK cell. 
 
11.3. 
Randomization and Stratification 
In the Dose Optimization Phase only, patients will be randomly assigned on C1D1 to either 
Cohort 1 or 2 on a 1:1 basis via a computer-generated randomization scheme. No stratification 
methodology will be employed in this study. 
11.4. 
Populations for Analysis 
The populations used for analysis will include the following: 
 Dose Optimization Efficacy Population, consisting of all patients who 1) receive at least 
one dose of study drug and 2) complete at least one cycle of treatment and 3) have at least 
one scan to assess disease response after completion of one cycle of treatment 
 The Safety Population, consisting of all patients receiving at least 1 dose of duvelisib 


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 The mITT Population, consisting of all patients who receive at least one dose of duvelisib 
which will be used for the Expansion Phase primary and secondary analyses as well as all 
safety analyses 
All patients enrolled into the study will be included in data listings. All primary and secondary 
analyses will be performed separately for patients in the Dose Optimization and Expansion 
phases. Additional analyses combining patients from the Dose Optimization and Expansion 
phases may be performed as applicable. Further details will be provided in the SAP. Summary 
statistics will be produced by dose level, for patients with dose changes and for the overall study 
population for both safety and biological effect parameters. 
11.5. 
Procedures for Handling Missing, Unused, and Spurious Data 
All available efficacy and safety data will be included in data listings and tabulations. Data that 
are potentially spurious or erroneous will be examined according to standard data management 
operating procedures. 
In general, missing data will be treated as missing and no data imputation will be applied, unless 
otherwise specified. 
11.6. 
Patient Disposition 
The number of screened patients, screen failures, treated patients, patients who completed the 
study, and patients who discontinued the study will be summarized. Reasons for discontinuation 
will also be summarized. 
11.7. 
Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be summarized in a descriptive fashion. Data to be 
tabulated will include gender, age, race, ethnicity, height, and weight, as well as disease-specific 
characteristics and other parameters as appropriate. These analyses will be conducted on the 
Safety Population. 
11.8. 
Exposure 
Treatment exposure will be summarized by cycle and overall. 
11.9. 
Efficacy Analyses 
For the Dose Optimization Phase, all primary and secondary efficacy analyses will be performed 
using the Dose Optimization Efficacy Population and will be based on the Investigator’s 
determination of response, with the IRC’s determination of response used for supportive efficacy 
analyses. Analysis of the Expansion Phase primary and secondary efficacy analyses will be 
performed using the mITT population and will be based on the IRC’s determination of response, 
with the Investigator’s determination of response used for supportive efficacy analyses. All time 


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to event analyses will present median times to event and 2-sided 95% confidence bounds. 
Censoring rules will be detailed in the SAP. Neither IRC or Investigator’s determination will 
require confirmation by a second assessment. 
Primary Efficacy Analysis:  
 ORR will be tabulated using response determination by the Investigator (Dose 
Optimization) or IRC (Expansion). Best overall response and response assessments over 
time will be presented along with 2-sided confidence intervals 
Secondary Efficacy Analyses: 
 DOR will be calculated for those patients with a CR or PR from the time of first response 
to PD, using Kaplan-Meier methods 
 The proportion of patients demonstrating DCR defined as CR + PR + SD ≥ 8 weeks, will 
also be presented along with 2-sided confidence intervals 
 The proportion of patients receiving the optimal dose of duvelisib will be summarized 
 PFS will be assessed using Kaplan-Meier methods from time of first treatment to PD, or 
death 
 OS will be assessed using Kaplan-Meier methods from time of first treatment to death 
11.10. 
Safety Analyses 
Safety analyses will be performed on the Safety population, and safety endpoints will be 
tabulated and presented. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) for 
purposes of summarization. All AEs occurring during the study will be included in by-patient 
data listings and tabulated by MedDRA system organ class and preferred term. Adverse events 
will be summarized overall, by relationship and by severity. Events leading to death, SAE, and 
events resulting in treatment discontinuation will be listed and, if warranted by the data, 
tabulated. 
Exposure to study drug and study drug compliance will be tabulated. 
A by-patient listing of ECOG performance status data will be prepared. 
The actual value and change from Baseline to each on-study evaluation will be summarized for 
vital sign measurements, as warranted by the data. By-patient listings of vital sign measurements 
will be prepared. 


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Individual patient laboratory parameter values and summary statistics over time will be prepared 
using descriptive statistics. Severity of select clinical laboratory measures will be determined 
using NCI CTCAE criteria and Grade 3 or 4 laboratory values will be presented in a separate 
patient listing. 
The use of concomitant medications, coded using World Health Organization Drug Dictionary, 
will be included in by-patient listing. 
Additional safety analyses may be performed to most clearly enumerate rates of toxicities and to 
further define the safety profile of duvelisib. 
11.11. 
Pharmacodynamic and Biomarker Data 
Pharmacodynamic and Biomarker analyses will be conducted on all or some of the Safety 
Population. Pharmacodynamic sample collection will only occur in the US. 
Biomarkers such as gene mutation status, gene translocations, immunophenotype, functional 
immune assays, gene expression, and cytokines, will be evaluated with regard to baseline levels 
and change to baseline levels. Additional exploratory analyses identified by the Sponsor also 
may be performed. Listing of individual patient and summary statistics for duvelisib effects on 
biomarkers and graphs of changes versus time will be prepared. Biomarker effects will be 
summarized using descriptive statistics and associations with clinical efficacy and/or safety 
outcomes may be explored. 
11.12. 
Pharmacokinetic Data 
Pharmacokinetic analyses will be conducted on the Safety Population. 
Blood samples will be taken for the analyses of duvelisib and possible metabolite(s) in plasma at 
the time points defined in the schedule of assessments. The relevant PK parameters will be 
determined using bioanalytical data. The PK data will be summarized using descriptive statistics 
and will be listed and summarized in tabular and/or graphical form. 
11.13. 
Interim Analyses 
During the Dose Optimization Phase, the ORR will be evaluated in the first 5 evaluable patients 
for each cohort. Enrollment may discontinue in either cohort if no CR/PR is noted in the first 
5 evaluable patients. 
After a sufficient number of patients from the Dose Optimization Phase are evaluable, all 
available data will be reviewed and an optimal dose for the Expansion Phase will be selected 
(Note: the optimal dose for the Expansion Phase has been selected and documented in Protocol 
Amendment 2, V3, 14 March 2019 – see Expansion Phase Dose Selection below and Section 
1.3). The interim results of the Optimization Phase may also drive changes to the Expansion 
Phase of the study such as modification to the study patient population, other aspects of entry 


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criteria, and the inclusion of patients from geographic regions outside the US; any such changes 
will be documented in an amendment to the protocol. The Secura Bio study team, in 
collaboration with the Investigators, will make the determination of duvelisib dose for the 
Expansion Phase of the study based on the safety and activity data. 
During the Expansion Phase, an assessment of ORR will be conducted after 40 patients have 
been followed for a minimum 4 months from the last patient’s first dose. Enrollment in the 
Expansion Phase may be held if ORR as assessed by IRC is less than 20%. At that time, the 
efficacy data (including durability of response) will be reviewed in combination with safety and 
PK and upon review, the study may be fully stopped for futility. 
Interim analyses may be performed at various timepoints during the Expansion Phase. The 
additional interim analyses should have no impact on statistical power, as the study is an open 
label single arm design. 
 


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12. 
ADMINISTRATIVE REQUIREMENTS 
12.1. 
Good Clinical Practice 
The study will be conducted in accordance with ICH-GCP and the appropriate regulatory 
requirement(s). The Investigator will be thoroughly familiar with the appropriate use of the study 
drug as described in the protocol and the IB. 
12.2. 
Ethical Considerations 
Before implementing this study, the protocol, the proposed patient informed consent forms and 
any other information provided to the patients, must be reviewed and approved by a properly 
constituted IRB/IEC/CEC. 
Any substantive change or addition to the protocol can only be made in a written protocol 
amendment that must be approved by the Sponsor, the IRB/IEC/CEC and the Regulatory 
Authority. 
The study will be conducted only at sites where IRB/IEC/CEC approval has been obtained. The 
protocol, IB, ICF, advertisements (if applicable), written information given to the patients 
(including diary cards), safety updates, annual progress reports, and any revisions to these 
documents will be provided to the IRB/IEC by the Investigator or the Sponsor, as required by 
local regulations. 
12.3. 
Informed Consent 
After the study has been fully explained, written informed consent will be obtained from either 
the patient or his/her guardian or legal representative prior to study participation. The method of 
obtaining and documenting the informed consent and the contents of the consent must comply 
with ICH-GCP and all applicable regulatory requirements. Patients who are detained by 
administrative or judicial order will be excluded from participating in the study. 
12.4. 
Patient Confidentiality and Disclosure 
The Investigator and Investigator's staff shall maintain the confidentiality of all patient records. 
To maintain patient privacy, all eCRFs, study drug records, reports and communications will 
identify the patient by initials where permitted and/or the assigned patient number. The patient's 
confidentiality will be maintained and will not be publicly available to the extent permitted by 
the applicable laws and regulations. 
12.5. 
Data Collection 
The Investigator is required to prepare and maintain adequate and accurate case histories 
designed to record all observations and other data pertinent to the study for each patient. 


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Secura Bio or designee will provide the study sites with secure access to and training on the 
electronic data capture system, sufficient to permit site personnel to enter or correct information 
in the eCRFs. eCRFs will be completed for each study patient. The Investigator is responsible for 
ensuring the accuracy, completeness, and timeliness of the data entered in the eCRF. The audit 
trail will indicate the user's identification information and date and time of entry and/or change. 
eCRFs should be completed in a timely manner, and every effort should be made to have forms 
completed and up-to-date. 
At the conclusion of the study, Secura Bio or a designee will retain the eCRF data and 
corresponding audit trails. A copy of the final archival eCRF in the form of a CD or other 
electronic media will be placed in the Investigator's study file. 
12.6. 
Patient Data Protection 
Patients will be assigned a unique identifier during Screening. Any patient records or datasets 
that are transferred to the Sponsor will contain the identifier only; patient names or any 
information that would make the patient identifiable will not be transferred. 
The patient must be informed that his/her personal study-related data will be used by the Sponsor 
in accordance with local data protection law. The level of disclosure must also be explained to 
the patient who will be required to give consent for their data to be used as described in the 
informed consent. 
The patient must be informed that his/her medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the Sponsor, by appropriate 
IRB/IEC/CEC members, and by inspectors from regulatory authorities. 
12.7. 
Data Quality Assurance and Monitoring 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
Monitoring details describing strategy (e.g., risk-based initiatives in operations and quality such 
as Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), methods, 
responsibilities, and requirements (including handling of noncompliance issues and monitoring 
techniques [central, remote, or on-site monitoring]) are provided in the Monitoring Plan. 
The Sponsor or designee is responsible for the data management of this study, including quality 
checking of the data. 
The Sponsor assumes accountability for actions delegated to other individuals (e.g., contract 
research organizations). 


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Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of patients are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study agreements, 
ICH GCP, and all applicable regulatory requirements. 
Upon study completion, the monitor will arrange for a final review of the study files, after which 
the file should be secured by storage for the appropriate period as specified in Section 12.12 
Retention of Documents. 
12.8. 
Auditing Procedures 
In addition to routine monitoring Secura Bio or designee, the IRB/IEC/CEC, or Regulatory 
Authority may inspect the study (during the study or after its completion) to evaluate compliance 
with the protocol and GCP. 
The Investigator agrees that representatives of the Sponsor and Regulatory Authorities will have 
direct access, both during and after the course of this study, to audit and review all study-relevant 
records. 
12.9. 
Investigator Compliance 
The Investigator will conduct the study in compliance with the protocol provided by Secura Bio 
and approved by the IRB/IEC/CEC and the appropriate regulatory authority. Modifications to the 
protocol will not be made without agreement of Secura Bio, the IRB/IEC/CEC and the 
regulatory authority, except where modification is needed to eliminate an immediate hazard to 
the patient. In this event, the Investigator will contact Secura Bio or designee to discuss the 
planned course of action. Any deviation from the protocol must be documented. 
12.10. 
Product Complaints 
If a product complaint indicating dissatisfaction regarding the study drug is received, the 
Investigator should contact Secura Bio or designee. A product complaint in and of itself is not an 
AE. If a product complaint results in an SAE, an SAE form should be completed per the defined 
procedure. 
12.11. 
Study Closure 
Secura Bio or designee will notify the Regulatory Authorities and IRB/IEC/CECs that the study 
has ended. 
Study participation by individual sites or the entire study may be prematurely terminated if in the 
opinion of the Investigator or Secura Bio there is sufficient reasonable cause. Written notification 
documenting the reason for study termination will be provided to the Investigator or Secura Bio 
by the terminating party. 


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Circumstances that may warrant termination include but are not limited to: 
 Determination of unexpected, significant, or unacceptable risk to patients 
 Failure to enter patients at an acceptable rate 
 Insufficient adherence to protocol requirements 
 Insufficient, incomplete, and/or unevaluable data 
 Plans to modify, suspend or discontinue the development of the study drug 
12.12. 
Retention of Documents 
The Investigator must maintain source documents for each patient according to ICH-GCP and 
applicable regulatory requirements. Records will be retained for at least 2 years after the last 
marketing application approval or 2 years after formal discontinuation of the clinical 
development of the investigational product or according to applicable regulatory requirements. If 
the Investigator withdraws from the responsibility of keeping the study records, custody must be 
transferred to a person willing to accept the responsibility and Secura Bio notified. 
12.13. 
Disclosure of Information 
All information provided to the Investigator by Secura Bio, Inc. or its designee, will be kept 
strictly confidential. The Investigator agrees to use this information to accomplish the study and 
will not use it for other purposes without consent from Secura Bio. No information about this 
study or its progress will be provided to anyone not involved in the study other than to Secura 
Bio or its designees, or in confidence to the IRB, or similar committee, except if required by law. 
Upon completion of the clinical study and evaluation of results by Secura Bio, the hospital or 
institution, and/or Investigator may publish or disclose the clinical study results pursuant to the 
terms contained in the applicable Clinical Study Agreement. Sponsor will comply with current 
regulatory requirements for disclosure and submission of study results. 
The results of this study may be published or presented at scientific meetings with prior approval 
of the Sponsor. The Investigator agrees to submit all manuscripts or abstracts to the Sponsor 
before submission. This allows the Sponsor to protect proprietary information and to provide 
comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multi-site studies only in their entirety and not as individual site data. In this case, a coordinating 
Investigator will be designated by mutual agreement between the Sponsor and the Investigators. 


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Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 


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13. 
REFERENCES 
Barrington et al. Role of imaging in the staging and response assessment of lymphoma: 
consensus of the International Conference on Malignant Lymphomas Imaging Working Group. 
J Clin Oncol. 2014 Sep 20; 32(27): 3048–3058. 
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, and Lister TA. 
Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-
Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014;32(27):3059-3067. 
Clayton E, Bardi G, Bell SE, Chantry D, Downes CP, Gray A, et al. A crucial role for the 
p110delta subunit of phosphatidylinositol 3-kinase in B cell development and activation. J Exp 
Med. 2002;196(6):753-763. 
Coutré SE, Barrientos JC, Brown JR, de Vos S, Furman RR, Keating MJ, et al. Management of 
adverse events associated with idelalisib treatment: expert panel opinion. Leuk Lymphoma. 
2015;56(10):2779-86.  
Fung-Leung WP. Phosphoinositide 3-kinase delta (PI3Kdelta) in leukocyte signaling and 
function. Cell Signal. 2011;23(4):603-608. 
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 
4;144(5):646-74. 
Horwitz SM, Koch R, Porcu P, et al: Activity of the PI3K-delta, gamma inhibitor duvelisib in a 
phase 1 trial and preclinical models of T-cell lymphoma. Blood. 2018;131:888-898. 
Laribi, K, Alani M, Truong C, et al. Recent advances in the treatment of Peripheral T-cell 
Lymphoma. The Oncologist. Sept 2018;23(9):1039-1053. 
Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. 
Cancer Res. 2006 Jan 15;66(2):605-12. 
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and 
response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5 (6):649-
55. 
Okkenhaug K, Bilancio A, Farjot G, Priddle H, Sancho S, Peskett E, et al. Impaired B and T cell 
antigen receptor signaling in p110delta PI 3-kinase mutant mice. Science. 2002;297(5583):1031-
1034.  
Park S, Ko YH. Peripheral T cell lymphoma in Asia. Int J Hematol. 2014;99(3):227-39. 


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Schmid MC, Avraamides CJ, Dippold HC, Franco I, Foubert P, Ellies LG, et al. Receptor 
tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3Kgamma, a single 
convergent point promoting tumor inflammation and progression. Cancer Cell. 2011 Jun 
14;19(6):715-27. 
Vanhaesebroeck B, Guillermet-Guibert J, Graupera M, Bilanges B. The emerging mechanisms 
of isoform-specific PI3K signaling. Nat Rev Mol Cell Biol. 2010;11(5):329-341. 
Vose J, Armitage J, Weisenburger D; International T-Cell Lymphoma Project. International 
peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical 
outcomes. J Clin Oncol. 2008;26(25):4124-30.  
Zinzani PL, Bonthapally V, Huebner D, Lutes R, Chi A, Pileri S. Panoptic clinical review of the 
current and future treatment of relapsed/refractory T-cell lymphomas: Peripheral T-cell 
lymphomas. Crit Rev Oncol Hematol. 2016;99:214-27. 


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14. 
APPENDICES 
APPENDIX 1: 
CONTRACEPTION GUIDANCE 
The effects of duvelisib on conception, pregnancy, and lactation are unknown. Every woman of 
childbearing potential (WCBP) and male patients with a partner who is a WCBP must use 
contraception as described below. A woman is considered to be a WCBP after menarche and 
until becoming postmenopausal (i.e., > 55 years and postmenopausal for at least 1 year), unless 
permanently sterile. 
At Screening, all male and female patients of reproductive potential (i.e., not surgically sterile or 
female patients who are not postmenopausal) must agree to use a highly effective method of 
contraception (see below) for the duration of study treatment, and for at least 3 months after the 
last dose of duvelisib. Male patients must also refrain from donating sperm during their 
participation in the study and for at least 3 months after the last dose of duvelisib. 
The use of contraceptive methods is not required if the male patient or the male partner (of the 
female patient) has a documented history of a vasectomy or if the female patient or the female 
partner (of the male patient) has a documented history of bilateral oophorectomy, hysterectomy, 
or tubal ligation, or if she is > 55 years of age and postmenopausal for at least 1 year. 
See Section 10.9 for requirements for pregnancy reporting. 
Highly Effective Forms of Contraception 
Methods that can achieve a failure rate of less than 1% per year when used consistently and 
correctly are considered as highly effective birth control methods. Such methods include: 
 combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulationa: 
 oral 
 intravaginal 
 transdermal 
 progestogen-only hormonal contraception associated with inhibition of ovulationa: 
 oral 
 injectable 
 implantableb 
 intrauterine device (IUD)b  
 intrauterine hormone-releasing system (IUS)b 
 bilateral tubal occlusionb 
 vasectomized partnerb,c 
 sexual abstinenced 


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a Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy of 
the contraception method.  
bThis method of contraception should preferably be used, in particular when contraception is introduced as 
a result of participation in the clinical study. 
cVasectomized partner is a highly effective birth control method provided that partner is the sole sexual 
partner of the WCBP study participant and that the vasectomized partner has received medical assessment 
of the surgical success. 
d Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study treatments. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual 
lifestyle of the patient. 
 


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APPENDIX 2: 
EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) SCALE 
FOR PERFORMANCE STATUS 
Grade 
Description 
0 
Normal activity. Fully active, able to carry on all predisease performance 
without restriction 
1 
Symptoms but ambulatory. Restricted in physically strenuous activity, but 
ambulatory and able to carry out work of a light or sedentary nature (e.g., light 
housework, office work) 
2 
In bed < 50% of the time. 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 
In bed > 50% of the time. Capable of only limited self-care, confined to bed or 
chair more than 50% of waking hours. 
4 
100% bedridden. Completely disabled. Cannot carry on any self-care. Totally 
confined to bed or chair 
5 
Dead 
Source: Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity 
and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5 
(6):649-55. 
 


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APPENDIX 3: 
MEDICATIONS OR FOODS KNOWN TO INHIBIT OR INDUCE 
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/DrugInteractio
nsLabeling/ucm080499.htm 
NOTE: Patients receiving duvelisib are prohibited from concomitant use of medications or 
foods that are known to be strong inhibitors or inducers of CYP3A. 
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 area under the curve 
(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 4: 
CYP3A OR CYP2C8 SUBSTRATES 
The following lists provide known sensitive CYP3A substrates, CYP3A substrates with a narrow 
therapeutic range, and CYP2C8 substrates. Drugs or foods that are substrates of CYP3A should 
only be used if medically necessary and therapeutic alternatives do not exist. Medications that 
are metabolized via CYP2C8 may be used as medically indicated but with caution. 
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 
cerivastatin 
repaglinide 
rosiglitazone 
pioglitazone 
 


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APPENDIX 5: 
P-GP SUBSTRATES AND MEDICATIONS THAT ARE 
INHIBITORS OF P-GP 
The following list provides medications that are substrates or inhibitors of P-gp, which should be 
used with caution during treatment with duvelisib. 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 
Loperamide  
Amiodarone 
Losartan 
Atorvastatin 
Lovastatin 
Cefoperazone 
Methadone 
Chlorpromazine 
Methotrexate 
Cimetidine 
Methylprednisolone 
Ciprofloxacin 
Morphine 
Clarithromycin 
Nadolol 
Colchicine 
Norfloxacin 
Cyclosporine 
Nortriptyline 
Dexamethasone 
Ondansetron 
Digoxin 
Omeprazole 
Diltiazem 
Pantoprazole 
Erythromycin 
Phenytoin 
Estradiol 
Pravastatin 
Fentanyl 
Propranolol 
Fexofenadine 
Quinidine 
Hydrocortisone 
Ranitidine 
Itraconazole 
Sirolimus 
Lansoprazole 
Tacrolimus 
Levofloxacin 
Timolol 
Lidocaine 
Trimethoprim 
 
Verapamil 
P-gp Inhibitors 
Amiodarone 
Lovastatin 
Amitriptyline 
Mefloquine 
Carvedilol 
Nicardipine 
Chlorpromazine 
Nifedipine 
Clarithromycin 
Ofloxacin 


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Cortisol 
Omeprazole 
Cyclosporine 
Pantoprazole 
Desipramine 
Progesterone 
Diltiazem 
Propafenone 
Dipyridamole 
Propranolol 
Doxepin 
Quinidine 
Erythromycin 
Rifampicin (Rifampin) 
Felodipine 
Saquinavir 
Fluphenazine 
Simvastatin 
Grapefruit juice 
Sirolimus 
Haloperidol 
Tacrolimus 
Itraconazole 
Testosterone 
Ketoconazole 
Verapamil 
Source: Atkinson AJ et al. Principles of Clinical Pharmacology, 2nd ed. Academic Press, Massachusetts, 2007. 
 
 


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APPENDIX 6: 
SUMMARY OF CHANGES 
Protocol Version 7.1 (Amendment 7.1), 24 November 2021 
AMENDMENT RATIONALE 
Language was added to allow additional interim analyses which may occur at various times 
during the expansion phase of the study. This protocol amendment is considered administrative 
in nature as there is no impact on statistical powering of the study, due to the open label single 
arm design.  Further, the additional interim analyses may be used to inform future health 
authority discussions. 
The revised protocol, Version 7.1, dated 24 November 2021 may be submitted by the 
Investigator(s) to all applicable IRBs, IECs, or CECs, as required by their institution and by 
Secura Bio, Inc. to all applicable Regulatory Authorities. 
 
Protocol Version 7.0 (Amendment 7), 20 July 2021 
AMENDMENT RATIONALE 
The protocol will be amended to allow for the addition of up to 30 Expansion Phase patients, 
with a target of approximately 24 additional patients. The statistical design has been updated to 
demonstrate the advantages and limitations of the increase in sample size. 
 
The purpose of this amendment is to increase the Expansion Phase sample size from 100 patients 
to approximately 120-130.  The key rationales for the increase in sample size are (1) to increase 
confidence in the efficacy results, with an expansion phase N analogous to those of other label 
enabling trials in relapsed/refractory PTCL; and (2) to include more patients that carry diagnoses 
of ALCL and NK cell subtypes, to more closely match the subtype percentage breakdowns noted 
in the epidemiologic literature regarding PTCL in Western populations.  
 
As the amendment was not based on lack-of-efficacy or safety concerns, this amendment has 
been deemed not substantial. 
 
The revised protocol, Version 7.0, dated 20 July 2021 will be submitted by the Investigator(s) to 
all applicable IRBs, IECs, or CECs, and by Secura Bio, Inc. to all applicable Regulatory 
Authorities. 
Protocol Version 6.1 (Amendment 6), 08 December 2020 
AMENDMENT RATIONALE 
Secura Bio, Inc. acquired the global rights in Oncology for the Investigational Medicinal Product 
(IMP), duvelisib (also referred to as Copiktra®) from Verastem. Updates were made in this 


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document in all sections, as applicable, to reflect that Secura Bio is now the Sponsor for this 
study. This is an administrative change that does not affect the planned study. 
In addition, minor language and format corrections were also done throughout the document.  
The revised protocol, Version 6.1, dated 08 December 2020 will be submitted by the 
Investigator(s) to all applicable IRBs, IECs, or CECs, and by Secura Bio, Inc. to all applicable 
Regulatory Authorities. 
Protocol Version 6.0 (Amendment 5), 16 September 2019 
AMENDMENT RATIONALE 
The primary purpose for this amendment was to clarify applicable protocol sections based on 
agency questions. The key updates included the following: clarifying selection of the optimal 
dose was completed based on interim data from the Dose Optimization Phase, to align pregnancy 
testing frequency with Clinical Trial Facilitation Group (CTFG) recommendations, to add an 
exclusion criterion for known hypersensitivity to duvelisib or its excipients, and to add 
prohibition on the use of live vaccines for 3 months after the last dose of study drug. 
A summary of key changes that were made to protocol Version 5.0, including the rationales for 
these changes, is provided below. 
Table 13 
Summary of Changes for Version 6.0  
Section(s) 
Description of Change 
Rationale for the Change 
Global 
Updated the version number and date of protocol 
from Version 5.0 dated 09 August 2019 to 
Version 6.0 dated 16 September 2019  
Administrative change 
Global 
Updated missing abbreviations, grammar, editorial 
as necessary. 
Administrative change 
Synopsis,  
Section 5.2 
Added exclusion criterion for patients with known 
hypersensitivity to duvelisib and/or its excipients 
To exclude patients who may have 
an adverse hypersensitivity reaction 
to treatment 
Synopsis, 
Section 1.3, 
Section 5.1 
Modified the units on CD4 lymphocyte count 
Correction of error  
Synopsis,  
Section 4.1.2, 
Section 10.13 
Modified text to indicate the optimal dose for the 
Expansion Phase has been selected and that the 
optimal dose was selected based on the interim 
results of the Dose Optimization Phase 
To improve the clarity of the 
description of optimal dose 
selection 
Table 2,  
Table 2 footnote 
#13,  
Section 6.10.2 
Increased frequency of pregnancy testing to 
monthly for the Expansion Phase. This was added 
as Cycle 4 column in Table 2 with footnote and 
also to body text. 
To align with CTFG (Final Version- 
2014- 09-15) recommendations on 
pregnancy testing in clinical studies 
List of 
Abbreviations, 
Table 8 
Added definition for the term “Gi”as 1 X 109 (1 
billion cells or giga) 
To clearly distinguish the “Gi” 
abbreviation from the “GI” 
abbreviation 


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Section(s) 
Description of Change 
Rationale for the Change 
Section 8.4 
Added new section: “End of Study Definition” 
To provide definition for End of  
Study 
Section 8.2 
Removed sentence about observing patients during 
follow-up 
Correction as after withdraw from 
study, no observation would occur 
Section 9.6.1 
Modified text to indicate that live vaccines are 
prohibited for 3 months after last dose of study 
drug  
To clarify the guidance on use of 
live vaccines after last dose of study 
drug 
Appendix 6 
Added Summary of Changes made to version 5.0 
and added Version History section and table. 
Administrative change 
 
 


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Protocol Version 5.0 (Amendment 4), 09 August 2019 
 
AMENDMENT RATIONALE 
The primary purpose for this amendment was to align pregnancy guidance to Clinical Trial 
Facilitation Group (CTFG), add Study Design Figure to align to ICH, include ongoing cardiac 
function per Investigator discretion and update vital sign collection at each visit to be 
independent of Investigator discretion.  
A summary of key changes that were made to protocol Version 4.0, including the rationales for 
these changes, is provided below. 
 
Table 14: 
Summary of Changes for Version 5.0 
Section(s) 
Description of Change 
Rationale for the Change 
Global 
Minor internal changes were made to syntax, 
grammar, and punctuation to improve clarity and 
eliminate inconsistencies among sections (e.g., 
changed subject to patient, Dose Escalation to Dose 
Optimization where applicable, aligned wording 
for Inclusion Criterion #3 in Section 5.1 and 
Exclusion Criterion #1 in Section 5.2 with wording 
in Synopsis, modification of CYP3A metabolism in 
Section 8.6.4) 
Administrative change 
Global 
Updated the version number and date of protocol 
from Version 4.0 dated 16 April 2019 to 
Version 5.0 dated 09 August 2019  
Administrative change 
After Synopsis, 
Section 4.1 
Added Figure 1 for Study Overview after the 
synopsis and removed text in Section 4.1 stating 
that the schematic diagram is contained in the 
training materials for the investigational sites 
To align to ICH recommendations 
to include a schematic diagram of 
the study design in the protocol 
Synopsis, 
Section 5.1, 
Section 8.5.3, 
Appendix 1 
Updated Inclusion Criterion 11 and birth 
control/contraception guidance  
To align to CTFG (Final Version- 
2014- 09-15) recommendations on 
contraception and pregnancy testing 
in clinical studies 
Table 2, 
Section 6.7 
Additional ECGs may be conducted on treatment 
and during follow-up per Investigator discretion 
An ECG was required during 
screening (per the Schedule of 
Events) but was not repeated during 
on-treatment or follow-up periods. 
Since duvelisib has non-significant 
cardiac toxicity, the test was added 
for on-treatment and follow-up 
periods with language “at the 
Investigator’s discretion” to allow 
for evaluation of this health 
parameter if needed to ensure 
patients are not negatively 
influenced by their participation in 
the clinical study. 


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Section(s) 
Description of Change 
Rationale for the Change 
Table 2, 
Section 6.8 
Additional echocardiograms may be conducted on 
treatment and during follow-up per Investigator 
discretion 
An echocardiogram during 
screening was required (per the 
Schedule of Events) but was not 
repeated during on-treatment or 
follow-up periods. Since duvelisib 
has non-significant cardiac toxicity, 
the test was added for on-treatment 
and follow-up periods with 
language “at the Investigator’s 
discretion” to allow for evaluation 
of this health parameter if needed to 
ensure patients are not negatively 
influenced by their participation in 
the clinical study. 
Table 2 
Revised vital sign collection to occur at every visit, 
including C1D8, C1D15 and C2D15 visits; 
therefore, removed “if clinically indicated” from 
footnote 11 
To allow for a thorough 
examination of the health status of 
study patients and rule out potential 
adverse events, vital signs are to be 
performed at each study visit. 
Section 1.2 
Inserted the following description of the 
differentiation capability of myeloid cells to the 
background on duvelisib: “tumor-associated 
macrophages that promote angiogenesis and 
augment tumor growth (Lewis et al, 2006).” 
To correct inadvertent deletion in 
the prior version. 
Section 6.13 
Clarified that the following samples will only be 
collected in the US: 
 
pharmacodynamic markers of target 
inhibition in PTCL and immune 
populations 
 
immunophenotypes and functional tests of 
major immune populations in the blood  
To indicate which samples will only 
be collected in the US 
Section 11.3 
Clarified that patients who are detained by 
administrative or judicial order will be excluded 
from participating in the study 
To provide information regarding 
the eligibility of patients who are 
detained by administrative or 
judicial order, per regulatory request 
Section 11.6, 
Section 11.7, 
Section 11.8 
Added new sections with details related to patient 
data protection and quality assurance; and 
combined previous section for monitoring 
procedures (11.8) with the new Section 11.7 
To provide more information on 
data protection and quality 
assurance, per regulatory request 
Section 11.13 
Expanded the disclosure of information to include 
details related to the publication policy 
To clarify the publication policy 
 


Clinical Study Protocol 
Duvelisib (IPI-145) 
VS-0145-225, Version 7.1 
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Confidential Information 
Version No. 7.1 24 November 2021 
 
Version History 
Table 15: 
Primary Reason for Each Version 
Version 
Primary Reason for Version 
7.1 
Addition of interim analyses language in the expansion phase of the study. 
7.0 
Increase sample size and updated statistics to match sample size increase. 
6.1 
To update Sponsor contact information 
6.0 
To clarify applicable protocol sections based on agency questions. The key updates 
included the following: clarifying selection of the optimal dose was completed based on 
interim data from the Dose Optimization Phase, to align pregnancy testing frequency 
with Clinical Trial Facilitation Group (CTFG) recommendations, to add an exclusion 
criterion for known hypersensitivity to duvelisib or its excipients, and to add prohibition 
on the use of live vaccines for 3 months after the last dose of study drug. 
5.0 
To align pregnancy guidance to Clinical Trial Facilitation Group (CTFG), add Study 
Design Figure to align to ICH, include ongoing cardiac function per Investigator 
discretion, and update vital sign collection at each visit to be independent of Investigator 
discretion 
4.0 
To add a requirement for central pathology review of FFPE slides to confirm PTCL 
diagnosis and update the toxicity management guidance to include febrile neutropenia 
3.0 
To update planned enrollment, number of clinical sites, some inclusion/exclusion 
criteria, objective/endpoint alignment, clarification of imaging scan information, 
population clarification, and Expansion Phase dose determination 
2.0 
To clarify that response to study treatment will be determined by IRC. The IRC’s 
determination of response to study treatment will be used in primary and secondary 
efficacy analyses. The Investigator’s determination of disease response will be used in 
supportive efficacy analyses 
1.0 
Original version 
 

SAP_001.pdf: 
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This statistical analysis plan contains confidential information and is the proprietary property of 
Secura Bio, Inc. This document may not be copied or made available for review by an unauthorized 
person or firm without the prior written authorization of Secura Bio, Inc. 
STATISTICAL ANALYSIS PLAN 
Protocol VS-0145-225 
A Multi-Center, Phase 2, Open-label, Parallel Cohort Study of Efficacy and Safety 
of Duvelisib in Patients with Relapsed or Refractory Peripheral T-cell Lymphoma 
(PTCL) 
Protocol Version: 
7.1 
Type of Analysis Plan: 
Final Analyses 
Version: 
7.0 
Date: 
August 7, 2023 
Author: 
 
 
 
Parexel International 
NCT #: NCT03372057


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SPONSOR SIGNATURE PAGE 
 
 
 
Approved by: 
 30 August 30, 2023 
 
 
Date 
 
Secura Bio, Inc. 


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Signatory 
 
Project Role: Biostatistics Lead 
Author 
 
PAREXEL SIGNATURE PAGE 
 
 
This document has been approved and signed electronically on the final page by the following: 
 
 
 
 


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REVISION HISTORY 
 
Version 
Date 
Brief Summary of Changes 
1.0 
December 18, 2018 
1.1 
May 9, 2019 
Update SAP after conclusion of Dose Optimization 
Phase and selection of optimal dose (based on the 
protocol v4.0) 
2.0 
November 7, 2019 
Final Version 
3.0 
March 13, 2020 
Add additional interim analysis for dose expansion 
phase. 
3.1 
February 4, 2021 
Add Japanese subgroup analyses. 
Add new interim analysis. 
Refine definition of disease control rate. Incorporate 
Sponsor change from Verastem to Secura Bio. 
4.0 
February 25, 2021 
Final Version 
4.1 
September 20, 2021 
Update to include additional subjects added to 
expansion phase per protocol v7.0 and add 
additional interim analysis 
4.2 
October 15, 2021 
Incorporate internal review comments 
5.0 
November 5, 2021 
Final Version 
5.1 
March 29, 2022 
Updates per Sponsor request to support FDA 
submission. 
6.0 
April 11, 2022 
Final Version 
6.1 
March 31, 2023 
Updates per Sponsor request to add additional 
analyses: 
- response and PFS by prognostic factors 
-response, PFS, DOR, and OS by major 
histologic subtypes 
- Summaries of Grade 3 or Higher SAEs, Grade 
3 SAEs, Grade 4 SAEs 
6.2 
May 10, 2023 
Add additional exploratory analyses 
7.0 
August 7, 2023 
Final Version 


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TABLE OF CONTENTS 
List of Abbreviations ...................................................................................................................................... 7 
1 
Introduction ............................................................................................................................................ 9 
2 
Study Objectives..................................................................................................................................... 9 
2.1 
Primary Objective ........................................................................................................................... 9 
2.1.1 
Dose Optimization Phase .........................................................................................................................9 
2.1.2 
Expansion Phase ......................................................................................................................................9 
2.2 
Secondary Objectives ...................................................................................................................... 9 
2.2.1 
Dose Optimization Phase .........................................................................................................................9 
2.2.2 
Expansion Phase ......................................................................................................................................9 
2.3 
Exploratory Objectives .................................................................................................................... 9 
2.3.1 
Dose Optimization Phase .........................................................................................................................9 
2.3.2 
Expansion Phase ......................................................................................................................................9 
Study Endpoints ........................................................................................................................................... 10 
2.4 
Primary Endpoint .......................................................................................................................... 10 
2.4.1 
Dose Optimization Phase .......................................................................................................................10 
2.4.2 
Expansion Phase ....................................................................................................................................10 
2.5 
Secondary Endpoints ..................................................................................................................... 10 
2.5.1 
Dose Optimization Phase .......................................................................................................................10 
2.5.2 
Expansion Phase ....................................................................................................................................10 
2.6 
Exploratory Endpoints................................................................................................................... 10 
2.6.1 
Dose Optimization Phase .......................................................................................................................10 
2.6.2 
Expansion Phase ....................................................................................................................................10 
3 
Study design ......................................................................................................................................... 11 
3.1 
Overview ....................................................................................................................................... 11 
3.1.1 
Dose Optimization Phase .......................................................................................................................11 
3.1.2 
Expansion Phase ....................................................................................................................................12 
3.2 
Randomization .............................................................................................................................. 13 
3.3 
Sample Size Considerations .......................................................................................................... 13 
3.4 
Blinding ......................................................................................................................................... 13 
3.5 
Interim Analysis and Data Review ................................................................................................ 14 
3.6 
Analysis Sets ................................................................................................................................. 14 
3.6.1 
Dose Optimization Efficacy Set.............................................................................................................14 
3.6.2 
Modified Intent-to-treat (mITT) Analysis Set........................................................................................14 
3.6.3 
Safety Analysis Set ................................................................................................................................15 
4 
General Statistical Methods and Data Handling................................................................................... 15 
4.1 
General Methods ........................................................................................................................... 15 
4.2 
Treatment-emergent Adverse Event (TEAE) Definition............................................................... 15 
4.2.1 
Definition of a Serious Adverse Event (SAE) .......................................................................................16 
4.3 
Handling of Missing Data ............................................................................................................. 16 
4.3.1 
Handling of Missing Dates/Months/Years for Determination of TEAEs ..............................................16 
4.3.2 
Handling of Missing Dates/Months/Years for Concomitant Medications .............................................16 
4.3.3 
Handling of Missing Dates for Disease History ....................................................................................17 
4.4 
Multiple Comparisons/Multiplicity Adjustment ........................................................................... 17 
4.5 
Subgroups ...................................................................................................................................... 17 
4.5.1 
Subgroups based on baseline demographics and disease characteristics ...............................................17 
4.5.2 
Prognostic factors .................................................................................................................................. 18 
4.6 
Visit Windows ............................................................................................................................... 18 
4.7 
Baseline Values ............................................................................................................................. 19 
4.8 
Computing and Coding Standards................................................................................................. 19 


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5 
Statistical Analyses............................................................................................................................... 19 
5.1 
Study Subjects ............................................................................................................................... 19 
5.1.1 
Disposition of Subjects ..........................................................................................................................19 
5.1.2 
Protocol Deviations ............................................................................................................................... 19 
5.1.3 
Demographic and Other Baseline Characteristics ..................................................................................20 
5.1.4 
Baseline Disease Characteristics ............................................................................................................20 
5.1.5 
Medical History .....................................................................................................................................20 
5.1.6 
Prior and Concomitant Medications ......................................................................................................20 
5.1.7 
Exposure to Study Drug .........................................................................................................................21 
5.2 
Efficacy Analyses .......................................................................................................................... 22 
5.2.1 
Analyses of Primary Endpoint ...............................................................................................................22 
5.2.2 
Analyses of Secondary and Exploratory Efficacy Endpoints ................................................................22 
5.2.3 
Exploratory Efficacy Analyses ..............................................................................................................24 
5.3 
Safety Analyses ............................................................................................................................. 25 
5.3.1 
Adverse Events ......................................................................................................................................25 
5.3.2 
Laboratory Data .....................................................................................................................................27 
5.3.3 
Vital Signs .............................................................................................................................................29 
5.3.4 
ECOG Performance Status ....................................................................................................................29 
5.3.5 
Electrocardiogram (ECG) ......................................................................................................................29 
5.3.6 
Echocardiogram .....................................................................................................................................29 
5.3.7 
Concomitant Medications and Procedures .............................................................................................30 
5.3.8 
Deaths ....................................................................................................................................................30 
5.3.9 
Pregnancy Test.......................................................................................................................................30 
5.4 
Pharmacokinetic Analyses ............................................................................................................ 30 
5.5 
Exploratory Endpoints................................................................................................................... 30 
6 
References ............................................................................................................................................ 31 


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List of Abbreviations 
Abbreviation 
Definition 
 
18FDG-PET 
[18F] Fludeoxyglucose-positron emission 
tomography 
AE 
Adverse event 
AITL 
Angioimmunoblastic T-cell lymphoma 
ALC 
Absolute lymphocyte count 
ALCL 
Anaplastic large cell lymphoma 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ATC 
Anatomical therapeutic chemical 
BID 
Twice daily 
BV-CHP 
Brentuximab Vendotin, Cyclophosphamide, 
Doxorubicin, Prednisone 
CHOEP 
Cyclophosphamide, Doxorubicin hydrochloride, 
Vincristine sulfate, Etoposide, Prednisone 
CHOP 
Cyclophosphamide, Doxorubicin hydrochloride, 
Vincristine sulfate, Prednisone 
CR 
Complete response 
CSP 
Clinical Study Protocol 
CT 
Computed tomography 
CX 
Cycle X 
DCR 
Disease control rate 
DNA 
Deoxyribonucleic acid 
DOR 
Duration of response 
DX 
Day X 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
ICF 
Informed consent form 
Ig 
Immunoglobulin 
IRC 
Independent Review Committee 
ITT 
Intent-to-treat 
IWG 
International Working Group 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic resonance imaging 
NCI CTCAE 
National Cancer Institute Common Terminology 
Criteria for Adverse Events 
ORR 
Objective response rate 
OS 
Overall survival 
PD 
Progressive disease 
PFS 
Progression-free survival 
PI3K 
Phosphoinositide-3-kinase 
PO 
Oral(ly) 
PR 
Partial response 
PT 
Preferred term 
PTCL 
Peripheral T-cell lymphoma 
PTCL-NOS 
Peripheral T-cell lymphoma – not otherwise 
specified 
SAE 
Serious adverse event 


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Abbreviation 
Definition 
SAP 
Statistical Analysis Plan 
SD 
Stable disease 
SOC 
System organ class 
TEAE 
Treatment-emergent adverse event 
US 
United States 
WBC 
White blood cell count 


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1 Introduction 
This statistical analysis plan (SAP) provides a detailed description of the statistical methods and analyses 
to be carried out in support for study VS-0145-225. 
2 Study Objectives 
2.1 
Primary Objective 
2.1.1 
Dose Optimization Phase 
 
• 
To determine the optimal duvelisib dose for utilization in the Expansion Phase by evaluating the 
ORR supported by safety, additional efficacy, and pharmacokinetics (PK) parameters as well as 
any other available data in the population of patients receiving the optimal dose of duvelisib for at 
least one cycle in patients with relapsed or refractory PTCL. 
2.1.2 
Expansion Phase 
 
• 
To determine the efficacy of the optimal dose of duvelisib in patients with relapsed or refractory 
PTCL 
2.2 
Secondary Objectives 
2.2.1 
Dose Optimization Phase 
 
• 
To evaluate additional efficacy parameters for duvelisib in the population of patients receiving 
duvelisib for at least one cycle in patients with relapsed or refractory PTCL 
• 
To characterize the tolerability and safety of duvelisib in patients with relapsed or refractory 
PTCL 
• 
To evaluate pharmacokinetics (PK) of duvelisib and if applicable, its metabolite(s) 
2.2.2 
Expansion Phase 
 
• 
To evaluate additional efficacy parameters for duvelisib 
• 
To characterize the tolerability and safety of duvelisib in patients with relapsed or refractory 
PTCL 
• 
To evaluate PK of duvelisib and if applicable, its metabolite(s) 
2.3 
Exploratory Objectives 
2.3.1 
Dose Optimization Phase 
 
• 
To evaluate pharmacodynamic and prognostic biomarkers 
2.3.2 
Expansion Phase 
 
• 
To evaluate pharmacodynamic and prognostic biomarkers 


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Study Endpoints 
2.4 
Primary Endpoint 
2.4.1 
Dose Optimization Phase 
 
Objective Response Rate (ORR, defined as complete response (CR) + partial response (PR)), as assessed 
by the Investigator, as determined using the Lugano criteria (Cheson et al, 2014), in the population of 
patients receiving the optimal dose of duvelisib for at least one cycle of study therapy. 
2.4.2 
Expansion Phase 
 
ORR (CR+PR), as assessed by the Independent Review Committee (IRC), in the modified 
Intent-to-treat (mITT) Population, according to Lugano criteria (Cheson et al, 2014) 
2.5 
Secondary Endpoints 
2.5.1 
Dose Optimization Phase 
• 
Duration of response (DOR), for those patients with CR or PR, defined as the time from the first 
documentation of response to the first documentation of progressive disease (PD), or death due to 
any cause 
• 
Treatment-emergent adverse events (TEAEs) and changes in laboratory values 
• 
Progression-free survival (PFS), defined as the time from the first study drug dose to the first 
documentation of PD, or death from any cause 
• 
Disease control rate (DCR), defined as CR + PR + stable disease ≥ 8 weeks 
• 
Overall survival (OS) and deaths 
• 
PK parameters of duvelisib and its metabolites 
2.5.2 
Expansion Phase 
 
• 
TEAEs and changes in laboratory values 
• 
DOR, for those patients with CR or PR, defined as the time from the first documentation of 
response to the first documentation of PD, as determined by the IRC, or death due to any cause 
• 
PFS, defined as the time from the first dose of study treatment to the first documentation of PD, 
as determined by the IRC, or death from any cause 
• 
DCR, defined as CR + PR + SD ≥ 8 weeks, calculated using IRC-determined responses 
• 
OS and deaths 
• 
PK parameters of duvelisib and its metabolites 
2.6 
Exploratory Endpoints 
2.6.1 
Dose Optimization Phase 
 
• 
Analysis of PTCL tumor pharmacodynamic markers in relation to PK, safety, and efficacy 
• 
Analysis of PTCL tumor prognostic markers in relation to safety and efficacy 
• 
Analysis of cytokines and non-tumor immune populations in relation to safety and efficacy 
• 
Additional exploratory analyses identified by the Sponsor may be performed on study samples 
2.6.2 
Expansion Phase 
 
• 
Analysis of duration of complete response 


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• 
Subgroup analysis of select efficacy and safety endpoints. 
• 
Analysis of PTCL tumor pharmacodynamic markers in relation to PK, safety, and efficacy 
• 
Analysis of PTCL tumor prognostic markers in relation to safety and efficacy 
• 
Analysis of cytokines and non-tumor immune populations in relation to safety and efficacy 
• 
Additional exploratory analyses identified by the Sponsor may be performed on study samples 
 
3 Study design 
3.1 
Overview 
This is a multi-center, parallel cohort, open-label, Phase 2 study of duvelisib, an oral dual inhibitor of 
PI3K-δ, γ, in patients with relapsed/refractory PTCL. 
The study has 2 phases, a Dose Optimization Phase and an Expansion Phase. 
Regardless of study phase, all patients will undergo screening assessments up to 30 days before the first 
study drug dose (Cycle 1, Day 1 [C1D1]). Patients meeting all of the entrance criteria, based on Screening 
assessments, will be enrolled in the study and receive the first study drug dose on C1D1. Thereafter, 
patients will attend study center visits as per the applicable Phase Schedule of Events (Dose Optimization: 
Study Protocol Table 1, Expansion Phase: Study Protocol Table 2). At screening, disease will be 
measured using 18F-fluorodeoxyglucose-positron emission tomography (18FDG-PET)-computed 
tomography (CT) scanning (PET-CT) (CT images along with PET should be diagnostic with contrast 
unless contraindicated), Where PET-CT is not feasible, CT with contrast or magnetic resonance imaging 
(MRI) may be used after discussion with the Medical Monitor. Subsequently, for FDG-avid PTCL, PET- 
CT will be used to assess disease status and for FDG-non-avid PTCL, CT with contrast or MRI will be 
appropriate substitutes. The modality chosen to evaluate response in each individual patient should be the 
same throughout the duration of the study. For the purposes of patient management during the conduct of 
the study, the Investigator’s assessment of disease response will be used. Images also will be centrally 
stored, and disease response will be determined by an IRC for futility and at the end of the study. 
3.1.1 
Dose Optimization Phase 
 
The Dose Optimization Phase will be conducted at up to approximately 15 centers in the US. 
In the Dose Optimization Phase, patients will be randomly assigned at a 1:1 ratio to 1 of 2 study cohorts, 
as follows: 
• 
Cohort 1: Duvelisib orally (PO) twice daily (BID) at a starting dose of 25 mg, with potential 
escalation on a per-patient basis to 50 mg BID and then 75 mg BID, based on the patient’s 
response to and tolerance of therapy, in 28-day cycles. 
 
• 
Cohort 2: Duvelisib 75 mg PO BID, administered in 28-day cycles. 
Approximately 10 patients each will be enrolled in Cohorts 1 and 2. Patients in the Dose Optimization 
Phase who discontinue before receiving at least 1 cycle of study drug may be replaced. Enrollment into 
the Dose Optimization Phase may continue until the initiation of the Expansion Phase. 


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For both cohorts, dose modification criteria for duvelisib will be applied if the starting dose or a 
subsequent dose of Duvelisib is deemed intolerable (see Section 8.4.2 of the Clinical Study Protocol 
(CSP)). Dose Optimization Phase patients will complete treatment as defined for their cohort. 
Cohort 1 
All patients will receive duvelisib at a starting dose of 25 mg PO BID (Level 1), with potential sequential 
escalation to 50 mg PO BID (Level 2), and then to 75 mg PO BID (Level 3). Intrapatient dosing decisions 
will occur as follows: 
 
• 
After completion of Cycle 1 and every 2 cycles thereafter: 
 
o Patients with CR or PR will have their duvelisib dose maintained at the current dose 
level. 
 
o Patients with stable disease (SD) who are, in the Investigator’s opinion, tolerating and 
otherwise suitable to continue receiving therapy, will have the duvelisib dose increased to 
the next level until the next response assessment or development of PD or intolerance, as 
determined by the Investigator. 
 
• 
Patients with PD who are not, in the Investigator’s opinion, tolerating therapy or otherwise not 
suitable to continue receiving therapy will discontinue duvelisib. 
In no case will the duvelisib dose be increased to a level > 75 mg BID (total daily dose 150 mg). 
All patients in Cohort 1 will receive duvelisib until development of PD or unacceptable toxicity, as 
determined by the Investigator. 
Cohort 2 
All patients in Cohort 2 will receive duvelisib 75 mg PO BID in 28-day cycles until development of PD 
or unacceptable toxicity, as determined by the Investigator. 
3.1.2 
Expansion Phase 
 
The Expansion Phase will be conducted at approximately 40-50 centers globally. 
At the conclusion of the Dose Optimization Phase, efficacy, PK, and safety data as well as any other 
available data will be taken into consideration to recommend the optimal dose for the Expansion Phase. In 
addition to recommending an optimal dose, the Expansion Phase may also involve modifications of the 
study patient population, other aspects of entry criteria, and the inclusion of patients from geographic 
regions outside the United States (US); any such changes will be documented in an amendment to the 
protocol. Patients will have disease assessment after Cycle 2 and every 2 cycles thereafter until the 
follow-up stage is reached and assessment will occur according to Table 4 of the CSP. 
With protocol amendment 7.0, 20-30 additional patients will be enrolled in the Expansion Phase for a 
total of up to 130 patients. 
Expansion Phase Dose Selection: 


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As of January 2, 2019, 20 patients met the criteria for the Dose Optimization efficacy population and 
available data as of February 11, 2019, was reviewed. A dosage of 75 mg BID for the first 2 cycles, 
followed by a mandatory reduction to 25 mg BID thereafter for those patients with CR, PR or SD, will be 
used for the Expansion Phase. The dose may be re-escalated to 75 mg BID based on response assessment 
and safety (see CSP Sections 1.3 and 8.1.2). 
3.2 
Randomization 
In the Dose Optimization Phase only, patients will be randomly assigned on C1D1 to either Cohort 1 or 2 
on a 1:1 basis via a computer-generated randomization scheme. No stratification methodology will be 
employed in this study. 
3.3 
Sample Size Considerations 
Approximately 20 patients will be enrolled in the Dose Optimization Phase, with approximately 10 
evaluable patients per cohort. However, enrollment may discontinue in either cohort if no CR/PR, as 
assessed by the Investigator, is noted in the first 5 evaluable patients per cohort. This stopping rule is 
based on the first stage decision rule of a Simon 2-stage design, with assumptions of a hypothesized ORR 
of 50% and a null rate of 15% with a one-sided alpha of 0.05 and a power of 85%. 
Patients in the Dose Optimization Phase who discontinue before receiving at least 1 cycle of study drug 
may be replaced. 
In the Expansion Phase, the target enrollment is approximately 100 patients with a centrally confirmed 
diagnosis of PTCL. It is anticipated up to 5% of patients may have a diagnosis that is not confirmed upon 
central pathology review. One-hundred patients will provide 99.2% power to distinguish between a null 
ORR of 20% and an alternative ORR of 40% with a two-sided alpha of 0.05. Further, with 100 patients 
treated at the optimal duvelisib dose, the obtained ORR will have 95% confidence bounds of no greater 
than ± 10% when the normal approximation method is employed (assumes 50% ORR). If the observed 
ORR is greater or less than 50%, the confidence bounds will be less than ± 10%. These bounds around the 
obtained ORR are thought to adequately characterize the effect of the optimal dose of duvelisib in this 
PTCL population. 
With protocol amendment 7.0, 20-30 additional patients will be enrolled in the expansion phase. 
Assuming a total of 120 or 130 patients the power to distinguish between a null hypothesis of ORR of 
20% and an alternative ORR of 40% will be 99.4% or 99.6%, respectively. 
The primary analysis for the Expansion Phase will be performed once approximately 100 patients with a 
centrally confirmed diagnosis of PTCL have been enrolled and evaluated for the primary endpoint. In the 
event that enrollment in the expansion phase exceeds 110% of the planned sample size, a sensitivity 
analysis will be performed on the first 100 patients enrolled in the Expansion Phase. 
The final analysis for the Expansion phase will be performed once all patients with a centrally confirmed 
diagnosis of PTCL have been enrolled and evaluated for the primary endpoint. The total number of 
patients (up to 130) will be determined by the Sponsor. An important driver of the final sample size may 
be the number of additional patients needed to add an additional 8-10 patients having PTCL subtype of 
either ALCL or NK cell. 
3.4 
Blinding 
No blinding of treatment assignment will be used in this study. 


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3.5 
Interim Analysis and Data Review 
As noted in Section 3.3, during the dose optimization phase, the ORR for each dose optimization cohort 
will be reviewed when 5 patients are determined to be evaluable. If no response of CR or PR has been 
observed in the cohort then enrolment in that cohort will be discontinued. Evaluation of response in this 
analysis will be based on Investigator assessments. 
In addition, at the conclusion of the Dose Optimization Phase, all available data will be reviewed and an 
optimal dose for the Expansion Phase will be selected. In addition to recommending an optimal dose, the 
Expansion Phase may also involve modifications of the study patient population, other aspects of entry 
criteria, and the inclusion of patients from geographic regions outside the US; any such changes will be 
documented in an amendment to the protocol. The Sponsor study team, in collaboration with the 
Investigators, will make the determination of duvelisib dose for the Expansion Phase of the study based 
on the totality of available safety and activity data. This evaluation does not constitute an interim analysis. 
During the expansion phase, two assessments of ORR will be conducted. The first will be a preliminary 
assessment of ORR after approximately 15 subjects have had an initial assessment of response by the 
investigator. During this assessment, the data from the expansion phase will be reviewed in the context of 
data from the dose optimization phase. 
The second assessment will occur after 40 patients have been followed for a minimum of 4 months from 
the last patient’s first dose and assessed for response by the IRC. At that time, enrollment in the 
Expansion Phase may be held if ORR is less than 20%. The efficacy data (including durability of 
response) will be reviewed in combination with safety and PK and upon review, the study may be fully 
stopped for futility. 
• 
Additional interim analyses will be used for planning purposes, FDA submission and discussion 
and possible publication of early efficacy and safety results. The final analysis of the study will 
be completed and submitted to health authorities and published as appropriate. The approximate 
timing of these interim analyses are when: At least 75 of expansion phase patients have been 
followed for a minimum of 6 months from the last patient’s first dose and assessed for response 
by the IRC. 
• 
All patients enrolled prior to protocol v7.0 (101 patients) who have been followed for a minimum 
of 6 months from the last patient’s first -scheduled response assessment (i.e., 8 months from their 
first dose) and who have response assessed by the IRC. 
3.6 
Analysis Sets 
3.6.1 
Dose Optimization Efficacy Set 
 
Dose Optimization Efficacy Set will consist of all patients who 1) receive at least one dose of study drug 
and 2) complete at least one cycle of treatment and 3) have at least one scan to assess disease response 
after completion of one cycle of treatment. 
Efficacy analyses for the dose optimization phase will be performed using the Dose Optimization 
Efficacy Set for all primary and secondary efficacy analyses using the response determined by the 
Investigator. The IRC’s determination of disease response will be used in supportive efficacy analyses. 
3.6.2 
Modified Intent-to-treat (mITT) Analysis Set 
 
The mITT Population will consist of patients who receive at least one dose of study drug. 


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Efficacy analyses for the dose expansion phase will be performed using the mITT Analysis Set for all 
primary and secondary efficacy analyses using the response determined by IRC. 
3.6.3 
Safety Analysis Set 
 
The Safety Population consists of all patients receiving at least 1 dose of duvelisib. 
Safety analyses will be performed using the Safety Analysis Set. 
4 General Statistical Methods and Data Handling 
4.1 
General Methods 
Summary statistics will be presented by treatment group, unless stated otherwise. 
Unless otherwise specified, descriptive statistics for continuous data will include the number of subjects 
with data to be summarized (n), mean, standard deviation, 25% quartile, median, 75% quartile, and 
minimum and maximum. The same number of decimal places as in the raw data will be presented when 
reporting the minimum and maximum, one more decimal place than the raw data will be presented when 
reporting mean and median, and 2 more decimal places than the raw data will be presented when 
reporting standard deviation. 
Descriptive statistics for categorical/qualitative data will include frequency counts and percentages. The 
total number of subjects in the treatment group will be used as the denominator for percent calculations, 
unless stated otherwise. All percentages will be presented with one decimal, unless otherwise specified. 
Percentages equal to 100 will be presented as 100, and percentages will not be presented for zero 
frequencies. 
Descriptive statistics associated with time-to-event analyses will include the number of events, the 
number of subjects censored, 25% quartile, median, 75% quartile, and 95% confidence interval for 
median. These statistics will be presented for all time-to-event analyses, unless stated otherwise. 
Listings will be provided for selected endpoints. 
4.2 
Treatment-emergent Adverse Event (TEAE) Definition 
An Adverse Event (AE) is defined as any untoward medical occurrence in a patient administered a 
medicinal product that does not necessarily have a causal relationship with this treatment. An AE can, 
therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of a medicinal (investigational) product, whether or not 
related to the study (investigational) product. This includes an exacerbation of pre-existing conditions or 
events, concurrent illnesses, drug interaction, or the significant worsening of the indication under 
investigation. Anticipated fluctuations of pre-existing conditions, including the disease under study that 
does not represent a clinically significant exacerbation or worsening, need not be considered AEs. 
Symptoms of the disease under study / lack of efficacy / disease progression should not be classified as an 
AE as long as they are within the normal day-to-day fluctuation or expected progression of the disease. 
The onset date of an AE will be compared to the first dose date and the last dose date plus 30 days 
(inclusive) to determine whether the AE is treatment-emergent or not. Adverse events occurring on the 
first dose date will be considered treatment emergent unless otherwise indicated on the eCRF. 


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4.2.1 
Definition of a Serious Adverse Event (SAE) 
 
An SAE is any untoward medical occurrence at any dose (including after the Informed Consent Form 
(ICF) is signed and prior to dosing) that: 
 
• 
Results in death 
• 
Is life-threatening (patient is at immediate risk of death from the event as it occurred) 
• 
Requires inpatient hospitalization (formal admission to a hospital for medical reasons) or 
prolongation of existing hospitalization 
• 
Results in persistent or significant disability/incapacity 
• 
Results in a congenital anomaly/birth defect 
Important medical events that may not result in death, are not immediately life-threatening, or do not 
require hospitalization may be considered SAEs when, based on appropriate medical judgment, they may 
jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes 
listed in this definition. Examples of such 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. 
4.3 
Handling of Missing Data 
4.3.1 
Handling of Missing Dates/Months/Years for Determination of TEAEs 
 
Adverse events with incomplete onset dates will be handled as follows for the purpose of determining 
treatment emergence according to the definition above. 
 
• 
If the start/end date of an AE is partially missing, the date will be compared as accurately as 
possible with the first dose of study drug and the date of last dose of study drug plus 30 days. 
The AE will be assumed to be treatment-emergent if it cannot be definitively shown that the AE 
did not start or worsen during the treatment-emergent period. 
 
• 
If the start date is completely missing, an AE will be considered treatment-emergent unless the 
stop date is before first dose of study drug. 
The original partial or missing date will be displayed in listings of AEs. 
4.3.2 
Handling of Missing Dates/Months/Years for Concomitant Medications 
 
Prior or concomitant medications with incomplete start dates will be handled as follows for the purpose of 
determining whether a non-study medication is a concomitant medication: 
 
• If the start/stop date of a medication is partially missing, the date will be compared as accurately as 
possible with the first dose date of study drug and the last dose date of study drug plus 30 days. The 
medication will be assumed to be concomitant if it cannot be definitively shown that the stop date is 
before first dose date of study drug, or the start date is more than 30 days after the last dose date of 
study drug. 
• If the start/stop dates are completely missing, a medication will be considered concomitant. 


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4.3.3 
Handling of Missing Dates for Disease History 
 
For the purpose of calculating the duration from initial diagnosis, partial/missing dates for diagnosis will 
be imputed as follows: 
 
• 
If both day and month are missing and the year is prior to the year of screening, the imputed date 
will be 01 July 
• 
If both day and month are missing and year is the same as the year of screening, the imputed date 
will be the middle point between 01 January of the year and the screening date. If the middle 
point falls between two dates, the first of the two dates will be used. 
• 
If day is missing and the month and year are prior to the month and year of screening, the 
imputed date will be the 15th day of the month. 
• 
If day is missing and the month and year are the same as the month and year of screening, the 
imputed date will be the middle point between the first day of the month and the screening date. 
If the middle point falls between two dates, the first of the two dates will be used. 
• 
No imputation will be performed if the year is missing. 
4.4 
Multiple Comparisons/Multiplicity Adjustment 
No adjustment for multiple comparisons will be performed for this study. 
4.5 
Subgroups 
4.5.1 
Subgroups based on baseline demographics and disease characteristics 
 
The following subgroups may be examined for key efficacy and safety endpoints. 
 
• 
Age group (< 65 years vs. ≥ 65 years) 
• 
Gender (Male, Female) 
• 
Race (Asian, Black or African America, White, Other) 
• 
Ethnicity (Hispanic or Latino, Not Hispanic or Latino) 
• 
Geographic Region (US, Europe, Japan) 
• 
Baseline BMI (kg/m2 ; < median, ≥ median) 
• 
Baseline ECOG performance status (0, 1, 2) 
• 
Time since initial diagnosis (< median, ≥ median) 
• 
Histopathological diagnosis* 
• 
Time since most recent relapse/refractory diagnosis (months; < median, ≥median) 
• 
Initial stage (I/II, III, IV) 
• 
Baseline stage (I/II, III, IV) 
• 
Initial Ann Arbor stage (A, B, E, S) 
• 
Baseline Ann Arbor stage (A, B, E, S) 
• 
Number of prior regimens (1, 2, 3 or more) 
• 
Time since most recent treatment (weeks; < median, ≥ median) 
• 
Best response to most recent prior treatment (CR, PR, SD, PD) 
• 
Prior radiotherapy (Yes, No) 
• 
Prior Surgery (Yes, No) 
• 
Prior CHOP (Yes, No) 
• 
Prior CHOEP (Yes, No) 
• 
Prior CHOP or CHOEP (Yes, No) 
• 
Prior Salvage Chemotherapy after CHOP or CHOEP (Yes, No) 


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• 
Prior BV-CHP (Yes, No) 
• 
Prior stem cell therapy (Yes, No) 
• 
By major histology (PTCL-NOS, AITL, ALCL, Other) 
• 
Non-AITL vs. AITL 
• 
Non-ALCL vs. ALCL 
*Categories for histopathological diagnosis will be based on the data observed and will include distinct 
categories for each common type (major histologic subtypes), and an “Other” category to combine types 
with less than 3 patients (minor histologic subtypes). 
Prior CHOP will be defined as patients who received cyclophosphamide, doxorubicin, vincristine, and 
prednisone in a single prior regimen that does not include etoposide. Prior CHOEP will be defined as 
patients who received cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone in a single 
prior regimen. Prior salvage chemotherapy after CHOP or CHOEP will be defined as patients who had 
any other chemotherapy regimen following a regimen of CHOP or CHOEP. Prior BV-CHP is defined as 
patients who received brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone in a single 
regimen. 
4.5.2 
Prognostic factors 
A subgroup analysis for the following prognostic factors and each of their components (where applicable) 
will be performed for key efficacy endpoints. 
• 
All major histologic subtypes except for anaplastic large-cell lymphoma (ALCL) 
• 
All major histologic subtypes except for Angioimmunoblastic T-cell lymphoma (AITL) 
• 
Baseline international prognostic index (IPI) score and each component 
• 
Received a stem cell transplant post baseline (yes, no) 
IPI score is derived by assigning one point for each of the 5 components. A score of 0-1 is considered 
‘Low’, a score of 2-3 is considered ‘Intermediate’, and a score of 4-5 is considered ‘High’. Components: 
 
• 
Age > 60 years 
• 
Baseline stage III or IV disease 
• 
Baseline ECOG score ≥ 2 
• 
Baseline lactate dehydrogenase > ULN 
• 
2 or more extranodal lesions (target or non-target) 
. 
 
 
 
 
4.6 
Visit Windows 
Treatment visits, cycles, and days are pre-defined for this study and are pre-specified on the CRF. In the 
presentation of study data using Study Day and Cycle Day, the following derivations will be used: 
 
• 
Day 1 of Study = Date of first dose for a patient 
• 
Study Day = Date – Date of first dose + 1, if Date is on or after Date of first dose 
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• 
Day 1 of Cycle = Date of cycle start, as reported on eCRF (per protocol, Day 1 of Cycle 1 should 
be Day 1 of Study) 
• 
Cycle Day = Date – Date of cycle start in current cycle + 1 
4.7 
Baseline Values 
Unless otherwise specified, the baseline value is defined as the most recent value prior to first study drug 
administration. 
4.8 
Computing and Coding Standards 
Computing, coding, and grading standards are provided in the following table. 
 
Table 1: Computing, coding and grading standards 
Table, listing, and figure production 
SAS Version 9.2 or higher 
Coding 
Adverse Events 
Medical Dictionary for Regulatory Activities 
(MedDRA) Version 20.1 or higher 
Medical Histories 
MedDRA Version 20.1 or higher 
Prior and Concomitant Medications 
WHODrug Version Mar. 2013 or higher 
Prior and post Systemic Therapy 
WHODrug Version Mar. 2013 or higher 
Grading 
AEs 
Common Terminology Criteria for Adverse 
Events (CTCAE) Version 5.0 
Laboratory Results 
CTCAE Version 5.0 
5 Statistical Analyses 
5.1 
Study Subjects 
5.1.1 
Disposition of Subjects 
 
The number and percentage of patients in each analysis set will be provided. This includes the Safety 
Analysis Set, mITT and the Dose Optimization Efficacy Set. The percentage will be based on the number 
of patients in the Safety Analysis Set. Disposition of patients will be summarized for the Safety Analysis 
Set. The number and percentage of enrolled patients, treated patients, patients entered follow-up, patients 
who completed the study, and patients who discontinued the study and reasons for discontinuation will be 
summarized. Disposition of patients will be summarized for the overall population as well as by different 
cohorts and by phase. 
Time to treatment discontinuation will be summarized for subjects who have discontinued treatment at 
time of data cut-off. Follow-up time (from 1st dose to last contact on or prior to data cut-off) will be 
descriptively summarized. For responders, follow-up time from first response to last contact on or prior to 
data cut-off will also be summarized. 
5.1.2 
Protocol Deviations 
 
Protocol deviations will be categorized as major or minor prior to data release for the futility analysis and 
final analysis of the primary endpoint. A summary table of the major protocol deviations will be provided 
by cohort and by phases for the mITT Analysis Set. A listing of major protocol deviations will be 
provided. 


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5.1.3 
Demographic and Other Baseline Characteristics 
 
Demographic variables and other baseline characteristics will be summarized by phase and treatment 
based on Safety Analysis Set. The variables to be summarized will include (but will not be limited to): 
 
• 
Age (continuous variable) 
• 
Age group (< 65 vs. ≥ 65) 
• 
Gender 
• 
Race 
• 
Ethnicity 
• 
Geographic Region (US, Europe, Japan) 
• 
Body mass index (BMI), calculated as weight (kg) / (height (m))2 
• 
ECOG performance status 
5.1.4 
Baseline Disease Characteristics 
 
Baseline PTCL characteristics will be summarized by phase and treatment based on Safety Analysis Set. 
The variables to be summarized will include (but will not be limited to): 
 
• 
Time since initial diagnosis 
• 
Histopathological diagnosis 
• 
Time since most recent relapse/refractory diagnosis 
• 
Initial stage and Ann Arbor staging 
• 
Current stage and Ann Arbor staging 
• 
Prior anticancer therapy, prior radiotherapy, and prior surgery 
o Number of regimens - continuous and categorical (1, 2, 3+) 
o Time since most recent treatment 
o Best response to any prior treatment 
o Best response to most recent prior treatment 
o Duration of response to most recent prior treatment 
o Prior CHOP (Yes, No) 
o Prior CHOEP (Yes, No) 
o Prior CHOP or CHOEP (Yes, No) 
o Prior Salvage Chemotherapy after CHOP or CHOEP (Yes, No) 
o Prior BV-CHP (Yes, No) 
o Prior stem cell therapy (Yes, No) 
 
5.1.5 
Medical History 
 
Medical history will be summarized by phase and treatment based on the Safety Analysis Set. 
Medical history will be summarized by system organ class (SOC) and preferred term (PT) using the 
number and percentage of patients who had at least one occurrence of an SOC or PT. The summary will 
be sorted alphabetically by SOC and by decreasing frequency of PT within an SOC. 
5.1.6 
Prior and Concomitant Medications 
 
Medications will be considered as prior if they stopped before the date of first dose of study drug. 


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Medications will be considered concomitant if they were taken at any time between the first dose of study 
drug and 30 days after the last dose of study drug, inclusive. If the start date or end date of a medication is 
completely or partially missing refer to Section 4.3.2 for the algorithm to determine whether a medication 
is concomitant. 
Prior medications and concomitant medications will be summarized separately. Both summaries will be 
based on the Safety Analysis Set. Prior anti-cancer systemic therapies will be summarized separately from 
other prior medications. 
Medications will be summarized by phase and treatment by anatomical therapeutic chemical (ATC) level 
1, ATC level 2, and preferred drug name for each cohort. The summary will be sorted by decreasing 
frequency in ATC level 1, ATC level 2 and preferred drug name. A patient taking the same drug multiple 
times will be counted once. 
A listing will be provided for all non-study medications taken on the study. An identifier will be provided 
to show if a medication is prior to concomitant. Medications that started more than 30 days after the last 
dose of study drug will be identified as post-treatment. 
Additional groupings of medications will be defined to identify medications administered to treat adverse 
events specific to the duvelisib risk profile. 
5.1.7 
Exposure to Study Drug 
 
Extent of exposure will be summarized by phase and treatment based on the Safety Analysis Set. 
Extent of exposure will be summarized for the following variables by cycle and overall: 
• 
Duration (weeks): (date of last dose – date of first dose + 1) divided by 7. 
• 
Treatment duration categories (≤56 days, 57 – 112 days, > 112 days) 
• 
Number of cycles started (continuous and categorical) 
• 
Cumulative dose received (mg) (continuous and categorical by quartiles) 
• 
Cumulative dose received (mg) during Cycles 1 and 2 (continuous and categorical by quartiles) 
• 
Dose Intensity (mg/day) defined as total actual dose divided by duration in days 
• 
Relative dose intensity, defined as 100% x (total dose received)/(planned cumulative dose for the 
duration of treatment) 
• 
Average daily dose received (mg) 
• 
Number and percentage of patients within Dose Optimization Cohort 1 with dose escalations to 
50mg BID and 75mg BID 
• 
Number and percentage of patients with a dose reduction 
• 
Number and percentage of patients with a dose hold 
• 
Number and percentage of patients for whom study drug was discontinued 
Cumulative dose quartiles will be based on doses for all patients in the safety analysis set with all 
treatment groups combined. 
For relative dose intensity, planned dose is defined as follows: 
• 
Dose Optimization Cohort 1: 25 mg × 2 × total days treated at starting dose. For subjects whose 
assigned dose escalated due to SD at the end of Cycles 1 and 3 as described in the CSP, raise the 
planned dose accordingly. 
• 
Dose Optimization Cohort 2: 75 mg × 2 × total days treated 


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• 
Expansion Phase: 75 mg × 2 × (28 × 2) + 25 mg × 2 × (total days treated – (28×2)) if patient 
receives > 2 cycles of treatment or 75 mg × 2 × total days treated if patient received < 2 cycles of 
treatment. 
Where total days treated = last dose date – first dose date + 1. 
 
A by-patient listing will be presented for exposure to study drug. A separate listing of dose modifications 
will be provided for patients who received at least one dose modification. 
5.2 
Efficacy Analyses 
For the Dose Optimization Phase, all primary and secondary efficacy analyses will be performed using 
the Dose Optimization Efficacy Set and will be based on the Investigator’s determination of response, 
with the IRC’s determination of response used for supportive efficacy analyses. Analysis of the 
Expansion Phase primary and secondary efficacy analyses will be performed using the mITT Analysis Set 
and will be based on the IRC’s determination of response, with the Investigator’s determination of 
response used for supportive efficacy analyses. Response will not require confirmation by a second 
assessment. 
Listings of efficacy endpoints will be provided. The listing of best overall response (including unknown 
response) will include histological type, reason for treatment discontinuation, flag for death, and time to 
death. 
5.2.1 
Analyses of Primary Endpoint 
5.2.1.1 
Primary Analysis of ORR/BOR 
ORR and BOR as determined by both the IRC and the Investigator will be presented along with 2-sided 
confidence intervals using normal approximation. 
Swimmer’s plots will be produced with time on study as the x-axis and patient ID along the y-axis. 
Different symbols representing the study day of each IRC response (CR, PR, SD, PD, NED), end of 
treatment reason (PD, AE, death, transplant, other), and end of study reason (death, other) will be plotted 
for each patient. Patients will be grouped by best overall response. 
5.2.1.2 
Subgroup Analysis of ORR/BOR 
Subgroup analysis of ORR by subject demographics and baseline disease characteristics will be tabulated 
using response determined by the IRC in the mITT Analysis Set. BOR will be analyzed by select 
subgroups. Potential subgroups to be included are described in Section 4.5. 
5.2.1.3 
ORR/BOR by prognostic factors 
The primary analysis will be repeated by the prognostic factors described in section 4.5.2. A forest plot 
will be presented for the expansion phase and for all patients combined plotting ORR with 95% CI for 
each prognostic factor and component. 
5.2.2 
Analyses of Secondary and Exploratory Efficacy Endpoints 
5.2.2.1 
Duration of Response 
Duration of response will be analyzed both for patients with ORR (CR or PR) and for patients with CR. 


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• 
Main DOR Analysis: DOR will only be calculated for those patients with a CR or PR from time 
to first response to PD or death (if death occurs prior to PD). Patients who withdraw from the 
study for any reason prior to PD and patients who have ongoing response at the time of the data 
cut will be censored at the date of their last response assessment. 
• 
Duration of complete response (DOCR): DOCR is calculated from the time of first CR and only 
includes patients who had at least one CR response. It is otherwise defined the same as the Main 
DOR endpoint. 
Estimates of the 25th percentile, median, and 75th percentiles will be for each of these DOR endpoints will 
be presented using the Kaplan-Meier method. A 2-sided 95% confidence interval for median DOR will 
be provided by using the Brookmeyer-Crowley method. Kaplan-Meier plots will be provided. 
In addition, the number and percent of patients with duration of response of at least 3 months, 6 months 
and 12 months will be tabulated. 
A summary of time to first response will also be presented in patients who achieved CR or PR and in 
patients who achieved CR. 
5.2.2.2 
Disease Control Rate 
The proportion of patients demonstrating DCR (defined as patients with best overall response of CR or 
PR or with best overall response of SD sustained for at least 8 weeks) will also be presented along with 2- 
sided confidence intervals. 
5.2.2.3 
Analysis of PFS 
For the PFS analyses, censoring of PFS will be performed as detailed in Table 2. Note that progression 
may be documented based on scheduled or unscheduled disease status assessment, and that unscheduled 
disease status assessments will be included in calculating the gap between adequate disease status 
assessments. 
 
PFS will be estimated for each cohort using the Kaplan-Meier method. PFS will be plotted by using the 
Kaplan-Meier method. Number of patients with events, type of events (progression or death), number of 
patients censored, number of patients for each reason of censoring, Kaplan-Meier estimates and 95% 
confidence intervals for the 25th percentile, median, and 75th percentile for PFS will be presented. A 2- 
sided 95% confidence interval for median PFS will be provided by using the Brookmeyer-Crowley 
method. Probabilities of remaining alive and progression free at selected time points may also be 
presented. 
PFS analysis will be repeated for the subset of enrolled Japanese patients and for each of the prognostic 
factors described in section 4.5.2 
Table 2: Primary PFS Censoring/Event Rule 
 
Situation 
Date of Event or Censoring 
Outcome 
No adequate baseline disease status assessment 
Date of randomization + 1 day 
Censored 
No adequate post-baseline disease status assessment 
unless death occurs prior to first scheduled post-baseline 
assessment 
Date of randomization + 1 day 
Censored 


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No documented progression or death 
Date of last adequate disease status 
assessment 
Censored 
Documented progression with ≤1 missing scheduled 
disease status assessment before progression 
Date of the earliest assessment that 
results in a finding of unequivocal 
progression 
Event 
Death before progression being documented with ≤1 
missing scheduled disease status assessment before death 
Date of death 
Event 
Documented progression or death following a gap 
between adequate disease status assessments equivalent to 
2 missed visits 
Date of last adequate disease status 
assessment before the gap 
Censored 
New anticancer treatment or procedure started before 
documented progression or death. 
Date of last adequate disease status 
assessment prior to start of new 
anticancer therapy 
Censored 
Note: Disease status assessment includes radiologic documentation (CT, PET/CT, MRI scans) (chest, abdomen and pelvis, others 
as clinically indicated), bone marrow biopsy/aspirate (may not be required of all patients at all scheduled disease status 
assessments), and focused physical examination (disease related symptoms, liver and spleen assessment). An adequate baseline 
disease assessment is any assessment with measurable target lesions from scans. An adequate post-baseline disease status 
assessment is any disease status assessment for which a disease status of CR, PR, SD or PD is arrived per revised International 
Working Group (IWG) response criteria for malignant lymphoma2. 
 
5.2.2.4 
Overall Survival 
OS will be assessed using Kaplan-Meier methods from time of first treatment to death using the same 
methods described for PFS. Patients without documented death will be censored at last alive date. OS 
analysis will be repeated for the subset of enrolled Japanese patients. 
 
5.2.2.5 
Sum of Target Lesions 
The best (minimum) percent change from baseline in sum of all target lesions will be summarized (mean, 
standard deviation, minimum, and maximum) for both IRC and investigator assessment of target lesions 
overall and by best overall response. A waterfall plot will be produced for each phase/treatment. Each 
subject’s best percent change will be classified by best overall response (CR, PR, SD, PD). 
5.2.3 
Exploratory Efficacy Analyses 
Logistic regression (ORR) and Cox regression models (time to event endpoints) may be used to explore 
the impact of prognostic factors and other important baseline characteristics on response. For each of 
these potential explanatory variables a simple model with each variable as the sole predictor will be run. 
In addition, models with multiple potential explanatory variables may be fit in the same model and model 
selection techniques used to examine which combination of variables best predict response (logistic 
regression models) or best describe the hazard function (Cox models). These exploratory analyses may or 
may not be presented formally. Further details on these analyses may be outlined in a separate analysis 
plan, and results may be summarized in a separate report. 


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5.3 
Safety Analyses 
5.3.1 
Adverse Events 
 
Adverse events will be coded using MedDRA Version 20.1 or higher. The severity grade of the TEAE 
will be assessed by the Investigator according to the NCI-CTCAE Version 5. If a TEAE is not included in 
the NCI-CTCAE definitions, the severity grade of the TEAE will be assessed by the Investigator 
according to the study protocols. 
TEAEs will be summarized by phase and treatment by MedDRA system organ class (SOC) and preferred 
term (PT), or PT only. For summary tables by SOC and PT, SOC will be sorted alphabetically, and PT 
will be sorted by decreasing frequency within each SOC. For summary tables by PT only, PT will be 
sorted by decreasing frequency. 
If multiple TEAEs of the same PT occur within a patient, only the maximum grade observed for this PT 
will be used in summary of TEAEs by grade; the patient will be counted only once per SOC and PT. 
An overview TEAE summary table will be provided including the number of patients with AEs in 
selected categories. In addition, TEAEs will be summarized for the following categories, and will be 
tabulated by SOC and PT: 
 
• 
TEAEs (All Grades, All Causalities) 
• 
Treatment-related TEAEs (All Grades) 
• 
TEAEs by maximum grade (All Causalities) 
• 
Treatment-related TEAEs by maximum grade 
• 
Grade 3 or higher TEAEs (All Causalities) 
• 
Grade 3 or higher treatment-related TEAEs 
• 
Treatment-emergent SAEs (All Causalities) 
• 
Grade 3 or higher SAEs (All Causalities) 
• 
Grade 3 SAEs (All Causalities) 
• 
Grade 4 SAEs (All Causalities) 
• 
Treatment-related treatment-emergent SAEs 
• 
TEAEs resulting in discontinuation of study drug (All Causalities) 
• 
TEAEs resulting in dose hold (All Causalities) 
• 
TEAEs resulting in dose reduction for duvelisib (All Causalities) 
• 
TEAEs resulting in any modification to study drug administration (All Causalities); defined as 
discontinuation, reduction, and/or dose hold 
• 
TEAEs resulting in death (All Causalities) 
• 
Treatment-related TEAEs resulting in death 
• 
TEAEs by PT (All Grades, All Causalities) 
• 
Treatment-related TEAEs by PT (All Grades) 
• 
Grade 3 or higher TEAEs by PT (All Causalities) 
• 
Treatment-emergent SAEs by PT (All Causalities) 
• 
Treatment-related treatment-emergent SAEs by PT 
Three tables summarized by SOC only will be provided, sorted by descending frequency: 
• 
All TEAEs 
• 
All SAEs 
• 
All TEAEs leading to treatment discontinuation. 


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A by-patient listing of the following AE categories will be presented. 
 
• 
All AEs (TEAEs will be flagged) 
• 
All SAEs (TEAEs will be flagged) 
• 
TEAEs resulting in dose hold 
• 
TEAEs resulting in dose reduction 
• 
TEAEs resulting in discontinuation of study drug 
• 
TEAEs resulting in death 
5.3.1.1 
Other Adverse Events of Interest 
Selected MedDRA PTs will be combined to create grouped PTs or categories to further characterize risks 
associated with duvelisib. The following risks will be summarized: 
 
Grouped Term 
Preferred Terms 
Diarrhea 
Diarrhoea, Diarrhoea hemorrhagic, Defecation urgency 
Colitis 
Colitis, Colitis erosive, Enterocolitis, Enterocolitis hemorrhagic, 
Colitis microscopic, Necrotising colitis, Colitis ulcerative 
Pneumonia 
Pneumonia, any PT containing the word/string "pneumonia" except for 
"Pneumonia aspiration", Atypical pneumonia, Atypical mycobacterial 
pneumonia, Bronchopneumonia, Bronchopulmonary aspergillosis 
Pneumonitis 
Pneumonitis, Interstitial lung disease, lung infiltration, acute 
interstitial pneumonitis 
Transaminase elevation 
Alanine aminotransferase increased, Aspartate aminotransferase increased, 
Transaminases increased, Hypertransaminasaemia, Hepatic enzyme increased, 
Acute hepatic failure, Drug-induced liver injury, Hepatic failure, Hepatocellular 
injury, Hepatotoxicity 
Cutaneous reactions 
Dermatitis, Dermatitis allergic, Dermatitis bullous, Dermatitis exfoliative, 
Dermatitis psoriasiform, Drug eruption, Drug reaction with eosinophilia and 
systemic symptoms, Erythema, Erythema multiforme, Generalised erythema, 
Exfoliative rash, Rash, Rash generalised, Rash erythematous, Rash follicular, 
Rash macular, Rash maculo-papular, Rash maculovesicular, Rash papular, Rash 
papulosquamous, Rash pruritic, Rash pustular, Rash vesicular, Toxic skin 
eruption, Palmar erythema, Palmoplantar keratoderma, Palmar-plantar 
erythrodysesthesia syndrome, Perivascular dermatitis, Skin reaction, skin 
toxicity, Stevens-Johnson syndrome, Toxic epidermal necrolysis 
Neutropenia 
Neutropenia, Neutrophil count decreased 
 
The specific PTs that will be combined for each risk will be defined in the analysis dataset programming 
specifications. 
For each risk, PTs will be summarized at the grouped PT and individual PT (and grouped SOC if 
applicable), at the patient level: 
• 
TEAEs (All Grades, All Causalities) 
• 
Treatment-related TEAEs (All Grades) 
• 
Grade 1 or 2 only TEAEs (All Causalities) 


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• 
Grade 3 or higher TEAEs (All Causalities) 
• 
Grade 4 TEAEs (All Causalities) 
• 
TEAEs resulting in death (All Causalities) 
• 
Treatment-emergent SAEs (All Causalities) 
• 
Treatment-related treatment-emergent SAEs 
• 
TEAEs resulting in dose hold (overall and by resolution) 
• 
TEAEs resulting in dose reductions (overall and by resolution) 
• 
TEAEs resulting in dose hold or reductions (overall and by resolution) 
• 
TEAEs resulting in discontinuation of study drug (overall and by resolution) 
• 
Time to initial onset (defined as AE start date – first dose date +1) 
• 
For all infections only a summary broken out by MedDRA High Level Terms (HLT) and High 
Level Group Terms (HLGT) 
• 
TEAEs by time on treatment (up to 56 days, 57 through 112 days, > 112 days) 
 
Only patients who entered the treatment period will be considered in summaries by treatment period (i.e., 
if a patient withdrew from treatment between days 57 and 112 they would be included in the up to 56 
days summary and in the 57 through 112 days summary, but not in the > 112 days summary). 
In addition, the following summaries will be created for each grouped PT within each grouped SOC, at 
the event level: 
 
• Duration of AE 
• Time to Onset of AE 
In addition, use of specific concomitant medications to treat each of the risks will be summarized. 
Concomitant medications can be associated with specific TEAEs in the clinical database, and for each 
adverse event of interest all medications associated with any preferred term in the group of terms will be 
summarized. 
5.3.1.2 
Adverse Event Subgroup Analysis 
Summaries of TEAEs and AESI by SOC and PT may be repeated for select subgroups including: sex, age 
group (<65 years, ≥65years), race, geographic region, cumulative dose quartiles, cumulative dose 
quartiles in cycles 1 and 2, and number of prior regimens (1,2, 3+). Cumulative dose quartiles will be 
based on doses for all patients in the safety analysis set with all treatment groups combined. 
5.3.2 
Laboratory Data 
 
Laboratory tests will be reported separately for hematology, blood chemistry and serum quantitative 
immunoglobulins (Ig). 
For the purposes of presentation in both tables and listings, the following laboratory test results will be 
converted to the International System of Units (SI) before presentation: sodium, potassium, chloride, 
bicarbonate (or CO2), albumin, total protein, creatinine, uric acid, calcium, phosphorus, magnesium, 
glucose, total and direct bilirubin, alkaline phosphatase, red blood cell (RBC) count, hemoglobin, 
hematocrit, platelets, white blood cell count (WBC) with 5-part differential performed manually or by 
flow cytometry (lymphocytes, neutrophils, monocytes, basophils, and eosinophils), amylase, lipase, 
alanine aminotransferase (ALT), aspartate aminotransferase (AST), IgA, IgM and IgG. Laboratory tests 
will be graded according to CTCAE Version 5.0. 


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If a laboratory test value is reported using a non-numeric qualifier (e.g., less than [<] a certain value or 
greater than [>] a certain value), the given numeric value will be used in the summary statistics, ignoring 
the non-numeric qualifier. 
For continuous laboratory results, descriptive statistics will be provided by visit for observed value and 
change from baseline. Plots of mean observed value over time will be produced for continuous laboratory 
test results. 
For laboratory tests graded by CTCAE, the following summary tables will be created by treatment arm: 
 
• 
Summary of worst post-baseline value on treatment, regardless of baseline value according to the 
following categories: 
o Any grade 
o Grade 1-2 
o Grade 3-4 
o Grade 3 
o Grade 4 
• 
Summary of worst post-baseline value on treatment that represents a worsening in grade from 
baseline (shift table) according to the following categories: 
o Any grade 
o Grade 1-2 
o Grade 3-4 
o Grade 3 
o Grade 4 
In addition, laboratory tests with Grade 3 or 4 laboratory values will be presented in a separate patient 
listing. 
Laboratory tests with bi-directional grades (e.g., hyperglycemia and hypoglycemia) will be presented 
separately for each direction within each by grade summary table. 
For laboratory tests not graded by CTCAE, the following summary tables will be created by treatment 
arm: 
• 
Summary of worst post-baseline value on treatment, regardless of baseline value according to the 
following categories: 
o Low (less than lower limit of normal) 
o Normal (greater than or equal to lower limit of normal and less than or equal to upper 
limit of normal) 
o High (greater than upper limit of normal) 
• 
Summary of worst post-baseline value on treatment that represents a worsening from baseline 
(shift table) according to the following categories: 
o Low (less than lower limit of normal) 
o Normal (greater than or equal to lower limit of normal and less than or equal to upper 
limit of normal) 
o High (greater than upper limit of normal) 
Patients with more than one post-baseline abnormality will be counted once for each type of abnormality 
(low, high). Only patients with no low or high abnormalities reported will be classified as normal. 


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5.3.3 
Vital Signs 
 
The actual values of vital sign parameters, including temperature, heart rate, weight and systolic and 
diastolic blood pressure, will be presented in a by-patient listing. Blood pressure will be summarized as 
follows by treatment arm: 
• 
Descriptive statistics, for systolic and diastolic blood pressure separately 
o Baseline value 
o Maximum on-treatment value 
o Change from baseline to maximum on-treatment value 
• 
Categorical summary of baseline value, maximum on-treatment value for systolic and diastolic 
blood pressure separately, with categories defined as follows: 
o Diastolic blood pressure 
▪ 
<80 mm Hg 
▪ 
80 – 89 mm Hg 
▪ 
90 or higher mm Hg 
o Systolic blood pressure 
▪ 
<120 mm Hg 
▪ 
120 – 129 mm Hg 
▪ 
130 – 139 mm Hg 
▪ 
140 or higher mm Hg 
• 
Categorical summary of baseline value, maximum on-treatment value for systolic and diastolic 
blood pressure combined using the categories define above (i.e., diastolic <80 mm Hg and 
systolic <120 mm Hg, diastolic <80 mm Hg and systolic 120 – 129 mm Hg) 
Heart rate will be summarized as follows by treatment arm: 
 
• 
Descriptive statistics for baseline value, minimum on-treatment value, maximum on treatment 
value, change from baseline to maximum on-treatment value 
• 
Categorical summary of baseline value, minimum on-treatment value, maximum on-treatment 
value, with categories defined as follows: 
o <60 bpm 
o 60 – 100 bpm 
o <100 bpm 
Plots of mean observed value over time will be produced for diastolic blood pressure, systolic blood 
pressure, heart rate and temperature. 
5.3.4 
ECOG Performance Status 
 
A by-patient listing will be presented for ECOG performance status data. 
5.3.5 
Electrocardiogram (ECG) 
 
A by-patient listing will be presented for ECGs. Per the protocol, ECGs are to be collected at baseline. 
5.3.6 
Echocardiogram 
 
A by-patient listing will be presented for echocardiogram baseline and post-baseline assessments (if any) 


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5.3.7 
Concomitant Medications and Procedures 
 
Please refer to Section 5.1.6 for the definition and summary of concomitant medications. Concomitant 
procedures will not be summarized. A by-patient listing will be presented. 
5.3.8 
Deaths 
 
On-treatment deaths are defined as deaths that occur within 30 days of the last dose of study medication. 
Deaths on treatment and causes for deaths occurring on treatment, deaths occurring prior to progression, 
and deaths during follow-up will be summarized. 
A by-patient listing of deaths on study will be presented. 
5.3.9 
Pregnancy Test 
 
A by-patient listing of pregnancy test results will be presented. 
5.4 
Pharmacokinetic Analyses 
Pharmacokinetic analyses will be conducted on the Safety Analysis Set. 
Blood samples will be taken for the analyses of duvelisib and possible metabolite(s) in plasma at the time 
points defined in the schedule of assessments. The relevant PK parameters will be determined using 
bioanalytical data. 
Presentation of PK data will include: 
 
• Descriptive statistics (n, mean, standard deviation, %CV, median, minimum, maximum) will be 
presented in tabular form by cohort, cycle and day. 
• Linear-linear and log-linear plots of mean and median by nominal time will be presented by cohort, 
cycle and day. 
PK analysis will be repeated for the subset of enrolled Japanese patients and non-Japanese patients. The 
Japanese patients will be presented separately for the Safety run-in patients (first 6 Japanese patients 
treated) and expansion phase patients (remaining expansion phase Japanese patients). 
5.5 
Exploratory Endpoints 
Descriptive statistics by visit will be presented for exploratory endpoints. The analyses of exploratory 
analyses may or may not be presented formally. Further details on these analyses may be outlined in a 
separate analysis plan, and results may be summarized in a separate report. Tumor biomarkers such as 
deoxyribonucleic acid (DNA) sequence variation, germline DNA sequence variations, DNA copy number 
variation, ribonucleic acid (RNA) expression, protein expression, and/or immune cell infiltrate will be 
evaluated using summary statistics for prognostic factors. 


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6 References 
1. Cella D, Webster K, Cashy J, Kutikova L, Burgess MF, Lin BK, Bowman L, Liepa AM, Gauthier 
JE, Gregory SA, Johnson SA, Cheson BD. Development of a measure of health-related quality of 
life for non-Hodgkin’s lymphoma clinical research: the functional assessment of cancer therapy- 
lymphoma (FACT-Lym). Blood 2005;106:750. 
2. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, and Lister TA. 
Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non- 
Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014;32(27):3059-3067. 


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