Clinical trial NCT02674750
Conditions: Relapsed and/or Refractory Diffuse Large B-cell Lymphoma Including With Myc Alterations
Keywords: DLBCL MYC
Sponsor: Curis, Inc.
Start date: 2016-07-01; Completion date: 2019-05-28
Enrollment: 70 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a Phase 2, open-label, multicenter trial designed to evaluate the efficacy and safety of CUDC-907 in subjects 18 years and older with Relapsed/Refractory (RR) MYC-altered Diffuse Large B-Cell Lymphoma (DLBCL).

Detailed description:
Patients with RR DLBCL will be eligible for treatment with CUDC-907, as long as they have tumor tissue available that can be tested for MYC-altered disease based on one of the following:

* Fresh tumor tissue obtained from biopsy accessible lesions , or
* Archived tumor tissue (most recent available)

Subjects will be required to submit archival tumor samples (most recent available) or fresh tumor samples for central FISH and IHC testing. Subjects whose tumors have been previously characterized as MYC-altered are strongly encouraged to enter the study. For subjects who enter the study with unconfirmed MYC-altered disease, fresh tumor samples are preferred.

Arms: arm 1: Group A: MYC translocation+ and/or MYC gene copy number gain by FISH arm 2: Group B: MYC expression in \> 40% of tumor cells by IHC arm 3: Group C: MYC translocation- by FISH, and MYC expression in \< 40% of tumor cells, and no MYC gene copy number gain by FISH
Interventions: intervention 1: CUDC-907
Intervention descriptions: intervention 1: None

Protocol documents:
Prot_SAP_000.pdf: 
CUDC-907 
 
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CLINICAL TRIAL PROTOCOL 
CUDC-907-201 
Open-Label, Phase 2 Study to Evaluate the Efficacy and Safety of CUDC-907 
in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma, 
Including Patients With MYC Alterations  
Trial Phase 
Phase 2 
IND Number 
115780 
Clinical Research Organization 
PRA Health Sciences 
4130 Park Lake Avenue, Suite 400 
Raleigh, NC 27612 
Phone:  (919) 786-8200 
Sponsor 
Curis, Inc. 
4 Maguire Road 
Lexington, MA  02421-3112 
Phone:  (617) 503-6500 
Fax:  (617) 503-6501 
Primary Medical Monitor 
Graciela Perez, MD, PhD 
PRA Health Sciences 
Medical Director NA 
Phone: (866) 326-5053 
Fax: (800) 280-7035 
Sponsor Medical Monitor 
Amir Hafeez, MD 
Senior Medical Director 
Phone: (617) 503-6647 
Fax: (617) 503-6501 
Clinical Trial Protocol Version 
Amendment 4 (Version 5.0) 
Issue Date 
30 August 2016 
Original Protocol 
18 November 2015 
 
Confidentiality Statement 
This document is the property of Curis, Inc.  The information in this document contains trade secrets 
and commercial information that are privileged or confidential and may not be disclosed without the 
express written permission of Curis, Inc. unless required by federal or state law or regulations.  Any 
person to whom the information is disclosed must be informed that the information is privileged or 
confidential and may not be further disclosed by them.  These restrictions on disclosure will apply 
equally to all future information supplied to you that is indicated as privileged or confidential. 




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PROTOCOL SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments, and provides 
the necessary assurances that this trial will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable United States federal regulations and International 
Conference on Harmonisation (ICH) guidelines. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator Signature  
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator Name  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Institution 


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1. 
SYNOPSIS 
Protocol Title:  
Open-Label, Phase 2 Study to Evaluate the Efficacy and Safety of CUDC-907 in Patients With 
Relapsed/Refractory Diffuse Large B-Cell Lymphoma, Including Patients With MYC 
Alterations  
Sponsor Protocol Number: 
CUDC-907-201 
Phase:  
Phase 2 
Sponsor: 
Curis, Inc. 
Name of Investigational Product: 
CUDC-907 
IND Number: 
115780 
EudraCT Number: 
2014-004509-34 
Trial Centers/Countries:  
Up to 65 sites in the United States (U.S.) and ex-U.S. 
Planned Trial Period: 
2 years 
Trial Objectives:  
Primary Objective: 
 To evaluate the efficacy of CUDC-907 as measured by the objective response rate (ORR) 
in subjects with relapsed and/or refractory (RR) diffuse large B-cell lymphoma (DLBCL) 
with MYC-altered disease. 
Secondary Objectives: 
 To evaluate progression-free survival (PFS), median PFS, and PFS at 6 months (PFS6). 
 To evaluate overall survival (OS). 
 To evaluate the disease control rate (DCR) and duration of response (DOR). 
 To evaluate the incidence and severity of adverse events (AEs), serious adverse events 
(SAEs), and other safety parameters in subjects receiving CUDC-907. 
 To characterize the pharmacokinetics (PK) of CUDC-907. 


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Trial Objectives (Continued): 
Exploratory Objectives: 
 To explore the effects of CUDC-907 on disease-associated biomarkers. 
 To explore the relationship between disease-associated biomarkers in plasma and tumor 
tissue.  Among biomarkers of interest, BCL2 and BCL6 protein expression and 
translocation status in particular will be tested in tumor tissue, where possible. 
 To explore biomarkers of response for patient selection. 
 To explore the relationship between additional biomarkers and biomarker profiles that 
may influence biologic and clinical responses to CUDC-907. 
 To explore the ORR according to Lugano classification (Cheson et al, 2014; Barrington 
et al, 2014). 
Study Design and Methods: 
This is a Phase 2, open-label, multicenter trial designed to evaluate the efficacy and safety of 
CUDC-907 in subjects 18 years and older with RR MYC-altered DLBCL. 
Figure 1 depicts the study design.  Patients with RR DLBCL will be eligible for treatment with 
CUDC-907 as long as they have tumor tissue available that can be tested for MYC-altered 
disease.  This is defined as MYC translocation by FISH, or MYC expression in ≥ 40% of tumor 
cells by IHC staining, and/or MYC gene copy number gain by FISH based on central testing of 
one of the following: 
 Fresh tumor tissue obtained from biopsy accessible lesions with low estimated risk for 
serious complications (less than 2%), or  
 Archived tumor tissue (most recent available) 
Subjects will be required to submit archival tumor samples (most recent available) or fresh 
tumor samples for central FISH and IHC testing.  Subjects whose tumors have been previously 
characterized as MYC-altered are strongly encouraged to enter the study.  For subjects who enter 
the study with unconfirmed MYC-altered disease, fresh tumor samples are preferred.  
All eligible subjects will receive the following treatment: 
 CUDC-907 60 mg (2 × 30 mg capsules) orally (PO) for 5 days on/2 days off (5/2) 
(21-day cycles). 
Based on central testing and review, subjects will be classified into one of the following 
categories:   
(1) Group A:  MYC translocation+ by FISH,  
(2) Group B:  MYC expression in ≥ 40% of tumor cells by IHC and/or MYC gene copy number 
gain by FISH, or  
(3) Group C:  MYC translocation¯ by FISH, and MYC expression in < 40% of tumor cells, and 
no MYC gene copy number gain by FISH.   
Subjects will be assigned to Groups A, B, or C according to their MYC status as described 
above.  Subjects who are both MYC translocation+ by FISH and have MYC expression in ≥ 40% 
of tumor cells by IHC and/or MYC gene copy number gain by FISH will be classified as MYC 
translocation+ and assigned to Group A.   
Enrollment may continue until the minimum number of subjects are enrolled in Groups A and B. 


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Study Design and Methods (Continued): 
Subjects in all groups will continue to receive treatment until they meet criteria for treatment 
discontinuation.  Efficacy evaluations will include restaging assessments, physical examination, 
review of lymphoma symptoms, survival status, and other procedures, as necessary.  Disease 
response by radiologic imaging will be assessed according to the Revised Response Criteria for 
Malignant Lymphoma (Cheson et al, 2007).  The exploratory efficacy endpoint of ORR will be 
assessed according to Lugano classification (Cheson et al, 2014; Barrington et al, 2014). 
Efficacy assessments will be performed using computed tomography/magnetic resonance 
imaging (CT/MRI) scans of the neck, chest, abdomen, and pelvis.  
Skull base-to-mid thigh positron emission tomography (PET) scan is recommended but not 
mandated. 
Contrast-enhanced MRI may be used to evaluate sites of disease that cannot be adequately 
imaged using CT or if contrast-enhanced CT scanning cannot be performed due to medical 
condition(s).  For each patient, the modality/modalities utilized at screening will be followed 
throughout the patient’s time on study. While additional modalities may be used depending on 
assessment needs and disease specifics, technologies used at screening will continue to be 
followed at each restaging assessment to enable direct comparison with the baseline assessment. 
Disease response will be assessed both by the local Investigator and the independent review 
committee. 
Safety will be assessed by the incidence and severity of AEs as determined by National Cancer 
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03).  Additional 
safety parameters will include physical examination and vital signs, as well as hematology and 
serum chemistry laboratory tests. 
Planned Number of Subjects:  Approximately 200 subjects will be enrolled in the study. 
Schedule of Visits and Assessments: 
During Treatment:  
Subjects will have 4 clinic visits during Cycle 1 (Days 1, 5, 12, and 15) and clinic visits every 
3 weeks on Day 1 of every cycle thereafter.  For the first 50 subjects enrolled on amendment 4, 
there will also be a Cycle 1 Day 8 visit. Subjects who continue past Cycle 13 will have clinic 
visits every 6 weeks on Day 1 of every other cycle (Cycles 14, 16, 18, etc.).  Safety assessments 
will be conducted at each clinic visit. 
Subjects will have efficacy assessments (CT/MRI) performed at the end of Cycles 2, 4, and 6 
(each ± 3 days).  If 18F-fluorodeoxyglucose (FDG)-PET/CT is acquired at baseline, follow-up 
FDG-PET/CT imaging at Cycle 4 and at Cycle 10 is required.  Scans will be sent for a central 
radiographic review. 
Subjects who continue to receive CUDC-907 after Cycle 6 will have disease response 
assessments (CT/MRI) performed every 12 weeks ± 1 week (i.e., Cycles 10, 14, 18) until 
Cycle 18 in the first 12 months with scans collected through the first year, then every 24 weeks ± 
2 weeks (i.e., Cycles 26, 34) until progressive disease (PD) or death, or up to 2 years, whichever 
occurs first.  After that, disease assessments may be performed as clinically indicated (i.e., at the 
discretion of the Investigator or per standard of care). 


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Schedule of Visits and Assessments (Continued): 
During Post-Treatment Follow-Up  
All subjects will have PFS and survival assessments every 12 weeks during the first 6 months, 
then every 24 weeks until PD or death, or up to 2 years, whichever occurs first.  After that, 
disease assessments may be performed as clinically indicated (i.e., at the discretion of the 
Investigator or per standard of care).  Overall survival may be checked by phone every 3 months 
and data entered in the electronic case report form (eCRF). 
Inclusion and Exclusion Criteria: 
Inclusion Criteria: 
1. Age ≥ 18 years. 
2. At least 2 but no more than 4 prior lines of therapy for the treatment of de novo DLBCL 
and ineligible for (or failed) autologous or allogeneic stem cell transplant (SCT) (salvage 
therapy, conditioning therapy and maintenance with transplant will be considered one 
prior treatment).  NOTE: For follicular lymphoma transformed to DLBCL 
(t-FL/DLBCL), single-agent non-cytotoxic therapy will not be considered as a line of 
therapy. 
3. Histopathologically confirmed diagnosis of one of the following:  
 RR DLBCL per the 2008 World Health Organization (WHO) classification of 
hematopoietic and lymphoid tumors (Swerdlow et al, 2008). 
 High grade B-cell lymphoma (HGBL), with MYC and BCL2 and/or BCL6 
rearrangements, or DLBCL, not otherwise specified (NOS), per the 2016 revision of 
the WHO classification of lymphoid neoplasms (Swerdlow et al, 2016). 
 Diagnosis of t-FL/DLBCL is allowed.  However, other B-cell lymphomas including 
other transformed indolent lymphomas/DLBCL per the 2008 WHO classification, 
HGBL, NOS per the 2016 WHO classification, and Burkitt lymphoma are not 
eligible. 
4. Confirmed availability of viable tissue (defined as most recent available archival tumor 
tissue, or fresh tumor samples) for central laboratory FISH and IHC testing prior to study 
dosing. For subjects who enter the study with unconfirmed MYC-altered disease, fresh 
tumor samples are preferred.    
NOTE: To facilitate early testing of MYC status, a separate informed consent form 
(ICF) specific for MYC testing will be available to be signed prior to sample testing and 
the signing of the main ICF. 
5. CT scan showing at least 1 or more clearly demarcated lymph node(s) with a long axis 
> 1.5 cm and short axis > 1.0 cm or 1 clearly demarcated extranodal lesion(s) with a long 
axis > 1.0 cm and short axis > 1.0 cm.  Baseline FDG-PET scans, if used, must 
demonstrate positive lesions compatible with CT-defined anatomical tumor sites. 


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Inclusion and Exclusion Criteria (Continued): 
Inclusion Criteria (Continued): 
6. Presence of RR disease per Revised Response Criteria for Malignant Lymphoma 
(Cheson et al, 2007). 
 Relapsed disease is defined by DLBCL confirmed by excisional/incisional biopsy 
(preferred) or fine needle aspiration (FNA) or core needle biopsy (CNB) after a 
complete response (CR) or unconfirmed complete response (CRu). 
o For relapse during prior treatment, biopsy/FNA reconfirmation of the 
lymphoma is recommended but not mandatory. 
 Refractory disease is defined by (a) PD during prior treatment, (b) stable disease 
(SD) after ≥ 3 cycles of prior treatment, or (c) partial response (PR) after ≥ 6 cycles 
of prior treatment, or for stage II disease, ≥ 3 cycles of treatment and definitive 
involved field radiotherapy. 
o For sustained PR after prior treatment, confirmation biopsy for DLBCL is 
preferred.  An FNA may be acceptable, but if inappropriate (e.g., due to 
biopsy inaccessibility), the Sponsor may determine eligibility following 
review of imaging results and disease history. 
o For SD or PD after prior treatment, reconfirmation of DLBCL by biopsy 
(preferred) or FNA is recommended but not mandatory. 
7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. 
8. Recovery to Grade 1 or baseline of any toxicity due to prior anticancer therapies 
(excluding alopecia). 
9. Absolute neutrophil count (ANC) ≥ 1,000/µL; platelets ≥ 75,000/µL; creatinine ≤ 1.5 × 
upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/minute as 
determined by Cockcroft-Gault (using actual body weight) or by 24-hour urine collection 
measurements of creatinine; aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) ≤ 2.5 × ULN; total bilirubin ≤ 1.5 × ULN or ≤ 3 ULN for 
patients with documented Gilbert’s syndrome.  Platelet transfusions and administration 
of granulocyte colony-stimulating factors to help patients meet eligibility criteria are not 
allowed within 1 week prior to screening complete blood count (CBC) or Cycle 1, Day 1 
treatment. 
10. Women of childbearing potential must have a negative serum or urine pregnancy test 
(not applicable after bilateral oophorectomy and/or hysterectomy).  
11. Men and women of childbearing potential and their partners must agree to use adequate 
birth control throughout their participation in the study and for 30 days following the last 
study treatment.  Adequate contraception is defined as hormonal birth control, 
intrauterine device, double barrier method or total abstinence.  Acceptable methods of 
contraception are described in Table 3.  
12. In the Investigator’s judgement, able to provide written informed consent and follow 
protocol requirements. 


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Inclusion and Exclusion Criteria (Continued): 
Exclusion Criteria: 
1. Known primary mediastinal, ocular, epidural, testicular or breast DLBCL. 
2. Patients must not have active CNS involvement of their malignancy. Patients with prior 
brain metastases are permitted, but must have completed treatment and have no evidence 
of active CNS disease (clear cerebrospinal fluid [CSF]) for at least 4 weeks prior to the 
first dose of CUDC-907.  Intrathecal chemoprophylaxis to prevent the emergence or 
recurrence of lymphoma in the CNS is permitted on study and may be administered per 
institutional guidelines.   
3. Known allergy or hypersensitivity to phosphatidylinositol 3-kinase (PI3K) inhibitors or 
any component of the formulations used in this study.   
4. Cytotoxic anticancer therapy (e.g., alkylating agents, anti-metabolites, purine analogues) 
within 2 weeks of study entry. 
5. Radiotherapy delivered to non-target lesions within one week prior to starting study 
treatment or delivered to target lesions that will be followed on the study (NOTE: prior 
sites of radiation will be recorded). 
6. Treatment with experimental therapy within 5 terminal half-lives (t1/2) or 4 weeks prior 
to enrollment, whichever is longer. 
7. Current or planned glucocorticoid therapy, with the following exceptions: 
 Doses ≤ 1 mg/kg/day prednisolone or equivalent glucocorticoid and inhalational 
therapies for conditions such as mild chronic obstructive pulmonary disease (COPD) 
and asthma are allowed. 
 Replacement dosing of steroids (defined as < 30 mg/day hydrocortisone or the 
equivalent) is allowed, provided that the steroid dose has been stable or tapering for 
at least 14 days prior to the first dose of CUDC-907. 
8. Graft versus host disease following transplant within 100 days prior to study treatment. 
9. Major surgery, other than diagnostic surgery, occurring 4 weeks prior to study treatment. 
10. Diabetes mellitus that is not controlled with medication. 
11. Serious infection requiring intravenous antibiotic therapy within 14 days prior to study 
treatment.  
12. Uncontrolled or severe cardiovascular disease, including myocardial infarction, unstable 
angina, or atrial fibrillation (AFib) within 6 months prior to study treatment, New York 
Heart Association (NYHA) Class II or greater congestive heart failure, serious 
arrhythmias requiring medication for treatment, clinically significant pericardial disease, 
cardiac amyloidosis, or QTc with Fridericia’s (QTcF) correction that is unmeasurable or 
≥ 480 msec on screening electrocardiogram (ECG).  (Note: for QTcF ≥ 480 sec on the 
screening ECG, the ECG may be repeated twice at least 24 hours apart; the mean QTcF 
from the three screening ECGs must be < 480 msec in order to meet eligibility for trial 
participation). 


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Inclusion and Exclusion Criteria (Continued):   
Exclusion Criteria (Continued): 
13. Gastrointestinal disease or disorder that could interfere with the swallowing, oral 
absorption, or tolerance of CUDC-907.  This includes uncontrolled diarrhea (> 1 watery 
stool/day), major abdominal surgery, significant bowel obstruction and/or 
gastrointestinal diseases that could alter the assessment of PK or safety, including but not 
limited to: irritable bowel syndrome, ulcerative colitis, Crohn’s disease and hemorrhagic 
coloproctitis. 
14. History of other invasive malignancy, unless adequately treated with curative intent and 
with no known active disease present within 1 year prior to the first dose of study drug, 
provided it is deemed to be at low risk for recurrence by the treating physician. 
 These conditions include but are not limited to non-melanoma skin cancer, carcinoma 
in situ, (including superficial bladder cancer), cervical intraepithelial neoplasia and 
organ-confined prostate cancer. 
15. Known infection with human immunodeficiency virus (HIV). 
16. Known active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. 
 Regardless of hepatitis B surface antigen (HBsAg) status, if hepatitis B core antibody 
(HBcAb) is positive, then HB DNA testing will be performed and if positive the 
patient will be excluded. 
 Regardless of hepatitis RNA level, patients who are positive for hepatitis C antibody 
(anti-HCV) will be permitted to enroll provided that they meet all eligibility criteria 
and are without evidence of cirrhosis.  Patients diagnosed with HCV < 6 months 
prior to enrollment will be considered to have acute HCV and excluded unless viral 
load is undetectable. 
17. Pregnant or breast-feeding women. 
18. Unstable or clinically significant concurrent medical condition that would, in the opinion 
of the Investigator, jeopardize patient safety and/or compliance with the protocol. 
Dose and Mode Of Administration/Dosing Schedule:  
Each cycle will consist of 21 days. 
 CUDC-907 60 mg (2 × 30 mg capsules) administered PO 5/2. 
Planned Duration of Treatment:  
CUDC-907 will be taken until disease progression, withdrawal from study, unacceptable 
toxicity, pregnancy, initiation of another anticancer or experimental therapy, noncompliance 
with study procedures, or study discontinuation. 
Dose and/or schedule intensity of CUDC-907 may be reduced due to toxicity. 


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Criteria for Evaluation: 
Efficacy: 
The Revised Response Criteria for Malignant Lymphoma (Cheson et al, 2007), will be used to 
evaluate all subjects on active treatment. 
Primary efficacy endpoint:  ORR (central determination) 
Secondary efficacy endpoints:  
 ORR (local determination) 
 PFS, median PFS, and PFS6 (central and local determination) 
 OS 
 DCR and DOR (central and local determination) 
Exploratory efficacy endpoint: 
 ORR according to Lugano classification (Cheson et al, 2014; Barrington et al, 2014) 
Safety: 
The incidence and severity of AEs, including treatment-related events, events leading to death, 
SAEs, and events resulting in study treatment discontinuation.  
Pharmacokinetics: 
Population PK of CUDC-907 will be evaluated in plasma samples based on prior established 
parameters. 
Biomarkers: 
Tumor, blood, and plasma samples will be evaluated in all subjects to identify other markers 
potentially predictive of response to CUDC-907.  Genomic material from tumor, blood and 
plasma samples will be assessed for aberrations in genes associated with disease and/or 
treatment targeted pathways.  Gene expression profiling will be applied to genomic material 
isolated from tumor tissue in part to determine cell of origin classification.  In addition, protein 
analysis will be conducted on tumor and plasma samples to evaluate baseline levels and/or 
changes in biomarkers related to the disease and/or targeted pathways, if feasible.  BCL2 and 
BCL6 protein expression and translocation status are among the disease-related biomarkers that 
will be tested in tumor tissue, if feasible. 
Statistical Considerations: 
Efficacy Endpoints: 
The primary efficacy endpoint is ORR as determined by the central determination of disease 
response.  Secondary endpoints include ORR as determined by the investigative site, and PFS, 
median PFS, PFS6, OS, DCR, and DOR as determined by both the central determination of 
disease response and investigator site.  An exploratory efficacy endpoint will assess ORR (CR, 
PR) according to Lugano classification (Cheson et al, 2014; Barrington et al, 2014). 


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Statistical Considerations (Continued): 
Analysis Populations Evaluable for Safety and Efficacy: 
The Intent-to-Treat (ITT) Population will consist of all subjects assigned to Groups A and B.  
The primary analyses of efficacy will be conducted based on the ITT Population. 
The Evaluable Population will consist of all subjects in Groups A and B who receive at least one 
full cycle of treatment and have at least one post-baseline disease assessment and have not had 
major protocol deviations that are thought to have materially impacted efficacy outcomes. Major 
protocol deviations will be identified prior to database lock.  Secondary analyses of efficacy will 
also be conducted based on the Evaluable Population. In addition, the primary efficacy endpoint 
(ORR) will also be assessed using the Evaluable Population as a secondary analysis.  
The Safety Population will consist of all subjects who receive any study treatment.  All safety 
analyses will be conducted based on this population.  
Sample Size Determination:  
The sample size for Groups A and B was determined based on the following: 
With a sample size of 50 subjects in Groups A and B with an ORR of 30.0%, a two-sided 95% 
confidence interval employing the exact binomial method will extend from 17.9% to 44.6%.  
This confidence bound (CB) about the observed ORR is thought to adequately characterize the 
disease response of these populations after receiving CUDC-907. 
Interim Analyses: 
 Interim analyses of efficacy using the Evaluable Population will be performed after ORR 
has been determined in 25 evaluable subjects for both Groups A and B, separately.  In 
both Groups A and B, the ORR using the local determination of disease response will be 
obtained.  If the lower bound of a single-sided 95% confidence interval using the exact 
binomial method is less than 10% (i.e., 5 responses or less out of 25 patients) in either 
group, enrollment in that group will not continue. 
Efficacy Analyses: 
The primary analyses of efficacy will be conducted based on the ITT Population and the interim 
analyses will be performed on the Evaluable Population.  However, secondary analyses will be 
performed on the ITT and Evaluable Populations.  The primary efficacy endpoint, ORR, will be 
based on the proportion of subjects with CR or PR using the central determination of disease 
response in both Groups A and B, separately.  The estimate will be accompanied by a two-sided 
exact binomial 95% CB.   
Progression-free survival, OS, and DOR will be summarized descriptively using the 
Kaplan-Meier method.  
Progression-free survival, median PFS, and PFS6 based on the Kaplan-Meier analyses will be 
reported.  For OS, the estimated rates at 3, 6, 9 and 12 months based on the Kaplan-Meier 
analyses will be reported.  For duration of objective response, the estimate of the median based 
on the Kaplan-Meier analyses will be reported.  Waterfall plots will be used to depict graphically 
the maximum decrease from baseline in the sum of the product diameters in measurable nodes 
and nodal masses.  Secondary analyses of efficacy will be conducted based on the Evaluable 
Population.  The estimate will be accompanied by a two-sided exact binomial 95% lower CB. 
 


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Statistical Considerations (Continued): 
Safety Analyses: 
The analyses of safety will be conducted based on the Safety Population.  Safety will be 
assessed based on AEs, SAEs, laboratory values, vital signs, and ECG results.  Summary tables 
will be produced for all reported treatment-emergent adverse events (TEAEs) (AEs that start or 
worsen on or after the first administration of study treatment) tabulated by the current version of 
the Medical Dictionary for Regulatory Activities (MedDRA) system organ class and preferred 
term.  Tabular summaries will be provided for: all TEAEs, TEAEs by relationship to study 
treatment, TEAEs by severity, TEAEs occasioning treatment modification, and serious TEAEs. 
Hematology and serum chemistries will be summarized using conventional summary statistics 
(mean, standard deviation, median, and range) for the following: baseline value, minimum and 
maximum post-baseline values, average post-baseline value, and last post-baseline value.  
Standard shift tables will also be prepared presenting worst post-baseline toxicity grade vs. 
baseline.  Vital signs and ECG results will be summarized in a descriptive manner by calculating 
the mean, standard deviation, median, and range by time point in the same manner described for 
laboratory values. 
Pharmacokinetic Analyses: 
Population PK analysis will be conducted to further understand the PK profile of CUDC-907 in 
patients with RR MYC-altered DLBCL.  Preliminary PK information has been collected during 
Phase 1, and the basic PK models of the drug have been established.  In this study, blood 
samples will be obtained at 2 hours post-dose on Cycle 1 Day 1, Cycle 4 Day 1, and on Day 1 of 
every other cycle thereafter (i.e., Day 1 of Cycles 6, 8, 10 etc.).  In addition, for the first 50 
subjects enrolled on amendment 4, blood samples will also be obtained 2 hours post-dose on 
Days 8 and 15 of Cycle 1.  


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2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
SPONSOR SIGNATURE ................................................................................................................2 
PROTOCOL SIGNATURE PAGE .................................................................................................3 
1. 
SYNOPSIS ...................................................................................................................4 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............14 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................20 
4. 
STUDY SCHEMATIC ...............................................................................................24 
5. 
SCHEDULE OF EVENTS .........................................................................................25 
5.1. 
Schedule of Events .....................................................................................................25 
6. 
INTRODUCTION:  BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE .............................................................................................................28 
6.1.1. 
Relapsed/Refractory MYC-Altered Diffuse Large B-Cell Lymphoma ......................28 
6.1.1.1. 
Diffuse Large B-Cell Lymphoma ...............................................................................28 
6.1.1.2. 
MYC Rearrangement in DLBCL ................................................................................29 
6.1.1.3. 
MYC Protein Expression in DLBCL ..........................................................................30 
6.1.2. 
Rationale for Development of CUDC-907 for the Treatment of MYC-
Altered DLBCL ..........................................................................................................31 
6.1.3. 
Clinical Rationale for CUDC-907 Use in RR MYC-Altered DLBCL .......................32 
6.2. 
Justification of Study Design Considerations .............................................................33 
6.3. 
Potential Risk and Benefits .........................................................................................33 
6.3.1. 
Potential Risks ............................................................................................................33 
6.3.2. 
Potential Benefits ........................................................................................................33 
6.4. 
Good Clinical Practice Statement ...............................................................................33 
7. 
TRIAL OBJECTIVES ................................................................................................34 
7.1. 
Primary Objective .......................................................................................................34 
7.2. 
Secondary Objectives .................................................................................................34 
7.3. 
Exploratory Objectives ...............................................................................................34 
8. 
STUDY DESIGN .......................................................................................................35 
8.1. 
Overall Study Design ..................................................................................................35 
8.2. 
Number of Subjects ....................................................................................................36 
8.3. 
Dose and Schedule ......................................................................................................36 


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8.3.1. 
Dose and Mode of Administration .............................................................................36 
8.3.2. 
Schedule of Visits and Assessments ...........................................................................37 
8.4. 
Planned Duration of Treatment ..................................................................................37 
9. 
SELECTION AND WITHDRAWAL OF SUBJECTS ..............................................38 
9.1. 
Patient Inclusion Criteria ............................................................................................38 
9.2. 
Patient Exclusion Criteria: ..........................................................................................39 
9.3. 
Criteria for Study Termination ...................................................................................41 
9.3.1. 
Withdrawal of Subject from Study Treatment ............................................................41 
9.3.2. 
Early Study Termination .............................................................................................41 
10. 
TREATMENT OF SUBJECTS ..................................................................................43 
10.1. 
Description of Study Drug ..........................................................................................43 
10.2. 
Supply, Packaging and Labeling ................................................................................43 
10.3. 
Storage and Dispensing ..............................................................................................43 
10.4. 
Investigational Product Accountability ......................................................................43 
10.5. 
Study Drug Administration .........................................................................................43 
10.5.1. 
CUDC-907  .................................................................................................................43 
10.5.2. 
Retreatment Criteria ....................................................................................................44 
10.5.3. 
Safety Criteria for Adjustment or Stopping CUDC-907 ............................................44 
10.5.3.1. 
Dose Delays and Discontinuation of CUDC-907 .......................................................44 
10.5.3.2. 
CUDC-907 Dose Reductions ......................................................................................45 
10.5.3.3. 
Dose Adjustments for CUDC-907 Hematologic and Non-hematologic 
Toxicity .......................................................................................................................45 
10.6. 
Concomitant Medications ...........................................................................................48 
10.6.1. 
Permitted Medications ................................................................................................48 
10.6.2. 
Drug Interactions/Precautions ....................................................................................48 
10.6.3. 
Contraception ..............................................................................................................48 
10.7. 
Treatment Compliance ................................................................................................49 
10.8. 
Group Allocation ........................................................................................................49 
11. 
STUDY ASSESSMENTS ..........................................................................................50 
11.1. 
Screening ....................................................................................................................50 
11.1.1. 
Patient Registration and Group Assignment ...............................................................50 
11.2. 
Safety Evaluations ......................................................................................................50 
11.2.1. 
Demographics and Medical History ...........................................................................50 


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11.2.2. 
Physical Exam ............................................................................................................50 
11.2.3. 
Eastern Cooperative Oncology Group (ECOG) Performance Status .........................50 
11.2.4. 
International Prognostic Index (IPI) ...........................................................................50 
11.2.5. 
Lymphoma Assessment ..............................................................................................51 
11.2.6. 
Vital Signs ..................................................................................................................51 
11.2.7. 
Clinical Laboratory Tests ...........................................................................................51 
11.2.8. 
Pregnancy Testing ......................................................................................................51 
11.2.9. 
Electrocardiogram .......................................................................................................51 
11.2.10. 
Adverse Events ...........................................................................................................53 
11.2.11. 
Concomitant Medications and Other Treatments .......................................................53 
11.3. 
Efficacy Evaluations ...................................................................................................53 
11.3.1. 
Baseline Disease Assessment .....................................................................................53 
11.3.2. 
Disease Response Assessments ..................................................................................54 
11.3.3. 
Survival Status ............................................................................................................54 
11.4. 
CUDC-907 Pharmacokinetic Analyses ......................................................................54 
11.5. 
Biomarker Assessments ..............................................................................................55 
11.5.1. 
Pharmacogenomic Assessments .................................................................................55 
11.5.2. 
Plasma Biomarker Assessments .................................................................................55 
11.5.3. 
Tumor Biomarker Assessments ..................................................................................55 
12. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS ..................................56 
12.1. 
Definition of an Adverse Event ..................................................................................56 
12.2. 
Recording Adverse Events .........................................................................................56 
12.3. 
Serious Adverse Events ..............................................................................................57 
12.4. 
Reporting of Adverse Experiences, Serious Adverse Experiences, Serious 
and Unexpected Adverse Experiences ........................................................................58 
12.4.1. 
Reporting Adverse Events and Serious Adverse Events to the Sponsor ....................58 
12.4.2. 
Reporting to the Institutional Review Board (IRB) ....................................................58 
12.4.3. 
Reporting to the Regulatory Authorities .....................................................................58 
12.4.4. 
Pregnancy Reporting ..................................................................................................59 
13. 
STUDY ACTIVITIES ................................................................................................60 
13.1. 
Prescreening (Before Day -28) and Screening (Days -28 to -1) .................................60 
13.1.1. 
Days -7 to -1 ...............................................................................................................61 
13.2. 
Treatment Period (Cycle 1 to End of Therapy Visit) .................................................61 


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13.2.1. 
Cycle 1 ........................................................................................................................61 
13.2.1.1. 
Cycle 1, Day 1 ............................................................................................................61 
13.2.1.2. 
Cycle 1, Days 2-4, Days 8-11, Days 16-19 ................................................................62 
13.2.1.3. 
Cycle 1, Days 5 and 12 ...............................................................................................62 
13.2.1.4. 
Cycle 1, Day 8 ............................................................................................................62 
13.2.1.5. 
Cycle 1, Day 15 ..........................................................................................................62 
13.2.2. 
Cycles 2 through 6 ......................................................................................................63 
13.2.2.1. 
Cycles 2 through 6, Day 1 ..........................................................................................63 
13.2.2.2. 
Cycles 2-6, Days 2-5, Days 8-12, Days 15-19 ...........................................................63 
13.2.3. 
Cycles 7+ ....................................................................................................................63 
13.2.3.1. 
Cycles 7+, Day 1.........................................................................................................64 
13.2.3.2. 
Cycles 7+, Days 2-5, Days 8-12, Days 15-19 .............................................................64 
13.2.4. 
End of Therapy Visit (Day 30) ...................................................................................64 
13.3. 
Post-Treatment Follow-up Visits ................................................................................65 
13.3.1. 
Follow-up Visits ≤ 6 Months (Every 12 Weeks) ........................................................65 
13.3.2. 
Follow-up Visits > 6 Months (Every 24 Weeks) ........................................................65 
14. 
STATISTICAL ANALYSES .....................................................................................67 
14.1. 
Overview of Study Design ..........................................................................................67 
14.2. 
Study Endpoints ..........................................................................................................67 
14.2.1. 
Primary Endpoint ........................................................................................................67 
14.2.2. 
Secondary Endpoints ..................................................................................................67 
14.2.3. 
Exploratory Endpoints ................................................................................................67 
14.3. 
Sample Size Considerations .......................................................................................68 
14.4. 
Statistical Analysis ......................................................................................................68 
14.4.1. 
Analysis Populations ..................................................................................................68 
14.4.2. 
Baseline Characteristics ..............................................................................................69 
14.4.3. 
Efficacy Analyses .......................................................................................................69 
14.4.3.1. 
Interim Analyses .........................................................................................................69 
14.4.4. 
Safety Analysis ...........................................................................................................70 
14.4.5. 
Pharmacokinetic Analysis ..........................................................................................71 
14.4.6. 
Multicenter Study .......................................................................................................71 
14.4.7. 
Adjustments for Covariates ........................................................................................71 


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14.4.8. 
Missing Data ...............................................................................................................71 
15. 
STUDY ADMINISTRATION ...................................................................................72 
15.1. 
Case Report Forms and Source Documentation .........................................................72 
15.2. 
Investigator Documentation ........................................................................................72 
15.3. 
Record Retention ........................................................................................................73 
15.4. 
Protocol Deviations and Amendment .........................................................................73 
15.5. 
Institutional Review Board/Independent Ethics Committee ......................................73 
15.6. 
Study Committees .......................................................................................................73 
15.7. 
Sponsor Monitoring ....................................................................................................74 
15.8. 
Publication/Data Sharing Policy .................................................................................74 
16. 
ETHICS/PROTECTION OF HUMAN PATIENTS ..................................................75 
16.1. 
Ethical Conduct of the Study ......................................................................................75 
16.2. 
Informed Consent .......................................................................................................75 
16.3. 
Confidentiality and Data Protection ...........................................................................75 
17. 
LIST OF REFERENCES ............................................................................................77 
APPENDIX A.  EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS SCALE .........................................................................82 
APPENDIX B.  ANN ARBOR CLASSIFICATION...................................................................83 
APPENDIX C.  RECOMMENDATIONS FOR INITIAL EVALUATION, STAGING, 
AND RESPONSE ASSESSMENT OF HODGKIN AND NON-HODGKIN 
LYMPHOMA: THE LUGANO CLASSIFICATION ................................................84 
APPENDIX D.  ROLE OF IMAGING IN THE STAGING AND RESPONSE 
ASSESSMENT OF LYMPHOMA: CONSENSUS OF THE 
INTERNATIONAL CONFERENCE ON MALIGNANT LYMPHOMAS 
IMAGING WORKING GROUP; 5-PS SCORE ........................................................86 
APPENDIX E.   INTERNATIONAL PROGNOSTIC INDEX (IPI) 
CLASSIFICATION ....................................................................................................87 
 


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LIST OF TABLES 
Table 1: 
Dose Reduction Steps for CUDC-907 ........................................................................45 
Table 2: 
CUDC-907 Dose Adjustments for Hematologic and Non-Hematologic 
Toxicities ....................................................................................................................46 
Table 3: 
Effective Methods of Contraception ...........................................................................49 
 
LIST OF FIGURES 
Figure 1: Study Design ..................................................................................................................24 
 
 


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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations are used in this study protocol. 
Abbreviations 
Abbreviation 
Definition 
5/2 
Five days on/two days off 
ABC 
Activated B-cell-like  
AE 
Adverse event 
AFib 
Atrial fibrillation 
AKT 
Protein kinase B 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
AST 
Aspartate aminotransferase 
BIW 
Twice weekly 
BUN 
Blood urea nitrogen 
CB 
Confidence bound 
CBC 
Complete blood count 
cfDNA 
Cell-free DNA 
CFR 
Code of Federal Regulations 
CNB 
Core needle biopsy 
CNS 
Central nervous system 
COO 
Cell of origin 
COPD 
Chronic obstructive pulmonary disease 
CR 
Complete response 
CRu 
Unconfirmed complete response 
CSF 
Cerebrospinal fluid 
CT 
Computed tomography 
DCR 
Disease control rate 
DE 
Double expressor 
DH 
Double hit 
DHAP 
Dexamethasone, cytarabine, and cisplatin 
DLBCL 
Diffuse large B-cell lymphoma 
DLT 
Dose-limiting toxicity 


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Abbreviation 
Definition 
DOR 
Duration of response  
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group  
eCRF 
Electronic case report form 
EFS 
Event free survival 
EOT 
End of Therapy 
FDA 
Food and Drug Administration 
FDG 
18F-fluorodeoxyglucose 
FIH 
First-in-human 
FISH 
Fluorescence in-situ hybridization 
FL 
Follicular lymphoma 
FNA 
Fine needle aspiration 
GCB 
Germinal center B-cell 
GCP 
Good Clinical Practice 
GEP 
Gene expression profiling 
GMP 
Good manufacturing practice 
HBcAb 
Hepatitis B core antibody 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
HDAC 
Histone deacetylase 
HGBL 
High grade B-cell lymphoma 
HIV 
Human immunodeficiency virus  
HL 
Hodgkin lymphoma 
IC50 
Half maximal inhibitory concentration 
ICF 
Informed consent form  
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IHC 
Immunohistochemistry 
IND 
Investigational New Drug Application 
IPI 
International Prognostic Index  
IRB 
Institutional Review Board 


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Abbreviation 
Definition 
ITT 
Intent-to-Treat 
IV 
Intravenous 
JAK 
Janus kinase  
LDH 
Lactate dehydrogenase 
MAPK 
Mitogen-activated protein kinase  
mCR 
Metabolic complete response 
MedDRA 
Medical Dictionary for Regulatory Activities 
MM 
Multiple myeloma 
MRI 
Magnetic resonance imaging 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NHL 
Non-Hodgkin lymphoma 
NOS 
Not otherwise specified 
NYHA 
New York Heart Association 
OR 
Objective response 
ORR 
Objective response rate  
OS 
Overall survival  
PD 
Progressive disease 
PET 
Positron emission tomography 
PFS 
Progression-free survival 
PI3K 
Phosphatidylinositol 3-kinase 
PI 
Principal Investigator 
PK 
Pharmacokinetic 
PO 
Per os (orally) 
PR 
Partial response 
PTEN 
Phosphatase and tensin  
QTcF 
QTc with Fridericia’s 
QD 
Once daily 
R-CHOP 
Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone 
RP2D 
Recommended Phase 2 dose 
RR 
Relapsed and/or refractory 
SAE 
Serious adverse event 
SCT 
Stem cell transplant 


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Abbreviation 
Definition 
SD 
Stable disease 
SRC 
Safety Review Committee 
STAT 
Signal transducer and activator of transcription 
t1/2 
Half-life 
TEAE 
Treatment-emergent adverse events 
t-FL/DLBCL 
Transformed follicular lymphoma subtype of diffuse large B-cell lymphoma 
TH 
Triple hit 
TIW 
Thrice weekly 
ULN 
Upper limit of normal 
U.S. 
United States 
WBC 
White blood cell 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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4. 
STUDY SCHEMATIC 
Figure 1: Study Design 
 
DLBCL = diffuse large B-cell lymphoma; RR = relapsed and/or refractory  
1Subjects with RR DLBCL who have had at least 2 but no more than 4 prior lines of therapy for DLBCL will receive CUDC-907.  Tumor samples from all 
subjects will be tested centrally to obtain full tumor MYC profile.  Upon central review of MYC status, subjects will be assigned to Groups A, B or C.  Subjects 
who qualify for both Groups A and B will be classified as MYC translocation+ and assigned to Group A. 
2Subjects who do not meet criteria for Groups A or B based on central laboratory testing and review will be assigned to Group C. 
 


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5. 
SCHEDULE OF EVENTS 
5.1. 
Schedule of Events  
Assessments 
Screening 
Treatment Period 
(21-Day Cycles)1 
Post-Treatment 
Days 
-28 
to  
-1 
Days 
-7 to 
-1 
Cycle 1 
Cycle 2-6 
Cycle 
7+ 
EOT 
F/U ≤ 6 
months 
F/U > 
6 
months 
Day  
12 
Day 
5  
Day 
8 
Day 
12 
Day 
15 
 Day 12 
Day 
12 
D30 
± 7d 
post 
last 
dose 
q12 
weeks 
±  
1 week 
q24 
weeks 
± 2 
weeks 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical and 
medication 
history/demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Archival/fresh tumor 
tissue3,21,22 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical examination2 
 
X 
X 
 
 
 
 
X 
X 
X 
 
 
Symptom-directed 
physical examination 
 
 
 
X 
 
X 
 
 
 
 
X4 
X4 
ECOG performance 
status 
 
X 
X 
 
 
 
 
X 
X 
X 
 
 
IPI score 
X 
 
 
 
 
 
 
 
 
 
X 
X 
Height 
 
X 
 
 
 
 
 
 
 
 
 
 
Vital signs5 
 
X 
X 
X 
 
X 
 
X 
X 
X 
 
 
ECG 
 
X 
 
 
 
 
 
 
 
X 
 
 
Pregnancy test6 
 
X 
X 
 
 
 
 
X 
X 
X 
 
 
Lymphoma 
assessment7 
 
 
X 
 
 
 
 
X 
X 
X8 
X4 
X4 
Radiologic 
assessment18 
(CT/MRI) 
X19 
 
 
 
 
 
 
X9 
X9 
X8 
X4 
X4 
Radiologic 
assessment18 
(FDG-PET/CT) 
X20 
 
 
 
 
 
 
X10 
X10 
X8 
X4 
X4 
Survival status11  
 
 
 
 
 
 
 
 
 
 
X 
X 
CBC w/diff 
 
X 
X 
X 
 
X 
 
X 
X 
X 
 
 
Chemistries12 
 
X 
X 
X 
 
X 
 
X 
X 
X 
 
 
Urinalysis 
X 
 
 
 
 
 
 
 
 
 
 
 
Plasma for biomarker 
sampling 
X 
 
 
 
 
 
 
X 
X 
 
 
 
Plasma for PK 
sampling13 
 
 
X 
 
X23 
 
X23 
X 
X 
 
 
 


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Definitions:  ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN =  blood urea nitrogen; 
C = cycle; CBC = complete blood count; CT = computed tomography; d = day (s); diff = differential; 
ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; eCRF = electronic case report form; 
EOT = End of Therapy; FISH = fluorescence in-situ hybridization; FDG-PET = 18F-fluorodeoxyglucose-positron 
emission tomography; F/U = follow-up; ICF = informed consent form; IHC = immunohistochemistry; 
IPI = International Prognostic Index; LDH = lactate dehydrogenase; MRI = magnetic resonance imaging; 
PD = progressive disease; PET = positron emission tomography; PFS = progression-free survival; 
PK = pharmacokinetic; q12 = every 12; q24 = every 24;  SAEs = serious adverse events 
Footnotes: 
1. The window for all treatment assessments/procedures is ± 2 days.  If extenuating circumstances prevent a 
subject from starting or completing treatment, or a scheduled procedure or assessment within the 
protocol-specified time, the subject may continue to be treated on the study only with permission of the 
Curis Medical Monitor or designee clinician. 
2. Physical exam, performance status, weight, CBC w/differentials and serum chemistry labs may be 
performed up to 3 days prior to Day 1 of each cycle.  Subjects who continue past Cycle 13 will only be 
required to have a Day 1 visit at the beginning of every other cycle (14, 16, 18, etc.).  The Cycle 1, Day 1 
physical examination is not required if the screening physical examination was conducted within 3 days 
prior to administration of the first dose of study drug (Cycle 1, Day 1). 
3. Subjects will be required to submit archival tissue samples (most recent available) or fresh tumor samples 
for central FISH and IHC testing.  For subjects with unconfirmed MYC-altered disease, fresh tumor 
samples (obtained from biopsy-accessible lesions with less than 2% estimated risk for serious 
complications) are preferred. 
4. Performed until time of disease progression, withdrawal of consent, or any other criteria that would make 
the subject unable to be followed for disease response. 
5. Vital signs include blood pressure, heart rate, respiratory rate, temperature, and weight. 
6. A serum or urine pregnancy test will be performed for women of childbearing potential at least once per 
cycle prior to dosing, or more frequently as clinically indicated, as well as during Screening and at the EOT 
visit. 
7. Lymphoma assessment consists of physical examination, a review of the subject’s current signs and 
symptoms, B symptoms, and concomitant medications. 
8. Lymphoma and radiologic assessments to be done only if not performed within 4 weeks of the EOT visit. 
9. Up to Cycle 6, radiologic assessments using CT/MRI scans of the neck, chest, abdomen, and pelvis are 
required during the last week (Day 15 -21 ) of Cycle 2, Cycle 4, and Cycle 6 (each ± 3 days).  After Cycle 
6, radiologic assessments (CT/MRI) are required every 12 weeks (± 1 week) (i.e., Cycles 10, 14, 18) until 
Cycle 18, and then every 24 weeks ± 2 weeks (i.e., Cycles 26, 34) until PD or death, or up to 2 years, 
whichever occurs first.  After that, disease assessments may be performed as clinically indicated (i.e., at the 
discretion of the Investigator or per standard of care).  Contrast-enhanced MRI may be used to evaluate 
sites of disease that cannot be adequately imaged using CT or if contrast-enhanced CT scanning cannot be 
performed due to medical condition(s).  For each subject, the modality/modalities utilized at screening will 
be followed throughout the subject’s time on study. 
Tissue for biomarker 
sampling14 
X 
 
 
 
 
 
X 
 
 
 
 
 
Pharmacogenomic 
sampling 
X 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medications 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
X15 
X15 
Adverse events 
 
 
X 
X 
 
 
X 
X 
X 
X 
X16 
X16 
CUDC-907 dosing 
 
 
5 days on/2 days off17 
 
 
 


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10. Skull base-to-mid thigh PET scan is recommended but not mandated.  If FDG-PET/CT is acquired at 
baseline, follow-up FDG-PET imaging at Cycle 4 and at Cycle 10 is required.  5-PS score of 1 and 2 are 
considered PET-negative; 5-PS score of 3, 4, or 5 are considered PET-positive. 
11. All subjects will have PFS and survival assessments every 12 weeks during the first 6 months, then every 
24 weeks until PD or death, or up to 2 years, whichever occurs first.  After that, disease assessments may 
be performed as clinically indicated (i.e., at the discretion of the Investigator or per standard of care).  
Overall survival may be checked by phone every 3 months and data entered in the eCRF. 
12. Sodium, potassium, magnesium, phosphate, total protein, chloride, bicarbonate, calcium, BUN, creatinine, 
uric acid, total bilirubin, alkaline phosphatase, AST, ALT, LDH, albumin, and glucose. 
13. Plasma for PK sampling will be drawn at 2 hours post-dose on Cycle 1 Day 1, Cycle 4 Day 1, and on Day 1 
of every other cycle thereafter (i.e., Day 1 of Cycles 6, 8, 10, etc.) for all subjects. 
14. Optional tumor biopsies (from subjects with accessible tumor lesion) for biomarker sampling should be 
obtained any time during screening up to pre-dose Cycle 1, Day 1 and within 8 hours post-dose on any 
dosing day from Cycle 1, Day 15 through Cycle 2, Day 1. 
15. Anti-cancer therapies only. 
16. Adverse events will be collected until 30 days post the last dose of study treatment.  After the post 30-day 
time point, only treatment-related SAEs will be captured. 
17. CUDC-907 will be administered in the clinic on all PK and tissue sampling days. 
18. Disease response by radiologic imaging will be assessed according to the Revised Response Criteria for 
Malignant Lymphoma (Cheson et al, 2007).  The exploratory efficacy endpoint of ORR will be assessed 
according to Lugano classification (Cheson et al, 2014; Barrington et al, 2014).  Assessments are 
performed both by the local Investigator and by the independent review committee. 
19. CT scan showing at least 1 or more clearly demarcated lymph node(s) with a long axis > 1.5 cm and short 
axis > 1.0 cm OR 1 clearly demarcated extra nodal lesion(s) with a long axis > 1.0 cm and short axis 
> 1.0 cm.  Every effort should be made to use the same imaging facility and scanner for each scan 
throughout the study to ensure reproducibility of measurements. 
20. Baseline FDG-PET scans, if used, must demonstrate positive lesions compatible with CT-defined 
anatomical tumor sites. 
21. To facilitate early testing of MYC status, and depending on local site requirements, a separate ICF specific 
for MYC testing will be available to be signed prior to sample testing and the signing of the main ICF. All 
other study tests and procedures must be done during the Screening period (Day -28 to Day -1). 
22. Local MYC results performed previously should be entered into the eCRF at screening although central 
testing is required for all patients. 
23. For the first 50 subjects enrolled on amendment 4, 2 additional blood draws will be required 2 hours post-
dose on Days 8 and 15 of Cycle 1. 


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6. 
INTRODUCTION:  BACKGROUND INFORMATION AND 
SCIENTIFIC RATIONALE 
CUDC-907 is a first-in-class, rationally-designed small molecule that dually inhibits histone 
deacetylase (HDAC) (class I and II) and phosphatidylinositol 3-kinase (PI3K) (class I α, β, and 
δ) enzymes (Qian et al, 2012).  This unique combination suppresses multiple signaling pathways 
critical for cell proliferation, survival, and migration by targeting oncogenic gene expression and 
protein activities critical for cancer growth and potentially mitigating the emergence of acquired 
drug resistance.  CUDC-907 has been shown to inhibit activation of PI3K/protein kinase B 
(AKT), Janus kinase (JAK)/signal transducer and activator of transcription (STAT), and 
mitogen-activated protein kinase (MAPK) signaling pathways in both solid tumor and 
hematologic cancer cell lines.  The anti-tumor growth and pro-apoptotic activity of CUDC-907 
has also been shown to be more potent than single-target HDAC or PI3K inhibitors, as 
demonstrated in a variety of cultured and implanted cancer cell lines representing B- and T-cell 
lymphomas, as well as other hematologic malignancies. 
6.1.1. 
Relapsed/Refractory MYC-Altered Diffuse Large B-Cell Lymphoma 
6.1.1.1. 
Diffuse Large B-Cell Lymphoma 
Diffuse large B-cell lymphoma (DLBCL), a biologically aggressive type of non-Hodgkin 
lymphoma (NHL) that arises from B cells, is the most common form of NHL in the United States 
(U.S.) and Europe.  DLBCL meets requirements for orphan disease status in the U.S. and 
Europe, with a prevalence of less than 200,000 persons in the U.S. and fewer than 5 persons per 
10,000, respectively (Howlader et al, 2014; Bray et al, 2013).  The U.S. Food and Drug 
Administration (FDA) granted CUDC-907 orphan drug status for this disease on April 2, 2015. 
DLBCL is a heterogeneous disease.  While subtypes differ in prognosis and response to 
treatment, the disease is rapidly fatal if untreated.  Clinically, patients with DLBCL usually 
present with advanced and often extranodal disease.  DLBCL can be primary (arising de novo) or 
secondary (representing progression or transformation of a less aggressive lymphoma, such as 
follicular lymphoma).  Since approval of rituximab for the treatment of DLBCL, this agent has 
become an integral part of various cytotoxic standards of care, including R-CHOP (rituximab, 
cyclophosphamide, doxorubicin, vincristine, and prednisone).  While R-CHOP is commonly 
used in 1st line treatment, a considerable proportion of patients with advanced stage disease and 
certain adverse clinical risk factors are not cured with this or other standard therapies (Friedberg 
and Fisher, 2008).  Approximately 40% of patients have refractory disease or disease that 
relapses after initial response and most patients with relapsed DLBCL ultimately succumb to the 
disease (Sehn, 2012).  Based on systematic review of the literature focused on interventions for 
relapsed and/or refractory (RR) DLBCL, median progression-free survival (PFS) ranges from 
1 - 10 months and median overall survival (OS) ranges from 4 to 13 months (Colosia et al, 
2014). 
The prognosis for subjects with DLBCL has long been considered to be dependent on risk 
factors such as those measured by the International Prognostic Index (IPI).  The IPI assigns 
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disease, elevated lactate dehydrogenase (LDH), and more than 1 extranodal site of disease) that 
correlate with 5 year OS ranging from 23% to 75% (Gandhi, 2014).  Since the IPI does not 
provide information to guide the choice of therapy, additional risk biomarkers – particularly 
those that might serve as targets for effective interventions – might better characterize subjects’ 
lymphoma subtypes and the interventions most likely to benefit them. 
Gene expression profiling (GEP) studies enable consideration of the molecular subtype of 
DLBCL and provide opportunities to identify subjects with particularly aggressive lymphomas 
that might benefit from a novel therapeutic agent.  Such studies have shown that DLBCL could 
be segregated into 2 distinct subgroups based on cell of origin (COO) referred to as germinal 
center B-cell (GCB) and the activated B-cell-like (ABC) subtypes.  The ABC DLBCL subtype 
has been associated with a more aggressive course and poorer prognosis (Carbone et al, 2014) as 
well as lower likelihood of response to R-CHOP used in the setting of de novo disease (Scott et 
al, 2015). Subjects with RR DLBCL of ABC subtype were also less likely to respond to a 
commonly used salvage regimen, R-DHAP (rituximab, dexamethasone, cytarabine, and cisplatin 
(Thieblemont et al, 2011). 
It has become apparent that the COO paradigm only accounts for a portion of the clinical picture 
in regards to prognosis for DLBCL subjects.  The adverse prognostic impact of rearrangement of 
the MYC oncogene has been well documented for over a decade, both pre- and post- the advent 
of rituximab (Savage et al, 2009).  More recently, overexpression of the MYC protein has also 
been associated with inferior survival (Horn et al, 2013). 
As will be discussed, subjects with MYC-altered DLBCL have much shorter survival (median 
OS of < 2 years) than subjects without MYC alterations, and the survival for subjects with RR 
MYC-altered DLBCL is usually measured in months.  For these subjects, there is no 
evidence-based standard of care.  Novel therapeutic approaches are needed, rather than simply 
intensifying cytotoxic therapy. 
6.1.1.2. 
MYC Rearrangement in DLBCL 
The significance of MYC in DLBCL has been well studied and the preponderance of studies (all 
retrospective) has shown that MYC-altered disease, defined as MYC translocation by 
fluorescence in-situ hybridization (FISH) and/or MYC protein overexpression by 
immunohistochemical (IHC) staining, and/or gene copy number gain by FISH, independently 
confers a negative prognosis as reflected by PFS and OS.  In a meta-analysis of 24 studies, 
18 studies showed that the presence of MYC aberrations was associated with shorter survival in 
DLBCL (Zhou et al, 2014). 
The detection rate for MYC rearrangement varies from 5% to 17% of de novo DLBCL cases 
evaluated (note: some studies have distinguished rearrangement of MYC alone from double hit 
[DH]/triple hit [TH] status) (Zhou et al, 2014).  A higher proportion of MYC rearrangements (up 
to 69%) are of the GCB (as opposed to ABC) subtype (Tzankov et al, 2014; Gupta et al, 2012; 
Zhou et al, 2014).  Cases with MYC translocation usually, but not invariably, show MYC protein 
overexpression (Kluk et al, 2012; Tzankov et al, 2014; Horn et al, 2013; Valera et al, 2013). 
There is evidence that MYC-only rearrangement is independently predictive of poor prognosis 
(Barrans et al, 2010; Klapper et al, 2008; Savage et al, 2009; Akyurek et al, 2012; Valera et al, 
2013), particularly when the tumor also overexpresses the MYC protein (Tzankov et al, 2014; 


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Kluk et al, 2012) and when the tumor is of the GCB subtype (Akyurek et al, 2012; Visco et al, 
2013).  These data suggest that FISH testing for MYC rearrangement should be performed for all 
patients with DLBCL (Savage et al, 2009).  Patients with MYC rearrangements in de novo 
DLBCL have been shown to have shorter OS as compared to those with MYC-negative de novo 
DLBCL (median OS: 7 vs 16 months).  Despite standard therapies, outcomes are similarly poor 
in patients with MYC alone as well as those DH disease defined by concurrent rearrangements of 
MYC/BCL2 or MYC/BCL6 (Macpherson et al, 1999; Li et al, 2016). 
This discussion has thus far centered on the implications of MYC-altered status for patients with 
de novo DLBCL.  In the setting of RR DLBCL in general, there are diminishing prospects for 
disease control (median OS of 4 to 13 months).  The prognosis for patients with RR 
MYC-altered DLBCL is even more discouraging.  The outcome of patients with DH disease who 
don’t respond to induction or progress after initial response is very poor, with reported 12-month 
post-progression survival of 20% (Oki et al, 2014), and median post-progression OS of 
17 months following salvage therapy (Petrich et al, 2014).  Retrospective analysis of the CORAL 
trial (Gisselbrecht et al, 2011) was performed to identify the prognostic significance of MYC 
aberrations in patients with RR DLBCL treated with chemotherapy followed by autologous stem 
cell transplantation (SCT).  Four-year OS was 29% in 27 patients who were MYC+ versus 62% 
for those with no MYC aberration (21 of these cases were also identified as DH) (Cuccuini et al, 
2012). 
Analysis of outcomes makes it clear that traditional approaches to relapsed DLBCL are not 
effective in MYC-altered DLBCL.  It is recommended that patients with MYC-altered B-cell 
lymphomas in need of further therapy be enrolled into prospective investigational protocols 
evaluating novel agents with either sound preclinical rationale or demonstrated activity in 
MYC-driven lymphomas (Cheah et al, 2015). 
6.1.1.3. 
MYC Protein Expression in DLBCL 
Recent advances in IHC, notably the commercial development of an anti-MYC antibody, allow 
quick and accurate detection of MYC protein levels.  MYC and BCL2 expression levels are now 
recognized to represent a more direct measure of the activity of the genes involved, and 
overexpression of these proteins has been shown to independently confer a very negative 
prognosis. 
Overexpression of MYC protein occurs in approximately one-third of DLBCL cases, of which 
one-third can be explained by a MYC translocation (Johnson et al, 2012).  It is expressed in both 
GCB and ABC subtypes, suggesting a biologic pathway independent of COO.  Results of a 
meta-analysis suggest that both event-free survival (EFS) and OS are inferior in DLBCL with 
MYC overexpression (Zhou et al, 2014; Gupta et al, 2012; Kluk et al, 2012; Perry et al, 2014; 
Johnson et al, 2012). 
It is even clearer that concurrent overexpression of MYC and BLCL2 is an indicator of poor 
prognosis.  Co-expression of MYC and BCL2 proteins is more common in DLBCL cases of the 
ABC subtype (> 40%) than with the GCB subtype (< 20%), has an adverse impact on survival 
and may be a driver of the generally inferior prognosis for patients with the ABC subtype (Hu et 
al, 2013).  Concurrent MYC/BCL2 expression is associated with a lower complete response 
(CR) rate, shorter OS, and shorter PFS (Green et al, 2012).  Median PFS for patients with 


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MYC/BCL2 expression was reported as 8 months, and median OS ranged from 12 to 18 months 
(Green et al, 2012; Oki et al, 2014). 
Dual positivity for MYC/BCL2 protein in IHC among RR aggressive B-cell lymphomas was 
more common than in the frontline (Miura et al, 2015).  In a study of patients with RR DLBCL, 
high grade follicular lymphoma (FL), or t-FL/DLBCL, 17/38 patients (45%) overexpressed both 
MYC and BCL2 proteins.  These patients had a lower response rate and shorter median PFS and 
OS, and fewer opportunities to receive consolidative therapies (HDT or SCT) following 
achievement of remission (Miura et al, 2015). 
6.1.2. 
Rationale for Development of CUDC-907 for the Treatment of MYC-Altered 
DLBCL 
MYC family genes are among the most frequently deregulated oncogenic drivers in human 
cancers.  MYC genes encode non-catalytic transcriptional regulators that have thus far proven 
undruggable; therefore, targeting upstream MYC regulators may be an effective strategy to 
suppress MYC and treat MYC-addicted tumors. 
Pharmacologic inhibition of HDAC activity and blockade of the PI3K pathway have both been 
shown to suppress MYC-induced oncogenic transcriptional programs.  HDAC activity is critical 
for MYC gene regulation, as MYC represses the transcription of a subset of its target genes 
through the recruitment of HDACs (Kurland et al, 2008; Zhang et al, 2012).  HDAC inhibitors 
restore the expression of genes coordinately suppressed by MYC family members and HDACs 
and induce rapid and sustained downregulation of expression of MYC itself (Kurland et al, 2008; 
Zhang et al, 2012; Polack et al, 1987; Chambers et al, 2003; Gui et al, 2004; Liu et al, 2007).  
HDAC inhibitors also downregulate expression of other oncogenes that cooperate with MYC to 
induce tumorigenesis, such as BCL2 (Duan et al, 2005).  The PI3K pathway plays a central role 
in regulating MYC homologs at the post-transcriptional level.  Activation of PI3K signaling 
either through mutational activation of PI3K or through loss of the phosphatase and tensin 
(PTEN) tumor suppressor leads to activation of the effector kinase AKT, which in turns 
phosphorylates and inhibits GSK3 (Cross et al, 1995).  As GSK3 normally phosphorylates 
MYC and its homologs, which facilitates their recognition by E3 ubiquitin ligases and 
subsequent ubiquitination and proteasomal degradation, activation of PI3K signaling leads to 
increased MYC family protein stability, whereas PI3K inhibitors decrease MYC family protein 
stability (Kenney et al, 2004; Asano et al, 2004; Kumar et al, 2006; Bechard and Dalton, 2009).  
A recent study showing that PTEN-deficient DLBCL cell lines are addicted to MYC signaling 
and hypersensitive to PI3K inhibition (Pfeifer et al, 2013) provides evidence that MYC-driven 
cancers may be particularly sensitive to PI3K inhibition. 
As HDACs and PI3K regulate MYC expression through non-overlapping mechanisms, 
simultaneous HDAC and PI3K inhibition may lead to enhanced MYC suppression. 
CUDC-907 is an orally bioavailable small-molecule dual HDAC and PI3K inhibitor that 
primarily inhibits class I and IIB HDACs and the PI3K, , and  isoforms (Qian et al, 2012).  
CUDC-907 shows greater in vitro and in vivo antitumor activity than single-target HDAC or 
PI3K inhibitors (Qian et al, 2012), especially in MYC-altered DLBCL models.  In preliminary 
preclinical testing of CUDC-907 in MYC-dependent DLBCL and NUT midline carcinoma cell 
lines, CUDC-907 treatment leads to a dose-dependent decrease in MYC protein expression, as 


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well as the inhibition of other critical oncogenic pathways such as the MAPK and STAT 
pathways.  CUDC-907 is also a more potent inhibitor of MYC expression in these cell lines than 
the HDAC inhibitor, panobinostat (LBH-589), and the pan-PI3K inhibitor, pictilisib 
(GDC-0941), either alone or in combination.  These findings raise the possibility that cancers 
driven by aberrant overexpression of MYC family genes would be more responsive to 
simultaneous HDAC and PI3K inhibition with CUDC-907 than single-target therapies. 
6.1.3. 
Clinical Rationale for CUDC-907 Use in RR MYC-Altered DLBCL 
The utility of HDAC and PI3K inhibitors for the treatment of hematological malignancies has 
been recognized by the U.S. FDA, which has approved 4 HDAC inhibitors and 1 PI3K inhibitor 
for various hematological cancer indications. 
The therapeutic potential of CUDC-907 is shown by safety and efficacy data from the completed 
dose escalation and ongoing expansion stages of ongoing study CUDC-907-101, the 
first-in-human (FIH) trial.  CUDC-907-101 is a Phase 1, open-label, multicenter, dose-escalation 
trial to evaluate the safety and tolerability of CUDC-907 as a single agent administered orally to 
subjects with RR lymphoma or multiple myeloma (MM).  In the completed dose-escalation 
phase of CUDC-907-101, subjects received CUDC-907 capsules orally, within 30 minutes of 
meals, in 21-day cycles according to one of three dosing schedules: once daily (QD), intermittent 
twice (BIW) or thrice weekly (TIW), and five days on/two days off (5/2).  Objective responses, 
in some cases of extended duration, were achieved with CUDC-907 monotherapy on all 
schedules tested.  On the basis of improved tolerability and comparable efficacy, CUDC-907 
administered at 60 mg on the 5/2 schedule was determined to be the recommended Phase 2 dose 
(RP2D). 
CUDC-907 monotherapy has demonstrated a manageable side effect profile and achieved 
objective responses (ORs) as well as sustained disease control, particularly in the setting of RR 
DLBCL.  The most common treatment-related AEs of any grade have been diarrhea, fatigue, 
thrombocytopenia, and nausea.  No dose-limiting toxicities (DLTs) were observed on the 60 mg 
5/2 schedule. 
As of the 15 March 2016 data cut-off, among 21 response-evaluable subjects with RR DLBCL 
receiving CUDC-907 monotherapy at the 60 mg 5/2 schedule (n = 18), or in combination with 
rituximab (n = 3), 9 (43%) achieved objective responses (3 CRs and 6 partial responses [PRs]); 
lasting a median of 2.6 months (range: < 1-14+).  Among the 5 response-evaluable subjects with 
MYC-altered DLBCL, 4 (80%) achieved objective responses (3 CRs and 1 PR).  Three of these 
response-evaluable subjects were found to overexpress MYC (≥ 40%) and BCL2 (≥ 70%) by 
IHC, meeting criteria applied to “double-expressor” (DE) DLBCL.  Two of the DE subjects 
attained objective responses: 1 CR (followed by autologous stem cell transplant) and 1 PR 
(lasting 4 months).  The third subject has experienced lengthy disease stabilization 
(5.7+ months).  All 3 CRs observed on this study occurred in subjects with MYC gene copy 
number gain, including the subject who also had DE DLBCL.  Durable clinical benefit in 
subjects with RR MYC-altered DLBCL in FIH testing further supports this Phase 2 study of 
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6.2. 
Justification of Study Design Considerations  
The following is a brief summary of key study design considerations: 
 Study subjects will be ≥ 18 years of age with histopathologically confirmed diagnosis 
of RR DLBCL (including t-FL/DLBCL) who have received at least 2 but no more 
than 4 prior lines of treatment for DLBCL , and ineligible for (or failed) autologous or 
allogeneic SCT. 
 Subjects will receive CUDC-907 60 mg administered orally on a 5/2 schedule until 
progression of disease or other criteria for discontinuation of treatment.  Each cycle 
will consist of 21 days. 
6.3. 
Potential Risk and Benefits 
Based on available preclinical and clinical safety and response data emerging from the ongoing 
CUDC-907-101 and CUDC-907-102 trials, ongoing clinical testing of CUDC-907 is considered 
justified using the dose and dosage regimen preliminarily shown to be reasonably safe and 
tolerable (Sections 6.1.2, Error! Reference source not found. and 6.1.3). 
6.3.1. 
Potential Risks 
In CUDC-907-101, low grade (Grade 1 and 2) diarrhea, fatigue, and nausea were the most 
common drug-related adverse events (AEs) reported in the study.  A total of 4 DLTs consisting 
of diarrhea and hyperglycemia occurred in 3 subjects treated at the highest doses on the QD 
(60 mg) and intermittent schedules (150 mg BIW and 150 mg TIW).  Other drug-related Grade 3 
or 4 AEs reported in 2 or more subjects included thrombocytopenia and neutropenia 
(hematologic AEs) as well as diarrhea, hyperglycemia, and fatigue (non-hematologic AEs).  As a 
result, stringent monitoring of blood counts will be performed. 
The planned CUDC-907 dose level, 60 mg 5/2, was reasonably tolerated in the dose-escalation 
phase of CUDC-907-101 and is currently undergoing further examination in the expansion phase 
of the trial in subjects with RR DLBCL. 
6.3.2. 
Potential Benefits 
Preliminary antitumor efficacy data from CUDC-907-101 evaluating CUDC-907 as 
monotherapy in subjects with RR DLBCL, including subjects with DE disease, have been 
promising.   
6.4. 
Good Clinical Practice Statement 
The study will be conducted in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with International Conference on Harmonisation, 
Good Clinical Practice (GCP) guidelines, applicable regulatory requirements, and Curis policies. 


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7. 
TRIAL OBJECTIVES 
7.1. 
Primary Objective 
 To evaluate the efficacy of CUDC-907 as measured by the objective response rate 
(ORR) in subjects with RR DLBCL with MYC-altered disease. 
7.2. 
Secondary Objectives 
 To evaluate PFS, median PFS, and PFS at 6 months (PFS6). 
 To evaluate OS. 
 To evaluate the disease control rate (DCR) and duration of response (DOR). 
 To evaluate the incidence and severity of AEs, serious adverse events (SAEs), and 
other safety parameters in subjects receiving CUDC-907. 
 To characterize the pharmacokinetics (PK) of CUDC-907. 
7.3. 
Exploratory Objectives 
 To explore the effects of CUDC-907 on disease-associated biomarkers. 
 To explore the relationship between disease-associated biomarkers in plasma and 
tumor tissue.  Among biomarkers of interest, BCL2 and BCL6 protein expression and 
translocation status in particular will be tested in tumor tissue, where possible. 
 To explore biomarkers of response for patient selection. 
 To explore the relationship between additional biomarkers and biomarker profiles that 
may influence biologic and clinical responses to CUDC-907. 
 To explore the ORR according to Lugano classification (Cheson et al, 2014; 
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8. 
STUDY DESIGN 
8.1. 
Overall Study Design 
This is a Phase 2, open-label, multicenter trial designed to evaluate the efficacy and safety of 
CUDC-907 in subjects 18 years and older with RR MYC-altered DLBCL. 
Figure 1 depicts the study design.  Patients with RR DLBCL will be eligible for treatment with 
CUDC-907 as long as they have tumor tissue available that can be tested for MYC-altered 
disease.  This is defined as MYC translocation by FISH, or MYC expression in ≥ 40% of tumor 
cells by IHC staining, and/or MYC gene copy number gain by FISH based on central testing of 
one of the following: 
 Fresh tumor tissue obtained from biopsy accessible lesions with low estimated risk 
for serious complications (less than 2%), or  
 Archived tumor tissue (most recent available) 
Subjects will be required to submit archival tumor samples (most recent available) or fresh tumor 
samples for central FISH and IHC testing.  Subjects whose tumors have been previously 
characterized as MYC-altered are strongly encouraged to enter the study.  For subjects who enter 
the study with unconfirmed MYC-altered disease, fresh tumor samples are preferred.  
All eligible subjects will receive the following treatment: 
 CUDC-907 60 mg (2 × 30 mg capsules) orally (PO) for 5 days on/2 days off (5/2) 
(21-day cycles). 
Based on central testing and review, subjects will be classified into one of the following 
categories:   
(1) Group A:  MYC translocation+ by FISH,  
(2) Group B:  MYC expression in ≥ 40% of tumor cells by IHC and/or MYC gene copy number 
gain by FISH, or  
(3) Group C:  MYC translocation¯ by FISH, and MYC expression in < 40% of tumor cells, and 
no MYC gene copy number gain by FISH.   
Subjects will be assigned to Groups A, B, or C according to their MYC status as described 
above.  Subjects who are both MYC translocation+ by FISH and have MYC expression in ≥ 40% 
of tumor cells by IHC and/or MYC gene copy number gain by FISH will be classified as MYC 
translocation+ and assigned to Group A. Enrollment may continue until the minimum number of 
subjects are enrolled in Groups A and B. 
Subjects in all groups will continue to receive treatment until they meet criteria for treatment 
discontinuation. 
Efficacy evaluations will include restaging assessments, physical examination, review of 
lymphoma symptoms, survival status, and other procedures, as necessary.  Disease response by 
radiologic imaging will be assessed according to the Revised Response Criteria for Malignant 
Lymphoma (Cheson et al, 2007).  The exploratory efficacy endpoint of ORR will be assessed 
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Efficacy assessments will be performed using computed tomography/magnetic resonance 
imaging (CT/MRI) scans of the neck, chest, abdomen, and pelvis. 
Skull base-to-mid thigh PET scan is recommended but not mandated.  Contrast-enhanced MRI 
may be used to evaluate sites of disease that cannot be adequately imaged using CT or if 
contrast-enhanced CT scanning cannot be performed due to medical condition(s).  For each 
subject, the modality/modalities utilized at screening will be followed throughout the subject’s 
time on study.  While additional modalities may be used depending on assessment needs and 
disease specifics, technologies used at screening will continue to be followed at each restaging 
assessment to enable direct comparison with the baseline assessment. 
Subjects will have efficacy assessments (CT/MRI) performed at the end of Cycles 2, 4, and 6 
(each ± 3 days).  If FDG-PET/CT is acquired at baseline, follow-up FDG-PET/CT imaging at 
Cycle 4 and at Cycle 10 is required.  Scans will be sent for a central radiographic review.  
Subjects who continue to receive CUDC-907 after Cycle 6 will have a disease assessment 
(CT/MRI) performed every 12 weeks ± 1 week (i.e., Cycles 10, 14, 18) until Cycle 18 in the first 
12 months with scans collected through the first year, then every 24 weeks ± 2 weeks (i.e., 
Cycles 26, 34) until PD or death, or up to 2 years, whichever occurs first.  After that, disease 
assessments may be performed as clinically indicated (i.e., at the discretion of the Investigator or 
per standard of care). 
Safety will be assessed by the incidence and severity of AEs as determined by National Cancer 
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03).  Additional 
safety parameters will include physical examination and vital signs, as well as hematology and 
serum chemistry laboratory tests (Section 11.2). 
8.2. 
Number of Subjects 
Approximately 200 subjects will be enrolled in the study. 
8.3. 
Dose and Schedule 
8.3.1. 
Dose and Mode of Administration 
Subjects will receive: 
 CUDC-907 60 mg (2 × 30 mg capsules) orally (PO) for 5 days on/2 days off (5/2) 
(21-day cycles) 
CUDC-907 will be administered PO with meals (± 30 minutes).  CUDC-907 will be 
administered in the clinic on days of PK blood sampling, biopsy sampling, and on Day 1 of each 
cycle up to Cycle 13.  Beginning on Cycle 14, in-clinic dosing will only be required on Day 1 of 
even numbered cycles (i.e., Cycles 14, 16, 18, etc.). 
If a dose is missed or vomited, the subject will be instructed to skip that dose and report it to the 
Principal Investigator (PI) as soon as possible.  Missed or vomited doses should not be made up. 
Subjects must meet retreatment criteria in order to continue receiving study treatment (see 
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Treatment delays and dose reductions will be allowed as specified in Section 10.5.3; however 
subjects who experience a Grade 4 DLT-like event must be discontinued from further study 
treatment. 
For full study treatment details, see Section 10. 
8.3.2. 
Schedule of Visits and Assessments 
Treatment and Follow-up Visits are summarized below; for full details see Section 5.1 for the 
Schedule of Events. 
During Treatment:  Subjects will have 4 clinic visits during Cycle 1 (Days 1, 5, 12, and 15) and 
clinic visits every 3 weeks on Day 1 of every cycle thereafter.  Subjects who continue past 
Cycle 13 will have clinic visits every 6 weeks on Day 1 of every other cycle (Cycles 14, 16, 18, 
etc.). 
Safety assessments will be conducted at each clinic visit. 
Subjects will have efficacy assessments (CT/MRI) performed at the end of Cycles 2, 4, and 6 
(each ± 3 days).  If FDG-PET/CT is acquired at baseline, follow-up FDG-PET/CT imaging at 
Cycle 4 and at Cycle 10 is required.  Scans will be sent for a central radiographic review.  
Subjects who continue to receive CUDC-907 after Cycle 6 will have a disease assessment 
(CT/MRI) performed every 12 weeks ± 1 week (i.e., Cycles 10, 14, 18) until Cycle 18 in the first 
12 months with scans collected through the first year, then every 24 weeks ± 2 weeks (i.e., 
Cycles 26, 34) until PD or death, or up to 2 years, whichever occurs first.  After that, disease 
assessments may be performed as clinically indicated (i.e., at the discretion of the Investigator or 
per standard of care). 
During Post-Treatment Follow-Up:  All subjects will have PFS and survival assessments every 
12 weeks during the first 6 months, then every 24 weeks until PD or death, or up to 2 years, 
whichever occurs first.  After that, disease assessments may be performed as clinically indicated 
(i.e., at the discretion of the Investigator or per standard of care).  Overall survival may be 
checked by phone every 3 months and data entered in the electronic case report form (eCRF). 
8.4. 
Planned Duration of Treatment  
CUDC-907 will be taken until disease progression, withdrawal from study, unacceptable 
toxicity, pregnancy, initiation of another anticancer or experimental therapy, noncompliance with 
study procedures, or study discontinuation. 
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9. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
9.1. 
Patient Inclusion Criteria 
1. Age ≥ 18 years. 
2. At least 2 but no more than 4 prior lines of therapy for the treatment of de novo DLBCL 
and ineligible for (or failed) autologous or allogeneic SCT (salvage therapy, conditioning 
therapy and maintenance with transplant will be considered one prior treatment).  
NOTE: For follicular lymphoma transformed to DLBCL (t-FL/DLBCL), single agent 
non-cytotoxic therapy will not be considered as a line of therapy. 
3. Histopathologically confirmed diagnosis of one of the following: 
 RR DLBCL per the 2008 World Health Organization (WHO) classification of 
hematopoietic and lymphoid tumors (Swerdlow et al, 2008).  
 HGBL, with MYC and BCL2 and/or BCL6 rearrangements or DLBCL, NOS per the 
2016 revision of the WHO classification of lymphoid neoplasms (Swerdlow et al, 
2016). 
 Diagnosis of t-FL/DLBCL is allowed.  However, other B-cell lymphomas including 
other transformed indolent lymphomas/DLBCL per the 2008 WHO classification, 
HGBL, NOS per the 2016 WHO classification, and Burkitt lymphoma are not 
eligible. 
4. Confirmed availability of viable tissue (defined as most recent available archival tumor 
tissue available, or fresh tumor samples) for central laboratory FISH and IHC testing 
prior to study dosing.  For subjects who enter the study with unconfirmed MYC-altered 
disease, fresh tumor samples are preferred. 
NOTE: To facilitate early testing of MYC status, a separate informed consent form (ICF) 
specific for MYC testing will be available to be signed prior to sample testing and the 
signing of the main ICF. 
5. CT scan showing at least 1 or more clearly demarcated lymph node(s) with a long axis 
> 1.5 cm and short axis > 1.0 cm or 1 clearly demarcated extranodal lesion(s) with a long 
axis > 1.0 cm and short axis > 1.0 cm.  Baseline FDG-PET scans, if used, must 
demonstrate positive lesions compatible with CT-defined anatomical tumor sites. 
6. Presence of RR disease per Revised Response Criteria for Malignant Lymphoma (Cheson 
et al, 2007). 
 Relapsed disease is defined by DLBCL confirmed by excisional/incisional biopsy 
(preferred) or fine needle aspiration (FNA) or core needle biopsy (CNB) after a CR or 
unconfirmed complete response (CRu). 
 For relapse during prior treatment, biopsy/FNA reconfirmation of the lymphoma 
is recommended but not mandatory. 
 Refractory disease is defined by (a) PD during prior treatment, (b) stable disease (SD) 
after ≥ 3 cycles of prior treatment, or (c) PR after ≥ 6 cycles of prior treatment, or for 
stage II disease, ≥ 3 cycles of treatment and definitive involved field radiotherapy. 


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 For sustained PR after prior treatment, confirmation biopsy for DLBCL is 
preferred.  An FNA may be acceptable, but if inappropriate (e.g., due to biopsy 
inaccessibility), the Sponsor may determine eligibility following review of 
imaging results and disease history. 
 For SD or PD after prior treatment, reconfirmation of DLBCL by biopsy 
(preferred) or FNA is recommended but not mandatory. 
7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. 
8. Recovery to Grade 1 or baseline of any toxicity due to prior anticancer therapies 
(excluding alopecia). 
9. Absolute neutrophil count (ANC) ≥ 1,000/µL; platelets ≥ 75,000/µL; creatinine ≤ 1.5 × 
upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/minute as 
determined by Cockcroft-Gault (using actual body weight) or by 24-hour urine collection 
measurements of creatinine; aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) ≤ 2.5 × ULN; total bilirubin ≤ 1.5 × ULN or ≤ 3 ULN for 
patients with documented Gilbert’s syndrome.  Platelet transfusions and administration of 
granulocyte colony-stimulating factors to help patients meet eligibility criteria are not 
allowed within 1 week prior to screening complete blood count (CBC) and Cycle 1, Day 
1 treatment. 
10. Women of childbearing potential must have a negative serum or urine pregnancy test (not 
applicable after bilateral oophorectomy) 
11. Men and women of childbearing potential and their partners must agree to use adequate 
birth control throughout their participation in the study and for 30 days following the last 
study treatment.  Adequate contraception is defined as hormonal birth control, 
intrauterine device, double barrier method or total abstinence.  Acceptable methods of 
contraception are described in Table 3.  
12. In the Investigator’s judgement, able to provide written informed consent and follow 
protocol requirements. 
9.2. 
Patient Exclusion Criteria: 
1. Known primary mediastinal, ocular, epidural, testicular or breast DLBCL. 
2. Patients must not have active CNS involvement of their malignancy. Patients with prior 
brain metastases are permitted, but must have completed treatment and have no evidence 
of active CNS disease (clear cerebrospinal fluid [CSF]) for at least 4 weeks prior to the 
first dose of CUDC-907.  Intrathecal chemoprophylaxis to prevent the emergence or 
recurrence of lymphoma in the CNS is permitted on study and may be administered per 
institutional guidelines.   
3. Known allergy or hypersensitivity to PI3K inhibitors or any component of the 
formulations used in this study. 
4. Cytotoxic anticancer therapy (e.g., alkylating agents, anti-metabolites, purine analogues) 
within 2 weeks of study entry. 
5. Radiotherapy delivered to non-target lesions within one week prior to starting study 
treatment or delivered to target lesions that will be followed on the study (note: prior sites 
of radiation will be recorded). 


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6. Treatment with experimental therapy within 5 terminal half-lives (t1/2) or 4 weeks prior to 
enrollment, whichever is longer. 
7. Current or planned glucocorticoid therapy, with the following exceptions:  
 Doses ≤ 1 mg/kg/day prednisolone or equivalent glucocorticoid and inhalational 
therapies for mild chronic obstructive pulmonary disease (COPD) or asthma are 
allowed. 
 Replacement dosing of steroids (defined as < 30 mg/day hydrocortisone or the 
equivalent) is allowed, provided that the steroid dose has been stable or tapering for at 
least 14 days prior to the first dose of CUDC-907. 
8. Graft versus host disease following transplant within 100 days prior to study treatment. 
9. Major surgery, other than diagnostic surgery, occurring 4 weeks prior to study treatment. 
10. Diabetes mellitus that is not controlled with medication. 
11. Serious infection requiring intravenous antibiotic therapy within 14 days prior to study 
treatment. 
12. Uncontrolled or severe cardiovascular disease, including myocardial infarction, unstable 
angina, or atrial fibrillation (AFib) within 6 months prior to study treatment, New York 
Heart Association (NYHA) Class II or greater congestive heart failure, serious 
arrhythmias requiring medication for treatment, clinically significant pericardial disease, 
cardiac amyloidosis, or QTc with Fridericia’s (QTcF) correction that is unmeasurable or 
≥ 480 msec on screening electrocardiogram (ECG).  (Note: for QTcF ≥ 480 sec on the 
screening ECG, the ECG may be repeated twice at least 24 hours apart; the mean QTcF 
from the three screening ECGs must be < 480 msec in order to meet eligibility for trial 
participation). 
13. Gastrointestinal disease or disorder that could interfere with the swallowing, oral 
absorption, or tolerance of CUDC-907.  This includes uncontrolled diarrhea (> 1 watery 
stool/day), major abdominal surgery, significant bowel obstruction and/or gastrointestinal 
diseases that could alter the assessment of PK or safety, including but not limited to: 
irritable bowel syndrome, ulcerative colitis, Crohn’s disease and hemorrhagic 
coloproctitis. 
14. History of other invasive malignancy, unless adequately treated with curative intent and 
with no known active disease present within 1 year prior to the first dose of study drug, 
provided it is deemed to be at low risk for recurrence by the treating physician. 
 These conditions include but are not limited to non-melanoma skin cancer, carcinoma 
in situ, (including superficial bladder cancer), cervical intraepithelial neoplasia and 
organ-confined prostate cancer. 
15. Known infection with human immunodeficiency virus (HIV). 


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16. Known active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. 
 Regardless of hepatitis B surface antigen (HBsAg) status, if hepatitis B core antibody 
(HBcAb) is positive, then HB DNA testing will be performed and if positive the 
patient will be excluded. 
 Regardless of hepatitis RNA level, patients who are positive for hepatitis C antibody 
(anti-HCV) will be permitted to enroll provided that they meet all eligibility criteria 
and are without evidence of cirrhosis.  Patients diagnosed with HCV < 6 months prior 
to enrollment will be considered to have acute HCV and excluded unless viral load is 
undetectable. 
17. Pregnant or breast-feeding women. 
18. Unstable or clinically significant concurrent medical condition that would, in the opinion 
of the Investigator, jeopardize patient safety and/or compliance with the protocol. 
9.3. 
Criteria for Study Termination 
9.3.1. 
Withdrawal of Subject from Study Treatment 
Subjects will be discontinued from further study treatment in the event of any of the following: 
 Unmanageable toxicity per Section 10.5.2. 
 Subject's decision/withdrawal of consent (e.g., subject declines further treatment). 
 Physician decision that continuation is not in the subject's best interest. 
 Termination of the study by the Sponsor. 
 Other reasons (e.g., major protocol violation, noncompliance). 
 Progressive disease. 
If the subject is withdrawn from the study the primary reason must be recorded in the eCRF.  If 
possible, the Investigator should arrange for the EOT visit assessments to be completed. 
9.3.2. 
Early Study Termination 
The Sponsor has the right to close the study at any time, although this should occur only after 
mutual consultation between the Sponsor and the Investigators.  Events that may trigger early 
study termination include but are not limited to: 
 Insufficient efficacy following interim analyses of Groups A and B. 
 Significant toxicity finding. 
 Insufficient bioavailability to achieve adequate study drug exposure. 
 Change in development plans for the study drug. 
 Slow recruitment. 
A Safety Review Committee (SRC) comprised of the Medical Monitor, PI, and Sponsor 
representatives will be convened to review safety information on an ongoing basis for safety 


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surveillance. The SRC is tasked with making a recommendation to continue or stop the trial 
based on their assessment of available efficacy and safety information. 
An initial review of safety data will be conducted by the SRC including all treated patients after 
the first 15 patients have completed at least one cycle of treatment. Additionally, any treatment-
related deaths will be cause for pausing enrollment and initiating SRC review of all safety data. 
The SRC will be tasked with making a recommendation to continue or stop the trial based on 
their assessment of the benefits or risks to patients based on all available safety information 
including: 
 Grade ≥ 3 toxicity regardless of relationship to treatment 
 Treatment discontinuation due to toxicity 
 Dose reduction due to toxicity 
 Death regardless of cause 
 
Guidelines for stopping criteria are as follows: 
 If a third or more of the patients have treatment-related Grade ≥ 3 toxicity, excluding:  
 Grade ≥ 3 thrombocytopenia that resolves (Grade < 3) within 7 days 
 Grade ≥ 3 diarrhea that resolves (to Grade < 3)  with standard therapy 
 > 10% incidence of colitis, pneumonitis, or severe hepatotoxicity  
 > 10% deaths due to Grade 4 treatment-related toxicity 
 


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10. 
TREATMENT OF SUBJECTS 
10.1. 
Description of Study Drug 
CUDC-907 mesylate is a synthetic small molecule inhibitor of HDAC and PI3K.  The chemical 
structure of CUDC-907 integrates the hydroxamic acid moiety of HDAC inhibitors into a 
morpholinopyrimidine pharmacophore of PI3K inhibitors. 
CUDC-907 is manufactured, labeled and packaged in accordance with Good Manufacturing 
Practices (GMP). 
CUDC-907 mesylate oral capsules are formulated with three excipients: silicified 
microcrystalline cellulose (Prosolv® HD90), sodium starch glycolate (Explotab®), and 
magnesium stearate.  The resulting dry blended mixture is filled into gelatin capsule shells. 
10.2. 
Supply, Packaging and Labeling 
CUDC-907 will be supplied as gelatin capsules containing 30 mg CUDC-907 and excipients. 
The capsules are packaged in high-density polyethylene bottles containing 35 capsules each, and 
appropriately labelled for clinical trial use as per national regulatory requirements. 
10.3. 
Storage and Dispensing 
The study drug should be stored at room temperature in a secure area with access limited to the 
Investigator and authorized site staff. 
Only subjects enrolled in the trial may receive investigational product.  The investigational 
materials are to be prescribed only by the PI or the sub-Investigators named in FDA Form 1572.  
In addition, the study drug may only be dispensed by authorized personnel at the institution(s) 
specified on Form 1572.  For self-administration, subjects may be provided with a sufficient 
number of capsules as are needed for 1 cycle of study drug administration. 
Under no circumstances is the investigational drug to be used other than as directed within this 
study protocol. 
10.4. 
Investigational Product Accountability 
Study drug accountability records will be maintained throughout the course of the study. The 
Investigator or designee will document the amount of study drug received, the amount dispensed 
to study subjects and the amount destroyed locally.  
Unused study drug remaining at the completion of the study will be destroyed at the site per 
institutional standard operating procedures provided that destruction is documented. 
10.5. 
Study Drug Administration 
10.5.1. 
CUDC-907  
Subjects will receive CUDC-907 60 mg in 21-day cycles. 


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CUDC-907 will be administered orally at the assigned dose level and schedule, 60 mg on a 5/2 
schedule. 
All doses of study drug (in clinic and self-administered) will be administered with meals 
(± 30 minutes) at approximately the same time each dosing day, if possible. 
Dose and/or schedule intensity of CUDC-907 may be reduced per protocol due to toxicity. 
In the absence of significant toxicity, each subject is expected to complete at least 1 cycle 
(21 days) of study treatment.  However, subjects may continue to receive additional 21-day 
cycles of CUDC-907 treatment until disease progression has been documented or other 
discontinuation criteria have been met (Section 9.3.1). 
10.5.2. 
Retreatment Criteria 
Subjects may continue to receive 21-day cycles of study treatment until disease progression has 
been documented or other discontinuation criteria have been met (Section 9.3.1). 
To continue dosing of CUDC-907 subjects must meet the following criteria: 
 ANC > 1,000/µL. 
 Platelets ≥ 50,000/µL. 
 AST and ALT ≤ 2.5 × ULN. 
 Bilirubin concentration ≤ 1.5 × ULN (or ≤ 3 ULN for patients with documented 
Gilbert’s syndrome). 
 Creatinine ≤ 1.5 × ULN. 
 ≤ Grade 2 diarrhea controlled by antidiarrheal treatment. 
10.5.3. 
Safety Criteria for Adjustment or Stopping CUDC-907 
10.5.3.1. Dose Delays and Discontinuation of CUDC-907 
In the event that any of the above criteria are not met, study drug dosing must be held until the 
retreatment criteria are met.  Treatment may then resume at the full dose of CUDC-907, as long 
as none of the criteria in Table 2 are met.  Beyond Cycle 1, subjects held for > 7 days may restart 
treatment after the subject has met the above criteria and following discussion and agreement 
between the Investigator and the Medical Monitor.  Beyond Cycle 2, subjects may have study 
drug held for up to 7 days between the end of a cycle and initiation of another (e.g., Cycle 2 Day 
21 to Cycle 3 Day 1).  This hold will be at the discretion of the Investigator and after discussion 
and agreement between the Investigator and Medical Monitor. 
Study treatment should be discontinued in the event of an unacceptable toxicity or treatment hold 
lasting more than 4 weeks, except in cases of clinical benefit determined by the Investigator with 
approval by the Sponsor Medical Monitor. 
Subjects who experience a DLT-like event will be either discontinued from further study 
treatment or their dose will be reduced following discussion and agreement between the 
Investigator and the Sponsor’s Medical Monitor.  A DLT-like event will be defined as any of the 
following AEs occurring at any time: 


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 Non-hematological ≥ Grade 3 AE, other than Grade 3 nausea or Grade 3 vomiting in 
subjects treated with less than optimal antiemetic therapy. 
 An AE resulting in a dose delay of ≥ 7 consecutive days (e.g., 6 consecutive missed 
doses). 
 Grade 4 neutropenia ≥ 7 days, or ≥ Grade 3 neutropenia with fever > 101.3ºF (38.5ºC) 
or ≥ Grade 3 neutropenia with infection. 
 Grade 4 thrombocytopenia ≥ 7 days, or ≥ Grade 3 thrombocytopenia and significant 
bleeding. 
NOTE: A DLT-like event excludes AEs that are clearly and incontrovertibly related to 
the underlying disease or extraneous factors. 
10.5.3.2. CUDC-907 Dose Reductions 
Table 1: 
Dose Reduction Steps for CUDC-907  
Reduction Steps: 
Schedule 
Dose 
Starting dose 
5/2 
60 mg 
   Dose Reductions 
Schedule 
Dose 
      First dose reduction 
4/3 
60 mg 
      Second dose reduction 
5/2 
30 mg 
      Final dose reduction 
4/3 
30 mg 
4/3 = 4 days on/3 days off; 5/2 = 5 days on/2 days off 
10.5.3.3. Dose Adjustments for CUDC-907 Hematologic and Non-hematologic Toxicity  
The administration of HDAC and PI3K inhibitors has been associated with predictable bone 
marrow suppression that is typically transient and reversible. 
The administration of HDAC and PI3K inhibitors has also been associated with hyperglycemia.  
This hyperglycemia does not generally result in severe metabolic complications and typically 
resolves with therapeutic intervention.  The treatment goal for glycemic control is fasting plasma 
glucose < 160 mg/dL; while making every attempt to avoid hypoglycemia.  Dose modifications 
of CUDC-907 are based on the severity of toxicities. 
CUDC-907 dose adjustments for hematologic and non-hematologic toxicities are shown in 
Table 2. 
 


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Table 2: 
CUDC-907 Dose Adjustments for Hematologic and Non-Hematologic Toxicities 
Toxicity 
Management  
Thrombocytopenia 
Grade 1 or 2  
No change in dose  
Grade 3 or 4 (platelets < 50,000/μL) 
Hold treatment until platelets ≥ 50,000/μL or baseline, 
then reduce dose to the next lower dose level (as 
applicable per Table 1). 
Grade 4 thrombocytopenia requiring platelet 
transfusion  
Hold treatment until platelets ≥75,000/μL or 
baseline, then dose reduce to the next lower dose 
level (as applicable per Table 1). 
Neutropenia 
Grade 1 or 2 
No change in dose  
Grade 3 or 4 (ANC < 1,000/uL)  
Hold treatment until ANC ≥ 1000/μL, then reduce 
dose to the next lower dose level (as applicable per 
Table 1). 
Grade 4 febrile (≥ 38.5°
 
C) neutropenia  
Hold treatment until febrile neutropenia resolves 
and ANC ≥ 1000/μL or baseline, then dose reduce 
to the next lower dose level (as applicable per 
Table 1). 
Anemia  
Grade 1 or 2  
No change in dose  
Grade 3 or 4  (hemoglobin < 8 g/dL)  
Hold treatment until hemoglobin ≥ 10 g/dL or baseline 
then reduce dose to the next lower dose level (as 
applicable per Table 1). 
Grade 4 anemia requiring transfusion  
Hold treatment until hemoglobin ≥ 10 g/dL or 
baseline, then dose reduce to the next lower dose 
level (as applicable per Table 1). 
Recurrence of Grade 3 or 4 hematologic toxicity will be cause for a second dose modification. 
If the starting dose does not permit dose modification, then study drug will be discontinued. 
Non-hematological 
AEs (excluding 
hyperglycemia) 
 
Grade 1 or 2  
No change in dose1  
Grade 3   
 
Hold treatment until resolution to ≤ Grade 1 or 
baseline 
 
If not recovered to ≤ Grade 1 or baseline within 
3 weeks, reduce to next lower dose level upon 
return to ≤ Grade 1 or baseline (as applicable per 
Table 1). 
Grade 4 
Discontinue treatment.2  
Recurrence of Grade 3 non-hematologic toxicity (excluding hyperglycemia) or inability to reduce dose (based on starting dose) will be grounds for 
discontinuation of study drug.  


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Table 2: CUDC-907 Dose Adjustments for Hematologic and Non-Hematologic Toxicities (Continued) 
Toxicity 
Management 
Hyperglycemia  
Grade 1/2 or Grade 3  
(> 250 – 500 mg/dL) asymptomatic 
No change in dose1  
Grade 3 (> 250 – 500 mg/dL) 
symptomatic or Grade 4 (> 500 mg/dL) 
Hold treatment until glucose < 250 mg/dL 
and asymptomatic;  
Reduce dose to the next lower dose level (as 
applicable per Table 1).  
≥ Grade 3 hyperglycemia not improving despite 
appropriate treatment for 1 week or 
symptomatic Grade 4 hyperglycemia (> 500 
mg/dL) 
Hold treatment until glucose < 250 mg/dL and 
asymptomatic;  
Reduce dose to the next lower dose level (as 
applicable per Table 1) upon return to ≤ Grade 1 or 
baseline.  
 
Recurrence of Grade 3 or 4 hyperglycemia will be cause for a second dose modification.  
If the starting dose does not permit dose modification, then study drug will be discontinued. 
Recurrence of Grade 3 or 4 hyperglycemia that does not recover to ≤ Grade 1 or baseline within 3 weeks after second modification (as applicable) will 
be grounds for discontinuation of study drug.2 
AEs = adverse events; ANC = absolute neutrophil count 
1 Transient Grade 1 or 2 hyperglycemia should be monitored per Investigator discretion and medical guidelines. 
2 An exception for ongoing treatment may be made in the case of Investigator-determined clinical benefit with approval from the Medical Monitor. 


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10.6. 
Concomitant Medications 
Information on concomitant medications will be collected from 30 days prior to study drug 
dosing through the EOT visit.  Information on subsequent anticancer treatments will be collected 
through the Follow-up visits. 
10.6.1. 
Permitted Medications 
Antidiarrheal treatment (e.g., loperamide) should be administered immediately upon the first 
onset of symptoms.  Each subject should be instructed to have loperamide or a comparable anti-
diarrheal medication (per institutional standard) readily available and to begin treatment for 
diarrhea at the first episode of poorly formed or loose stools or the earliest onset of bowel 
movements more frequent than normally expected for the subject until diarrhea free.  Subjects 
will be instructed to notify the Investigator if diarrhea occurs and will be evaluated in the clinic 
for significant dehydration, possible electrolyte imbalance, and/or ongoing losses.  If clinically 
significant dehydration is present, rehydration and electrolyte repletion per institutional standard 
will be required.  Additionally, subjects will be monitored following rehydration for the risk of 
recurrence and electrolyte imbalances and also advised regarding appropriate fluid management 
to reduce the likelihood of subsequent dehydration events. 
Antiemetics may be given prophylactically after the first episode of nausea or vomiting per 
standard of care at each study center. 
Unless otherwise prohibited (See Section 10.6.2), supportive therapy for optimal medical care 
may be administered per institutional standard of care at the study centers. 
Growth factor support is permitted for neutropenia or neutropenic fever. 
10.6.2. 
Drug Interactions/Precautions 
In vitro, CUDC-907 competitively inhibits cytochrome P450 isoenzymes CYP2C9, CYP2C19, 
CYP2D6 and CYP3A4 with half maximal inhibitory concentration (IC50) values of > 10, > 10, > 
10, and 0.28 to 13.58 μM, respectively.  Currently, it is not known whether achievable plasma 
exposures of CUDC-907 in humans will approach these in vitro determined values.  These data 
suggest that CUDC-907 may inhibit cytochrome P450 isoenzymes CYP2C9, CYP2C19, 
CYP2D6, and CYP3A4, although the clinical significance of this potential interaction has not 
been investigated.  Subjects receiving concomitant medications metabolized by these enzymes 
should be monitored at the discretion of the Investigator. 
Please refer to the CUDC-907 Investigator’s Brochure for additional drug interaction 
information. 
10.6.3. 
Contraception 
Subjects of childbearing potential and their partners must agree to use adequate birth control 
throughout their participation in the study and for 30 days following the last study treatment for 
subjects receiving CUDC-907.  Adequate contraception is defined as hormonal birth control, 
intrauterine device, double barrier method or total abstinence. 
NOTE: vomiting and diarrhea may cause oral contraceptives to be ineffective. 


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Table 3: 
Effective Methods of Contraception 
Barrier Methods 
Intrauterine Device Methods 
Hormonal Methods 
Male condom plus spermicide 
plus one additional 
contraceptive method 
Cap plus spermicide plus one 
additional contraceptive method 
Diaphragm plus spermicide plus 
one additional contraceptive 
method 
Copper T 
Progesterone T1 
Levonorgestrel-releasing 
intrauterine system1 
Implants 
Hormonal shot or injection 
Combined pill 
Minipill 
Patch 
1Also considered hormonal methods of contraception. 
10.7. 
Treatment Compliance 
To facilitate and ascertain treatment compliance, subjects may be provided with and trained to 
complete a Dosing Diary, which must be returned to the clinic for review at each clinic visit. 
10.8. 
Group Allocation 
Based on central testing and review, subjects receiving treatment will be classified into one of 
the following categories for purposes of analysis:  (1) Group A:  MYC translocation+ by FISH, 
(2) Group B:  MYC expression in ≥ 40% of tumor cells by IHC and/or MYC gene copy number 
gain by FISH, or (3) Group C:  MYC translocation¯ by FISH, and MYC expression in < 40% of 
tumor cells by IHC, and no MYC gene copy number gain by FISH (Figure 1).   
To facilitate early testing of MYC status, a separate ICF specific for MYC testing will be 
available to be signed prior to sample testing and the signing of the main ICF.  
All subjects who enter into the Screening period of the study (defined as the point at which the 
patient signs the main ICF) will receive a unique screening number. Once all eligibility criteria 
are confirmed and the subject is enrolled in the study, a subject identification number will be 
assigned.  This number will be used to identify the subject throughout the study and must be used 
on all study documentation related to that subject. 
The study is open-label and therefore no provisions will be made for blinding. 


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11. 
STUDY ASSESSMENTS 
11.1. 
Screening 
The PIs at each site are responsible for maintaining a record of all screened subjects, including 
both those who enter the study and those who are excluded.  Screening procedures performed as 
part of standard-of-care, in advance of signing the ICF, need not be repeated for study purposes 
if performed within the 28-day screening visit window. 
11.1.1. 
Patient Registration and Group Assignment 
Inclusion and exclusion criteria will be reviewed for each potential subject.  By central testing, 
the threshold for MYC-altered status is defined as MYC translocation+ by FISH and/or MYC 
expression in ≥ 40% of tumor cells by IHC, and/or MYC gene copy number gain by FISH.  
Subjects will be required to submit archival (most recent available) or fresh tumor samples for 
central FISH and IHC testing.  For subjects who enter the study with unconfirmed MYC-altered 
disease, fresh tumor samples are preferred.  
Collection details and shipping address will be provided in the laboratory manual. 
Centralized registration and group assignment for eligible subjects will be completed according 
to a process defined by the Sponsor (Section 10.8). 
11.2. 
Safety Evaluations 
11.2.1. 
Demographics and Medical History 
Each patient’s complete medical history will be documented during Screening, including 
demographic information, relevant medical history, current primary cancer diagnosis, and prior 
cancer treatments (chemo- and immunotherapies, radiation therapy, surgeries). 
11.2.2. 
Physical Exam  
A complete physical exam will be performed at Screening, Day 1 of each cycle, and at the EOT 
visit.  Symptom-directed physical exams are required on Days 5 and 12 of Cycle 1 and at the 
Post-Treatment Follow-up visits (until time of disease progression, withdrawal of consent, or any 
other criteria that would make the patient unable to be followed for disease response). 
11.2.3. 
Eastern Cooperative Oncology Group (ECOG) Performance Status 
ECOG performance status (scale provided in Appendix A) will be assessed at Screening, Day 1 
of each Cycle, and at the EOT visit. 
11.2.4. 
International Prognostic Index (IPI) 
The IPI will be performed for each subject at Screening and at Post-Treatment Follow-up visits. 


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11.2.5. 
Lymphoma Assessment 
Lymphoma assessment, consisting of a physical examination, a review of the subject’s current 
signs and symptoms, B symptoms (drenching night sweats, fevers > 101°F [38.3°C], chills, 
unexplained weight loss of over 10% of body mass over 6 months), and concomitant 
medications, will be conducted on Day 1 of every cycle, and at the EOT and Post-Treatment 
Follow-up visits (until time of disease progression, withdrawal of consent, or any other criteria 
that would make the subject unable to be followed for disease response). 
11.2.6. 
Vital Signs 
Vital signs will include resting supine blood pressure, heart rate, respiratory rate, temperature, 
and weight (kg).  Height will be measured only at Screening.  Blood pressure, heart rate, 
respiratory rate, temperature, and weight will be measured at scheduled visits per protocol (see 
Schedule of Events in Section 5.1). 
11.2.7. 
Clinical Laboratory Tests 
Local laboratories will perform all clinical laboratory tests and results will be provided to the 
Investigator.  Samples will be collected at scheduled study visits before the administration of 
study drug unless otherwise noted, and more frequently if clinically indicated.  In the event of a 
clinically significant ≥ Grade 2 laboratory toxicity, more frequent laboratory tests should be 
performed until resolution or stabilization to ≤ Grade 1.  After Cycle 1, clinical laboratory tests 
may be performed within 2 business days prior to scheduled visits. 
Hematology tests include complete blood count (hemoglobin, hematocrit, white blood cell 
[WBC], platelets) with WBC differential (total neutrophils, eosinophils, basophils, lymphocytes 
and monocytes). 
Blood chemistry tests include sodium, potassium, magnesium, phosphate, total protein, chloride, 
bicarbonate, calcium, blood urea nitrogen (BUN), creatinine, uric acid, total bilirubin, alkaline 
phosphatase, AST, ALT, LDH, albumin, and glucose. 
In addition, serum LDH will be measured during Screening. 
Laboratory tests will be performed at the time points specified in the Schedule of Events  
(Section 5.1). 
11.2.8. 
Pregnancy Testing 
A serum or urine pregnancy test will be performed for female subjects of childbearing potential 
at Screening, at least once per cycle prior to dosing, and at the EOT visit.  The result must be 
negative for the subject to be enrolled in the study.  A positive result observed following 
enrollment should be confirmed with a repeat serum pregnancy test.  Pregnancy tests may be 
performed more frequently as clinically indicated. 
11.2.9. 
Electrocardiogram  
Standard, single 12-lead ECGs at Screening and the EOT visit will include heart rate, respiratory 
rate, and pulse rate, QRS, and QTcF (Fridericia’s formula) intervals.  The Investigator will be 


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responsible for a thorough review of the tracings for any untoward changes from the baseline 
ECG for each individual subject. 
During the screening ECG, if a patient has a QTcF ≥ 480 sec on the screening ECG, the ECG 
may be repeated twice (at least 24 hours apart) and the mean QTcF from the three screening 
ECGs must be < 480 msec in order to meet eligibility criteria for trial participation. 
During treatment, based on triplicate ECGs, if a patient has a mean QTcF ≥ 480 msec or the 
mean is an increase from the mean baseline (pretreatment on Day 1 of Cycle 1) QTcF of 
> 60 msec, the ECG may be repeated 2 more times within 5 minutes.  The following will be 
applied based on the mean of the results for all (up to 5) of the ECGs:  
 Continue ECG testing hourly until the increase resolves.  If not resolved in 6 hours, 
discontinue further treatment and refer to in-hospital care.  
 If resolved in < 6 hours, resume dosing but repeat the ECG schedule specified above 
on the next day of dosing.  
 If prolongation of QTcF meeting these criteria occurs again, discontinue further 
treatment and, if not resolved in 6 hours, refer to in-hospital care.  
 If QTc prolongation does not reoccur, continue treatment as specified in the 
protocol. 
On any ECG if sustained (>3 beats) ventricular tachycardia is detected, the patient should be 
referred immediately to in-hospital care.  
If on any ECG, AFib is detected, the patient should be referred for appropriate cardiology care, 
and within no more than 6 hours after discharge from the clinic, have Holter monitoring 
instituted and continued for at least 48 hours.  Withhold treatment until review of the Holter 
results: 
 If AFib did not resolve within 3 hours or by the time of the start of the Holter 
monitoring if longer than 3 hours after discharge from the clinic, discontinue further 
treatment.  
 If during the Holter monitoring AFib was present for > 3 hours, either sustained or as 
accumulated AFib duration, discontinue further treatment. 
 If AFib had resolved within 3 hours or by the time of the start of the Holter 
monitoring if longer than 3 hours after discharge from the clinic, and did not reoccur 
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 On the next day of dosing perform: 
 ECGs per the schedule outlined above.  
 Conduct Holter monitoring for 24 hours starting at least 1 hour prior to the dose. 
 Withhold the subsequent dose until review of the Holter results. 
 If AFib is again detected on ECG or of duration > 30 minutes on Holter 
monitoring, discontinue treatment. 
 If AFib does not reoccur, continue treatment as specified in the protocol. 
11.2.10. 
Adverse Events 
Monitoring and recording of AEs will be conducted throughout the study.  Adverse events, 
including SAEs, will be captured on the case report forms (CRFs) from the first day of study 
drug dosing until the EOT visit (30 ± 7 days post the last dose of study treatment).  After the 
EOT visit, only treatment-related SAEs will be captured.  Treatment-related SAEs that are 
ongoing at the time of Follow-up visits should continue to be followed until resolution, return to 
baseline or are deemed the subject’s new baseline, or until they are ≤ Grade 1 (and following 
consultation and agreement by the Medical Monitor).  Definitions, documentation, and reporting 
of AEs are described in detail in Section 12.  Following the Follow-up visits, any SAE 
determined by the Investigator to be potentially related to study treatment must also be reported. 
11.2.11. 
Concomitant Medications and Other Treatments 
Information on concomitant medications and other treatments, including blood products, will be 
collected from 30 days prior to study drug dosing through the Follow-up visits (see Section 10.6) 
and will be updated at every study visit.  Beginning with the Follow-up visits, only anti-cancer 
therapies will be documented. 
11.3. 
Efficacy Evaluations 
11.3.1. 
Baseline Disease Assessment 
Cancer staging procedures should be performed during screening according to Ann Arbor 
classification (Appendix B), utilizing appropriate modalities for disease assessment such as 
PET-CT scanning, MRI scans, bone marrow assessment, and/or other laboratory assessments.  
The subject’s most recent tumor samples, either archived or fresh, must be sent to the central 
laboratory for verification of diagnosis. 
For confirmation of relapsed disease (defined as PD after a CR or Cru), biopsy is preferred but 
FNA is acceptable.  For relapse during prior treatment, biopsy/FNA reconfirmation of the 
lymphoma is recommended but not mandatory. 
In subjects with refractory disease (defined as [a] PD during prior treatment, [b] SD after 
≥ 3 cycles of prior treatment, or [c] PR after ≥ 6 cycles of prior treatment, or for stage II disease, 
SD after ≥ 3 cycles of treatment and definitive involved-field radiotherapy) with sustained PR, a 
confirmation biopsy for DLBCL is preferred but an FNA may be acceptable.  If an FNA is 
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following review of imaging results and disease history.  For subjects with SD or PD after prior 
treatment, reconfirmation of DLBCL by biopsy (preferred) or FNA is recommended but not 
mandatory. 
11.3.2. 
Disease Response Assessments 
The Investigator and independent review committee will evaluate each subject for response to 
therapy according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al, 
2007).  The independent review committee will be blinded to the investigator’s assessment of 
response. 
Efficacy assessments will be performed using CT/MRI scans of the neck, chest, abdomen, and 
pelvis. 
Skull base-to-mid thigh PET scan is recommended but not mandated. 
Contrast-enhanced MRI may be used to evaluate sites of disease that cannot be adequately 
imaged using CT or if contrast-enhanced CT scanning cannot be performed due to medical 
condition(s). 
For each subject, the modality/modalities utilized at screening will be followed throughout the 
subject’s time on study.  While additional modalities may be used depending on assessment 
needs and disease specifics, technologies used at screening will continue to be followed at each 
restaging assessment to enable direct comparison with the baseline assessment. 
 The exploratory efficacy endpoint of ORR will be assessed according to Lugano classification 
(Cheson et al, 2014; Barrington et al, 2014).  All subjects on active treatment will have disease 
response assessments (CT/MRI) performed during the last week (Day 15 – 21) of Cycles 2, 4, 
and 6 (each ± 3 days).  If FDG-PET/CT is acquired at baseline, follow-up FDG-PET is required 
at Cycle 4 and at Cycle 10.  PET findings with score 1 and 2 by 5-PS score are considered as 
PET-negative and PET findings with score 3, 4, and 5 by 5-PS score are considered as 
PET-positive.  Subjects who continue to receive CUDC-907 after Cycle 6 will have disease 
response assessments (CT/MRI) performed approximately every 12 weeks ± 1 week (i.e., Cycles 
10, 14, 18) until Cycle 18 in the first 12 months with scans collected through the first year, then 
every 24 weeks ± 2 weeks (i.e., Cycles 26, 34) until PD or death, or up to 2 years, whichever 
occurs first.  After that, disease assessments may be performed as clinically indicated (i.e., at the 
discretion of the Investigator or per standard of care). 
11.3.3. 
Survival Status 
Information on survival status will be collected for all subjects at the Post-Treatment Follow-up 
Visit time points. 
11.4. 
CUDC-907 Pharmacokinetic Analyses 
Subjects will have blood samples collected for the measurement of plasma concentrations of 
CUDC-907 and its major metabolite(s).  For all subjects, samples will be drawn 2 hours post-
dose on Day 1 of Cycles 1 and 4, and on Day 1 of every other cycle thereafter (i.e., Day 1 of 
Cycles 6, 8, 10, etc.).  In addition, for the first 50 subjects enrolled on amendment 4, blood 
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mL) will be collected using lithium heparin plasma tubes (e.g., Becton Dickinson Vacutainers 
Cat # 367884 or similar).  One additional blood sample may be obtained at a later time point to 
assess for possible study drug accumulation. 
A full description of sample handling procedures is included in the laboratory manual. 
11.5. 
Biomarker Assessments 
11.5.1. 
Pharmacogenomic Assessments 
PAXgene® blood samples for pharmacogenomic assessment will be collected during the 
Screening period.  Collection details and shipping address will be provided in the laboratory 
manual. 
11.5.2. 
Plasma Biomarker Assessments 
Blood samples (20 mL) for plasma biomarker analysis will be drawn during the Screening period 
and on Day 1 of scheduled clinic visits per protocol (see Schedule of Events in Section 5.1).  The 
plasma samples will be analyzed for cell-free DNA (cfDNA) and potential markers of 
CUDC-907 activity, such as changes in cytokine levels. 
These time points may be administratively adjusted or discontinued at the discretion of the 
Sponsor; however, the total number of blood samples will not be increased. 
Collection details and shipping address will be provided in the laboratory manual. 
11.5.3. 
Tumor Biomarker Assessments 
Optional tumor samples (i.e., CNB or FNA biopsy samples for subjects with accessible lesions) 
may be obtained prior to the first dose and within 8 hours post-dose on Cycle 1, Day 15 through 
Cycle 2, Day 1.  If available, archival tumor tissue samples and corresponding pathology report 
will also be collected.  Samples will be analyzed to evaluate baseline levels and/or changes in 
biomarkers related to the disease and/or targeted pathways, if feasible.  BCL2 and BCL6 
expression and gene translocation status are among disease-related biomarkers to be tested. 
Collection details and shipping address will be provided in the laboratory manual. 


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12. 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS  
12.1. 
Definition of an Adverse Event 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not considered drug related.  An AE can therefore be any unfavorable and unintended sign, 
symptom, or disease temporally associated with the use of a drug, without any judgment about 
causality.  An AE can arise from any use of the drug from any route of administration, 
formulation, or dose, including an overdose. 
An AE includes: 
 An exacerbation of a pre-existing illness 
 An increase in frequency or intensity of a pre-existing episodic event or condition 
 A condition detected or diagnosed after study drug administration even though it may 
have been present prior to the start of the study 
An AE does not include: 
 Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, 
transfusion); the condition that leads to the procedure is an AE 
 Pre-existing diseases or conditions present or detected at the start of the study that do 
not worsen in severity or frequency 
 Situations where an untoward medical occurrence has not occurred (e.g., 
hospitalization for elective surgery, social and/or convenience admissions) 
 Overdose of either study drug or concomitant medication without any signs or 
symptoms 
A clinical laboratory AE is any laboratory value that is considered clinically significant by the 
Investigator and has caused a medical intervention, dose hold, dose reduction or schedule 
change.  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. 
Disease progression is a worsening of a subject’s condition attributable to the disease for which 
the study medication is being given.  This may be an increase in severity of the disease or an 
increase in the symptoms of the disease.  New or increasing signs and symptoms related to 
disease progression should be reported as an AE; however, disease progression and death from 
disease progression should not be recorded as an AE unless death occurs within 30 days of the 
subject’s last dose of CUDC-907. 
12.2. 
Recording Adverse Events 
All AEs will be reported from the first dose of study drug through the EOT visit (30 ±7 days 
following the last day of study treatment).  Only treatment-related AEs will be captured from 


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EOT through Follow-up visits.  All treatment-emergent SAEs will be followed until resolution or 
stabilization. 
Whenever possible, a diagnosis should be given when signs and symptoms are due to common 
etiology (e.g., cough, runny nose, sneezing, sore throat, and head congestion should be reported 
as “upper respiratory infection”).  AE reporting and severity grading will be assessed using the 
NCI Common Toxicity Criteria (CTC), Version 4.03 (June 2010).  For those events without 
assigned CTCAE grades, the recommendation on page 1 of the CTCAE that converts mild, 
moderate and severe into CTCAE grades should be used.  A copy of the NCI CTC is available 
online at: http://evs.nci.nih.gov/ftp1/CTCAE/About.html. 
The causal relationship to study treatment will be determined by the Investigator according to 
best medical judgment, as follows: 
 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 treatment administration.  The AE is unlikely to be caused by a 
concurrent and/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 treatment administration, but the AE could also have been caused by 
the concurrent/underlying illness, other drugs, or procedures.  Information regarding 
study drug withdrawal may be lacking or unclear.  “Possible” should be used when 
study treatment administration is one of several biologically plausible causes of the 
AE. 
 Unlikely related: The AE is most likely due to a non-study-treatment-related cause.  
However, association with the study treatment 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 treatment 
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. 
12.3. 
Serious Adverse Events 
An SAE is any AE or suspected adverse reaction that is considered “serious” if, in the view of 
either the Investigator or Sponsor, it results in any of the following outcomes: 
 Is fatal; 
 Is life-threatening (defined as an immediate risk of death from the event as it 
occurred); 
 Requires in-patient hospitalization or prolongation of existing hospitalization 
(Exception:  Hospitalization for elective treatment of a pre-existing condition that did 


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not worsen during the study and is not considered an AE.  Note: Complications that 
occur during hospitalization are AEs and if a complication prolongs hospitalization, 
then the event is serious); 
 Results in persistent or significant disability/incapacity, or substantial disruption of 
the ability to conduct normal life functions; 
 Is a congenital anomaly/birth defect, or; 
 Though not included in the above definitions, may be considered serious when, based 
upon appropriate medical judgment, they may jeopardize the subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this 
definition. 
Examples of important medical events which may meet the definition of a SAE include:  
intensive treatment in the emergency room or at home for allergic bronchospasm, certain 
abnormalities (e.g., blood dyscrasias), convulsions that do not result in hospitalization, or the 
development of drug dependency or drug abuse. 
Grade 4 laboratory abnormalities will not be reported as SAEs except in those cases when the 
abnormality is associated with a clinical diagnosis, which is a recorded SAE. 
12.4. 
Reporting of Adverse Experiences, Serious Adverse Experiences, 
Serious and Unexpected Adverse Experiences 
12.4.1. 
Reporting Adverse Events and Serious Adverse Events to the Sponsor 
All SAEs, regardless of relationship to the study treatment, must be reported to the Sponsor 
within 24 hours of the Investigator becoming aware of the event.  Written SAE notification must 
follow within the 24-hour reporting timeframe, via an SAE Report submitted to Novella Clinical 
Safety Management via email at pvgsafety@novellaclinical.com or by fax at 1-866-761-1275.  
Where appropriate, follow-up SAE reports must be submitted by the Investigator as new 
information becomes available.  All treatment-emergent SAEs should be followed until 
resolution, return to baseline or stabilization. 
If the Investigator becomes aware of safety information involving a subject who participated in 
the study that appears to be drug related, even after an individual subject has completed the 
study, this should also be reported to the Sponsor.   
12.4.2. 
Reporting to the Institutional Review Board (IRB) 
SAEs will be reported to the IRB by the Investigator according to local or national requirements 
and the IRB’s policy and procedures. 
12.4.3. 
Reporting to the Regulatory Authorities 
The Sponsor will be responsible for reporting all AEs and SAEs to the appropriate regulatory 
authority (e.g., U.S. FDA), Investigators, and central IRB in accordance with all applicable 
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12.4.4. 
Pregnancy Reporting  
Pregnancy testing must be performed in all female subjects of childbearing potential at 
Screening, at least once per cycle prior to dosing, at the EOT visit, and as clinically indicated.  In 
the event of a positive test result, subjects will be discontinued from study drug and will be 
followed for the outcome of their pregnancy. 
If a female subject suspects she might be pregnant (e.g., missed or late menstrual period) or a 
male subject suspects he may have fathered a child at any time during the study through the final 
Follow-up visit, they must notify the Investigator immediately.  The Investigator will follow the 
subject or subject’s partner to determine the outcome of the pregnancy. 
Information regarding pregnancy must be reported immediately to the Sponsor and the outcome 
information provided once the outcome is known. 
The Investigator should complete the Initial Pregnancy Notification report form and forward it to 
the Sponsor (or designee) within 24 hours of knowledge of the pregnancy.  If there is an 
associated serious outcome, then both the Initial Pregnancy Notification report form and SAE 
report form should be completed. 
The Investigator should follow-up with the subject or subject’s female partner until delivery or 
termination of pregnancy even if the subject was withdrawn from the clinical study or if the 
clinical study has finished.  At that time, the Pregnancy Outcome report form should be 
completed and submitted to the Sponsor within 24 hours after the Investigator becomes aware of 
the pregnancy outcome. 
In the event the pregnancy outcome occurs following the end of the study and database lock, the 
Investigator will report the pregnancy outcome to the Sponsor (or designee) within 24 hours after 
the outcome of the pregnancy is known to the Investigator in accordance with the procedure for 
reporting SAEs (see Section 12.3). 


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13. 
STUDY ACTIVITIES 
During the treatment period, all treatment assessments/procedures should occur within ± 2 days 
of the scheduled time points.  If extenuating circumstances prevent a subject from starting or 
completing treatment, or a scheduled procedure or assessment within the protocol-specified time, 
the subject may continue to be treated on the study only with permission of the Curis Medical 
Monitor or designee clinician. 
All times should be recorded using the 24-hour clock (e.g., 23:20, rather than 11:20 PM). 
13.1. 
Prescreening (Before Day -28) and Screening (Days -28 to -1) 
The following procedures may be performed between Days -28 and -1: 
 Informed consent 
o Based on local site requirements, the following ICF procedures are 
acceptable: 
 An ICF specific for MYC testing will be signed before the tumor 
sample is sent for central testing (Prescreening). 
 The main ICF will be signed to begin the Screening period (Day -28 to 
Day -1). 
 Review inclusion/exclusion criteria 
 Subject demographics, medical history, and medication history 
 Obtain archival or fresh tumor sample (preferred) for central FISH and IHC testing 
and review 
 If archival, it must be the most recently available tumor sample 
 Fresh tumor tissue should be obtained from biopsy-accessible lesions with low 
estimated risk for serious complications (less than 2%) 
 Local MYC results performed previously should be entered into the eCRF at 
screening although central testing is required for all patients 
 IPI score 
 Radiologic assessment (CT/MRI and FDG-PET/CT, if applicable) 
 Urinalysis 
 Collect plasma for biomarker sampling 
 Optional tissue collection for biomarker sampling (from subjects with accessible 
tumor lesion) (may be obtained anytime up to pre-dose Cycle 1, Day 1) 
 Pharmacogenomic sampling 
 Update concomitant medications 


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13.1.1. 
Days -7 to -1 
A second set of screening procedures may be performed between Days -7 to -1: 
 Physical examination 
 Determine ECOG performance status 
 Obtain height and vital signs (blood pressure, heart rate, respiratory rate, temperature, 
and weight) 
 ECG 
 Pregnancy test (women of childbearing potential)  
 A serum or urine pregnancy test will be performed during Screening, as well as at 
least once per cycle prior to dosing or more frequently as clinically indicated, and 
at the End of Therapy (EOT) visit. 
 CBC with differentials 
 Serum chemistries to include sodium, potassium, magnesium, phosphate, total 
protein, chloride, bicarbonate, calcium, BUN, creatinine, uric acid, total bilirubin, 
alkaline phosphatase, AST, ALT, LDH, albumin, and glucose. 
 Update concomitant medications 
13.2. 
Treatment Period (Cycle 1 to End of Therapy Visit) 
Note:  Physical exam, performance status, vital signs including weight, CBC w/differentials and 
serum chemistry labs may be performed up to 3 days prior to Day 1 of each cycle. 
Pregnancy tests (serum or urine) will be performed for women of childbearing potential at least 
once per cycle prior to dosing, or more frequently as clinically indicated, as well as during 
Screening and at the EOT visit. 
13.2.1. 
Cycle 1 
13.2.1.1. Cycle 1, Day 1  
The following procedures will be performed on Cycle 1, Day 1: 
 Physical examination 
o Note:  The Cycle 1, Day 1 physical examination is not required if the 
Screening physical examination was conducted within 3 days prior to 
administration of the first dose of study drug (Cycle 1, Day 1). 
 Update ECOG performance status 
 Vital signs (blood pressure, heart rate, respiratory rate, temperature, and weight) 
 Lymphoma assessment (includes physical examination, a review of the subject’s 
current signs and symptoms, B symptoms, and concomitant medications) 
 CBC with differentials 


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 Serum chemistries (sodium, potassium, magnesium, phosphate, total protein, 
chloride, bicarbonate, calcium, BUN, creatinine, uric acid, total bilirubin, alkaline 
phosphatase, AST, ALT, LDH, albumin, and glucose) 
 Pregnancy test (women of childbearing potential)  
 Collect plasma for PK sampling (2 hours post-dose) 
 CUDC-907 will be administered in the clinic on PK sampling days 
 Update concomitant medications 
 Collect AEs 
 CUDC-907 dosing (CUDC-907 is taken PO for 5 days on/2 days off) 
13.2.1.2. Cycle 1, Days 2-4, Days 8-11, Days 16-19 
 CUDC-907 dosing (CUDC-907 is taken PO for 5 days on/2 days off) 
13.2.1.3. Cycle 1, Days 5 and 12  
The following procedures will be performed on Cycle 1, Days 5 and 12: 
 Symptom-directed physical examination 
 Vital signs (blood pressure, heart rate, respiratory rate, temperature, and weight) 
 CBC with differentials 
 Serum chemistries (sodium, potassium, magnesium, phosphate, total protein, 
chloride, bicarbonate, calcium, BUN, creatinine, uric acid, total bilirubin, alkaline 
phosphatase, AST, ALT, LDH, albumin, and glucose) 
 Update concomitant medications 
 Collect AEs 
 CUDC-907 dosing (CUDC-907 is taken PO for 5 days on/2 days off) 
13.2.1.4. Cycle 1, Day 8 
 Collect plasma for PK sampling (2 hours post-dose, for first 50 subjects enrolled on 
amendment 4) 
- 
CUDC-907 will be administered in the clinic on PK sampling days 
13.2.1.5. Cycle 1, Day 15  
The following procedures will be performed on Cycle 1, Day 15: 
 Optional tissue collection for biomarker sampling (from subjects with accessible 
tumor lesion) may be obtained within 8 hours post-dose on any dosing day from 
Cycle 1, Day 15 through Cycle 2, Day 1. 
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 Update concomitant medications 
 Collect AEs 
 Collect plasma for PK sampling (2 hours post-dose, for first 50 subjects enrolled on 
amendment 4) 
 CUDC-907 dosing (CUDC-907 is taken PO for 5 days on/2 days off) 
13.2.2. 
Cycles 2 through 6 
13.2.2.1. Cycles 2 through 6, Day 1  
The following procedures will be performed on Day 1 of Cycles 2 through 6: 
 Physical examination 
 Update ECOG performance status 
 Vital signs (blood pressure, heart rate, respiratory rate, temperature, and weight) 
 Lymphoma assessment (includes physical examination, a review of the subject’s 
current signs and symptoms, B symptoms, and concomitant medications) 
 Radiologic assessment (CT/MRI are required at the end of Cycle 2 (± 3 days), 
Cycle 4 (± 3 days) and Cycle 6 (± 3 days).  If FDG-PET/CT is acquired at baseline, 
follow-up FDG-PET/CT imaging at Cycle 4 is required) 
 CBC with differentials 
 Serum chemistries (sodium, potassium, magnesium, phosphate, total protein, 
chloride, bicarbonate, calcium, BUN, creatinine, uric acid, total bilirubin, alkaline 
phosphatase, AST, ALT, LDH, albumin, and glucose) 
 Pregnancy test (women of childbearing potential)  
 Collect plasma for biomarker sampling 
 Collect plasma for PK sampling on Cycle 4, Day 1 only (2 hours post-dose) 
 CUDC-907 will be administered in the clinic on PK sampling days. 
 Update concomitant medications 
 Collect AEs 
 CUDC-907 dosing (CUDC-907 is taken PO for 5 days on/2 days off) 
13.2.2.2. Cycles 2-6, Days 2-5, Days 8-12, Days 15-19 
 CUDC-907 dosing (CUDC-907 is taken PO for 5 days on/2 days off) 
13.2.3. 
Cycles 7+  
Note:  Subjects who continue past Cycle 13 will only be required to have a Day 1 visit at the 
beginning of every other cycle (14, 16, 18, etc.). 


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13.2.3.1. Cycles 7+, Day 1  
The following procedures will be performed on Day 1 of Cycles 7+: 
 Physical examination 
 Update ECOG performance status 
 Vital signs (blood pressure, heart rate, respiratory rate, temperature, and weight) 
 Lymphoma assessment (includes physical examination, a review of the subject’s 
current signs and symptoms, B symptoms, and concomitant medications) 
 Radiologic assessment (CT/MRI [If FDG-PET/CT is acquired at baseline, follow-up 
FDG-PET/CT imaging at Cycle 10 is required]) 
 CBC with differentials 
 Serum chemistries (sodium, potassium, magnesium, phosphate, total protein, 
chloride, bicarbonate, calcium, BUN, creatinine, uric acid, total bilirubin, alkaline 
phosphatase, AST, ALT, LDH, albumin, and glucose) 
 Pregnancy test (women of childbearing potential)  
 Collect plasma for biomarker sampling 
 Update concomitant medications 
 Collect AEs 
 Collect plasma for PK sampling (2 hours post-dose) every other cycles (i.e., Cycles 6, 
8, 10, etc.) 
 CUDC-907 will be administered in the clinic on PK sampling days. 
 CUDC-907 dosing (CUDC-907 is taken PO for 5 days on/2 days off) 
13.2.3.2. Cycles 7+, Days 2-5, Days 8-12, Days 15-19 
 CUDC-907 dosing (CUDC-907 is taken PO for 5 days on/2 days off) 
13.2.4. 
End of Therapy Visit (Day 30) 
The following procedures will be performed at the EOT visit: 
 Physical examination 
 Update ECOG performance status 
 Vital signs (blood pressure, heart rate, respiratory rate, temperature, and weight) 
 ECG 
 Pregnancy test (women of childbearing potential) 
 A serum or urine pregnancy test will be performed at the EOT visit, as well as 
during Screening and at least once per cycle prior to dosing, or more frequently as 
clinically indicated. 


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 Lymphoma assessment (includes physical examination, a review of the subject’s 
current signs and symptoms, B symptoms, and concomitant medications) 
 Done only if not performed within 4 weeks of the EOT visit 
 Radiologic assessment (CT/MRI) 
 Done only if not performed within 4 weeks of the EOT visit 
 CBC with differentials 
 Serum chemistries (sodium, potassium, magnesium, phosphate, total protein, 
chloride, bicarbonate, calcium, BUN, creatinine, uric acid, total bilirubin, alkaline 
phosphatase, AST, ALT, LDH, albumin, and glucose) 
 Update concomitant medications 
 Collect AEs 
13.3. 
Post-Treatment Follow-up Visits 
13.3.1. 
Follow-up Visits ≤ 6 Months (Every 12 Weeks) 
 Symptom-directed physical examination (performed until time of disease progression, 
withdrawal of consent, or any other criteria that would make the subject unable to be 
followed for disease response) 
 IPI score 
 Lymphoma assessment (includes physical examination, a review of the subject’s 
current signs and symptoms, B symptoms, and concomitant medications) 
 Radiologic assessment (CT/MRI) 
 Survival status 
 Update concomitant medications (anti-cancer therapies only) 
 Collect AEs (only treatment-related SAEs will be captured) 
13.3.2. 
Follow-up Visits > 6 Months (Every 24 Weeks) 
 Symptom-directed physical examination (performed until time of disease progression, 
withdrawal of consent, or any other criteria that would make the subject unable to be 
followed for disease response) and updated  
 IPI score 
 Lymphoma assessment (includes physical examination, a review of the subject’s 
current signs and symptoms, B symptoms, and concomitant medications) 
 Radiologic assessment (CT/MRI) 
 Survival status 
 Update concomitant medications (anti-cancer therapies only) 


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 Collect AEs (only treatment-related SAEs will be captured) 
 


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14. 
STATISTICAL ANALYSES 
14.1. 
Overview of Study Design 
The safety and preliminary efficacy of CUDC-907 will be evaluated when administered in 
subjects with RR MYC-altered DLBCL.  Patients with RR DLBCL will be tested for 
MYC-altered disease, defined as MYC translocation by FISH, or MYC expression in ≥ 40% of 
tumor cells by IHC staining and/or MYC gene copy number gain by FISH based on fresh or 
archived tumor tissue sample (most recent available). 
Based on central testing and review, subjects will be classified into one of the following 
categories:  (1) Group A:  MYC translocation+ by FISH, (2) Group B:  MYC expression in ≥ 40% 
of tumor cells by IHC and/or MYC gene copy number gain by FISH, or (3) Group C:  MYC 
translocation¯ by FISH and MYC expression in < 40% of tumor cells and no MYC gene copy 
number gain by FISH.   
Subjects in all groups will continue to receive treatment until they meet criteria for treatment 
discontinuation. 
14.2. 
Study Endpoints 
14.2.1. 
Primary Endpoint 
 ORR (central determination) 
14.2.2. 
Secondary Endpoints 
 ORR (local determination) 
 PFS, median PFS, and PFS6 (central and local determination) 
 OS 
 DCR and DOR (central and local determination) 
 To evaluate the incidence and severity of AEs, SAEs, and other safety parameters in 
subjects receiving CUDC-907. 
 To characterize the PK of CUDC-907. 
14.2.3. 
Exploratory Endpoints 
 To explore the effects of CUDC-907 on disease-associated biomarkers. 
 To explore the relationship between disease-associated biomarkers in plasma and 
tumor tissue.  Among biomarkers of interest, BCL2 and BCL6 protein expression and 
translocation status in particular will be tested in tumor tissue, where possible. 
 To explore biomarkers of response for patient selection. 
 To explore the relationship between additional biomarkers and biomarker profiles that 
may influence biologic and clinical responses to CUDC-907. 


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 To explore the ORR according to Lugano classification (Cheson et al, 2014; 
Barrington et al, 2014). 
14.3. 
Sample Size Considerations 
The sample size for Groups A and B was determined based on the following: 
With a sample size of 50 subjects in Groups A and B with an ORR of 30.0%, a two-sided 95% 
confidence interval employing the exact binomial method will extend from 17.9% to 44.6%. This 
confidence bound (CB) about the observed ORR is thought to adequately characterize the 
disease response of these populations after receiving CUDC-907. 
Below are the 95% confidence intervals for various response rates using a sample size of 
50 subjects and employing the exact binomial methodology. 
Sample Size 
ORR 
Lower 95% 
Confidence Bound 
Upper 95% 
Confidence Bound 
50 
15 (30%) 
17.9% 
44.6% 
50 
14 (28%) 
16.2% 
42.5% 
50 
13 (26%) 
14.6% 
40.4% 
50 
12 (24%) 
13.1% 
38.2%) 
Enrollment within a group or overall may also terminate early due to other considerations such 
as those that may preclude timely completion of the study (e.g., low prevalence of MYC-altered 
DLBCL). 
14.4. 
Statistical Analysis 
The statistical analyses will be performed using SAS® version 9.4 or later (SAS Institute Inc., 
Cary, NC).  A comprehensive statistical analysis plan (SAP) will be finalized prior to database 
lock. 
14.4.1. 
Analysis Populations  
The Intent-to-Treat (ITT) Population will consist of all subjects in Groups A and B.  The primary 
analyses of efficacy will be conducted based on the ITT Population. 
The Evaluable Population will consist of all subjects in Groups A and B who receive at least one 
full cycle of treatment and have at least one post-baseline disease assessment and have not had 
major protocol deviations that are thought to have materially impacted efficacy outcomes. Major 
protocol deviations will be identified prior to database lock.  Secondary analysis of efficacy will 
also be conducted based on the Evaluable Population.  In addition, the primary efficacy endpoint 
(ORR) will also be assessed using the Evaluable Population as a secondary analysis. 
The Safety Population will consist of all subjects who receive any treatment.  All safety analyses 
will be conducted based on this population. 


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14.4.2. 
Baseline Characteristics 
Demographic and baseline disease characteristics will be summarized.  Data to be tabulated will 
include demographic features such as sex, age, race, and weight, as well as disease-specific 
characteristics, such as tumor stage and histology. 
14.4.3. 
Efficacy Analyses 
The primary analyses of efficacy will be based on the ITT Population.  The interim analyses will 
be performed on the Evaluable Population. 
The primary efficacy endpoint, ORR, will be based on the proportion of subjects with CR or PR 
using the central determination of disease response in Groups A and B, separately.  The estimate 
will be accompanied by a two-sided exact binomial 95% CB.   
Progression-free survival, OS, and DOR will be summarized descriptively for Groups A and B 
using the Kaplan-Meier method.  For such subjects, the progression or censoring date will be 
determined based on described conventions (Food and Drug Administration, 2007). 
Progression-free survival, median PFS, and the estimated rate at 6 months (PFS6) based on the 
Kaplan-Meier analyses will be reported separately for Groups A and B.  For OS, the estimated 
rates at 3, 6, 9, and 12 months based on the Kaplan-Meier analyses will be reported for Groups A 
and B.  For DOR, the estimate of the median based on the Kaplan-Meier analyses for Groups A 
and B will be reported. 
Waterfall plots will be used to depict graphically the maximum decrease from baseline in the 
sum of the product diameters in measurable nodes and nodal masses. 
Secondary analyses of efficacy will be conducted based on the ITT and Evaluable Populations 
using response as determined by both the central determination of disease response and 
investigator site.  In these analyses, the primary efficacy endpoint, ORR, will be estimated using 
the proportion of subjects with CR or PR.  The estimate will be accompanied by a two-sided 
exact binomial 95% lower CB. 
14.4.3.1. Interim Analyses 
Interim analyses of efficacy using the Evaluable Population will be performed after ORR has 
been determined in 25 evaluable subjects for both Groups A and B, separately. In both Groups A 
and B, the ORR using the local determination of disease response will be obtained. If the lower 
bound of a single-sided 95% confidence interval using the exact binomial method is less than 
10% (i.e., 5 responses or less out of 25 patients) in either group, enrollment in that group will not 
continue. Below are the 95% single-sided lower confidence intervals for various response rates 
using a sample size of 25 patients and employing the exact binomial methodology. 


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Sample Size 
ORR 
Lower 95%  
Single-Sided Confidence Bound 
25 
7 (28%) 
14.0% 
25 
6 (24%) 
11.0% 
25 
5 (20%) 
8.2%1 
25 
4 (16%) 
5.7%1 
1 Would result in stopping enrollment in that particular group(s). 
14.4.4. 
Safety Analysis 
The analyses of safety will be conducted based on the Safety Population.  Analyses will be 
stratified by treatment.  Safety will be assessed based on AEs, SAEs, laboratory values, vital 
signs, and ECG results. 
Summary tables will be produced for all reported treatment-emergent AEs (TEAEs), defined as 
AEs that start or worsen on or after the first administration of study treatment.  The reported AE 
term will be assigned a standardized preferred term using the current version of the Medical 
Dictionary for Regulatory Activities (MedDRA). 
TEAEs will be summarized based on the number and percentage of subjects experiencing the 
event by MedDRA system organ class and preferred term.  The causal relationship between the 
occurrence of an AE and study treatment will be judged by the Investigator.  In the event a 
subject experiences repeat episodes of the same AE, then the event with the highest severity 
grade and the event with the strongest causal relationship to study drug will be used for purposes 
of incidence tabulations. 
Tabular summaries will be provided for: 
 All TEAEs 
 TEAEs by relationship to study treatment 
 TEAEs by severity 
 TEAEs occasioning treatment modification  
 Serious TEAEs 
All deaths that occur on study (defined as during treatment or within 30 days of treatment 
discontinuation) will be reported in a subject listing, which will include the primary cause of 
death and the number of days between the date of the last dose of study treatment and death.  For 
subjects on combination treatment, the listing will show the date of last dose of each component. 
Hematology and serum chemistries will be summarized using conventional summary statistics 
(mean, standard deviation, median, and range) for the following: baseline value, minimum and 
maximum post-baseline values, average post-baseline value, and last post-baseline value.  
Standard shift tables will also be prepared presenting worst post-baseline toxicity grade vs 
baseline.  Vital signs and ECG results will be summarized in a descriptive manner by calculating 


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the mean, standard deviation, median, and range by time point in the same manner described for 
laboratory values. 
Prior and concomitant medications will be coded to the generic term using the current version of 
the World Health Organization Drug Dictionary and will be tabulated by group and listed by 
subject. 
14.4.5. 
Pharmacokinetic Analysis 
Population PK analysis will be conducted to further understand the PK profile of CUDC-907 in 
patients with RR MYC-altered DLBCL.  Linear mixed-effect modeling and/or a nonlinear 
mixed-effect modeling approach will be used in the study to better understand the PK profile of 
CUDC-907 in general Preliminary PK information has been collected during Phase 1, and the 
basic PK models of the drug have been established.  In this study, blood samples will be obtained 
at 2 hours post-dose on Cycle 1 Day 1, Cycle 4 Day 1, and on Day 1 of every other cycle 
thereafter (i.e., Day 1 of Cycles 6, 8, 10, etc.). In addition, for the first 50 subjects enrolled on 
amendment 4, blood samples will also be obtained 2 hours post-dose on Days 8 and 15 of Cycle 
1. 
14.4.6. 
Multicenter Study 
Data will be pooled across centers for all analyses. 
14.4.7. 
Adjustments for Covariates 
No adjustments for covariates will be made. 
14.4.8. 
Missing Data 
Unless otherwise stated, there will be no imputation of missing data, but dates for AEs and 
concomitant medications may be imputed conservatively if partial. 


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15. 
STUDY ADMINISTRATION 
Regulatory authorities, the IRB/Independent Ethics Committee (IEC), and/or the Sponsor’s 
clinical quality assurance group, or its designee, may request access to all source documents, 
eCRFs, and other study documentation for on-site audit or inspection.  Direct access to these 
documents must be guaranteed by the Investigator, who must provide support at all times for 
these activities. 
15.1. 
Case Report Forms and Source Documentation 
For each subject, an eCRF and corresponding source records will be maintained at each clinical 
site.  The eCRFs should be completed in a timely manner, and every effort should be made to 
have electronic forms completed and up-to-date in anticipation of a visit by the Sponsor’s 
monitor. 
The Investigator must prepare and maintain adequate and accurate records of all observations 
and other data pertaining to the clinical study for each study participant. 
All aspects of the study will be carefully monitored with respect to GCP and standard operating 
procedures for compliance with applicable government regulations.  The study monitor will be 
an authorized individual designated by the Sponsor.  The study monitor will have access to all 
records necessary to ensure integrity of the data and will periodically review the progress of the 
study with the PI. 
An electronic data capture system to manage data collection will be utilized during this trial.  
The electronic data capture system is a software tool designed to ensure quality assurance and 
facilitate data capture during clinical trials.  The system is fully compliant with Code of Federal 
Regulations 21 Part 11. 
The Investigator will ensure the accuracy, completeness, and timeliness of the data reported to 
the Sponsor.  Data collection processes and procedures will be reviewed and validated to ensure 
completeness, accuracy, reliability, and consistency. 
A complete audit trail will be maintained of all data changes.  The Investigator (or designee) will 
cooperate with the Sponsor (or its representative[s]) for the periodic review of study documents 
to ensure the accuracy and completeness of the data capture system at each scheduled monitoring 
visit. 
15.2. 
Investigator Documentation 
Study staff will maintain appropriate medical and research records for this study, in compliance 
with International Conference on Harmonisation (ICH) E6, Section 4.9 and regulatory and 
institutional requirements for the protection of confidentiality of subjects.  Study staff will permit 
authorized representatives of regulatory agencies to examine (and when required by applicable 
law, to copy) research records for the purposes of quality assurance reviews, audits, and 
evaluation of the study safety, progress and data validity. 
The Investigator will provide the Sponsor with a fully executed FDA Form 1572 including the 
Investigator’s curriculum vitae.  The Investigator will indicate on Form 1572 the name and 


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location of the clinical laboratory which will be used for subject evaluation.  The laboratory’s 
certification, certification number, and date of certification and the laboratory normal values will 
be provided.  Any changes in the clinical laboratory or laboratory values will be provided 
promptly to the Sponsor who will report the changes to the FDA as required. 
15.3. 
Record Retention 
The Investigator will retain a copy of all study records in a secure location for a period of 2 years 
after the last approval of a marketing application and until there are no pending or contemplated 
marketing applications OR until at least 3 years have elapsed since the formal discontinuation of 
clinical development of the investigational product. 
15.4. 
Protocol Deviations and Amendment 
The Investigator is not permitted to alter or deviate from the protocol without written agreement 
from the Sponsor.  Any such agreement should be reported by the Investigator to their IRB/IEC.  
An immediate and unapproved deviation is permitted if immediate health care concerns mandate 
it. 
All protocol revisions (amendments) must originate with and be documented by the Sponsor.  
The Investigator must submit the amendment to his/her IRB/IEC for review and approval prior to 
implementation.  Documentation of approval signed by the chairperson or designee must be sent 
to the Sponsor. 
15.5. 
Institutional Review Board/Independent Ethics Committee 
The protocol, ICF(s), recruitment materials, and all patient materials will be submitted to the 
IRB/IEC for review and approval.  Approval of both the protocol and the consent form must be 
obtained before any patient is enrolled at any given investigative center, and a copy of the 
approval letter supplied to the Sponsor or Sponsor’s designee.  Any amendment to the protocol 
will require review and approval by the IRB/IEC before the changes are implemented in the 
study. 
During the course of the study, the Investigator shall make timely and accurate reports to the 
IRB/IEC on study progress at intervals not exceeding one year, as well as satisfying any other 
local IRB/IEC reporting regulations.  Copies of all reports to, and correspondence with, the 
IRB/IEC must be provided to the Sponsor or Sponsor’s designee.  Further, within three months 
of the completion or early termination of the study, a final report should be made to the IRB/IEC 
and Sponsor by the Investigator. 
It is the Investigator’s obligation to maintain an IRB/IEC correspondence file and to make this 
available for review to Sponsor representatives as part of the routine study monitoring process. 
15.6. 
Study Committees 
A Safety Review Committee (SRC) comprised of the Medical Monitor, PI, and Sponsor 
representatives will be convened to review safety information for ongoing safety surveillance. 


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  The SRC is tasked with making a recommendation to continue or stop the trial based on their 
assessment of available efficacy and safety information (see Section 9.3.2 for SRC stopping 
criteria). 
15.7. 
Sponsor Monitoring 
Monitoring and auditing procedures approved by the Sponsor will be followed in order to 
comply with GCP guidelines.  After satisfactory receipt of all necessary regulatory paperwork, 
the Sponsor’s monitor will arrange that all study material be delivered to the study site at a 
mutually convenient time.  An initiation visit by the Sponsor and its monitoring personnel will be 
made.  At this meeting, all personnel expected to be involved in the conduct of the study will 
undergo an orientation to include review of study protocol, instruction for eCRF completion and 
overall responsibilities, including those for drug accountability and study file maintenance. 
Throughout the course of the study, the Sponsor’s monitor will make frequent contact with the 
Investigator.  This will include telephone and/or on-site visits.  On-site checking of the eCRFs 
for completeness and clarity, cross-checking with source documents, and clarification of 
administrative matters will be performed.  As part of the data audit, it is expected that source 
documents (e.g., hospital records, office records) will be made available for review by the 
monitor.  The monitor also will perform drug accountability checks, and may periodically 
request review of the Investigator’s study file to assure completeness of documentation in all 
respects of study conduct. 
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 15.3.  The 
Investigator or appointed delegate will receive the Sponsor’s representative during these on-site 
visits and will cooperate in providing the documents for inspection and responding to inquiries 
that may arise as part of this review.  The Investigator will also permit inspection of the study 
files by authorized representatives of the FDA and regulatory authorities of other countries. 
15.8. 
Publication/Data Sharing Policy 
Publication by the sites of any data from this study must be in accordance with the clinical trial 
agreement. 


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16. 
ETHICS/PROTECTION OF HUMAN PATIENTS 
16.1. 
Ethical Conduct of the Study 
The study will be conducted in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH, GCP guidelines, applicable regulatory 
requirements, and Curis policies.  The Investigator will ensure that this study is conducted in full 
conformity with the principles set forth in The Belmont Report: Ethical Principles and 
Guidelines for the Protection of Human Patients of Research, as drafted by the U.S. National 
Commission for the Protection of Human Patients of Biomedical and Behavioral Research 
(18 April 1979) and codified in 45 Code of Federal Regulations (CFR) Part 46 and/or the ICH 
E6. 
16.2. 
Informed Consent 
Informed consent is a process that is initiated prior to the individual agreeing to participate in the 
study and continues throughout study participation.  Extensive discussion of risks and possible 
benefits of study participation will be provided to patients and their families, if applicable.  A 
consent form describing in detail the study procedures and risks will be given to the patient.  
Before each patient is enrolled in the clinical study, written informed consent will be obtained 
from the patient according to the regulatory and legal requirements of the participating country.  
The patient will receive all information that is required by regulatory authorities and ICH 
guidelines.  The Investigator (or designee) will provide the Sponsor with a copy of the IRB-/ 
IEC-approved ICF prior to the start of the study. 
The ICF must be signed and dated; one copy will be given to the patient and the Investigator will 
retain a copy as part of the clinical study records.  The Investigator will not undertake any 
investigation specifically required for the clinical study until written consent has been obtained.  
The terms of the consent and when it was obtained must also be documented.  Patients will be 
given the opportunity to discuss the study with their surrogates or think about it prior to agreeing 
to participate.  They may withdraw consent at any time throughout the course of the study.  The 
rights and welfare of the patients will be protected by emphasizing to them that the quality of 
their clinical care will not be adversely affected if they decline to participate in this study. 
If a protocol amendment is required, then the ICF may need to be revised to reflect the changes 
to the protocol.  If the ICF is revised, it must be reviewed and approved by the responsible 
IRB/IEC and signed by all subjects subsequently enrolled in the clinical study as well as those 
currently enrolled in the clinical study. 
Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) 
authorization will be obtained and documented from each patient prior to entry into the study.  
The consent process will be documented in the eCRF. 
16.3. 
Confidentiality and Data Protection 
All clinical study findings and documents will be regarded as confidential.  Study documents 
(protocols, Investigator’s Brochures, and other material) will be stored appropriately to ensure 


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their confidentiality.  Patient data will be made available upon request to monitors from the 
Sponsor, the FDA, the Institutional Review Board, and to other government agencies that have 
responsibility for clinical research activities. 
The anonymity of participating subjects must be maintained.  Data that are released by the 
Investigator to the Sponsor, the FDA, or IRB/IEC will not be directly traceable to the patient.  
Documents that identify the patient (e.g., the signed informed consent document) must be 
maintained in confidence by the Investigator.  In the event that a publication of this research 
incorporates a patient's medical data, that data will not identify the patient. 


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17. 
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Gisselbrecht G, Glass B, Laurent G, Gill DS, Linch MD, Trneny M, et al.  Maintenance with 
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Green TM, Young KH, Visco C, Xu-Monette ZY, Orazi A, Go RS, et al.  Immunohistochemical 
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Gui CY, Ngo L, Xu WS, Richon VM, Marks PA.  Histone deacetylase (HDAC) inhibitor 
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Gupta M, Maurer MJ, Wellik LE, Law ME, Han JJ, Ozsan N, et al.  Expression of Myc, but not 
pSTAT3, is an adverse prognostic factor for diffuse large B-cell lymphoma treated with 
epratuzumab/R-CHOP.  Blood.  2012 Nov 22;120(22):4400-6. 
Horn H, Ziepert M, Becher C, Barth TF, Bernd HW, Feller AC, et al; German High-Grade Non-
Hodgkin Lymphoma Study Group.  MYC status in concert with BCL2 and BCL6 expression 
predicts outcome in diffuse large B-cell lymphoma.  Blood.  2013 Mar 21;121(12):2253-63. 


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Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, et al (eds).  SEER 
Cancer Statistics Review, 1975-2011, National Cancer Institute.  Bethesda, MD, 
http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted 
to the SEER web site, April 2014. 
Hu S, Xu-Monette ZY, Tzankov A, Green T, Wu L, Balasubramanyam A, et al.  MYC/BCL2 
protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse 
large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The 
International DLBCL Rituximab-CHOP Consortium Program.  Blood.  2013 May 16; 
121(20):4021-31. 
Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S, et al.  Concurrent 
expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus 
cyclophosphamide, doxorubicin, vincristine, and prednisone.  J Clin Oncol.  2012 Oct 
1;30(28):3452–3. 
Kenney AM, Widlund HR, Rowitch DH.  Hedgehog and PI-3 kinase signaling converge on 
Nmyc1 to promote cell cycle progression in cerebellar neuronal precursors.  Development.  2004 
Jan;131(1):217-28. 
Klapper W, Stoecklein H, Zeynalova S, Ott G, Kosari F, Rosenwald A, et al; German 
High-Grade Non-Hodgkin's Lymphoma Study Group.  Structural aberrations affecting the MYC 
locus indicate a poor prognosis independent of clinical risk factors in diffuse large B-cell 
lymphomas treated within randomized trials of the German High-Grade Non-Hodgkin's 
Lymphoma Study Group (DSHNHL).  Leukemia.  2008 Dec;22(12):2226-9. 
Kluk MJ, Chapuy B, Sinha P, Roy A, Dal Cin P, Neuberg DS, et al.  Immunohistochemical 
detection of MYC-driven diffuse large B-cell lymphomas.  PLoS One.  2012;7(4):e33813. 
Kumar A, Marqués M, Carrera AC.  Phosphoinositide 3-kinase activation in late G1 is required 
for c-Myc stabilization and S phase entry.  Mol Cell Biol.  2006 Dec;26(23):9116-25.   
Kurland JF, Tansey WP.  Myc-mediated transcriptional repression by recruitment of histone 
deacetylase.  Cancer Res.  2008 May 15;68(10):3624-9. 
Li S, Weiss VL, Wang XJ, Desai PA, Hu S, Yin CC, et al.  High-grade B-cell Lymphoma With 
MYC Rearrangement and Without BCL2 and BCL6 Rearrangements Is Associated With High 
P53 Expression and a Poor Prognosis. Am J Surg Pathol. 2016 Feb;40(2):253-61. 
Liu T, Tee AE, Porro A, Dwarte T, Liu PY, Iraci N, et al.  Activation of tissue transglutaminase 
transcription by histone deacetylase inhibition as a therapeutic approach for Myc oncogenesis.  
Proc Natl Acad Sci USA. 2007 Nov 20; 104(47):18682-7. 
Lister TA, Crowther D, Sutcliffe SB, Glatstein E, Canellos GP, Young RC, et al.  Report of a 
committee convened to discuss the evaluation and staging of patients with Hodgkin's disease:  
Cotswolds meeting.  J Clin Oncol.  1989 Nov 1;7(11):1630-6. 
Macpherson N, Lesack D, Klasa R, Horsman D, Connors JM, Barnett M, et al.  Small 
noncleaved, non-Burkitt's (Burkit-Like) lymphoma: cytogenetics predict outcome and reflect 
clinical presentation.  J Clin Oncol.  1999 May;17(5):1558-67. 


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Miura K, Takahashi H, Nakagawa M, Izu A, Sugitani M, Kurita D, et al.  Clinical significance of 
co-expression of MYC and BCL2 protein in aggressive B-cell lymphomas treated with a second 
line immunochemotherapy.  Leuk Lymphoma.  2015 Oct 22:1-7.  
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 
Dec;5(6):649-655. 
Oki Y, Noorani M, Lin P, Davis RE, Neelapu SS, Ma L, et al.  Double hit lymphoma:  the MD 
Anderson Cancer Center clinical experience.  Br J Haematol.  2014 Sep;166(6):891-901. 
Perry AM, Alvarado-Bernal Y, Laurini JA, Smith LM, Slack GW, Tan KL, et al.  MYC and 
BCL2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated 
with rituximab.  Br J Haematol.  2014 May;165(3):382-91. 
Petrich AM, Gandhi M, Jovanovic B, Castillo JJ, Rajguru S, Yang DT, et al.  Impact of induction 
regimen and stem cell transplantation on outcomes in double-hit lymphoma:  a multicenter 
retrospective analysis.  Blood.  2014 Oct 9;124(15):2354-61. 
Pfeifer M, Grau M, Lenze D, Wenzel SS, Wolf A, Wollert-Wulf B, et al.  PTEN loss defines a 
PI3K/AKT pathway-dependent germinal center subtype of diffuse large B-cell lymphoma.  Proc 
Natl Acad Sci U S A.  2013 Jul 23;110(30):12420-5. 
Polack A, Eick D, Koch E, Bornkamm GW.  Truncation does not abrogate transcriptional 
downregulation of the c-myc gene by sodium butyrate in Burkitt's lymphoma cells.  EMBO J.  
1987 Oct;6(10):2959-64. 
Qian C, Lai CJ, Bao R, Wang DG, Wang J, Xu GX, et al.  Cancer network disruption by a single 
molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase 
signaling.  Clin Cancer Res.  2012 Aug 1;18(15):4104-13. 
Savage KJ, Johnson NA, Ben-Neriah S, Connors JM, Sehn LH, Farinha P, et al.  MYC gene 
rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients 
treated with R-CHOP chemotherapy.  Blood.  2009 Oct 22;114(17):3533-7. 
Scott DW, Mottok A, Ennishi D, Wright GW, Farinha P, Ben-Neriah S, et al.  Prognostic 
significance of diffuse large B-cell lymphoma cell of origin determined by digital gene 
expression in formalin-fixed paraffin-embedded tissue biopsies.  J Clin Oncol.  2015 Sep 
10;33(26):2848-56. 
Sehn LH.  Paramount prognostic factors that guide therapeutic strategies in diffuse large B-cell 
lymphoma.  Hematology Am Soc Hematol Educ Program.  2012;2012:402-9. 
Swerdlow SH, Campo E, Harris NL, et al, eds.WHO classification of tumours of 
haematopoieticand lymphoid tissues. In: Bosman FT, Jaffe ES,Lakhani SR, Ohgaki H, eds. 
World Health Organization Classification of Tumours. Lyon,France: I ARC; 2008. 
Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization 
classification of lymphoid neoplasms. Blood. 2016 May 19;127(20):2375-90 
Thieblemont C, Briere J, Mounier N, Voelker HU, Cuccuini W, Hirchaud E, et al.  The germinal 
center/activated B-cell subclassification has a prognostic impact for response to salvage therapy 


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in relapsed/refractory diffuse large B-cell lymphoma:  a bio-CORAL study.  J Clin Oncol. 2011 
Nov 1;29(31):4079-87. 
Tzankov A, Xu-Monette ZY, Gerhard M, Visco C, Dirnhofer S, Gisin N, et al.  Rearrangements 
of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with 
rituximab-CHOP.  Mod Pathol.  2014 Jul;27(7):958-71. 
Valera A, López-Guillermo A, Cardesa-Salzmann T, Climent F, González-Barca E, Mercadal S, 
et al; Grup per l’Estudi dels Limfomes de Catalunya i Balears (GELCAB).  MYC protein 
expression and genetic alterations have prognostic impact in patients with diffuse large B-cell 
lymphoma treated with immunochemotherapy.  Haematologica.  2013 Oct;98(10):1554-62. 
Visco C, Tzankov A, Xu-Monette ZY, Miranda RN, Tai YC, Li Y, et al.  Patients with diffuse 
large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, 
irrespective of MYC status:  a report from an International DLBCL rituximab-CHOP 
Consortium Program Study.  Haematologica.  2013 Feb;98(2):255-63. 
Zhang X, Zhao X, Fiskus W, Lin J, Lwin T, Rao R, et al.  Coordinated silencing of 
MYC-mediated miR-29 by HDAC3 and EZH2 as a therapeutic target of histone modification in 
aggressive B-Cell lymphomas.  Cancer Cell.  2012;22(4):506-23. 
Zhou K, Xu D, Cao Y, Wang J, Yang Y, Huang M.  C-MYC aberrations as prognostic factors in 
diffuse large B-cell lymphoma:  a meta-analysis of epidemiological studies.  PLoS One.  
2014 Apr 16;9(4):e95020. 


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APPENDIX A. EASTERN COOPERATIVE ONCOLOGY GROUP 
(ECOG) PERFORMANCE STATUS SCALE 
 
ECOG Performance Status 
Grade Description 
0 
Fully active, able to carry on all predisease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities.  Up and 
about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled.  Cannot carry on any selfcare.  Totally confined to bed or chair 
5 
Dead 
Source: Oken et al, 1982 


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APPENDIX B. ANN ARBOR CLASSIFICATION 
1. Stage According to Sites Involved by Lymphoma 
Stage Features 
I 
Involvement of a single lymph node region* or lymphoid structure 
II 
Involvement of two or more lymph node regions,* or localized involvement of one 
extranodal site and one or lymph node regions, all on the same side of the diaphragm 
III 
Involvement of lymph node regions* or structures on both sides of the diaphragm 
IV 
Diffuse or disseminated involvement of one or more extralymphatic organs, OR isolated 
extralymphatic organ involvement without adjacent regional lymph node involvement, 
but with disease in distant site(s), OR any involvement of the liver, bone marrow, pleura 
or CSF 
* Lymph node regions include: right cervical (including cervical, supraclavicular, occipital, and preauricular lymph 
nodes), left cervical, right axillary, left axillary, right infraclavicular, left infraclavicular, mediastinal, hilar, 
periaortic, mesentery, right pelvic, left pelvic, right inguinal femoral, and left inguinal femoral 
2. Relevant Suffixes 
Suffix Meaning 
A 
Absence of constitutional symptoms 
B 
Constitutional symptoms:  fever (> 38°C), drenching sweats, weight loss (10% body 
weight over 6 months) 
E 
Involvement of a single, extranodal site contiguous or proximal to a known nodal site 
(stages I to III only; additional extranodal involvement is stage IV) 
S 
Splenic involvement 
X 
Bulky disease, defined as one or more site of disease of > 10 cm diameter, or 
mediastinal widening to > 1/3 of the chest width on chest X-ray 
Other designations may include involved extranodal site(s): M = marrow, L = lung, H = liver, P = pleura, O = bone, 
D = skin and subcutaneous tissue; and the number of disease sites (e.g. II2, II4) 
 
Source:  Adapted from Carbone et al, 1971 and Lister et al, 1989 


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APPENDIX C. RECOMMENDATIONS FOR INITIAL EVALUATION, 
STAGING, AND RESPONSE ASSESSMENT OF 
HODGKIN AND NON-HODGKIN LYMPHOMA: THE 
LUGANO CLASSIFICATION 
 
 


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Source: Cheson et al, 2014 


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APPENDIX D. ROLE OF IMAGING IN THE STAGING AND RESPONSE 
ASSESSMENT OF LYMPHOMA: CONSENSUS OF THE 
INTERNATIONAL CONFERENCE ON MALIGNANT 
LYMPHOMAS IMAGING WORKING GROUP; 5-PS 
SCORE 
The 5-PS scores the most intense uptake in a site of initial disease, if present, as follows: 
 1. No uptake above background 
 2. Uptake < mediastinum 
 3. Uptake > mediastinum but < liver 
 4. Uptake moderately higher than liver 
 5. Uptake markedly higher than liver and/or new lesions 
 X. New areas of uptake unlikely to be related to lymphoma 
Source:  Barrington et al, 2014 


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APPENDIX E. 
INTERNATIONAL PROGNOSTIC INDEX (IPI) 
CLASSIFICATION 
One point is assigned for each of the following risk factors: 
 Age greater than 60 years 
 Stage III or IV disease 
 Elevated serum LDH 
 ECOG/Zubrod performance status of 2, 3, or 4 
 More than 1 extranodal site 
Source:  The International Non-Hodgkin’s Lymphoma Prognostic Factors Project, 1993 

ICF_001.pdf: 
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INFORMED CONSENT DOCUMENT 
AGREEMENT TO BE IN A RESEARCH STUDY 
 
 
NAME OF SPONSOR COMPANY:  
 
 
Curis, Inc. 
STUDY NUMBER AND TITLE: 
 
 
 
 
 
 
 
PRINCIPAL INVESTIGATOR: 
 
ADDRESS OF STUDY SITE(S):  
 
 
CUDC-907-201: “Open-Label, Phase 2 Study to 
Evaluate the Efficacy and Safety of CUDC-907 in 
Patients with Relapsed/Refractory Diffuse Large B-Cell 
Lymphoma, Including Patients with MYC Alterations” 
 
 
 
«Name_of_investigator» 
 
«Study_site_1» 
«Study_site_1_address» 
«Study_site_1_city», «Study_site_1_state» 
«Study_site_1_zip» 
 
TELEPHONE NUMBER(S), DAYTIME: 
AFTER HOURS: 
 
«Site_phone_number» 
«After_hours_number» 
 
 
 
INFORMED CONSENT FOR CUDC-907-201 STUDY 
A. INTRODUCTION 
This is a clinical trial, a type of research study. Your study doctor will explain the clinical trial to 
you. Clinical trials include only people who choose to take part.  Please take your time to make 
your decision about taking part. You may discuss your decision with your friends and family.  
You can also discuss it with your health care team. If you have any questions, you can ask your 
study doctor for more explanation. 


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You are being asked to participate in this study because you have diffuse large B-Cell lymphoma 
that has not responded to or has persisted after receiving up to two but not more than four prior 
therapies. Researchers want to find out if an investigational drug called CUDC-907 can help 
people with your condition. CUDC-907 is intended to block the function of the MYC gene, a 
gene that appears to be important in the growth of cancer cells in your type of lymphoma. We do 
not yet know whether blocking the function of this gene will prove to be an effective treatment 
for lymphoma. 
B. WHY IS THIS STUDY BEING DONE? 
CUDC-907 is an investigational drug that has not been approved by the United States Food and 
Drug Administration (FDA). This is a phase II clinical trial, which means that it is designed to 
test the safety and preliminary effectiveness of an experimental treatment.  
C. HOW LONG WILL THE STUDY LAST AND HOW MANY PEOPLE WILL 
TAKE PART IN THE STUDY? 
About 200 patients are expected to be in this study and it will last about 2 years.  
If you qualify for the study and wish to participate, you may stay on this study and continue to 
receive study treatment until (1) your disease has progressed (worsened), (2) your study doctor 
thinks it is best that you stop treatment, (3) you no longer wish to receive treatment, (4) you are 
not able to keep your study appointments, (5) the study ends (6) you become pregnant, (7) you 
start other treatment for your cancer, (8) if you develop CMV infection at any point during the 
study.  
D. HOW DO I KNOW IF I CAN BE IN THE STUDY? 
Before you can start the study, you will be asked to sign this consent form.  
After you sign the informed consent, you will need to have tests performed and provide 
information about you and your disease to find out if you can take part in the study. 
Some of these tests may be part of your regular medical care for your disease, even if you do not 
join the study. Your study doctor can tell you which of these tests would be part of your regular 
care, even if you do not join the study. 
If you have had some of the tests done recently, you may not need to have them done again; your 
study doctor can tell you which of these tests do not need to be repeated. 
The following tests and information will be needed to determine if you can take part in this 
study:     
1. Your medical history, medicines that you are taking or have taken, and information about 
your gender, age, and race/ethnicity will be recorded.  
2. A physical exam will be done which will include height, weight and vital signs 
(temperature, blood pressure, heart rate and breathing rate). 


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3. You will be asked how well you are able to do your normal activities like bathing, 
driving, shopping and working. 
4. An electrocardiogram (ECG), which records the electrical activity of your heart, will be 
performed. 
5. Blood samples (about 2,5 tablespoons) will be taken for routine tests to check your blood 
counts (numbers of different types of cells in your blood), chemistries (elements and 
minerals in your body),  and how well your organs are functioning. You will also be 
tested for cytomegalovirus (CMV).  Cytomegalovirus (CMV) is a common virus that 
occurs widely throughout the population but rarely causes symptoms.  However, in those 
with weakened immune systems CMV could cause serious illness and death.  People with 
active CMV infection will not be able to participate in this study 
6. If you are a woman who is able to become pregnant, ½ teaspoon of blood or a urine 
sample will be taken for pregnancy testing.  The study doctor or study staff will tell you if 
the pregnancy results are positive.  The results of the pregnancy test must be negative in 
order for you to be in this study. 
7. Testing to determine the current status of your lymphoma. This testing may consist of a 
CT or MRI scan. You may also be asked to have a test called an FDG-PET/CT scan 
which provides different information than the other tests, and can be important for 
judging how well the treatment is working. It is likely that you will be familiar with some 
or all of these tests from your previous treatment. 
8. A sample of your tumor must be available for testing to help predict how your cancer 
might respond to CUDC-907.   
A. A tumor sample that was already obtained from you previously (most recent 
available) may be used for this testing. 
B. Your study doctor can talk with you about what samples of your tumor are 
available for testing and if there is a need to obtain a new sample.  
 If there is a need to obtain a new sample, your study doctor will talk with 
you about the procedure. 
C. Your tumor sample may also be tested for “tumor biomarkers” (parts of your 
tumor that may be used to study and/or measure your disease).  
9. A sample of your blood will be tested to better understand your disease, and these tests 
will include the following:  
o Approximately 1 tablespoon of blood will be used to better understand how genes 
play a role in how your cancer responds to CUDC-907. 


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o Approximately 2 tablespoons of blood will be used to test for “plasma 
biomarkers”, parts of your blood that may be used to study and/or measure your 
disease. 
10. Urinalysis  
11. You have the option to provide a separate sample of your tumor to analyze markers 
related to disease and/or pathways targeted by CUDC-907 (may be taken anytime up to 
first dose). 
It is possible that after the test results are reviewed, you will not be able to take part in the study. 
If this is the case, your study doctor and study staff can talk to you about the reason why you 
cannot take part in the study. 
If you are able to take part in the study and you agree to receive the study drug, you will need to 
come to the study site at various times to have procedures done as described in the next section. 
E. WHAT WILL HAPPEN DURING THE STUDY? 
After you sign the consent form, agreeing to be part of the study; and, the results of your tests 
show that you can be part of the study you will be enrolled into the study. 
After you are enrolled, you will be scheduled to receive study dosing. 
Treatment on the study will be stopped if you are taken off the study, become pregnant, start any 
other anticancer treatment, if you develop CMV infection at any point during the study ,if you 
are unable to keep scheduled study visits or tests, or if the study is stopped. 
  
1. Study Dosing  
a. Study Dosing of CUDC-907  
  
You will be scheduled to take CUDC-907, an investigational agent. CUDC-907 is not approved 
by the FDA or any other drug approving agency to treat your disease. Section F will tell you 
more about the possible risks in taking CUDC-907. 
You will take CUDC-907 by mouth once daily for 5 days in a row with meals ± 30 minutes, then 
for the next 2 days you will not take CUDC-907; this will complete 1 week of study dosing. You 
will repeat this weekly dosing schedule (5 days of dosing with CUDC-907 followed by 2 days of 
no dosing) in a 21-day cycle until your disease has progressed (worsened), your study doctor 
thinks it is best that you stop treatment, or you no longer wish to receive this treatment. CUDC-
907 dosing may be lowered, delayed or suspended if you develop signs of health problems that 
may be caused by CUDC-907.  CUDC-907 will be stopped if you are taken off the study, 
become pregnant, start any other anticancer treatment, if you are unable to keep scheduled study 
visits or tests, or if the study is stopped. 
 


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You will write each dose of CUDC-907 you take in a dosing diary. You will take your dosing 
diary with you to each of your study clinic visits. The study staff will review your dosing diary 
with you on each visit.  
.  
2. Study Visits 
You will be scheduled for regular study visits to complete important study tests and procedures.  
You need to make every effort to attend each scheduled study visit, and complete all scheduled 
tests and procedures for each of these visits, as it will help your study doctor learn how you are 
doing on the study. 
Your study visits will be grouped by Study Cycles; each Study Cycle will be 3 weeks (21 days). 
On Day 1 of the first 6 Study Cycles you will  receive a 3 week supply of CUDC-907 with 
instructions on how to take it.  
After the first 6 Study Cycles, you may keep taking CUDC-907.  If you continue taking CUDC-
907, you will need to return for additional study visits.  More information about these study visits 
is below, under “Study Cycles 7 and Beyond”. 
The following tells about what to expect during each Study Cycle, and each study visit.  
a. Study Visits Cycle 1:  
You will have up to 4 study visits during the first 3 weeks you are on the study; each visit will be 
about a week apart. These first 3 weeks are named Cycle 1, since this is your first 3 weeks of 
CUDC-907 dosing. 
During your first study visit (Cycle 1, Day 1) the following will be done:  
1. A physical exam will be done which will include weight and vital signs (temperature, 
blood pressure, heart rate and breathing rate). You will also be asked about: 
o Your current health and how you are feeling.  
o Any changes in how you are feeling since you last visited the study doctor. 
o Any medicines you are taking, and how long you have been taking them. 
2. You will be asked how well you are able to do your normal activities like bathing, 
driving, shopping and working. 
3. Blood samples (about 2 tablespoons) will be taken for routine tests to check your blood 
counts (numbers of different types of cells in your blood), chemistries (elements and 
minerals in your body), how well your organs are functioning.  
4. Blood sample (about 1 teaspoon) will be taken to measure levels of CUDC-907 and its 
metabolites in your blood 2 hours after the first dose (pharmacokinetics). 
5. If you are a woman who is able to become pregnant, ½ teaspoon of blood or a urine 
sample will be taken for pregnancy testing.  The study doctor or study staff will tell you if 


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the pregnancy results are positive. The results of the pregnancy test must be negative in 
order for you to be in this study. 
6. You will be given a bottle containing capsules of the investigational drug, CUDC-907.  
o You will take CUDC-907 the same time within 30 minutes of eating (at 
approximately the same time each day) on the 5 dosing days.  Every time you take 
your capsules you will need to write it down in your dosing diary. 
o You will take the pill container and the dosing diary with you each time you go to 
a study visit.  
o On days you come into the clinic for study visits, you will take your CUCD-907 
dose while at the clinic rather than at home. 
 
During your second and third study visits (Cycle 1, Days 5 and 12) the following will be done:  
1. A physical exam will be done which will include weight and vital signs (temperature, 
blood pressure, heart rate and breathing rate). You will also be asked about the following: 
o Your current health and how you are feeling.  
o Any changes in how you are feeling since you last visited the study doctor. 
o Any medicines you are taking, and how long you have been taking them. 
2. Blood samples (about 2 tablespoons) will be taken for routine tests to check your blood 
counts (numbers of different types of cells in your blood), chemistries (elements and 
minerals in your body),  and how well your organs are functioning. 
3. Your bottle of CUDC-907 and your dosing diary will be reviewed with you. 
During your fourth study visit (Cycle 1, Day 15) the following will be done:  
1. You will be asked about the following: 
o Your current health and how you are feeling.  
o How you have been feeling since your last study visit. 
o The medicines you are taking, and how long you have been taking them. 
2. A count of capsules in your CUDC-907 bottle and your dosing diary 
o  You will be asked about any problems or questions you may have about taking 
CUDC-907. 
3. Note: If you are within the first 50 subjects to start the study under amendment 4 (your 
Study Doctor will let you know), 2 extra blood samples (each about 1 teaspoon) will be 
required, 2 hours after receiving CUDC-907 on Days 8 and 15 of Cycle 1. These 
samples will be used to measure how much CUDC-907 and its metabolites are in your 
blood (pharmacokinetics). 


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You may have a sample of your tumor taken to analyze markers related to disease and/or 
pathways targeted by CUDC-907 (may be obtained 8 hours post-dose on any dosing day from 
Cycle 1 Day 15 through Cycle 2, Day 1).   
A. Your study doctor will talk with you about how the tissue sample will be taken. 
  
b. Study Visits Cycles 2, 3, 4, 5, and 6: 
After Cycle 1, you will have a study visit every 3 weeks. During these study visits the following 
will be done:  
1. A physical exam will be done which will include weight and vital signs (temperature, 
blood pressure, heart rate and breathing rate). You will also be asked about the 
following: 
o Your current health and how you are feeling.  
o Any changes in how you are feeling since you last visited the study doctor. 
o Any medicines you are taking, and how long you have been taking them. 
2. You will be asked how well you are able to do your normal activities like bathing, 
driving, shopping and working. 
3. A CT or MRI scan will be done to measure your disease every 6 weeks. If your doctor 
considers it necessary, a FDG-PET/CT scan may also be performed.  
4. Blood samples (about 2,5 tablespoons) will be taken for routine tests to check your 
blood counts (numbers of different types of cells in your blood), chemistries (elements 
and minerals in your body), pregnancy test, and how well your organs are functioning. 
You will be tested for CMV infection on Day 1 of every other Cycle starting with Cycle 
2. 
5. A sample of your blood (will be tested to better understand your disease, tests will 
include the following:  
o Approximately 2 tablespoon of blood will be used to test for “plasma 
biomarkers”, parts of your blood that may be used to study and/or measure your 
disease. 
6. If you are a woman who is able to become pregnant, ½ teaspoon of blood or a urine 
sample will be taken for pregnancy testing.  The study doctor or study staff will tell you 
if the pregnancy results are positive. The results of the pregnancy test must be negative 
in order for you to continue in this study. 
7. A count of capsules in your CUDC-907 bottle and your dosing diary will be checked. 
o  You will be asked about any problems or questions you may have about taking 
CUDC-907. 
8. You will be given a new bottle of the investigational drug, CUDC-907.  


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o You will take CUDC-907 the same time once each day within 30 minutes of 
eating a meal for 5 days in a row; then, you will not take CUDC-907 for 2 days in 
a row. This will be repeated (5 days taking CUDC-907, then 2 days not taking 
CUDC-907) on a continuous basis as your study doctor tells you. 
o Every time you take CUDC-907 you will need to write it down in your dosing 
diary. 
o You will take the pill container and the dosing diary with you each time you go to 
a study visit.  
9. On Day 1 of Cycles 4 and 6, a blood sample (about 1 teaspoon) will be taken to measure 
levels of CUDC-907 and metabolites 2 hours after receiving the dose on that day.   
 
a. Study Visits Cycles 7 and Beyond: 
You may keep taking CUDC-907 until the end of study. 
While you are taking CUDC-907 in Cycles 7-13, you will have a study visit every 3 weeks. If 
you continue past Cycle 13 you will only be required to have a Day1 visit at the beginning of 
every other cycle (14, 16, 18, etc). The following will be done at these visits: 
1. A physical exam will be done that includes weight and vital signs (temperature, blood 
pressure, heart rate and breathing rate). You will also be asked about the following: 
o Your current health and how you are feeling.  
o Any changes in how you are feeling since you last visited the study doctor. 
o Any medicines you are taking, and how long you have been taking them 
2. You will be asked how well you are able to do your normal activities like bathing, 
driving, shopping and working 
3. Blood samples (about 2,5 tablespoons) will be taken for routine tests to check your blood 
counts (numbers of different types of cells in your blood), chemistries (elements and 
minerals in your body), pregnancy test and how well your organs are functioning. You 
will continue to be tested for CMV infection on Day 1 of every other Cycle starting with 
Cycle 2 
4. Blood samples (about 1 teaspoon each) will be taken on Day 1 every other cycles (i.e., 
Day 1 of Cycles 8, 10, etc.) starting on Day 1 of Cycle 8, 2 hours after receiving CUDC-
907 on that day.  These samples will be used to measure levels of CUDC-907 and its 
metabolites (pharmacokinetics). 
5. If you are a woman who is able to become pregnant, ½ teaspoon of blood or a urine 
sample will be taken for pregnancy testing.  The study doctor or study staff will tell you if 
the pregnancy results are positive. The results of the pregnancy test must be negative in 
order for you to be in this study. 
6. A sample of your blood (will be tested to better understand your disease, tests will 
include the following:  


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o Approximately 2 tablespoon of blood will be used to test for “plasma 
biomarkers”, parts of your blood that may be used to study and/or measure your 
disease. 
7. A count of capsules in your CUDC-907 bottle and your dosing diary will be checked. 
o  You will be asked about any problems or questions you may have about taking 
CUDC-907 
8. You will be given a new bottle of the investigational drug, CUDC-907.  
o You will take CUDC-907 the same time every day 30 minutes before or after 
eating food at for 5 days in a row; then, you will not take CUDC-907 for 2 days in 
a row. This will be repeated (5 days taking CUDC-907, then 2 days not taking 
CUDC-907) on a continuous basis as your study doctor tells you. 
o Every time you take CUDC-907 you will need to write it down in your dosing 
diary. 
o You will take the pill container and the dosing dairy with you each time you go to 
a study visit.  
9. A CT scan or MRI scan will be done to measure your disease every 4th visit (about every 
12 weeks, or Cycles 10, 14 and 18), until you have complete 12 months of CUDC-907 
dosing. You will then have this same test done every 24 weeks (Cycles 26, 34, etc.) until 
you no longer take CUDC-907. If your doctor considers it necessary, an FDG-PET/CT 
scan may also be performed.  
b. Study Visit After Completing CUDC-907 Dosing (End of Dosing Visit) 
After you complete all study dosing, or discontinue from further treatment, you will be scheduled 
for an end of dosing study visit. The following will be done at this visit: 
1. A physical exam will be done that includes weight and vital signs (temperature, blood 
pressure, heart rate and breathing rate). You will also be asked about the following: 
o Your current health and how you are feeling.  
o Any changes in how you are feeling since you last visited the study doctor. 
o Any medicines you are taking, and how long you have been taking them. 
2. You will be asked how well you are able to do your normal activities like bathing, 
driving, shopping and working. 
3. An electrocardiogram (ECG), which records the electrical activity of your heart, will be 
performed. 
4. If you are a woman who is able to become pregnant, ½ teaspoon of blood or urine sample 
will be taken for pregnancy testing.  The study doctor or study staff will tell you if the 
pregnancy results are positive.  The results of the pregnancy test must be negative in 
order for you to be in this study. 


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5. A CT scan or MRI scan will be done to measure your disease, if this has not been done in 
the last 4 weeks.  If your doctor considers it necessary, a FDG-PET/CT scan may also be 
performed to measure your disease. 
6. Blood samples (about 2 tablespoons) will be taken for routine tests to check your blood 
counts (numbers of different types of cells in your blood), chemistries (elements and 
minerals in your body),  and how well your organs are functioning. 
7. A count of capsules in your CUDC-907 bottle and your dosing diary will be checked. 
o You will be asked about any problems or questions you may have about taking 
CUDC-907. 
c. Follow-Up Visits After All Study Dosing 
After you complete your End of Dosing Visit, you will continue to have about 3 study visits in 
the next 12 months.  
o For the first 6 months after your End of Dosing Visit, you will have a study visit 
every 12 weeks (about 2 visits during this 6 month time). 
o For the next 6 months, you will have a study visit every 24 weeks (about 1 visit 
during this 6 month time).  
The following will be done at these visits:  
1. A physical exam will be done. You will also be asked about the following: 
o Your current health and how you are feeling.  
o Any changes in how you are feeling since you last visited the study doctor. 
o Any medicines you are taking, and how long you have been taking them. 
2. A CT scan or MRI scan will be done to measure your disease. If your doctor considers it 
necessary, a FDG-PET/CT scan may also be performed to measure your disease. 
 
F. WHAT ARE THE POTENTIAL STUDY RISKS AND DISCOMFORTS?  
While on the study, you are at risk for side effects.  You should discuss any side effects that you 
have with the study doctor.  The study doctor may suggest treatment to help make side effects 
less serious and uncomfortable.  Ask the study doctor what treatments you may receive for side 
effects (and any risks these medications may have). 
Many side effects are mild or moderate and go away shortly after the study drug is stopped, but 
in some cases, side effects can be serious, long-lasting or permanent, and in rare cases, fatal 
(causing death). 


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a. What are the Possible Side Effects and Risks of Taking CUDC-907 
CUDC-907 works by inhibiting two enzymes, called HDAC (histone deacetylase) and PI3K 
(phosphoinositide 3-kinase).  Each of these enzymes can cause different types of side effects 
through different mechanisms. 
Studies conducted in animals have shown that CUDC-907 may make you less hungry, lose 
weight, reduce blood cell levels (especially white blood cells); and/or affect your kidneys, 
thymus gland, and the gastrointestinal (GI) tract, which may cause vomiting and diarrhea.  
Over 90 patients have been treated with CUDC-907.  The following potential side effects were 
reported as serious and/or have occurred in 2 or more patients, or resulted in a patient stopping 
CUDC-907 dosing: 
Common (Greater than 20% chance that this will happen) 
 Diarrhea (loose stools) 
 Fatigue (feeling tired) 
 Nausea (feeling sick to your stomach) 
 Decreased appetite (feeling less hungry) 
Occasional (Between a 4 to 20% chance that this will happen) 
 Low platelet counts, which may increase your risk for bleeding (one patient had a serious 
nose bleed) 
 Cough 
 Throat pain 
 Muscle spasms 
 Low white blood cell counts, which may increase your risk for infection 
 Constipation 
 High blood sugar levels, which could be from interference in glucose metabolism 
 Itchy skin 
 Raised body temperature/fever 
 Rash 
 Sinus Congestion 
 Sinus and/or throat infection 
 Back pain 
 Heartburn 


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 Difficulty speaking 
 Bloody nose 
 Numbness 
 Decreased levels of potassium in the blood, which can cause irregular heart beat 
 Low magnesium, which may result in muscle cramps, weakness, tremors or irregular 
heartbeat 
 Low blood pressure 
 Inflammation of the lungs, which can cause shortness of breath and difficulty breathing 
 Lung infection 
 Dehydration 
Your doctor will provide you with medication to take for diarrhea, and will carefully monitor 
your blood test results to see if a treatment break is needed.   
Other commonly reported or serious side effects from drugs that are similar to CUDC-907 are: 
 Stomach and intestinal problems, including diarrhea, nausea, vomiting, weight loss, and 
loss of appetite 
 Fatigue (feeling tired) 
 Chills 
 Anemia (a low red blood cell count that could make you feel tired) 
 Taste changes 
 Increase in blood creatinine, which could indicate kidney damage 
 Increased liver blood tests, which could indicate liver injury 
 Rash 
 Pneumonia (an infection of the lung) 
 Inflammation of the lungs, which could cause difficulty breathing and a cough 
 Neutropenic fever (low white blood counts with fever) 
 Changes in ECG readings, which could indicate damage to the heart 
 
 
 
\ 


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If you do not understand what any of these side effects mean, please ask the study doctor or 
study staff to explain these terms to you. Because CUDC-907 is investigational, all of its side 
effects may not be known. There may be rare and unknown side effects. Some of these may be 
life threatening. You must tell the study doctor or study staff about all side effects that you have. 
Please tell them if you have any other problems with your health or the way you feel during the 
study, whether or not you think they are related to the study drug. 
c. What are the Other Potential Risks and Discomforts in Being in the Study?  
There are potential risks and discomforts with some of the study tests you will need to take; these 
are listed in the following section. Your study doctor and talk to you about these risks and 
answer any questions you may have.   
1. Blood Samples   
Your study doctor or study staff will take your blood by sticking a needle in your arm. You will 
give about 1½ to 5½ tablespoons of blood during each study visit.  There may be side effects of 
having blood drawn such as: 
 Fainting (temporary loss of conscious) 
 Dizziness 
 Pain 
 Bruising  
 Bleeding 
 Infection 
2. Electrocardiogram (ECG): 
The ECG test is harmless. The sticky pads used may sometimes cause some discomfort such as 
redness or itching. If the skin under the patches needs to be shaved, irritation from shaving also 
could occur. 
3. Magnetic Resonance Imaging (MRI): 
An MRI is a way of producing images of body structures and organs. You will lie down on a 
large magnet. A magnetic signal will be sent through your body and then received back. This 
process is safe for most people. Subjects with metal near important organs may not receive an 
MRI. The metal may be drawn away from the body and towards the large magnet, which could 
cause injury. 
4. Computerized Tomography (CT) Scan: 
A CT scan is a computerized picture which is used to find and measure the size of your tumor. 
You may feel some discomfort or anxiety when lying inside of the CT scanner. The dye that is 
injected into your body may cause you to have a metallic taste in your mouth, to feel warm, and 


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rarely cause nausea and vomiting. You will be exposed to a limited and medically acceptable 
dose of radiation during the scan. There is always a slight risk of damage from being exposed to 
any radiation. 
5. FDG-PET/CT Scan:   
You will be asked to fast (no food) for about 4 to 6 hours before the scan.  A small amount of 
radioactive sugar will be injected into your blood about 1 hour before the scan.  You may 
experience discomfort related to lying still in an enclosed space for a long period.  You will be 
exposed to a limited and medically acceptable dose of radiation during the scan.  There is always 
a slight risk of damage from being exposed to any radiation.  
6. Tumor Biopsy: 
Possible side effects from the collection of the tumor biopsy include: 
 Pain 
 Inflammation (redness) 
 Bleeding 
 Swelling 
 Infection  
 There is a rare possibility of tumor cells spreading from the tumor into the nearby area 
7. Allergic Reaction: 
Sometimes people have allergic reactions to drugs.  If you have a very bad allergic reaction, you 
could die.  Some things that happen during an allergic reaction are: 
 Rash  
 Having a hard time breathing 
 Wheezing when you breathe 
 Sudden drop in blood pressure 
 Swelling around the mouth, throat, or eyes 
 Fast pulse 
 Sweating 
You should get medical help and contact the study doctor or study staff if you have any of these 
or any other side effects during the study. 
G. BIRTH CONTROL, DANGERS OF PREGNANCY AND BREASTFEEDING 
Female subjects of Childbearing Age 
You cannot be in this study if you are:  


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 Pregnant 
 Planning to become pregnant during the study 
 Nursing a child 
If you are pregnant or nursing a child while participating in this study, there may be risks to your 
unborn baby or nursing child.  Nobody knows what these risks are right now.  Some drugs cause 
women to have their babies prematurely (early) or to have babies with birth defects. 
If you are a woman who can have children, the study doctor will talk to you about birth control 
methods you must use during the study and for 30 days after your last dose of CUDC-907.   
Some methods of birth control will not work when you are taking certain drugs. 
If you are a woman of child bearing potential the study doctor will require women who join the 
study to have a pregnancy test during screening.  A pregnancy test does not keep you from 
becoming pregnant.   You should not breastfeed your baby while on this study or for 30 days 
after last dose of study drug. 
If you think you are pregnant during the study or within 30 days from receiving your last dose of 
CUDC-907, you must tell the study doctor immediately.  If you become pregnant, you will have 
to leave the study.  The study doctor may ask for information about the pregnancy and the birth 
of the baby.  The study doctor may share this information with the sponsor and the Institutional 
Review Board (IRB). 
Male Subjects Able to Father Children 
If you are a man, there may be risks to an unborn baby you father during or after the study.  The 
study doctor will talk to you about the birth control options you and/or your partner must use 
during the study and for 30 days after your last dose of study drug. If your partner becomes 
pregnant during the study or within 30 days from receiving your last dose of CUDC-907, you 
must tell the study doctor immediately.  The study doctor will contact your partner/spouse to get 
her permission to collect information about the pregnancy and birth of the baby.  If you and/or 
your partner choose not to share this information, it will not result in any penalty or loss of 
benefits to which you are otherwise entitled. 
 
H. 
POSSIBLE BENEFITS OF THE STUDY 
You may receive no benefit by being in this study, but the information learned may help others 
in future studies. There is no promise that your disease will get better. It might stay the same or it 
might get worse. 
I. 
WHAT IF NEW INFORMATION BECOMES AVAILABLE? 
During the research study, you will be notified of newly discovered significant findings that may 
affect your willingness to participate in this study.  In this case, you may be asked to sign a new 


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consent form that shows that you have been informed of new information relating to this 
research study. 
J. 
WHAT HAPPENS IF I EXPERIENCE A STUDY RELATED INJURY? 
In the case of injury or illness resulting from this study, emergency medical treatment will be 
provided.  This study center has no program for financial compensation or other forms of 
compensation for injuries, which you may incur as a result of participation in this study. 
The sponsor may pay for injuries or hospitalizations that are directly related to the study 
drug, as long as those costs are not covered by your health care payer.  
The study doctor and sponsor will decide on a case by case basis whether your injury or illness 
was directly related to the study drug.  You may have to pay the costs of diagnosing and treating 
a condition or injury that you or others think is a direct result of your being in the study.  This 
could happen if: 
 
The sponsor and/or the study doctor do not think the condition or injury is a direct result 
of your being in the study. 
 
You have not followed the directions the study doctor or study staff gave you about the 
study. 
Compensation for other expenses is not routinely available.  You do not give up any of your 
legal rights by signing this form. 
K.  DO YOU HAVE TO BE IN THIS STUDY? 
Your decision to be in this study is voluntary.  You do not have to be in the study if you do not 
want to, and you can change your mind at any time.  There will be no penalty to you, and you 
will not lose any benefits. 
The study doctor or sponsor can remove you from the study at any time, even if you want to stay 
in the study.  This could happen if:  
 The study doctor believes it is best for you to stop being in the study. 
 You are experiencing unacceptable side effects. 
 You develop an active CMV infection 
 You do not follow directions about the study. 
 The sponsor stops the study for any reason. 
 Your disease gets worse. 
If you want to stop being in the study, tell the study doctor or study staff and return all unused 
study drug.  No matter what decision you make, there will be no penalty to you and you will not 
lose any of your regular benefits.  Leaving the study will not affect your medical care. 


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If you stop being in the study early, the study doctor or study staff may ask you some questions 
about being in the study and may continue to follow-up with how you are doing.  To help you 
leave the study safely, the study doctor will ask you to complete the End of Treatment visit.  
RELEASE OF YOUR MEDICAL RECORDS AND CONFIDENTIALITY  
Your records of being in this study will be kept private except when ordered by law.  The 
following people will have access to your study records: 
 Study Doctor 
 Sponsor company or representative 
 The United States Food and Drug Administration (FDA) 
 Other state or federal regulatory agencies 
 Independent Review Board (IRB)  
The groups listed above may inspect and copy your records, which may have your name on 
them.  Therefore, your total privacy cannot be guaranteed.  If the study results are presented at 
meetings or printed in publications, your name will not be used. 
The description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law. The website will not include information that can identify you. At most, 
the website will include a summary of the results. You can search this website at any time. 
L. WHAT OTHER OPTIONS ARE THERE? 
You do not have to be in this study to get help for your condition.  The study doctor will talk to 
you about other things you can do for your condition, including the important risks and benefits.  
Some other things you may be able to do are: 
 
Receive a different drug approved by the FDA for your condition.   
 
Receiving no treatment at this time  
 
Receive care that will not help your disease but may help you feel more comfortable. 
 
Participate in another research study with other investigational drugs. 
M. WILL YOU GET PAID? 
You will not get paid for being in this study. 
N. WHO IS PAYING FOR THIS STUDY? 


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A company called Curis, Inc., the sponsor of the study, is paying for this study.  Curis, Inc. is 
also paying this study center to compensate for institutional research related costs.  
 
WILL IT COST ANYTHING TO BE IN THIS STUDY? 
All clinic fees, professional fees, diagnostic and laboratory fees that are part of this study and are 
done for research purposes only, including some physical examinations, ECGs, some blood 
tests, and pregnancy tests will be provided at no cost to you. The study drug CUDC-907 
will be given to you free of charge while participating in the study.  
Additional costs from procedures not needed by this study will not be paid for by the sponsor. 
You, your insurance company or other third party payers will be responsible for the costs of your 
routine care.  You or your insurance company will have to pay for any medication you take for 
side effects. You should check with your insurance company before you enroll in this research 
study. 
 
WHOM DO YOU CALL IF YOU HAVE QUESTIONS OR PROBLEMS? 
You can ask questions about the study at any time.  You can call the study doctor at any time if 
you have any concerns or complaints.  You should call the study doctor if you have questions 
about the study procedures, study costs (if any), or if you get hurt or sick during the study.    
Questions are encouraged.  If there are any questions about this research study or if you 
experience a research related injury, please contact: [Insert PI and site staff contact info here].  
Questions about the rights of research subjects may be addressed to the [Add IRB contact info 
here]. 
 
 


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TESTING FOR BIOMARKERS 
A. What are biomarkers and how will my samples be used to test them? 
Biomarkers are naturally-occurring substances in the body. Examples of biomarkers include but 
are not limited to: proteins, peptides, or nucleic acid (DNA and RNA) in therapy-related 
biological pathways. Testing to see if biomarkers are present and/or the amount of biomarkers 
present can help to predict patient response (this is what we are mainly interested in), diagnose a 
certain disease, and/or determine the severity of the disease. Biomarker identification for 
lymphoma is a very active research field.  New discoveries can improve the diagnosis and help 
predict patient response to treatment, which is why specific markers will not be listed. However, 
only therapy and indication-related biomarkers will be included in this study.  
Curis would like to use your biological samples in biomarker testing. Your biological samples 
may also be stored for future testing when new biomarkers in lymphoma are identified. Curis, 
not the study doctor, will be conducting the biomarker research.  
Throughout the study, the study doctor will collect samples for biomarkers - genes or proteins 
that may predict or show how your body may respond to CUDC-907.   
B. Optional Tissue Sampling  
Optional tumor biopsies may be taken to test for biomarkers in the tissue before you receive your 
first dose of CUDC-907, and within eight hours after taking one of your CUDC-907 doses on 
Cycle 1 Day 15 through Cycle 2 Day 1.  
These tissue samples are optional and you may choose to have one, none, or multiple tissue 
samples to be taken without any effect on being able to take part in the study.   
1. Would you like to consent to have optional tumor biopsies taken  
(please indicate yes, or no below)? 
Yes: ______     No: ______      
SIGNATURE BY THE SUBJECT  
 
 
 
 
 
 
 
Printed Name of Subject 
Signature of Subject 
Date of Signature 
 
 
C. How will Curis protect your identity? 
Your samples will not have your name on them.  Your samples will be labeled with a code.  The 
code will link your samples to information about the test results.   
D. Where will my biomarker samples go? 


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People who work for Curis, Inc. will store your samples in a secure laboratory.  Tests will be 
performed on these samples, as stated above.  They will store your samples at least 24 months 
after the study is completed or CUDC-907 is no longer being tested in clinical trials.   
E. Will I get the results of my biomarker tests? 
Your test results are for research only.  You will not get your test results.  The test results will 
not be put in your medical records.  Curis will not give your test results to any insurance 
company, your employer, your family, the study doctor, any other doctor, or anyone else, except 
as specified above for research purposes for this study.  The test results are not for personal use, 
like making decisions about your medical care and whether or not to have children. 
F. Will I get payment if Curis makes new tests and medications? 
The samples you give for this biomarker study might help Curis come up with new tests or 
medications in the future.  If Curis makes new tests or medications, you will not get any money 
for these tests or medications.  Curis will own the results of this study and any new tests or 
medications the sponsor makes because of this study. 
 
HIPAA AUTHORIZATION 
 
Federal regulations give you certain rights related to your health information.  These include the 
right to know who will receive the information and how it will be used.  The study doctor must 
obtain your authorization (permission) to use or release any health information that might 
identify you. 
 
As part of the study, the study doctor and his [her] staff at will keep records of your study 
participation. These study records will include the results of tests you have during the study or 
had before the study, information about your response to treatments you have in the study, and 
other medical information about your participation in the study. Under federal law, your study 
records cannot be used or disclosed by [Institution] for research purposes unless you sign this 
authorization. 
 
You may not participate in the study unless you sign this authorization form. If you sign it, you 
will be agreeing to the disclosures below: 
 
Some or all of the test results and other information will be reported to the sponsor and any 
consultants that are helping the sponsor conduct the study. The sponsor and its consultants will 
look at these results and may report the results to the US FDA or agencies in other countries. 
Your study records will be given a code number by the study doctor, and you will not be 
identified by name in the study records that are sent to the sponsor. However, the sponsor will 
have the right to see your complete study records, as well as your medical records, and may 
choose to do so. 
 
The sponsor or study doctor may publish reports or articles on the study, and the sponsor may 
also give your study records to other researchers involved with the study to write reports or 
articles on the study for publication, or for other study-related purposes. However, you will not 


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be identified by name in any reports or articles written by the sponsor or any of the researchers of 
the study. 
 
Also, the Sponsor or its representatives will visit the study site to check on the conduct of the 
study, and they will review your study records and your medical records during these visits. 
 
Health care providers that treat you while you are in this study [or that treated you before you 
came into the study for the condition or disease that is the subject of this study] may give your 
medical records to the study doctor and his [her] staff to look at during the study. 
 
The study doctor and the Institutional Review Board will review and use your study records only 
to monitor the conduct of the study. They will keep your identity confidential and, except for the 
disclosures described above, will not disclose your study records to other people or agencies 
unless required by law. After the study doctor discloses information in your study records or 
medical records to the sponsor, that information may no longer be protected under federal 
privacy protection laws. However, the sponsor will use your information only for the study and 
will not disclose your study records to agencies other than the FDA and and/or other government 
agencies, unless required by law. Your study records will be kept by the study doctor for at least 
2 years from the date of FDA approval of the study drug or, for at least 2 years from the date the 
study drug development is stopped by Sponsor, whichever is longer. You may have access to 
your medical records.  
 
This Authorization does not have an expiration date. If you do not withdraw this Authorization in 
writing, it will remain in effect indefinitely.  
 
You have the right to take back your authorization at any time. You can do this by giving written 
notice to the study doctor, telling him [her] that you are revoking your authorization for the 
sponsor and researchers to use and disclose your medical and study records. The study doctor’s 
contact information is listed on page 1 of this form below.  
 
If you take back your authorization to let the sponsor and/or researchers use and disclose your 
medical and study records, you cannot continue your participation in the study. 
 
If you take back your authorization for any reason, the information that has already been 
collected in your study record may continue to be used and disclosed, but only as needed to 
protect the science of the study.  
 
If you withdraw your permission, no new health information will be gathered unless you have a 
side effect related to the study. 
 
Your decision to withdraw your Authorization or not to participate will not involve any penalty 
or loss of access to treatment or other benefits to which you are entitled. 
 
 
 
 


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02FEB2017 (CUDC-907-201 Version 6.0) 
 
 
By signing below, you are consenting to participate in this research study.  You have read the 
information given or someone has read it to you. You have had the opportunity to ask questions, 
which have been answered satisfactorily to you by the study personnel. You do not waive any of 
your legal rights by signing this consent document. You will be given a copy of the signed and 
dated consent document for your records. 
SIGNATURE BY THE SUBJECT  
 
 
 
 
 
 
 
Printed Name of Subject 
Signature of Subject 
Date of Signature 
 
SIGNATURE BY THE INVESTIGATOR/INDIVIDUAL AUTHORIZED TO OBTAIN 
CONSENT: 
I attest that all the elements of informed consent described in this document have been discussed 
fully in non-technical terms with the subject.  I further attest that all questions asked by the 
subject were answered to the best of my knowledge.   
 
 
 
 
Printed Name of Individual Obtaining Consent 
 
 
 
                                                                                    
Signature of Individual Obtaining Consent 
 
 
______________ 
Date of Signature