A Phase 2 Study Evaluating the Efficacy and Safety of DKN-01 as a Monotherapy or in Combination With Paclitaxel in Patients With Recurrent Epithelial Endometrial, Epithelial Ovarian Cancer, or Carcinosarcoma
Phase: PHASE2
Conditions: Endometrial Cancer, Uterine Cancer, Ovarian Cancer, Carcinosarcoma
Sponsor: Leap Therapeutics, Inc.

Protocol DEK-DKK1-P204 
A Phase 2 Study Evaluating the Efficacy and Safety of DKN-01 as a Monotherapy or in 
Combination with Paclitaxel in Patients with Recurrent Epithelial Endometrial Cancer, Epithelial 
Ovarian Cancer, or Carcinosarcoma 
NCT03395080 
Original Protocol 
17 May 2017 (Version 1.0) 
Amendment 1 
31 July 2017 (Version 2.0) 
Amendment 2 
05 September 2017 (Version 3.0) 
13 September 2017 (Version 3.1) 
Amendment 3 
18 May 2018 (Version 4.0) 
Amendment 4 
13 March 2019 (Version 5.0) 
Amendment 5 
01 July 2020 (Version 6.0) 

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CONFIDENTIAL 
Leap Therapeutics, Inc. 
CLINICAL STUDY PROTOCOL 
Protocol DEK-DKK1-P204 
A Phase 2 Study Evaluating the Efficacy and Safety of DKN-01 as a 
Monotherapy or in Combination with Paclitaxel in Patients With Recurrent 
Epithelial Endometrial Cancer, Epithelial Ovarian Cancer, or Carcinosarcoma 
This study will be conducted according to the protocol and in compliance with 
Good Clinical Practice, the ethical principles stated in the Declaration of Helsinki, 
and other applicable regulatory requirements. 
Study Sponsor: 
Leap Therapeutics, Inc. 
47 Thorndike Street, Suite B1-1 
Cambridge, MA 02141   
Sponsor Signatory 
Cynthia Sirard, MD 
Chief Medical Officer 
Telephone:  617-714-0357 
IND number:  
Document Version: 
135924 
Original Protocol 
Amendment 1 
Amendment 2 
 
Amendment 3 
Amendment 4 
Amendment 5 
17 May2017 (Version 1.0) 
31 July 2017 (Version 2.0) 
05 September 2017 (Version 3.0) 
13 September 2017 (Version 3.1) 
18 May 2018 (Version 4.0) 
13 March 2019 (Version 5.0) 
01 July 2020 (Version 6.0) 
CONFIDENTIALITY NOTE: 
This document contains information that is confidential and proprietary to Leap Therapeutics, Inc. This 
information is being provided to you solely for the purpose of evaluation and/or conducting a clinical trial 
for Leap Therapeutics, Inc. You may disclose the contents of this document only to study personnel under 
your supervision and/or to your institutional review board(s) or ethics committee(s) who need to know the 
contents for this purpose and who have been advised on the confidential nature of the document. 

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Leap Therapeutics, Inc. 
SIGNATURE PAGE 
Protocol Title: 
A Phase 2 Study Evaluating the Efficacy and Safety of DKN-01 as 
a Monotherapy or in Combination with Paclitaxel in Patients With 
Recurrent Epithelial Endometrial Cancer, Epithelial Ovarian 
Cancer, or Carcinosarcoma 
Protocol Number: 
DEK-DKK1-P204 
Protocol Version: 
6.0 
 
REVIEWED/APPROVED BY: 
 
 
 
 
 
 
 
 
 
Cynthia Sirard, MD 
 
 
Chief Medical Officer 
Leap Therapeutics, Inc. 
Signature  
Date 
 
Cynthia Sirard
Electronically signed by: Cynthia Sirard
Reason: person(s) who reviewed and are
responsible to approve document
Date: Jul 1, 2020 14:53 EDT
07/01/2020

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Leap Therapeutics, Inc. 
INVESTIGATOR STATEMENT 
I understand that all documentation provided to me by Leap Therapeutics, Inc. or its designated 
representative(s) concerning this study that has not been published previously will be kept in the 
strictest confidence. This documentation includes the study protocol, Investigator’s Brochure, 
case report forms, and other scientific data. 
This study will not commence without the prior written approval of a properly constituted 
Institutional Review Board or Ethics Committee. No changes will be made to the study protocol 
without the prior written approval of Leap Therapeutics, Inc. and the Institutional Review Board 
or Ethics Committee, except where necessary to eliminate an immediate hazard to the patient. 
I have read, understood, and agree to abide by all the conditions and instructions contained in 
this protocol. 
 
 
 
Investigator Name 
 
Investigator Signature 
 
Date 
 
Name and address of investigational site / institution  
(please print) 
 

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Leap Therapeutics, Inc. 
CLINICAL STUDY SYNOPSIS 
Name of Sponsor: 
Leap Therapeutics, Inc.  
Name of Investigational 
Product: 
DKN-01 
Protocol Title: 
A Phase 2 Study Evaluating the Efficacy and Safety of DKN-01 as a 
Monotherapy or in Combination with Paclitaxel in Patients With 
Recurrent Epithelial Endometrial Cancer, Epithelial Ovarian Cancer, 
or Carcinosarcoma 
Protocol Number: 
DEK-DKK1-P204 
Study Phase: 
2 
Study Centers: 
Approximately 20 study centers 
Objectives: 
This study employs a “basket” design to concurrently investigate 
DKN-01 as monotherapy and in combination with paclitaxel in 
patients with recurrent epithelial endometrial cancer (EEC), epithelial 
ovarian cancer (EOC), or carcinosarcoma (malignant mixed Mullerian 
tumor [MMMT]) (see Study Design for details). Thus, 6 distinct 
patient groups are being independently investigated:  
1. DKN-01 monotherapy in recurrent EEC (Group 1) 
2. DKN-01+paclitaxel in recurrent EEC (Group 2) 
3. DKN-01 monotherapy in recurrent EOC (Group 3) 
4. DKN-01+paclitaxel in recurrent EOC (Group 4) 
5. DKN-01 monotherapy in recurrent carcinosarcoma (MMMT) 
(Group 5)  
6. DKN-01+paclitaxel in recurrent carcinosarcoma (MMMT) 
(Group 6)  
The primary objective in each independent study group (Groups 1-4) 
is: 
• 
To determine the objective response rate (ORR). 
Secondary objectives in each independent study group (Groups 1-4) 
are: 
• 
To determine the objective disease control rate (ODCR). 
• 
To determine overall survival (OS). 
• 
To determine progression-free survival (PFS). 

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• 
To evaluate additional measures of efficacy, including time to 
progression (TTP), duration of response (DoR), duration of 
complete response (DoCR), duration of clinical benefit 
(DoCB), and time to treatment failure (TTTF).  
• 
To evaluate the safety of the study treatment regimen. 
• 
To characterize the pharmacokinetics (PK) of DKN-01 as 
monotherapy and in combination with paclitaxel in patients 
with recurrent EEC or EOC.  
• 
To detect anti-DKN-01 antibodies in human serum.  
The primary objectives in each independent study group (Groups 5-6) 
are: 
• 
To characterize the safety of DKN-01 600 mg ± paclitaxel in 
patients with recurrent carcinosarcoma (MMMT). 
• 
To identify the recommended Phase 2 dose (RP2D) of 
DKN-01 ± paclitaxel in patients with recurrent 
carcinosarcoma (MMMT) based on safety, PK, and 
pharmacodynamics (PcD). 
Secondary objectives in each independent study group (Groups 5-6) 
are: 
• 
To determine the ORR. 
• 
To determine the ODCR. 
• 
To determine overall OS. 
• 
To determine PFS. 
• 
To evaluate additional measures of efficacy, including TTP, 
DoR, DoCR, DoCB, and TTTF.  
• 
To characterize the PK of DKN-01 as monotherapy and in 
combination with paclitaxel in patients with recurrent 
carcinosarcoma (MMMT).  
• 
To detect anti-DKN-01 antibodies in human serum.  
The exploratory objectives in each independent study group 
(Groups 1-6) are: 
• 
To evaluate response to therapy in patients with and without 
activating β-catenin mutations and/or Wnt signaling genetic 
alterations. 
• 
To evaluate Dickkopf-1 (DKK1) concentration in serum and 
plasma relative to safety and efficacy outcomes. 

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• 
To evaluate tumor genetics, gene expression levels (e.g., 
RNA-Seq), DKK1 expression (e.g., RNAscope in situ 
hybridization), immunohistology, infiltrating immune cells 
and additional immunohistochemistry (IHC) staining (DKK1 
and associated downstream elements [e.g., β-catenin]) on 
tumor tissue relative to safety and efficacy outcomes. 
Endpoints: 
 
Efficacy: 
The primary efficacy endpoint in each independent study group 
(Groups 1-4) is: 
• 
ORR (i.e., best overall response [BOR] of complete response 
[CR] + partial response [PR]), as assessed by the Investigator 
using the Response Evaluation Criteria in Solid Tumors, 
version 1.1 (RECIST 1.1) (Eisenhauer et al. 2009). 
Secondary efficacy endpoints in each independent study group 
(Groups 1-4) are: 
• 
ODCR (i.e., CR+PR+ stable disease [SD] > 6 weeks), as 
assessed by the Investigator using RECIST 1.1. 
• 
OS, defined as the time from first study drug dose (i.e., 
Cycle 1, Day 1 [C1D1]) to death from any cause.  
• 
PFS, defined as the time from first study drug dose (C1D1) to 
first radiographically-documented progressive disease (PD), as 
determined using RECIST 1.1, or death due to any cause. 
• 
TTP, defined as the time from first study drug dose (C1D1) 
until the date of first radiographically-documented PD, as 
determined using RECIST 1.1. 
• 
DoR, defined as the time from initial response (≥PR) until 
radiographically-documented PD or death; PD is defined 
using RECIST 1.1. 
• 
DoCR, defined as the time from initial CR until 
radiographically-documented PD or death; PD is defined 
using RECIST 1.1. 
• 
DoCB, defined as the time from the first tumor assessment of 
CR, PR or SD to the time of PD, as determined using RECIST 
1.1, or death due to any cause. 
• 
TTTF, defined as the time from first study drug dose (C1D1) 
until the date of treatment discontinuation of DKN-01 for any 
reason, including PD, toxicity, and death. 

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In support of objectives relating to an investigation of the safety and 
clinical effectiveness of a DKN-01 dose exceeding 300 mg, the 
secondary endpoints for Group 5 and Group 6 are equivalent to those 
specified as efficacy endpoints for Groups 1-4.   
Safety: 
Safety endpoints in each independent study group are: 
• 
Incidence of treatment-emergent adverse events (TEAEs), 
Grade 3 /4 / 5 TEAEs, serious adverse events (SAEs), and 
TEAEs leading to study drug discontinuation. 
• 
Incidence of treatment-emergent Grade 3 / 4 clinical 
laboratory abnormalities. 
• 
Incidence of infusion reactions. 
• 
Changes from baseline in clinical laboratory parameters 
(serum chemistry, hematology, coagulation, and urinalysis). 
• 
Changes from baseline in vital signs and electrocardiogram 
(ECG) parameters. 
• 
Shift from baseline in Eastern Cooperative Oncology Group 
(ECOG) performance status.  
In support of objectives relating to an investigation of the safety and 
clinical effectiveness of a DKN-01 dose exceeding 300 mg, the 
primary endpoints for Group 5 and Group 6 include those specified as 
safety endpoints. In addition, the evaluation of the higher DKN-01 
dose will also be based on a review of pharmacokinetic and 
pharmacodynamic data. 
Additionally, for Groups 5 and 6: 
• 
Incidence of DLTs. 
Pharmacokinetic:  
• 
Peak drug concentration (Cmax), time to peak concentration 
(Tmax), and areas under the concentration-time curve (AUCs). 
Immunogenicity (ADA): 
• 
Anti-DKN-01 antibodies. 

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Exploratory: 
The exploratory endpoints in each independent study group are: 
• 
DKK1 concentration in serum and plasma relative to safety 
and efficacy outcomes. 
• 
Tumor genetics, gene expression levels (e.g., RNA-Seq), 
DKK1 expression (e.g., RNAscope in situ hybridization), 
immunohistology, infiltrating immune cells and additional 
IHC staining (e.g., DKK1 and associated downstream 
elements, [e.g., β-catenin]) on tumor tissue relative to safety 
and efficacy outcomes 
Study Design: 
Study DEK-DKK1-P204 is a Phase 2 basket study designed to 
evaluate DKN-01 activity either in combination with paclitaxel or as a 
monotherapy in patients with recurrent EEC or recurrent 
platinum-resistant/refractory EOC, or recurrent carcinosarcoma 
(MMMT) who have received at least one prior systemic therapy for 
advanced disease. Note that this basket study is enriching for 
activating β-catenin mutations and/or Wnt signaling alterations (see 
Screening). A maximum of 124 evaluable patients aged 18 years or 
older with histologically-confirmed recurrent EEC or recurrent 
platinum-resistant/refractory EOC, or recurrent carcinosarcoma 
(MMMT) requiring therapy will be enrolled in the study.  
Patients who are not eligible to receive paclitaxel, as determined by 
the Investigator, will be enrolled in the monotherapy group by primary 
tumor. Four distinct patient groups are being enrolled with up to 
21 evaluable patients in Groups 1, 3, and 4, up to 31 evaluable patients 
in Group 2, up to 10 evaluable patients in Group 5, and up to 
20 evaluable patients in Group 6. 
Group 1: DKN-01 monotherapy in recurrent EEC 
Group 2: DKN-01+paclitaxel in recurrent EEC 
Group 3: DKN-01 monotherapy in recurrent EOC 
Group 4: DKN-01+paclitaxel in recurrent EOC 
Group 5: DKN-01 monotherapy in recurrent carcinosarcoma 
(MMMT) 
Group 6: DKN-01+paclitaxel in recurrent carcinosarcoma 
 
(MMMT) 
Groups 1-4 employ a 2-stage design conducted separately for each 
group. For each monotherapy group (Groups 1 and 3), after 
12 evaluable patients are enrolled (Stage 1), an additional 9 evaluable 
patients will be enrolled in that group (Stage 2) if 1 or more patients 
respond (i.e., experience CR or PR). If there are no responses in Stage 

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1, then preliminary anti-tumor activity in the group will be rejected 
and no further patients will be enrolled in that group. For the EEC 
combination therapy group (Group 2), after 20 evaluable patients are 
enrolled (Stage 1), if 3 or more patients respond (i.e., experience CR 
or PR), an additional 11 evaluable patients will be enrolled in that 
group (Stage 2). If there are fewer than 3 responses in Stage 1, then 
preliminary anti-tumor activity in the group will be rejected and no 
further patients will be enrolled in that group. For the EOC 
combination therapy group (Group 4), after 16 evaluable patients are 
enrolled (Stage 1), if 2 or more patients respond (i.e., experience CR 
or PR), an additional 5 evaluable patients will be enrolled in that group 
(Stage 2). If there are fewer than 2 responses in Stage 1, then 
preliminary anti-tumor activity in the group will be rejected and no 
further patients will be enrolled in that group. 
Groups 5 and 6 are exploratory in nature. Group 5 will enroll 
approximately 10 evaluable patients and Group 6 will enroll 
approximately 20 evaluable patients. 
For Groups 5 and 6, 3 patients in each group will initially be enrolled 
in a safety run-in phase. If the first 2 of 3 patients in a group have a 
dose-limiting toxicity (DLT), the maximum tolerated dose (MTD) will 
have been exceeded and a cohort will be enrolled to evaluate DKN-01 
at a dose of 300 mg (±paclitaxel, depending on group assignment) (see 
Synopsis Dose-Limiting Toxicity Determination and Maximum 
Tolerated Dose Definition). If none of the 3 treated patients in a 
group develop a DLT after a minimum of one cycle of treatment, 
enrollment into the group will proceed according to the planned 
schedule. If a DLT is observed in 1 of the 3 patients in a group, up to 
an additional 3 patients will be enrolled and treated. If no further 
DLTs are observed within the expanded group of 6, enrollment into 
the group will proceed. If ≥2 of 6 patients within a group experience a 
DLT, the MTD will have been exceeded and a cohort will be enrolled 
to evaluate DKN-01 at a dose of 300 mg (±paclitaxel, depending on 
group assignment). 
For the Rollover Treatment Phase, patients remain on the same dose 
and schedule as they received in the previous study part. 
 
The study has 6 distinct periods, as follows: 
Screening 
Potentially eligible patients will sign informed consent prior to 
undergoing any study-related procedures. Patients will undergo 
Screening assessments for protocol eligibility within 28 days of study 
entry, as outlined in Table 6.  

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Fresh tumor tissue samples are required to be collected from all 
patients during Screening for genomic cancer profiling (i.e., CTNNB1 
mutation and Wnt-signaling mutation), gene expression levels (e.g., 
RNA-Seq), DKK1 expression (e.g., RNAscope in situ hybridization), 
immunohistology, infiltrating immune cells and additional IHC 
staining (DKK1 and associated downstream elements, [e.g., 
β-catenin]). Although fresh biopsy is preferred, an archived specimen 
collected within 3 months of C1D1 may be acceptable, with the prior 
approval of the Medical Monitor. 
This basket study is enriching for activating β-catenin mutations 
and/or Wnt signaling alterations, whereby approximately 50% of all 
evaluable patients enrolled in each group, in Stage 1 and in Stage 1 
and 2 combined (Groups 1-4) and in Groups 5 and 6, are required to 
have an activating β-catenin mutation (CTNNB1 mutation) or other 
Wnt signaling alteration (e.g., LRP5/6, APC, AXIN1/2, GSK3B, 
RNF43, ZNRF3, RSPO2/3, FBXW7, ARID1A, or CBP/CREBBP; see 
full list in Appendix 12.6), based on testing of the Screening tumor 
tissue sample or previously documented alteration by a Clinical 
Laboratory Improvement Amendments (CLIA)-accredited laboratory.  
To allow-for real-time testing of Screening tumor tissue samples, the 
Screening period may be extended to 42 days, with results obtained 
and confirmed to be positive before the performance of additional 
Screening procedures. Note that all other Screening assessments must 
be performed within 28 days before C1D1.  
Patients with prior documentation of a known activating β-catenin 
mutation (CTNNB1 mutation) or other Wnt signaling alteration by a 
CLIA-accredited laboratory will be permitted to enroll based on this 
documentation. In such patients, a Screening tumor sample will be 
collected and analyzed centrally; however, confirmatory results are not 
required for study enrollment. 
Groups 1-4 employ a 2-stage design conducted separately for each 
group. For each monotherapy group (Groups 1 and 3), once 
6 evaluable patients are enrolled who do not have activating β-catenin 
mutation and/or Wnt signaling alterations, Stage 1 enrollment for that 
group will continue only with patients with activating β-catenin 
mutation and/or Wnt signaling alterations. For combination therapy 
Group 2, once 10 evaluable patients are enrolled who do not have 
activating β-catenin mutation and/or Wnt signaling alterations, Stage 1 
enrollment for that group will continue only with patients with 
activating β-catenin mutation and/or Wnt signaling alterations. For 
combination therapy Group 4, once 8 evaluable patients are enrolled 
who do not have activating β-catenin mutation and/or Wnt signaling 

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alterations, Stage 1 enrollment for that group will continue only with 
patients with activating β-catenin mutation and/or Wnt signaling 
alterations. At any time for Groups 1, 3, or 4, once 10 evaluable 
patients who do not have a documented activating β-catenin mutation 
and/or other Wnt signaling alteration have been enrolled in a group, 
enrollment in that group will continue only with patients with 
activating β-catenin mutation (CTNNB1 mutation) or other identified 
Wnt signaling alteration.  
At any time for Group 2, once 15 evaluable patients who do not have a 
documented activating β-catenin mutation and/or other Wnt signaling 
alteration have been enrolled, enrollment in that group will continue 
only with patients with activating β-catenin mutation (CTNNB1 
mutation) or other identified Wnt signaling alteration. 
 
Study Treatment Period 
The Study Treatment Phase includes either DKN-01 monotherapy or 
DKN-01 in combination with paclitaxel; patients will be assigned to 
receive monotherapy or combination therapy at the Investigator’s 
discretion. Patients who initially start combination therapy but 
subsequently discontinue paclitaxel may continue to receive DKN-01 
as monotherapy during the Treatment Period. 
Patients are to begin study treatment as soon as possible (and 
preferably within 24 hours) after completion of all screening 
procedures and confirmation of study eligibility. Study visits will be 
performed as outlined in Table 6.  
During the Treatment Period, tumor measurements are to be 
performed using the same radiographic methods used during 
Screening. Tumor response, including PD, is to be assessed by the 
Investigator within ±7 days of the first study drug dose in every other 
cycle, starting in C3, and at the End of Treatment (EOT) Visit using 
RECIST 1.1.  
The severity of TEAEs will be graded according to the United States 
National Cancer Institute Common Terminology Criteria for Adverse 
Events (NCI CTCAE), version 5.0. 
Rollover Treatment Phase 
The Rollover Treatment Phase will permit patients who are still 
experiencing clinical benefit continued access to study drug(s) until 
they meet discontinuation criteria as per Section 6.4.1. Study visits 
will be performed as outlined in Table 7. 
Study Treatment Discontinuation 

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All patients will continue study treatment in the Treatment Phase until 
development of radiographically-documented PD or unacceptable 
toxicity or another discontinuation criterion is met, as determined by 
the Investigator. All patients will return for an EOT Visit 
approximately 30 days (+7 days) after the last treatment administration 
in the Treatment Period. The reason for discontinuation from study 
treatment will be documented in the electronic case report form 
(eCRF). 
Progressive Disease Follow-up Phase 
To ensure accuracy and completeness for the disease response-related 
endpoints, patients who permanently discontinued study treatment 
prior to PD will continue to be followed up in the PD follow-up phase 
until radiographically documented PD.  
During this PD follow-up period, efficacy assessments for disease 
response and PD per RECIST 1.1 will be performed every 8 weeks 
[see Table 6 and (Table 7 for the Rollover Treatment Phase only)]. 
Patients are expected not to start any other anti-cancer therapy during 
the PD follow-up phase prior to radiographically documented PD; 
however, if alternate therapy is started, patients will continue to be 
followed for radiologic progression even after starting subsequent 
therapy. After radiographically-documented PD, all patients will be 
followed for survival in the Survival Follow-up Phase.  
Survival Follow-up Phase 
After discontinuation of treatment and radiographic documentation of 
PD, all patients will be followed in the survival follow-up phase for 
survival until death, withdrawal of consent, loss to follow-up, 
implementation of the rollover treatment phase, or closure of the study 
by the Sponsor. Survival follow-up will occur 4 times per year (every 
12 weeks [±14 days]) after the EOT visit or end of PD Follow-up 
Phase, as applicable, and may be conducted via telephone or office 
visit. During survival follow-up, the following information will be 
collected: survival and subsequent anti-cancer therapies. 

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Dose-Limiting Toxicity 
Determination and Maximum 
Tolerated Dose/Recommended 
Phase 2 Dose Definitions: 
A DLT is defined as an AE during C1 that is possibly related to the 
study drug(s) and fulfills any one of the following criterion using the 
NCI CTCAE version 5.0. 
• 
Grade 4 neutropenia lasting ≥ 5 days or Grade 3 or 4 
neutropenia with fever and/or infection 
• 
Grade 4 thrombocytopenia (or Grade 3 with bleeding) 
• 
Grade 4 anemia 
• 
Grade 3 or 4 non-hematological toxicity (excluding Grade 3 
vomiting and Grade 3 diarrhea including the clinical sequelae 
[e.g., electrolyte abnormalities] despite optimal supportive 
care and excluding alopecia) 
• 
Dosing delay greater than 14 days due to treatment-emergent 
AEs or related severe laboratory abnormalities 
• 
Grade 3 hypersensitivity reaction to DKN-01 with 
premedication (Grade 3 hypersensitivity reaction to DKN-01 
without premedication is not considered a DLT) 
• 
Grade 4 hypersensitivity reaction to DKN-01 with or without 
premedication 
• 
Any Grade 5 AE 
• 
Any treatment-related AE that causes the patient to 
discontinue treatment during C1. 
A drug-related fever ≤ Grade 3 will not be considered a DLT. 
Patients in Group 6 must have completed 100% of the DKN-01 doses 
and 75% of the paclitaxel doses in C1 to be evaluable for DLT. 
Furthermore, in any study part, if a patient experiences a TEAE 
meeting the definition of DLT in the first cycle of treatment, he/she 
will be discontinued from study treatment. 
The MTD is defined as the highest tested dose level below the dose 
level at which a DLT is seen in 2 or more patients. 
The RP2D is defined as the MTD or up to the highest planned dose 
level evaluated in Groups 5-6 without identification of the MTD. 
Number of Patients Planned: 
A maximum of 124 evaluable patients are planned to be enrolled, with 
up to 21 evaluable patients in Groups 1, 3, and 4; up to 31 evaluable 
patients in Group 2, up to 10 evaluable patients in Group 5, and up to 
20 evaluable patients in Group 6. 

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Diagnosis and Main Criteria for 
Inclusion: 
Patients meeting all of the following criteria will be considered 
eligible for study entry: 
Epithelial Endometrial Cancer 
1. Must have a histologically confirmed diagnosis (by either 
primary surgical specimen or biopsy for recurrence) of 
recurrent previously treated EEC. 
Epithelial Ovarian Cancer 
2. Must have a histologically confirmed diagnosis (by either 
primary surgical specimen or biopsy for recurrence) of 
recurrent platinum-resistant/refractory EOC, primary 
peritoneal, or fallopian tube cancer (i.e., disease recurrence 
within 6 months of completion of or progression during 
platinum-based chemotherapy). 
Carcinosarcoma/Malignant Mixed Mullerian Tumors 
(Groups 5-6) 
3. Must have a histologically confirmed diagnosis (by either 
primary surgical specimen or biopsy for recurrence) of 
recurrent uterine or ovarian carcinosarcoma (MMMT). 
4. Patient must have had only 1 prior chemotherapeutic regimen 
for management of recurrent or advanced carcinosarcoma that 
may have included chemotherapy (including in adjuvant 
setting with refractory or disease recurring within 6 months), 
chemotherapy and radiotherapy, and/or 
consolidation/maintenance therapy.  
General 
5. Must be refractory or intolerant to at least one prior standard 
therapy(ies) for metastatic or locally advanced disease (see 
Inclusion Criterion #4 for Groups 5-6). 
a. 
If prior therapy consisted of palliative 
chemoradiation therapy, it will be considered one 
line of therapy. 
b. 
Prior treatment with paclitaxel as part of a definitive 
therapy regimen is acceptable, provided the patient 
is not intolerant of paclitaxel. 
c. Patients who are not eligible to receive paclitaxel will 
be allowed to receive single agent DKN-01. 
6. Tumor tissue for mandatory pre-treatment and on–treatment 
evaluation (fresh biopsy during Screening preferred; archived 

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specimen (≤3 months) may be acceptable with prior approval 
from the Medical Monitor).  
7. One or more tumors measurable on radiographic imaging as 
defined by RECIST 1.1. 
8. Ambulatory and ≥18 years of age. 
9. ECOG performance status (PS) of 0 or 1. 
a. PS of 2 on the ECOG scale may be eligible upon the 
review and approval of the Medical Monitor. 
10. Estimated life expectancy of at least 3 months, in the 
judgment of the Investigator. 
11. Disease-free of active second/secondary or prior 
malignancies for ≥2 years with the exception of currently 
treated basal cell, squamous cell carcinoma of the skin, or 
carcinoma in-situ of the cervix or breast. 
12. Acceptable liver function: 
a. Total bilirubin ≤2.0 × upper limit of normal 
(ULN). 
b. Aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT) ≤2.5 × ULN. If liver 
metastases are present, then ≤5 × ULN is allowed. 
13. Acceptable renal function: 
a. Creatinine normal for age: if serum creatinine is 
abnormal for age the patient must have a calculated 
creatinine clearance ≥30 mL/min using the 
Cockcroft and Gault Method (Cockroft and Gault 
1976). 
14. Acceptable hematologic status: 
a. Granulocyte ≥1500 cells/mm3. 
b. Hemoglobin ≥9 g/dL (transfusion permitted within 
30 days of study entry). 
c. Platelet count ≥75,000 cells/mm3. 
15. Acceptable coagulation status: 
a. Prothrombin time (PT)/partial thromboplastin time 
(PTT) ≤1.2 × ULN (unless receiving 
anticoagulation therapy, in which case, eligibility 
will be based upon International Normalized Ratio 
[INR], see below). 

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b. If receiving anticoagulant: INR ≤3.0 and no active 
bleeding, (i.e., no clinically significant bleeding 
within 14 days prior to first dose of study therapy). 
16. Females of child-bearing potential and male partners of 
female patients must agree to use adequate contraception 
(hormonal or barrier method of birth control) during the 
study and for 6 months after their last dose of study drug. 
Should a patient become pregnant or suspect she is pregnant 
while participating in the study, the Investigator should be 
immediately informed. 
17. Reliable and willing to make themselves available for the 
duration of the study and are willing to follow study-
specific procedures. 
18. Provided written informed consent prior to any study-
specific procedures. 
Rollover Treatment Phase: 
19. Received DKN-01 either as a monotherapy or in 
combination with paclitaxel in this study and is tolerating 
study drug(s) and currently displaying clinical benefit, in 
the Investigator’s opinion. 
 
Exclusion Criteria: 
Patients meeting any of the following criteria are not eligible for study 
entry: 
1. Any of the following pure histologies of endometrial or 
ovarian cancer: germ cell, sex cord stroma, or sarcoma. 
2. New York Heart Association Class III or IV cardiac disease, 
myocardial infarction within the past 6 months, or unstable 
arrhythmia. 
3. Have Fridericia-corrected QT interval (QTcF) >470 msec, 
or history of congenital long QT syndrome. Any ECG 
abnormality that in the opinion of the Investigator would 
preclude safe participation in the study; patients with 
pacemakers where QTc is not a reliable measure will 
require an evaluation by a cardiologist to exclude co-
existing cardiac conditions which would prohibit safe 
participation in the study. 
4. Active, uncontrolled bacterial, viral, or fungal infections, 
within 7 days of study entry requiring systemic therapy. 

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5. Known to be human immunodeficiency virus (HIV) 
positive, have hepatitis B surface antigen (HBSAg), or 
hepatitis C antibodies (HCAb), unless hepatitis C virus 
ribonucleic acid (HCV RNA) undetected/negative. 
6. History of major organ transplant (i.e., heart, lungs, liver, or 
kidney). 
7. History of autologous/allogenic bone marrow transplant. 
8. Serious nonmalignant disease that could compromise 
protocol objectives in the opinion of the Investigator and/or 
Sponsor. 
9. Pregnant or nursing. 
10. History of osteonecrosis of the hip or evidence of structural 
bone abnormalities in the proximal femur on MRI scan that 
are symptomatic and clinically significant. Degenerative 
changes of the hip joint are not exclusionary. Screening of 
asymptomatic patients is not required. 
11. Symptomatic central nervous system (CNS) malignancy or 
metastasis. Patients with treated CNS metastases are 
eligible provided their disease is radiographically stable, 
asymptomatic, and they are not currently receiving 
corticosteroids and/or anticonvulsants. Screening of 
asymptomatic patients without a history of CNS metastases 
is not required.  
12. Known osteoblastic bony metastasis. Screening of 
asymptomatic patients without a history of metastatic bony 
lesions is not required. 
Medication-Related 
13. Treatment with surgery or chemotherapy within 21 days 
prior to study entry (42 days for nitrosoureas or mitomycin 
C). 
14. Any hormonal therapy directed at the malignant tumor must 
be discontinued at least one week prior to study entry. 
15. Clinically significant peripheral neuropathy at the time of 
study entry. Patients with pre-existing peripheral 
neuropathy will be allowed to receive single agent DKN-01. 
16. History of hypersensitivity reactions to paclitaxel or other 
drugs formulated in Cremophor® EL (polyoxyethylated 
castor oil). Patients who exhibit these hypersensitivities will 
be eligible to receive single agent DKN-01. 

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17. Prior radiation therapy within 14 days prior to study entry. 
18. Currently receiving any other investigational agent or 
received an investigational agent within last 30 days of 
study entry. 
19. Previously treated with an anti-DKK1 therapy. 
20. Significant allergy to a pharmaceutical therapy that, in the 
opinion of the Investigator, poses an increased risk to the 
patient. 
Lifestyle-Related 
21. Active substance abuse. 
Test Products, Doses, and Mode 
of Administration: 
The study treatment regimens for Groups 1-4 are: 
• 
DKN-01 monotherapy:  DKN-01 300 mg on D1 and 15 every 
28 days. 
• 
DKN-01+paclitaxel:  DKN-01 300 mg on D1 and 15 + 
paclitaxel 80 mg/m2 on D1, 8, and 15 every 28 days. 
The study treatment regimens for Groups 5-6 are: 
• 
DKN-01 monotherapy:  DKN-01 600 mg on D1 and 15 every 
28 days. 
• 
DKN 01+paclitaxel:  DKN-01 600 mg on D1 and 15 + 
paclitaxel 80 mg/m2 on D1, 8, and 15 every 28 days. 
DKN-01 will be administered intravenously (IV) over a minimum of 
30 minutes and up to a maximum of 2 hours given on D1 and 15 of 
each cycle without interruption.  
For patients receiving DKN-01 in combination, paclitaxel will be 
administered IV over 1 hour on days 1, 8, and 15 of each 28-day cycle 
according to standard clinical practice. The dose for paclitaxel is 
80 mg/m2. For patients receiving the combination, DKN-01 will be 
administered first followed by paclitaxel as separate infusions on D1 
and 15 of each cycle.  
Additionally, for Groups 5 and 6, 3 patients in each group will initially 
be enrolled in a safety run-in phase. If the first 2 of 3 patients in a 
group have a DLT, the MTD will have been exceeded and a cohort 
will be enrolled to evaluate DKN-01 at a dose of 300 mg (±paclitaxel, 
depending on group assignment) (see Synopsis Dose-Limiting 
Toxicity Determination and Maximum Tolerated Dose Definition). 
If none of the 3 treated patients in a group develop a DLT after a 
minimum of one cycle of treatment, enrollment into the group will 
proceed according to the planned schedule. If a DLT is observed in 

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1 of the 3 patients in a group, up to an additional 3 patients will be 
enrolled and treated. If no further DLTs are observed within the 
expanded group of 6, enrollment into the group will proceed. If ≥2 of 
6 patients within a group experience a DLT, the MTD will have been 
exceeded and a cohort will be enrolled to evaluate DKN-01 at a dose 
of 300 mg (±paclitaxel, depending on group assignment). 
Premedication for paclitaxel will be given according to local standard 
of care prior to each infusion. Suggested premedications include 
dexamethasone 20 mg orally [PO] 12 to 6 hours prior; 
diphenhydramine 50 mg IV 30 to 60 minutes prior; and cimetidine or 
ranitidine 50 mg IV 30 to 60 minutes prior) or equivalents. 
For the Rollover Treatment Phase, patients remain on the same dose 
and schedule as they received in the previous study part.  
Duration of Treatment: 
No maximum duration of treatment has been set; patients may 
continue treatment until the development of PD or unacceptable 
toxicity or another discontinuation criterion has been met. 
Duration of Study: 
It is estimated that the total study duration will be approximately 
36 months, assuming a 24-month accrual period and 12 months 
of follow-up for the last patient enrolled. Patients who are still 
experiencing clinical benefit will continue to have access to 
study drug(s) in the Rollover Treatment Phase, until they meet 
discontinuation criteria as per Section 6.4.1. 
Sample Size Calculation: 
This is a proof-of-concept basket study designed primarily to seek 
information on the safety and efficacy of DKN-01 in combination with 
paclitaxel and as DKN-01 monotherapy in patients with recurrent EEC 
or EOC with and without activating β-catenin mutation and/or Wnt 
signaling alterations, or carcinosarcoma (MMMT). A maximum of 
124 evaluable patients (monotherapy groups and combination groups) 
will be enrolled in the study. This is an exploratory open-label study 
with 6 groups. Groups 1-4 employ a 2-stage study design conducted 
separately for each group. Up to 21 evaluable patients are enrolled in 
each of Groups 1, 3, and 4, and up to 31 evaluable patients in Group 2. 
Groups 5 and 6 are exploratory in nature and will have up to 10 and 
20 evaluable patients enrolled and dosed at the RP2D, respectively. 
The sample sizes of 10 and 20 patients for Groups 5 and 6, 
respectively, are based on practical considerations and clinical 
judgement to obtain sufficient information on the safety, initial clinical 
effectiveness, and PK data in the carcinosarcoma groups at the 600-mg 
dose. 
The sample size of Groups 1 through 4 employ a 2-stage study design 
and were calculated as follows: For each monotherapy group (Groups 

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1 and 3), after 12 evaluable patients are enrolled (Stage 1), an 
additional 9 evaluable patients will be enrolled in that group (Stage 2) 
if 1 or more patients respond (i.e., experience CR or PR). If there are 
no responses in Stage 1, then preliminary anti-tumor activity in the 
group will be rejected and no further patients will be enrolled in that 
group. If the group continues to Stage 2, a total of 21 evaluable 
patients will be studied for that group. The group will be considered 
successful if ≥3 treated patients respond.  
This design is applied to each monotherapy group separately and is 
based on a 2-stage Simon Minimax design (Simon 1989) for a total of 
21 evaluable patients (null hypothesis that ORR ≤5% versus the 
alternative hypothesis that ORR ≥20% with alpha=0.080 and 
power=0.803).  
For combination therapy Group 2, after 20 evaluable patients are 
enrolled (Stage 1), an additional 11 evaluable patients will be enrolled 
in that group (Stage 2) if 3 or more patients respond (i.e., experience 
CR or PR). If there are fewer than 3 responses in Stage 1, then 
preliminary anti-tumor activity in the group will be rejected and no 
further patients will be enrolled in that group. If the group continues to 
Stage 2, a total of 31 evaluable patients will be studied for that group. 
The group will be considered successful if ≥6 treated patients respond. 
This design is applied to combination therapy Group 2 separately and 
is based on a 2-stage Simon Minimax design for a total of 
31 evaluable patients (null hypothesis that ORR ≤12% versus the 
alternative hypothesis that ORR ≥25% with alpha=0.150 and 
power=0.802). 
For combination therapy Group 4, after 16 evaluable patients are 
enrolled (Stage 1), an additional 5 evaluable patients will be enrolled 
in that group (Stage 2) if 2 or more patients respond (i.e., experience 
CR or PR). If there are fewer than 2 responses in Stage 1, then 
preliminary anti-tumor activity in the group will be rejected and no 
further patients will be enrolled in that group. If the group continues to 
Stage 2, a total of 21 evaluable patients will be studied for that group. 
The group will be considered successful if ≥4 treated patients respond. 
This design is applied to combination therapy Group 4 separately and 
is based on a 2-stage Simon Minimax design for a total of 
21 evaluable patients (null hypothesis that ORR ≤10% versus the 
alternative hypothesis that ORR ≥25% with alpha=0.149 and 
power=0.803).  
There are no formal comparisons planned between groups. Any 
statistical results will be interpreted in the perspective of the 
exploratory nature of the study.  

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Analysis Populations: 
Study Population Definitions  
Several study populations will be used for analysis, as follows:  
• 
Evaluable Analysis Set (EAS): All patients who received any 
amount of DKN-01 and have at least one evaluable post-
baseline RECIST tumor response assessment or were 
discontinued due to toxicity.  
The EAS will be the primary population for analyses of ORR, 
ODCR, PFS, DoR, DoCR, DoCB, and TTP. 
• 
Full analysis set (FAS): All enrolled patients who receive any 
amount of DKN-01. The FAS will be used for analyses of OS, 
TTTF, sensitivity analysis of select tumor-related endpoints, 
and exploratory endpoints. 
• 
Safety population, defined as all enrolled patients who receive 
any amount of study treatment (either DKN-01 or paclitaxel). 
All safety analyses will be based on this population. The 
safety population and FAS are identical, unless a patient 
received paclitaxel but did not receive DKN-01. 
• 
A Per-Protocol (PP) subset may also be used to analyze select 
efficacy endpoints and will be based on study drug exposure 
(compliance and/or time on study drug) and major protocol 
deviations. The criteria for inclusion in the PP subset will be 
finalized and documented. The PP set will be defined and 
finalized separately for each group. 
• 
PK Analysis Set: All enrolled patients who receive at least a 
single dose of DKN-01 and have sufficient data to determine 
PK parameters. 

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Statistical Methodology: 
General Considerations 
Summaries will be tabulated for each group and within each group, 
where applicable, by presence of Wnt signaling alterations and/or 
CTNNB1 activating mutations. Select parameters may also be 
summarized by dose and will be detailed in the Statistical Analysis 
Plan (SAP). 
Descriptive statistics (N, mean, standard deviation, median, minimum, 
and maximum) will be presented for continuous variables. Frequency 
distributions (counts and associated percentages) will be presented for 
categorical variables. Median, 25th and 75th percentiles and standard 
error will be presented for time-to-event data. 
This study is descriptive in nature; no formal comparisons between 
groups will be performed. All confidence intervals (CIs) will be 95%, 
unless stated otherwise. 
Individual patient data listings will be provided to support summary 
tables.  
The effects of noncompliance, treatment discontinuations, premature 
study withdrawals, subsequent therapies, and covariates will be 
assessed to determine the impact on the general applicability of results 
from this study. 
 
Efficacy Analysis 
Efficacy data will be summarized for each group. Selected summaries 
may also be done within each group, as applicable, by presence of 
Wnt signaling alterations and/or CTNNB1 activating mutations, and 
by subgroups as described in the SAP. The EAS will be the primary 
population for analysis of ORR, ODCR, PFS, DoR, DoCR, DoCB, 
and TTP. Secondary and exploratory analyses of efficacy endpoints 
(including OS and TTTF) will be performed using the FAS.  
The proportion of patients with ORR and ODCR, along with a 95% CI 
based on the Clopper-Pearson interval, will be reported. The 
Kaplan-Meier method will be used to summarize OS, PFS, TTP, 
TTTF, DoR, DoCR, and DoCB. The Investigator disease response 
assessments according to RECIST 1.1 will be used as the primary 
measures for analysis. 

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Safety Analyses 
All safety analyses will be conducted in the safety population and 
presented by group.  
Adverse events (AEs) will be coded according to the current version 
of the Medical Dictionary for Regulatory Activities (MedDRA). The 
severity of AEs will be graded according to the United States NCI 
CTCAE, version 5.0. 
Treatment-emergent adverse events (TEAEs) are defined as any AE 
with onset or (worsening of a pre-existing condition) after the first 
dose of study drug through 30 days following the last dose of study 
drug. Events including TEAEs, AEs leading to dose 
reduction/interruption, AEs related to study drug, SAEs, AEs leading 
to study drug discontinuation, and AEs with an outcome of death will 
be summarized by system organ class and preferred term for each 
treatment group. A summary of AEs of NCI CTCAE Grade 3 or 
higher, as well as the most frequent AEs (preferred terms), and AEs by 
relationship to study treatment, will be provided.  
For Groups 5 and 6, incidence of DLTs will be summarized. 
Number and percent of patients with infusion-related reactions will be 
summarized by group, overall and by visit.  
Values and changes from baseline in clinical laboratory results will be 
summarized by visit. Clinical laboratory values will be graded 
according to the NCI CTCAE, for applicable tests. Shifts in toxicity 
grades from baseline grade will be summarized. Shifts from baseline 
in ECOG performance status also will be summarized.  
Vital sign, ECG, and concomitant medication data will be 
summarized. 
PK Analyses 
Peak drug concentration (Cmax), time to peak concentration (Tmax), and 
areas under the concentration-time curve (AUCs) will be reported, as 
feasible. Data may be pooled with data from other studies to conduct 
population PK modeling. 
Immunogenicity Analyses 
Details regarding immunogenicity analyses will be provided in the 
SAP. 
Exploratory Analyses 
Exploratory analysis will be evaluated for exploratory endpoints. 
Details for these exploratory analyses will be provided in the SAP. 

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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ADA 
Anti-DKN-01 antibodies  
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ALP 
Alkaline phosphatase 
ANC 
Absolute neutrophil count 
AST 
Aspartate aminotransferase  
AUC 
Area under the serum concentration-time curve 
BOR 
Best overall response 
BP 
Blood pressure 
BSA 
Body surface area 
BUN 
Blood urea nitrogen 
C1D1 
Cycle 1, Day 1 (pattern set for cycle and days [e.g., C1D8, C2D1, etc.]) 
CI 
Confidence interval 
CK 
Creatine kinase 
Cmax 
Peak drug concentration in serum / plasma 
CEA 
Carcinoembryonic antigen 
CLIA 
Clinical Laboratory Improvement Amendments 
CL/F (or CL) 
Apparent systemic clearance 
CNS 
Central nervous system 
CR 
Complete response 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
D 
Day 
DKK1 
Dickkopf-1 
DLT 
Dose-limiting toxicity 
DoCB 
Duration of clinical benefit 
DoCR 
Duration of complete response 
DoR 
Duration of response 
EAS 
Evaluable analysis set 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 

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Abbreviation 
Definition 
EEC 
Epithelial endometrial carcinoma 
ELISA 
Enzyme-linked immunosorbent assay 
EOC 
Epithelial ovarian carcinoma 
EOT 
End of Treatment 
FDG-PET 
Fludeoxyglucose-positron emission tomography 
GCP 
Good Clinical Practice 
HEENT 
Head, eyes, ears, nose, and throat 
HBSAg 
Hepatitis B surface antigen  
HCAb 
Hepatitis C antibodies 
HCV RNA 
Hepatitis C virus ribonucleic acid 
HIV 
Human immunodeficiency virus 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization 
IgG4 
Immunoglobulin G4 
IHC 
Immunohistochemistry 
IRB / IEC 
Institutional review board / Independent ethics committee 
INR 
International normalized ratio 
IV 
Intravenous(ly) 
Leap 
Leap Therapeutics, Inc. 
LD 
Longest diameter 
LDH 
Lactate dehydrogenase 
Mab 
Monoclonal antibody 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
Mg 
Milligram 
MM 
Multiple myeloma  
MMMT 
Malignant mixed Mullerian tumor 
MRI 
Magnetic resonance imaging 
MTD 
Maximum tolerated dose 
NCI 
National Cancer Institute 
NE 
Not evaluable 
NLR 
Neutrophil-to-lymphocyte ratio 
NSCLC 
Non-small cell lung cancer 

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Abbreviation 
Definition 
ODCR 
Objective disease control rate 
ORR 
Objective response rate 
OS 
Overall survival 
PcD 
Pharmacodynamic(s) 
PD 
Progressive disease 
PET 
Positron emission tomography 
PFS 
Progression-free survival 
PK 
Pharmacokinetic 
PP 
Per population 
PR 
Partial response 
PS 
Performance status 
PT/PTT 
Prothrombin time / Partial thromboplastin time 
QW 
Once weekly 
Q2W 
Once every 2 weeks 
QTcF 
Fridericia-corrected QT interval 
RBC 
Red blood cells 
RDW 
Red blood cell distribution width 
RECIST 1.1 
Response Evaluation Criteria in Solid Tumors, Version 1.1 
RP2D 
Recommended Phase 2 dose 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Stable disease 
SI 
Système internationale d'unités (International System of Units) 
TEAE 
Treatment-emergent adverse event 
TTP 
Time to progression 
TTTF 
Time to treatment failure 
ULN 
Upper limit of normal 
WBC 
White blood cells 
WMA 
World Medical Association 
 

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TABLE OF CONTENTS 
SIGNATURE PAGE .................................................................................................................... ii 
INVESTIGATOR STATEMENT ............................................................................................. iii 
CLINICAL STUDY SYNOPSIS ............................................................................................... iv 
LIST OF ABBREVIATIONS ................................................................................................ xxiv 
TABLE OF CONTENTS ...................................................................................................... xxvii 
LIST OF TABLES IN THE TEXT ...................................................................................... xxxii 
LIST OF FIGURES IN THE TEXT .................................................................................... xxxii 
1. 
Introduction ...................................................................................................................... 1 
1.1. 
Background .......................................................................................................... 1 
1.1.1. 
DKN-01 .................................................................................................. 1 
1.1.2. 
Dickkopf-1 (DKK1) ................................................................................ 1 
1.1.3. 
Wnt/β-Catenin Signaling Pathway and Gynecological 
Cancers.................................................................................................... 2 
1.2. 
Rationale and Justification for the Study .......................................................... 2 
1.3. 
Rationale for the Dose Selected .......................................................................... 3 
1.4. 
Justification of the Study Design ........................................................................ 8 
2. 
Study Objectives and Endpoints..................................................................................... 9 
2.1. 
Study Objectives................................................................................................... 9 
2.1.1. 
Primary Objective ................................................................................... 9 
2.1.2. 
Secondary Objectives ............................................................................. 9 
2.1.3. 
Exploratory Objectives ......................................................................... 10 
2.2. 
Study Endpoints ................................................................................................. 10 
2.2.1. 
Efficacy Endpoints ................................................................................ 10 
2.2.2. 
Safety Endpoints ................................................................................... 11 
2.2.3. 
Pharmacokinetic Endpoint .................................................................... 11 
2.2.4. 
Immunogenicity Endpoint .................................................................... 12 
2.2.5. 
Exploratory Endpoints .......................................................................... 12 
3. 
Investigational Plan ....................................................................................................... 13 
3.1. 
Overall Design and Plan of the Study .............................................................. 13 
3.2. 
Study Periods ...................................................................................................... 14 
3.2.1. 
Screening .............................................................................................. 14 

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3.2.2. 
Study Treatment Period ........................................................................ 15 
3.2.3. 
Rollover Treatment Phase ..................................................................... 15 
3.2.4. 
Study Treatment Discontinuation ......................................................... 16 
3.2.5. 
Progressive Disease Follow-up Phase .................................................. 16 
3.2.6. 
Survival Follow-up Phase ..................................................................... 16 
3.3. 
Study Termination ............................................................................................. 16 
4. 
Study Population ............................................................................................................ 18 
4.1. 
Number of Patients ............................................................................................ 18 
4.2. 
Inclusion Criteria ............................................................................................... 18 
4.3. 
Exclusion Criteria .............................................................................................. 20 
5. 
Study Treatments ........................................................................................................... 22 
5.1. 
Clinical Trial Materials ..................................................................................... 22 
5.1.1. 
DKN-01 ................................................................................................ 22 
5.1.2. 
Paclitaxel ............................................................................................... 22 
5.2. 
Blinding, Packaging and Labeling ................................................................... 22 
5.2.1. 
Blinding and Breaking the Blind .......................................................... 22 
5.2.2. 
Packaging and Labeling ........................................................................ 22 
5.3. 
Method of Assigning Patients to Treatment .................................................... 22 
5.4. 
Study Drug Accountability and Disposal ......................................................... 23 
5.5. 
Assessment of Treatment Compliance ............................................................. 23 
5.6. 
Administration of Study Drug(s) ...................................................................... 23 
5.6.1. 
DKN-01 Administration ....................................................................... 24 
5.6.2. 
Paclitaxel Administration ..................................................................... 24 
5.6.3. 
Rollover Treatment Phase ..................................................................... 25 
6. 
Treatment of Patients .................................................................................................... 26 
6.1. 
Criteria for Initiation of a New Treatment Cycle ........................................... 26 
6.1.1. 
Criteria for Treatment on Days 8 and 15 of a Treatment 
Cycle ..................................................................................................... 26 
6.2. 
Dosing Modifications, Reductions and Re-escalations, and Delays .............. 26 
6.2.1. 
DKN-01 Dosing and Dose Adjustments ............................................... 26 
6.2.2. 
Paclitaxel Dosing and Dose Adjustments ............................................. 27 
6.2.3. 
Dose Delays .......................................................................................... 28 

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6.3. 
Duration of Study Participation and Treatment............................................. 29 
6.4. 
Withdrawal and Replacement of Patients ....................................................... 29 
6.4.1. 
Withdrawal from Treatment or the Study ............................................. 29 
6.4.2. 
Replacement of Study Patients ............................................................. 30 
6.5. 
Concomitant Medications, Therapies and Supportive Care .......................... 30 
7. 
Study Assessments ......................................................................................................... 32 
7.1. 
Clinical Procedures and Safety Assessments ................................................... 32 
7.1.1. 
Informed Consent ................................................................................. 32 
7.1.2. 
Inclusion / Exclusion Criteria Review .................................................. 32 
7.1.3. 
Demographics, Medical and Disease History ....................................... 32 
7.1.4. 
Physical Examination ........................................................................... 32 
7.1.5. 
Vital Signs and Weight ......................................................................... 33 
7.1.6. 
Electrocardiograms ............................................................................... 33 
7.1.7. 
Eastern Cooperative Oncology Group Performance Status 
(ECOG PS) ........................................................................................... 33 
7.1.8. 
Clinical Laboratory Evaluations ........................................................... 33 
7.1.9. 
Concomitant Medications / Procedures Review ................................... 35 
7.1.10. 
Adverse Event Monitoring.................................................................... 35 
7.1.11. 
Medical Events of Interest .................................................................... 35 
7.2. 
Blood Sample Collection for Pharmacokinetics, 
Pharmacodynamics, and Exploratory Assessments ....................................... 36 
7.2.1. 
Blood Sample Collection for DKK1 ..................................................... 36 
7.2.2. 
Pharmacokinetic Samples ..................................................................... 36 
7.2.3. 
Samples for Immunogenicity Research ................................................ 36 
7.2.4. 
Samples for Exploratory Biomarkers ................................................... 37 
7.3. 
Tumor Tissue Samples ...................................................................................... 37 
7.4. 
Efficacy and Response Assessments ................................................................. 38 
7.5. 
Post-Treatment Follow-up and Mortality Assessments ................................. 38 
8. 
Adverse Events ............................................................................................................... 40 
8.1. 
Definitions, Documentation, and Reporting .................................................... 40 
8.1.1. 
Adverse Event Definition ..................................................................... 40 
8.1.2. 
Serious Adverse Event Definition ........................................................ 40 

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8.2. 
Procedures for Recording and Reporting AEs and SAEs .............................. 41 
8.3. 
Monitoring of Adverse Events and Period of Observation ............................ 43 
9. 
Statistical Considerations .............................................................................................. 44 
9.1. 
Sample Size Determination ............................................................................... 44 
9.2. 
Randomization ................................................................................................... 45 
9.3. 
Populations for Analysis .................................................................................... 45 
9.4. 
Procedures for Handling Missing, Unused and Spurious Data ..................... 45 
9.5. 
Interim Analyses ................................................................................................ 45 
9.6. 
Statistical Methods ............................................................................................. 46 
9.6.1. 
General Methods ................................................................................... 46 
9.6.2. 
Disposition of Patients .......................................................................... 46 
9.6.3. 
Baseline Characteristics ........................................................................ 46 
9.6.4. 
Efficacy Analysis .................................................................................. 47 
9.6.5. 
Safety Analysis ..................................................................................... 49 
9.6.6. 
Pharmacokinetic Analyses .................................................................... 50 
9.6.7. 
Immunogenicity Analyses .................................................................... 50 
9.6.9. 
Procedures for Reporting Deviations to the Original 
Statistical Analysis Plan........................................................................ 51 
10. 
Administrative Requirements ....................................................................................... 52 
10.1. Good Clinical Practice ....................................................................................... 52 
10.2. Ethical Considerations....................................................................................... 52 
10.3. Patient Information and Informed Consent .................................................... 52 
10.4. Patient Confidentiality....................................................................................... 52 
10.5. Protocol Compliance .......................................................................................... 52 
10.6. Direct Access to Source Data ............................................................................ 53 
10.7. Case Report Form Completion ......................................................................... 53 
10.8. Record Retention ............................................................................................... 53 
10.9. Liability and Insurance ..................................................................................... 54 
10.10. Publication of Study Findings and Use of Information .................................. 54 
11. 
References ....................................................................................................................... 55 
12. 
Appendices ...................................................................................................................... 59 
12.1. Schedule of Assessments .................................................................................... 60 

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12.2. Response Evaluation Criteria in Solid Tumors (RECIST) Quick 
Reference Guide ................................................................................................. 66 
12.3. NCI-CTCAE v 5.0 Infusion-related Reactions ................................................ 72 
12.4. Management of DKN-01 Infusion-related Reactions ..................................... 73 
12.5. Management of DKN-01-related Adverse Reactions ...................................... 74 
12.6. Wnt Signaling Alterations ................................................................................. 77 
12.7. Declaration of Helsinki ...................................................................................... 78 
 

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LIST OF TABLES IN THE TEXT 
Table 1 
DKN-01 Dose Adjustments for Groups 1-4 .................................................................... 27 
Table 2  
DKN-01 Dose Adjustments for Groups 5 and 6 .............................................................. 27 
Table 3 
Paclitaxel Dose Modifications for Peripheral Neuropathy .............................................. 28 
Table 4 
Paclitaxel Dose Modifications for Neutropenia and Thrombocytopenia ......................... 28 
Table 5 
Paclitaxel Dose Adjustments ........................................................................................... 28 
Table 6 
Schedule of Assessments ................................................................................................. 60 
Table 7 
Schedule of Assessments- Rollover Treatment Phase ..................................................... 64 
 LIST OF FIGURES IN THE TEXT 
Figure 1 
Predicted Maximal Free Serum DKK1 (Cmax) Concentrations after 300 mg 
DKN-01 IV Dosing Administered Once Every Two Weeks (Q2W) ................................. 4 
Figure 2 
Predicted Maximal Free Serum DKK1 (Cmax) Concentrations after 600 mg 
DKN-01 IV Dosing Administered Once Every Two Weeks (Q2W) ................................. 5 
 
 
 

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1. 
INTRODUCTION 
1.1. 
Background 
1.1.1. 
DKN-01 
DKN-01 (formerly known as LY2812176) is a potent humanized monoclonal antibody (Mab) 
(immunoglobulin G4 [IgG4]) with neutralizing activity against dickkopf-1 (DKK1), a modulator 
of Wnt signaling pathways that influences a number of important processes such as cell growth 
and differentiation, bone development, and adult bone homeostasis (Sato et al. 2010; 
Gavriatopoulou et al. 2009; Vallet et al. 2010; Pinzone et al. 2009). DKN-01 is in development 
as an anti-cancer agent and is being investigated in a variety of solid tumors. 
To date, DKN-01 has been evaluated in a 30-subject healthy volunteer study and in 
approximately 167 patients with cancer in 5 clinical studies. Results from completed Phase 1 
Study DEK-DKK1-P100, in which DKN-01 was administered as monotherapy to patients with 
cancer at doses up to 600 mg every other week, demonstrated an acceptable safety profile. 
Based on these results, clinical evaluation of DKN-01 in combination was initiated, with DKN-
01 also shown to be well tolerated when administered in combination with commercially 
available anti-neoplastic agents. Across all studies, there have been no safety concerns 
identified that relate to significant injection site reactions or systemic infusion reactions. 
Furthermore, there have been no known undesirable effects identified with administration of 
DKN-01. DKN-01 has been observed to be well-tolerated over multiple treatment cycles.  
Evidence of an anti-tumor effect of DKN-01 as a monotherapy has been seen in patients with 
non-small cell lung cancer (NSCLC). Additionally, evidence of an anti-tumor effect has been 
seen with DKN-01 in combination in patients with esophageal cancer, particularly those with 
adenocarcinoma of the esophagus or gastro-esophageal junction who had received fewer lines 
of therapy, and in patients with biliary tract cancer. 
Full information on DKN-01 is provided in the Investigator’s Brochure. 
1.1.2. 
Dickkopf-1 (DKK1) 
Wnt signaling is a multifaceted pathway that regulates stem cell maintenance, cell fate 
decisions, cell proliferation, survival, migration, and polarity determination during development 
and adult tissue homeostasis (Logan and Nusse 2004; MacDonald et al. 2009; Clevers and 
Nusse 2012; Clevers et al. 2014; Sedgwick and D'Souza-Schorey 2016). DKK1 is a secreted 
modulator of Wnt signaling and is best characterized as an antagonist of the canonical 
Wnt/β-catenin signaling pathway, however it has also been implicated in the activation of 
noncanonical Wnt signaling pathways and PI3K/AKT signaling (Niehrs et al. 2006; Wang and 
Zang 2011; Kimura et al. 2016).  
DKK1 protein, is over-expressed in a variety of tumor types and this is associated with a poor 
prognosis such as decreased overall survival (OS) of cancer patients, including NSCLC, 
esophageal cancer, breast cancer, cholangiocarcinoma, liver cancer, and ovarian cancer 
(Shizhuo et al. 2009; Tung et al. 2011; Xu et al. 2012; Shi et al. 2013; Hiss 2012). DKK1 has 
direct tumor effects by increasing tumor growth, metastasis, and angiogenesis and through 
favoring a stem cell-like phenotype (Smadja et al. 2010; Krause et al. 2014; Malladi et al. 2016; 
Thudi et al. 2011). Furthermore, DKK1 has been implicated in promoting an 

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immunosuppressive tumor microenvironment by activating myeloid derived suppressor cells 
and through the downregulation of NK activating ligands on cancer cells (D’Amico et al. 2016; 
Malladi et al. 2016). Based on these data, neutralizing DKK1 has been hypothesized to not only 
directly impede tumor growth but also promote an anti-tumor immune response.  
1.1.3. 
Wnt/β-Catenin Signaling Pathway and Gynecological Cancers 
Elevated levels of DKK1 have been observed in patients with gynecological cancer (Jiang et 
al. 2009; Chamorro et al. 2005; Shizhuo et al. 2009; Wang and Zang 2011). Assessment of 
DKK1 levels in the sera of 104 patients with gynecological cancer, including ovarian (N=36), 
cervical (N=40), and endometrial (N=28) cancers, revealed significantly higher DKK1 levels in 
patients with either cervical cancer (314.13 pg/mL, p < 0.001) or with endometrial cancer 
(46.95 pg/mL, p < 0.001) relative to healthy individuals (29.45 [11.86] pg/mL). Furthermore, 
the serum levels of DKK1 were associated with clinical stage in all patients in this study (Jiang 
et al. 2009). 
Mutations of CTNNB1, the gene that encodes β-catenin, have been identified in a high 
percentage of patients with endometrioid endometrial carcinoma and low-grade endometrioid 
ovarian carcinoma (Liu et al. 2014; McConechy et al. 2014). CTNNB1 mutations that are 
associated with active canonical Wnt/β-catenin signaling have been identified in an aggressive 
subset of endometrioid endometrial carcinoma occurring in younger women (Lui et al. 2014). 
Activation of canonical Wnt/β-catenin signaling that can occur through CTNNB1 mutations 
leads to increased expression of DKK1 and this may further promote tumor growth (Chamorro 
et al. 2005; Niida et al. 2004; Chen et al. 2016; Bu et al. 2008). Furthermore, patients with 
tumors that co-stain for β-catenin, a marker of active canonical Wnt/β-catenin signaling, and 
DKK1 frequently have a worse prognosis (Yu et al. 2009; Xu et al. 2012; Chen et al. 2014). 
Taken together these results suggest that patients with activated Wnt/β-catenin signaling may 
benefit from a DKK1 neutralizing therapy.  
1.2. 
Rationale and Justification for the Study 
Molecular subtyping of cancers may inform diagnosis, prognosis, and selection of appropriate 
targeted therapies. The development of molecular-targeted therapies has been a growing area of 
interest for the treatment of both endometrioid ovarian carcinoma (Matsuzaki et al. 2015; 
Banerjee and Kay 2013; Bast 2011; Hiss 2012; Twu and Han 2012; Sudo 2012; Weberpals et al. 
2011) and endometrioid endometrial carcinoma (Uppendahl et al. 2017; Bookman et al. 2014; 
Bansal et al. 2009), with a number of potential targets identified. Molecularly-targeted agents 
hold the promise of greater selectivity with lower toxicity than conventional chemotherapy 
(Banerjee 2013).  
As stated previously, CTNNB1 mutations have been seen both in patients with endometrioid 
endometrial carcinoma and endometrioid ovarian carcinoma (Liu et al. 2014; McConechy et al. 
2014; Markowska et al. 2014). Furthermore, high expression levels of DKK1 have been 
observed in patients with gynecological cancers, including ovarian and endometrial (Jiang et al. 
2009). Activation of canonical Wnt/β-catenin signaling that can occur through CTNNB1 
mutations is associated with increased expression of DKK1 (Chamorro et al. 2005; Niida et al. 
2004; Chen et al. 2016; Bu et al. 2008). Furthermore, patients with tumors that co-stain for β-

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catenin, a marker of active canonical Wnt/β-catenin signaling, and DKK1 frequently have a 
worse prognosis (Yu et al. 2009; Xu et al. 2012; Chen et al. 2014).  
This study will enroll patients with either epithelial endometrial cancer (EEC) or epithelial 
ovarian cancer (EOC) (Groups 1-4), or carcinosarcoma (malignant mixed Mullerian tumor 
[MMMT]) (Groups 5-6) and for all groups will enrich for activating β-catenin mutations 
(CTNNB1 mutation) or other Wnt signaling alterations (e.g., LRP5/6, APC, AXIN1/2, GSK3B, 
RNF43, ZNRF3, RSPO2/3, FBXW7, ARID1A, or CBP/CREBBP; see full list in Appendix 
12.6), whereby approximately 50% of all patients enrolled are required to have such mutations 
or alterations.   
DKN-01 will be administered as monotherapy or, at the Investigator’s discretion, in 
combination with paclitaxel in the current study. Paclitaxel is indicated as first-line and 
subsequent treatment in advanced ovarian cancer and has been studied extensively in patients 
with endometrial cancer and is recommended as a chemotherapeutic option in this disease 
setting (NCCN Guidelines Version 1.2017; Bestvina and Flemming 2016).  
1.3. 
Rationale for the Dose Selected 
DKN-01 will be administered at a dose of 300 mg (Groups 1-4) or 600 mg (Groups 5 and 6) 
intravenously (IV) on Days (D) 1 and 15 every 28 days either as monotherapy or, at the 
Investigator’s discretion, in combination with paclitaxel.  
DKN-01 is selective for the DKK1 member of the dickkopf family. It binds human DKK1 with 
high affinity and, as a consequence, potently neutralizes DKK1. The levels of the protein DKK1 
are elevated in a variety of tumor types and have been implicated in tumor growth and disease 
progression. A preclinical NSCLC A549 xenograft model study demonstrated that suppression 
of free (unbound) DKK1 concentrations correlated with an inhibition of tumor growth. 
A target-mediated disposition model was utilized to fit the clinical DKN-01/DKK1 
concentration data. The model incorporated two DKN-01 clearance pathways, one non-specific 
(linear) clearance pathway, and one target-mediated (nonlinear) clearance that included 
saturable binding to DKK1. The resulting one-target model assumed quasi-equilibrium (QE) 
and was utilized to simultaneously fit both total DKN-01 and total DKK1 serum concentrations. 
This approach was used to assess the degree of target engagement (formation of the DKN01/ 
DKK1 complex) by DKN-01 and the resulting suppression of free DKK1 concentrations in 
serum.  
Based on modeling in combination with xenograft results, DKK1 neutralization (lower free 
DKK1) was associated with maximal tumor growth inhibition in an A549 xenograft study (see 
Investigators Brochure, Section 5.1.6). In order to relate these preclinical results to clinical data, 
model simulations were generated to predict human clinical DKN-01 and the resulting free 
DKK1 serum concentrations after IV drug administration once every 2 weeks (Q2W). These 
simulations focused on the maximal concentration for free DKK1 (DKK1 peak drug 
concentration [Cmax]) over the Q2W dosing interval. The initial baseline value of free DKK1 
was approximately 5.4 ng/mL (data not shown). The graphs below demonstrate that DKK1 Cmax 
is substantially reduced (relative to baseline) by the administration DKN-01.  

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These plots illustrate that in the majority of patients (> 95%), DKK1 Cmax concentrations could 
be suppressed to 1.5 ng/mL or less after one dose of 300 mg DKN-01 (Figure 1). In addition, 
after repeat 300 mg Q2W dosing, the highest free DKK1 Cmax levels declined to approximately 
0.76 ng/mL or less for 95% of patients (Figure 1). Simulations showed that when the DKN-01 
dose was increased to 600 mg, the highest free DKK1 Cmax was decreased to approximately 
0.8 ng/mL after the first dose, and then to 0.4 ng/mL after repeat Q2W dosing to steady-state 
(Figure 2). 
Figure 1 
Predicted Maximal Free Serum DKK1 (Cmax) Concentrations after 300 mg 
DKN-01 IV Dosing Administered Once Every Two Weeks (Q2W) 
P r e d o s e  W e e k  1
P r e d o s e  W e e k  5
P r e d o s e  W e e k  9
P r e d o s e  W e e k  1 3
P r e d o s e  W e e k  1 7
P r e d o s e  W e e k  2 1
P r e d o s e  W e e k  2 5
0 . 0
0 . 5
1 . 0
1 . 5
F r e e  D K K 1  C m a x   ( n g / m L )
0 .7 6  n g / m L
1 . 5  n g / m L
D o s e  =  3 0 0  m g  Q 2 W
 
Note: Plot whiskers represent an interval containing 80% of patients. 
 

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Figure 2 
Predicted Maximal Free Serum DKK1 (Cmax) Concentrations after 600 mg 
DKN-01 IV Dosing Administered Once Every Two Weeks (Q2W) 
P r e d o s e  W e e k  1
P r e d o s e  W e e k  5
P r e d o s e  W e e k  9
P r e d o s e  W e e k  1 3
P r e d o s e  W e e k  1 7
P r e d o s e  W e e k  2 1
P r e d o s e  W e e k  2 5
0 . 0
0 . 5
1 . 0
F r e e  D K K 1  C m a x   ( n g / m L )
0 .4  n g / m L
0 .8  n g / m L
D o s e  =  6 0 0  m g  Q 2 W
 
*Plot whiskers represent an interval containing 90% of patients. 
Several ongoing clinical studies have been conducted to determine the effect of DKN-01 on a 
variety of cancers. In Study DEK-DKK1-P102 (P102; NCT02013154), DKN-01 was dosed in 
combination with paclitaxel as well as in a separate monotherapy substudy. In this study, 
patients were administered DKN-01 at doses of 150 or 300 mg Q2W over a 28-day cycle. 
Patients in Study DEK-DKK1-P103 (P103; NCT02375880) were administered DKN-01 at 
doses of 150 or 300 mg in combination with gemcitabine and cisplatin on Days 1 and 8 of each 
21-day cycle. The dosing cycles for P102 and P103 are not comparable and the simulations 
above only apply to a Q2W dosing schedule, such as that used in P102. 
In both of these clinical studies, pharmacokinetic (PK)/pharmacodynamic (PcD) modeling 
showed a dose-dependent decrease in free DKK1 Cmax concentrations. For example, in 
Study P102, the median free DKK1 Cmax after a 150 mg DKN-01 dose was 0.95 ng/mL (after 
the last dose for each patient), whereas the median value was 0.55 ng/mL in the 300 mg dose 
group. Although this last value is higher than the steady-state values in the 300 mg Q2W 
simulation above, it should be noted that many patients were not dosed to steady-state in the 
P102 clinical study.   
In P102 and P103, preliminary modeling showed that for patients with a partial response (PR), 
the median free DKK1 Cmax was 0.39 ng/mL and 0.50 ng/mL (respectively), and the highest 
individual free DKK1 Cmax was 0.86 and 0.77 ng/mL, respectively. In non-responders, the 
median Cmax was 0.65 and 0.61 ng/mL (respectively) and the highest individual free Cmax 
observed was 5.7 and 10.8 ng/mL, respectively. Thus, for patients showing a PR, maximal free 
DKK1 Cmax levels did not exceed 0.86 ng/mL and the median free Cmax values were lower than 
those for the non-responders. Currently, it is not understood if the 0.86 ng/mL threshold is a 

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meaningful target for efficacy, or if median free DKK1 Cmax values (≤ 0.39-0.50 ng/mL) are 
important. However, it can be stated that there is an overall trend for lower free DKK1 levels in 
partial responders versus non-responders. By extension, higher doses of DKN-01 (i.e., 600 mg) 
should lower free DKK1 levels sufficiently to see additional efficacy in patients. 
Safety data for DKN-01 are available from 30 healthy subjects treated with a single dose of 
DKN-01 monotherapy and 229 patients with cancer treated with DKN-01, of whom 65 received 
DKN-01 monotherapy; 7 received DKN-01 in combination with lenalidomide/dexamethasone; 
69 received DKN-01 in combination with paclitaxel; 51 patients received DKN-01 in 
combination with gemcitabine/cisplatin; and 37 received DKN-01 in combination with 
pembrolizumab. 
Study DEK-DKK1-P100 was a 2-part (Parts A and B), Phase 1, multicenter, nonrandomized, 
open-label, multiple-dose, dose-escalation study of DKN-01 administered IV to patients 
30 years of age or older. Study Part A (dose escalation) consisted of a standard 3 + 3 dose 
escalation designed to determine the maximum tolerated dose (MTD) and dose-limiting 
toxicities (DLTs) of DKN-01 in patients with multiple myeloma (MM) or advanced solid 
tumors. Study Part B (dose confirmation) was designed to administer DKN-01 at the MTD (or 
highest dose tested if the MTD is not reached) to further characterize safety and tolerability and 
to evaluate progression-free survival in patients with relapsed/refractory NSCLC.  
A total of 32 patients were enrolled in the study and received study treatment. Thirteen patients 
were enrolled and treated in Part A and 19 patients in Part B. In Part A, DKN-01 doses of 75, 
150, and 300 mg were administered IV (once weekly) QW and 600 mg was administered IV 
Q2W to different cohorts of patients. There were no DLTs observed in Part A; therefore, study 
Part B proceeded with enrolling a total of 19 patients who received 300 mg DKN-01 Q2W. 
DKN-01 given IV at escalating doses from 75 mg QW to 600 mg Q2W in Part A and as a single 
IV agent at a dose of 300 mg Q2W in Part B was safe and well tolerated. All treatment-related 
adverse events (TEAEs) were Grade 1 or 2 in severity. There were no related serious adverse 
events (SAEs) and no discontinuations due to a TEAE. 
Study DEK-DKK1-P102 is an ongoing Phase 1 non-randomized, dose-escalating, open-label, 
multicenter study conducted in multiple parts (Parts A through F). In addition, a separate 
monotherapy substudy is being conducted concurrently with Parts B through F. A maximum of 
approximately 224 patients aged 18 years or older with histologically confirmed recurrent or 
refractory esophageal, gastro-esophageal junction or gastric cancer with progressive disease 
requiring therapy will be enrolled in the study. 
As of 20 August 2018, 124 patients have been enrolled, including 9 patients in Part A; 20 in 
Part B; 25 in Part C, 3 in Part D; 2 in Part E; 37 in Part F; and 28 in the monotherapy substudy. 
Overall, 3 patients have received DKN-01 150 mg+paclitaxel; 56 have received DKN-01 
300 mg+paclitaxel; 2 have received DKN-01 150 mg+pembrolizumab; 35 have received 
DKN-01 300 mg+pembrolizumab; and 28 patients have received DKN-01 300 mg as 
monotherapy in this study. 
Among patients treated with DKN-01 as monotherapy (N=28) in the monotherapy substudy, the 
most common type of TEAEs were gastrointestinal disorders (18 patients; 64%) and the most 

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common individual TEAEs were fatigue (13 patients; 46%), vomiting (8 patients; 29%), 
dehydration (7 patients; 25%), and nausea, constipation, and anemia (each 6 patients; 21%). 
At least 1 TEAE was considered by the Investigator to be DKN-01-related for 16 (57%) 
patients, with the most common such events being fatigue (7 patients; 25%), anemia and 
vomiting (each 4 patients; 14%), and nausea and decreased appetite (each 3 patients; 11%). All 
other DKN-01-related TEAEs were reported for ≤2 patients. 
One (4%) patient treated with DKN-01 monotherapy experienced DKN-01-related Grade 3 
TEAEs, hyponatremia and lymphopenia. All other DKN-01-related TEAEs were Grade 1 or 2 
in intensity. 
Among patients treated with DKN-01 300 mg+paclitaxel (N=56), the most common type of 
TEAEs were gastrointestinal disorders (41 patients; 73%) and the most common individual 
TEAEs were fatigue (29 patients; 52%), anemia (27 patients; 48%), alopecia and peripheral 
sensory neuropathy (each 19 patients; 34%), neutropenia (17 patients; 30%), cough (16 patients; 
29%), and dyspnea (14 patients; 25%). 
Among the 3 patients treated with the lower DKN-01 dose of 150 mg+paclitaxel, the TEAE 
profile was similar to that seen with the 300 mg dose, with the most common TEAEs being 
diarrhea and fatigue (each 3 patients; 100%) and arthralgia, headache, and toothache (each 
2 patients; 67%). All other TEAEs were reported for 1 patient only at this dose level. 
Thirty-two (57%) of 56 patients treated with DKN-01 300 mg +paclitaxel experienced a 
DKN-01-related TEAE, most commonly fatigue (13 patients; 23%), diarrhea (7 patients; 13%), 
nausea (6 patients; 11%), anemia and decreased appetite (each 5 patients; 9%), and constipation 
and neutropenia (each 4 patients; 7%). 
Six (11%) patients experienced a DKN-01-related Grade 3 TEAE, including hypophosphatemia 
(2 patients; 4%), anemia, monocytosis, neutropenia, and peripheral neuropathy (1 patient; 2%).  
DKN-01-related TEAEs reported with DKN-01 150 mg + paclitaxel included single incidences 
of dysgeusia, fatigue, headache, peripheral sensory neuropathy, and stomatitis, with fatigue and 
peripheral sensory neuropathy being Grade 3 in intensity. 
Among the 56 patients who received DKN-01 300 mg + paclitaxel, 22 (39%) experienced at 
least 1 SAE, with infections and infestations being the most common type (9 patients; 16%). 
Individual SAEs reported for >1 patient included pneumonia (4 patients; 7%), and aspiration, 
lung infection, and pulmonary embolism (each 2 patients; 4%). All SAEs were considered by 
the Investigator to be unrelated to DKN-01. 
Three patients experienced a Grade 5 TEAE, including aspiration (2 patients) and pulmonary 
embolism and respiratory failure in 1 patient each. For all 3 patients, the TEAE resulting in 
death was considered by the Investigator to be unrelated to DKN-01. 
For summaries of the clinical safety of DKN-01 300 mg administered in conjunction with 
pembrolizumab (Study DEK-DKK1-P102) or in conjunction with gemcitabine and cisplatin 
(Study DEK-DKK1-P103), please refer to the Investigator’s Brochure. 
In the current study, as of 20 August 2018, the most common TEAEs among patients receiving 
DKN-01 as monotherapy (N=5) and in combination with paclitaxel (N=10) in Study 

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DEK-DKK1-P204 are summarized. Overall, 11 (73%) of 15 patients experienced at least 
1 TEAE. TEAEs reported for >1 patient included arthralgia, constipation, hypokalemia, and 
lymphopenia. 
Eight (53%) patients experienced at least 1 TEAE that was considered by the Investigator to be 
DKN-01-related. Such events reported for >1 patient included hypokalemia and lymphopenia 
(each 2 patients), with 1 case of lymphopenia assessed as Grade 3 in intensity. All other 
DKN-01-related TEAEs were Grade 1 or 2 in intensity. 
The dose of paclitaxel selected for use in the current study, 80 mg/m2, is the same as that 
employed in combination with DKN-01 in Study P102. For detailed information related to 
clinical safety, please refer to the Investigator’s Brochure.  
1.4. 
Justification of the Study Design 
This study employs a “basket” design, a relatively new form of oncologic clinical study design 
predicated on the hypothesis that the presence of a molecular marker predicts response to a 
targeted therapy independent of tumor histology (Redig and Jänne 2015; Mandrekar et al. 2015; 
Menis et al. 2014). Several recent studies have employed this type of design, including the large 
(estimated 1000 patients) “NCI-MATCH” study (i.e., National Cancer Institute Molecular 
Analysis for Therapy Choice) (ClinicalTrials.gov identifier NCT02465060) and “CUSTOM” 
study (i.e., Molecular Profiling and Targeted Therapies in Advanced Thoracic Malignancies) 
(ClinicalTrials.gov identifier NCT01306045).  
Per the basket design, patients will be assigned to 1 of 4 specific treatment groups in a 
non-randomized fashion, with each group essentially representing an independent Phase 2 study 
conducted in parallel, with each group employing a 2-stage design. According to this design, a 
particular group may be stopped if a preliminary lack of antitumor activity is seen in that group 
in Stage 1 without impacting the other study groups. Conversely, patients will be enrolled in 
Stage 2 for a particular group if Stage 1 did not reveal a preliminary lack of antitumor activity.  
The Sponsor, Monitor, and Investigators will perform this study in compliance with the 
protocol, Good Clinical Practice (GCP) and International Council for Harmonisation (ICH) 
guidelines, and applicable regulatory requirements. 

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2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Study Objectives 
2.1.1. 
Primary Objective 
The primary objective in each independent study group (Groups 1-4) of this study is: 
• To determine the objective response rate (ORR). 
The primary objectives in each independent study group (Groups 5-6) are: 
• To characterize the safety of DKN-01 600 mg ± paclitaxel in patients with recurrent 
carcinosarcoma (MMMT). 
• To identify the recommended Phase 2 dose (RP2D) of DKN 01 ± paclitaxel in 
patients with recurrent carcinosarcoma (MMMT) based on safety, PK, and PcD. 
2.1.2. 
Secondary Objectives 
The secondary objectives in each independent study group (Groups 1-4) of this study are: 
• To determine the objective disease control rate (ODCR). 
• To determine OS. 
• To determine progression-free survival (PFS). 
• To evaluate additional measures of efficacy, including time to progression (TTP), 
duration of response (DoR), duration of complete response (DoCR), duration of clinical 
benefit (DoCB), and time to treatment failure (TTTF).  
• To evaluate the safety of the study treatment regimen. 
• To characterize the PK of DKN-01 as monotherapy and in combination with paclitaxel 
in patients with recurrent EEC or EOC.  
• To detect anti-DKN-01 antibodies in human serum. 
The secondary objectives in each independent study group (Groups 5-6) of this study are: 
• To determine the ORR. 
• To determine the ODCR. 
• To determine OS. 
• To determine PFS. 
• To evaluate additional measures of efficacy, including TTP, DoR, DoCR, DoCB, and 
TTTF.  
• To characterize the PK of DKN-01 as monotherapy and in combination with paclitaxel 
in patients with recurrent carcinosarcoma (MMMT).  
• To detect anti-DKN-01 antibodies in human serum. 

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2.1.3. 
Exploratory Objectives 
The exploratory objectives of this study in each independent study group (Groups 1-6) are: 
• To evaluate response to therapy in patients with and without activating β-catenin 
mutations and/or Wnt signaling genetic alterations. 
• To evaluate DKK1 concentration in serum and plasma relative to safety and efficacy 
outcomes. 
• To evaluate tumor genetics, gene expression levels (e.g., RNA-Seq), DKK1 expression 
(e.g., RNAscope in situ hybridization), immunohistology, infiltrating immune cells and 
additional immunohistochemistry (IHC) staining (DKK1 and associated downstream 
elements [e.g., β-catenin]) on tumor tissue relative to safety and efficacy outcomes. 
• To evaluate the frequency of myeloid derived suppressor cells (MDSCs) and T effector 
memory cells in peripheral blood mononuclear cells relative to safety and efficacy 
outcomes. 
2.2. 
Study Endpoints 
In support of objectives relating to an investigation of the safety and clinical effectiveness of a 
DKN-01 dose exceeding 300 mg, the secondary efficacy endpoints for Group 5 and Group 6 are 
those specified as primary and secondary endpoints for Groups 1-4. Safety endpoints for 
Group 5 and Group 6 include those specified as safety endpoints for Groups 1-4, with the 
addition of a summary of the incidence of DLTs for Groups 5 and 6. In addition, the evaluation 
of the higher DKN-01 dose will also be based on a review of pharmacokinetic and PcD data. 
2.2.1. 
Efficacy Endpoints 
The primary efficacy endpoint in each independent study group (Groups 1-4) is: 
• ORR (i.e., best overall response [BOR] of complete response [CR] + partial response 
[PR]), as assessed by the Investigator using the Response Evaluation Criteria in Solid 
Tumors, version 1.1 (RECIST 1.1) (Eisenhauer et al. 2009). 
Secondary efficacy endpoints in each independent study group (Groups 1-4) are: 
• ODCR (i.e., CR+PR+ stable disease [SD] > 6 weeks), as assessed by the Investigator 
using RECIST 1.1. 
• OS, defined as the time from first study drug dose (i.e., Cycle 1, Day 1 [C1D1]) to death 
from any cause.  
• PFS, defined as the time from first study drug dose (C1D1) to first radiographically-
documented PD, as determined using RECIST 1.1, or death due to any cause. 
• TTP, defined as the time from first study drug dose (C1D1) until the date of first 
radiographically-documented PD, as determined using RECIST 1.1. 
• DoR, defined as the time from initial response (≥PR) until radiographically-documented 
PD or death; PD is defined using RECIST 1.1. 
• DoCR, defined as the time from initial CR until radiographically-documented PD or 
death; PD is defined using RECIST 1.1. 

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• 
DoCB, defined as the time from the first tumor assessment of CR, PR or SD to the time 
of PD, as determined using RECIST 1.1, or death due to any cause 
• TTTF, defined as the time from first study drug dose (C1D1) until the date of 
discontinuation of DKN-01 for any reason, including PD, toxicity, and death. 
Secondary efficacy endpoints in each independent study group (Groups 5-6) are: 
• ORR (i.e., BOR of CR + PR), as assessed by the Investigator using RECIST 1.1. 
• ODCR (i.e., CR+PR+SD > 6 weeks), as assessed by the Investigator using RECIST 1.1. 
• OS, defined as the time from first study drug dose (i.e., C1D1) to death from any cause.  
• PFS, defined as the time from first study drug dose (C1D1) to first radiographically-
documented PD, as determined using RECIST 1.1, or death due to any cause. 
• TTP, defined as the time from first study drug dose (C1D1) until the date of first 
radiographically-documented PD, as determined using RECIST 1.1. 
• DoR, defined as the time from initial response (≥PR) until radiographically-documented 
PD or death; PD is defined using RECIST 1.1. 
• DoCR, defined as the time from initial CR until radiographically-documented PD or 
death; PD is defined using RECIST 1.1. 
• DoCB, defined as the time from the first tumor assessment of CR, PR or SD to the time 
of PD or death due to any cause; PD is defined using RECIST 1.1. 
• 
TTTF, defined as the time from first study drug dose (C1D1) until the date of treatment 
discontinuation of DKN-01 for any reason, including PD, toxicity, and death. 
2.2.2. 
Safety Endpoints 
The safety endpoints in each independent study group (Groups 1-6) are: 
• Incidence of TEAEs, Grade 3 /4 / 5 TEAEs, serious adverse events (SAEs), and TEAEs 
leading to study drug discontinuation. 
• Incidence of treatment-emergent Grade 3 / 4 clinical laboratory abnormalities. 
• Incidence of infusion reactions. 
• Changes from baseline in clinical laboratory parameters (serum chemistry, hematology, 
coagulation, and urinalysis). 
• Changes from baseline in vital signs and electrocardiogram (ECG) parameters. 
• Shift from baseline in Eastern Cooperative Oncology Group (ECOG) performance 
status. 
Additionally, for Groups 5 and 6: 
• Incidence of DLTs. 
2.2.3. 
Pharmacokinetic Endpoint 
The PK endpoint is: 

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• Cmax, time to peak concentration (Tmax), and areas under the concentration-time curve 
(AUCs). 
2.2.4. 
Immunogenicity Endpoint 
The immunogenicity endpoint is: 
• Anti-DKN-01 antibodies. 
2.2.5. 
Exploratory Endpoints 
The exploratory endpoints in each independent study group are: 
• DKK1 concentration in serum and plasma relative to safety and efficacy outcomes. 
• Tumor genetics, gene expression levels (e.g., RNA-Seq), DKK1 expression (e.g. 
RNAscope in situ hybridization), immunohistology, infiltrating immune cells and 
additional IHC staining (e.g., DKK1 and associated downstream elements, [e.g., β-
catenin]) on tumor tissue relative to safety and efficacy outcomes. 

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3. 
INVESTIGATIONAL PLAN 
3.1. 
Overall Design and Plan of the Study 
Study DEK-DKK1-P204 is a Phase 2 basket study designed to evaluate DKN-01 activity either 
as monotherapy or, at the Investigator’s discretion, in combination with paclitaxel in patients 
with recurrent EEC, recurrent platinum-resistant/refractory EOC (Groups 1-4), or recurrent 
carcinosarcoma (MMMT) (Groups 5-6) who have received at least one prior systemic therapy 
for advanced disease. For Groups 1-4, this basket study will enrich for activating β-catenin 
mutation and/or Wnt signaling alterations (see Screening, Section 3.2.1). A maximum of 124 
evaluable patients aged 18 years or older with histologically confirmed recurrent EEC, 
recurrent platinum-resistant/refractory EOC, or recurrent carcinosarcoma (MMMT) with PD 
requiring therapy will be enrolled in the study. Patients who are not eligible to receive paclitaxel 
will be enrolled in the monotherapy group by primary tumor. Six (6) distinct patient groups are 
being enrolled with up to 21 evaluable patients in Groups 1, 3 and 4, up to 31 evaluable patients 
in Group 2, up to 10 evaluable patients in Group 5, and up to 20 evaluable patients in Group 6, 
as follows:  
• Group 1: DKN-01 monotherapy in recurrent EEC 
• Group 2: DKN-01+paclitaxel in recurrent EEC 
• Group 3: DKN-01 monotherapy in recurrent EOC 
• Group 4: DKN-01+paclitaxel in recurrent EOC 
• Group 5: DKN-01 monotherapy in recurrent carcinosarcoma (MMMT) 
• Group 6: DKN-01+paclitaxel in recurrent carcinosarcoma (MMMT) 
Groups 1-4 employ a 2-stage design conducted separately for each group. For each 
monotherapy group (Groups 1 and 3), after 12 evaluable patients are enrolled (Stage 1), an 
additional 9 evaluable patients will be enrolled in that group (Stage 2) if 1 or more patients 
respond (i.e., experience CR or PR). If there are no responses in Stage 1, then preliminary anti-
tumor activity in the group will be rejected and no further patients will be enrolled in that group. 
For the EEC combination therapy group (Group 2), after 20 evaluable patients are enrolled 
(Stage 1), if 3 or more patients respond (i.e., experience CR or PR), an additional 11 evaluable 
patients will be enrolled in that group (Stage 2). If there are fewer than 3 responses in Stage 1, 
then preliminary anti-tumor activity in the group will be rejected and no further patients will be 
enrolled in that group. For the EOC combination therapy group (Group 4), after 16 evaluable 
patients are enrolled (Stage 1), if 2 or more patients respond (i.e., experience CR or PR), an 
additional 5 evaluable patients will be enrolled in that group (Stage 2). If there are fewer than 
2 responses in Stage 1, then preliminary anti-tumor activity in the group will be rejected and no 
further patients will be enrolled in that group. 
Groups 5 and 6 are exploratory in nature. Group 5 will enroll approximately 10 evaluable 
patients and Group 6 will enroll approximately 20 evaluable patients. 
For Groups 5 and 6, 3 patients in each group will initially be enrolled in a safety run-in phase. If 
the first 2 of 3 patients in a group have a DLT (see Section 5.6.2.1), the MTD will have been 
exceeded (see Section 5.6.2.1) and a cohort will be enrolled to evaluate DKN-01 at a dose of 

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300 mg (±paclitaxel, depending on group assignment). If none of the 3 treated patients in a 
group develop a DLT after a minimum of one cycle of treatment, enrollment into the group will 
proceed according to the planned schedule. If a DLT is observed in 1 of the 3 patients in a 
group, up to an additional 3 patients will be enrolled and treated. If no further DLTs are 
observed within the expanded group of 6, enrollment into the group will proceed. If ≥2 of 
6 patients within a group experience a DLT, the MTD will have been exceeded and a cohort 
will be enrolled to evaluate DKN-01 at a dose of 300 mg (±paclitaxel, depending on group 
assignment). 
For the Rollover Treatment Phase, patients remain on the same dose and schedule as they 
received in the previous study part. 
3.2. 
Study Periods 
The study has 6 distinct periods, as follows: 
3.2.1. 
Screening 
Potentially eligible patients will sign informed consent prior to undergoing any study-related 
procedures. Patients will undergo Screening assessments for protocol eligibility within 28 days 
of study entry, as outlined in Table 6.  
Fresh tumor tissue samples are required to be collected from all patients during Screening for 
genomic cancer profiling (i.e., CTNNB1 mutation and Wnt-signaling mutation), gene 
expression levels (e.g., RNA-Seq), DKK1 expression (e.g., RNAscope in situ hybridization), 
immunohistology, infiltrating immune cells and additional IHC staining (DKK1 and associated 
downstream elements, [e.g., β-catenin]). Although fresh biopsy is preferred, an archived 
specimen collected within 3 months of C1D1 may be acceptable, with the prior approval of the 
Medical Monitor. 
This basket study is enriching for activating β-catenin mutations and/or Wnt signaling 
alterations, whereby approximately 50% of all evaluable patients enrolled in each group, in 
Stage 1 and in Stage 1 and 2 combined (Groups 1-4) and in Groups 5 and 6, are required to have 
an activating β-catenin mutation (CTNNB1 mutation) or other Wnt signaling alteration (e.g., 
LRP5/6, APC, AXIN1/2, GSK3B, RNF43, ZNRF3, RSPO2/3, FBXW7, ARID1A, or 
CBP/CREBBP; see full list in Appendix 12.6), based on testing of the Screening tumor tissue 
sample or previously documented alteration by a Clinical Laboratory Improvement 
Amendments (CLIA)-accredited laboratory.  
To allow-for real-time testing of Screening tumor tissue samples, the Screening period may be 
extended to 42 days, with results obtained and confirmed to be positive before the performance 
of additional Screening procedures. Note that all other Screening assessments must be 
performed within 28 days before C1D1.  
Patients with prior documentation of a known activating β-catenin mutation (CTNNB1 
mutation) or other Wnt signaling alteration by a CLIA-accredited laboratory will be permitted 
to enroll based on this documentation. In such patients, a Screening tumor sample will be 
collected and analyzed centrally; however, confirmatory results are not required for study 
enrollment. 

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Groups 1-4 employ a 2-stage design conducted separately for each group. For each 
monotherapy group (Groups 1 and 3), once 6 evaluable patients are enrolled who do not have 
activating β-catenin mutation and/or Wnt signaling alterations, Stage 1 enrollment for that 
group will continue only with patients with activating β-catenin mutation and/or Wnt signaling 
alterations. For Group 2, once 10 evaluable patients are enrolled who do not have activating 
β -catenin mutation and/or Wnt signaling alterations, Stage 1 enrollment for that group will 
continue only with patients with activating β-catenin mutation and/or Wnt signaling alterations. 
For combination therapy Group 4, once 8 evaluable patients are enrolled who do not have 
activating β-catenin mutation and/or Wnt signaling alterations, Stage 1 enrollment for that 
group will continue only with patients with activating β-catenin mutation and/or Wnt signaling 
alterations. At any time for Groups 1, 3, or 4, once 10 evaluable patients who do not have a 
documented activating β-catenin mutation and/or other Wnt signaling alteration have been 
enrolled in a group, enrollment in that group will continue only with patients with activating β-
catenin mutation (CTNNB1 mutation) or other identified Wnt signaling alteration. At any time 
for Group 2, once 15 evaluable patients who do not have a documented activating β-catenin 
mutation and/or other Wnt signaling alteration have been enrolled, enrollment in that group will 
continue only with patients with activating β-catenin mutation (CTNNB1 mutation) or other 
identified Wnt signaling alteration. 
3.2.2. 
Study Treatment Period  
The Study Treatment Phase includes either DKN-01 monotherapy or DKN-01 in combination 
with paclitaxel; patients will be assigned to receive monotherapy or combination therapy at the 
Investigator’s discretion. Patients who initially start combination therapy but subsequently 
discontinue paclitaxel may continue to receive DKN-01 as monotherapy during the Treatment 
Period. 
Patients are to begin study treatment as soon as possible (and preferably within 24 hours) after 
completion of all screening procedures and confirmation of study eligibility. Study visits will be 
performed as outlined in Table 6. 
During the Treatment Period, tumor measurements are to be performed using the same 
radiographic methods used during Screening. Tumor response, including PD, is to be assessed 
by the Investigator within ±7 days of the first study drug dose in every other cycle, starting in 
C3, and at the End of Treatment (EOT) Visit, using RECIST 1.1.  
The severity of adverse events (AEs) will be graded according to the United States National 
Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. 
3.2.3. 
Rollover Treatment Phase 
The Rollover Treatment Phase will permit patients who are still experiencing clinical benefit 
continued access to study drug(s) until they meet discontinuation criteria as per Section 6.4.1. 
Study visits will be performed as outlined in Table 7. 
 

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3.2.4. 
Study Treatment Discontinuation 
All patients will continue study treatment in the Treatment Phase until development of 
radiographically-documented PD or unacceptable toxicity or another discontinuation criterion is 
met, as determined by the Investigator. All patients will return for an EOT Visit approximately 
30 days (+7 days) after the last treatment administration in the Treatment Period. The reason for 
discontinuation from study treatment will be documented in the electronic case report form 
(eCRF). 
3.2.5. 
Progressive Disease Follow-up Phase 
To ensure accuracy and completeness for the disease response-related endpoints, patients who 
permanently discontinued study treatment prior to PD will continue to be followed up in the PD 
follow-up phase until radiographically documented PD. During this PD follow-up period, 
efficacy assessments for disease response and PD per RECIST 1.1 will be performed every 
8 weeks [see Table 6 (Table 7 for Rollover Treatment Phase only)]. Patients are expected not to 
start any other anti-cancer therapy during the PD follow-up phase prior to radiographically 
documented PD; however, if alternate therapy is started, patients will continue to be followed 
for radiologic progression even after starting subsequent therapy. After radiographically-
documented PD, all patients will be followed for survival in the Survival Follow-up Phase. 
3.2.6. 
Survival Follow-up Phase 
After discontinuation of treatment and documentation of PD, all patients will be followed in the 
Survival Follow-up Phase for survival until death, withdrawal of consent, loss to follow-up, 
implementation of the rollover treatment phase, or closure of the study by the Sponsor. Survival 
follow-up will occur 4 times per year (every 12 weeks [±14 days]) after the EOT visit or end of 
PD follow-up phase, as applicable, and may be conducted via telephone or office visit. During 
survival follow-up, the following information will be collected: survival and subsequent anti-
cancer therapies. 
3.3. 
Study Termination 
The study may be prematurely terminated if, in the opinion of the Investigator or Leap 
Therapeutics, Inc. (Leap), there is sufficient reasonable cause. Written notification documenting 
the reason for study termination will be provided to the Investigator or Leap by the terminating 
party.  
Circumstances that may warrant termination of the study or discontinuation of a study site 
include, but are not limited to, the following: 
• Determination of unexpected, serious, or unacceptable risk to patients enrolled in the 
study. 
• Failure to enter patients at an acceptable rate. 
• Failure to comply with pertinent regulations of appropriate regulatory authorities. 
• Submission of knowingly false information from the research facility to the Sponsor. 
• Insufficient adherence to protocol requirements. 
• Insufficient complete and/or evaluable data. 

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• Plans to modify, suspend, or discontinue the development of the study drug. 
• Availability of an open label extension study of DKN-01 trials, under which patients 
who are participating in a study with DKN-01 and who in the opinion of the investigator 
are receiving clinical benefit could continue to receive access to DKN-01 as a 
monotherapy or in combination.  
Should the study be closed prematurely, all study materials must be returned to Leap or its 
designee. 

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4. 
STUDY POPULATION 
The study population will consist of a confirmed diagnosis of recurrent EEC or recurrent 
platinum-resistant/refractory EOC, primary peritoneal or fallopian tube cancer, or recurrent 
carcinosarcoma (MMMT).  
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, are not permitted. 
4.1. 
Number of Patients 
A maximum of 124 evaluable patients are planned to be enrolled, with up to 21 evaluable 
patients in each of treatment Groups 1, 3, and 4, up to 31 evaluable patients in Group 2, up to 
10 evaluable patients in Group 5, and up to 20 evaluable patients in Group 6. 
4.2. 
Inclusion Criteria 
Patients may be included in the study if they meet all of the following inclusion criteria during 
Screening prior to first dose of study drug.  
Epithelial Endometrial Cancer 
1. Must have a histologically confirmed diagnosis (by either primary surgical 
specimen or biopsy for recurrence) of recurrent previously treated EEC. 
Epithelial Ovarian Cancer 
2. Must have a histologically confirmed diagnosis (by either primary surgical 
specimen or biopsy for recurrence) of recurrent platinum-resistant/refractory EOC, 
primary peritoneal, or fallopian tube cancer (i.e., disease recurrence within 6 months 
of completion or progression during platinum-based chemotherapy). 
Carcinosarcoma/Malignant Mixed Mullerian Tumors (Groups 5-6) 
3. Must have a histologically confirmed diagnosis (by either primary surgical specimen 
or biopsy for recurrence) of recurrent uterine or ovarian carcinosarcoma (MMMT). 
4. Patient must have had only 1 prior chemotherapeutic regimen for management of 
recurrent or advanced carcinosarcoma that may have included chemotherapy 
(including in adjuvant setting with refractory or disease recurrence within 6 months), 
chemotherapy and radiotherapy, and/or consolidation/maintenance therapy.  
General 
5. Must be refractory or intolerant to at least one prior standard therapy(ies) for metastatic 
or locally advanced disease (see Inclusion Criterion #4 for Groups 5-6). 
a. If prior therapy consisted of palliative chemoradiation therapy, it will be considered 
one line of therapy. 
b. Prior treatment with paclitaxel as part of a definitive therapy regimen is acceptable 
provided the patient is not intolerant of paclitaxel. 
c. Patients who are not eligible to receive paclitaxel will be allowed to receive single 
agent DKN-01. 

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6. Tumor tissue for mandatory pre-treatment and on–treatment evaluation (fresh biopsy 
during Screening preferred; archived specimen (≤3 months) may be acceptable with 
prior approval from the Medical Monitor).  
7. One or more tumors measurable on radiographic imaging as defined by RECIST 1.1. 
8. Ambulatory and ≥18 years of age. 
9. ECOG performance status (PS) of 0 or 1.  
a. PS of 2 on the ECOG scale may be eligible upon the review and approval of the 
Medical Monitor. 
10. Estimated life expectancy of at least 3 months, in the judgment of the Investigator. 
11. Disease-free of active second/secondary or prior malignancies for ≥2 years with the 
exception of currently treated basal cell, squamous cell carcinoma of the skin, or 
carcinoma in-situ of the cervix or breast. 
12. Acceptable liver function: 
a. Total bilirubin ≤2.0 × upper limit of normal (ULN). 
b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
≤2.5 × ULN. If liver metastases are present, then ≤ 5 × ULN is allowed. 
13. Acceptable renal function: 
a. Creatinine normal for age: if serum creatinine is abnormal for age the patient 
must have a calculated creatinine clearance ≥30 mL/min using the Cockcroft 
and Gault Method (Cockroft and Gault 1976). 
14. Acceptable hematologic status: 
a. Granulocyte ≥1500 cells/mm3. 
b. Hemoglobin ≥9 g/dL (transfusion permitted within 30 days of study entry). 
c. Platelet count ≥75,000 cells/mm3. 
15. Acceptable coagulation status: 
a. Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.2 x ULN (unless 
receiving anticoagulation therapy, in which case eligibility will be based upon 
International Normalized Ratio [INR], see below). 
b. If receiving anticoagulant: INR ≤ 3.0 and no active bleeding, (i.e., no 
clinically significant bleeding within 14 days prior to first dose of study 
therapy). 
16. Females of child-bearing potential and male partners of female patients must agree 
to use adequate contraception (hormonal or barrier method of birth control) during 
the study and for 6 months after their last dose of study drug. Should a patient 
become pregnant or suspect she is pregnant while participating in the study, the 
Investigator should be immediately informed.  

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17. Reliable and willing to make themselves available for the duration of the study and 
are willing to follow study-specific procedures. 
18. Provided written informed consent prior to any study-specific procedures. 
Rollover Treatment Phase 
19. Received DKN-01 either as a monotherapy or in combination with paclitaxel in this 
study and is tolerating study drug(s) and currently displaying clinical benefit, in the 
Investigator’s opinion. 
4.3. 
Exclusion Criteria 
Patients with any of the following characteristics will be ineligible for study entry: 
1. Any of the following pure histologies of endometrial or ovarian cancer: germ cell, sex 
cord stroma, or sarcoma. 
2. New York Heart Association Class III or IV cardiac disease, myocardial infarction 
within the past 6 months, or unstable arrhythmia. 
3. Have Fridericia-corrected QT interval (QTcF) >470 msec, or history of congenital 
long QT syndrome. Any ECG abnormality that in the opinion of the Investigator 
would preclude safe participation in the study; patients with pacemakers where QTc 
is not a reliable measure will require an evaluation by a cardiologist to exclude co-
existing cardiac conditions which would prohibit safe participation in the study. 
4. Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study 
entry requiring systemic therapy. 
5. Known to be human immunodeficiency virus (HIV) positive, have hepatitis B 
surface antigen (HBSAg), or hepatitis C antibodies (HCAb) unless hepatitis C virus 
ribonucleic acid (HCV RNA) undetected/negative. 
6. History of major organ transplant (i.e., heart, lungs, liver, or kidney). 
7. History of autologous/allogenic bone marrow transplant. 
8. Serious nonmalignant disease that could compromise protocol objectives in the 
opinion of the Investigator and/or Sponsor. 
9. Pregnant or nursing. 
10. History of osteonecrosis of the hip or evidence of structural bone abnormalities in the 
proximal femur on magnetic resonance imaging (MRI) scan that are symptomatic and 
clinically significant. Degenerative changes of the hip joint are not exclusionary. 
Screening of asymptomatic patients is not required. 
11. Symptomatic central nervous system (CNS) malignancy or metastasis. Patients with 
treated CNS metastases are eligible provided their disease is radiographically stable, 
asymptomatic, and they are not currently receiving corticosteroids and/or 
anticonvulsants. Screening of asymptomatic patients without a history of CNS 
metastases is not required.  

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12. Known osteoblastic bony metastasis. Screening of asymptomatic patients without a 
history of metastatic bony lesions is not required. 
Medication-Related 
13. Treatment with surgery or chemotherapy within 21 days prior to study entry (42 days 
for nitrosoureas or mitomycin C). 
14. Any hormonal therapy directed at the malignant tumor must be discontinued at least 
one week prior to study entry. 
15. Clinically significant peripheral neuropathy at the time of study entry. Patients with 
pre-existing peripheral neuropathy will be allowed to receive single agent DKN-01. 
16. History of hypersensitivity reactions to paclitaxel or other drugs formulated in 
Cremophor® EL (polyoxyethylated castor oil). Patients who exhibit these 
hypersensitivities will be eligible to receive single agent DKN-01.  
17. Prior radiation therapy within 14 days prior to study entry. 
18. Currently receiving any other investigational agent or received an investigational 
agent within last 30 days of study entry. 
19. Previously treated with an anti-DKK1 therapy. 
20. Significant allergy to a pharmaceutical therapy that, in the opinion of the Investigator, 
poses an increased risk to the patient. 
Lifestyle-Related 
21. Active substance abuse. 

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5. 
STUDY TREATMENTS 
5.1. 
Clinical Trial Materials 
5.1.1. 
DKN-01 
DKN-01 supplied for this study is for investigational use and only to be used within the context 
of this clinical study. DKN-01 will be supplied to the Investigator by Leap or its designee. 
DKN-01 is provided in a glass vial as a lyophilized powder for reconstitution. Each vial is 
manufactured to deliver 20 mg of DKN-01 and contains the inactive ingredients sucrose, 
polysorbate 80, sodium chloride, citric acid, and sodium citrate. DKN-01 vials should be stored 
refrigerated at 2º – 8ºC. 
Detailed instructions for the preparation and handling of DKN-01 will be provided by Leap or 
its designee in the pharmacy manual.  
5.1.2. 
Paclitaxel 
TAXOL® (paclitaxel) Injection is a clear, colorless to slightly yellow viscous solution. It is 
supplied as a nonaqueous solution intended for dilution with a suitable parenteral fluid prior to 
IV infusion. TAXOL® is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) 
multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel, 527 mg of 
purified Cremophor® EL1 (polyoxyethylated castor oil) and 49.7% (v/v) dehydrated alcohol, 
USP (Bristol-Myers Squibb Company, 2011). 
Paclitaxel will be provided using commercial supplies. 
5.2. 
Blinding, Packaging and Labeling 
5.2.1. 
Blinding and Breaking the Blind 
This is an open-label study; no blinding methods will be employed. 
5.2.2. 
Packaging and Labeling 
Vials of DKN-01 vials are manufactured in accordance with Good Manufacturing Practices and 
packaged and labeled to meet applicable regulatory requirements.  
Study drug labels will not bear any statement that is false or misleading in any manner or 
represent that the study drug is safe or effective for the purposes for which it is being 
investigated.  
5.3. 
Method of Assigning Patients to Treatment 
Patients who meet all eligibility criteria, as defined in Section 4.2 and Section 4.3, will be 
enrolled. Patients who are considered eligible for paclitaxel, based on the Investigator’s 
judgement, may be assigned to a combination therapy group, based on their primary diagnosis. 
Patients who are not considered eligible to receive paclitaxel, based on the Investigator’s 
judgement, will be enrolled to a monotherapy group, based on their primary diagnosis. 
 
1 
Cremophor® EL is the registered trademark of BASF Aktiengesellschaft. Cremophor® EL is further purified by a Bristol-
Myers Squibb Company proprietary process before use. 

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Before each patient’s enrollment into the study, an eligibility check may be conducted between 
the investigational site and Leap to confirm that each patient meets all enrollment criteria. Note 
that tumor tissue must be collected during Screening (fresh biopsy preferred; archived specimen 
[≤3 months] may be acceptable with prior approval from Medical Monitor) for a patient to be 
eligible for enrollment in the study. Upon confirmation of eligibility, the Sponsor or designee 
will confirm the identification number assignment and group for each patient.  
5.4. 
Study Drug Accountability and Disposal 
All study drug will be stored, inventoried, reconciled, and destroyed according to applicable 
regulations. 
Accountability for the study drug at the study site is the responsibility of the Investigator. The 
Investigator will ensure that the study drug is used only in accordance with this protocol. Where 
allowed, the Investigator may choose to assign drug accountability responsibilities to a 
pharmacist or other appropriate individual. Drug accountability records indicating the date of 
delivery of the study drug to the site, inventory at the site, amount dispensed to and returned by 
each patient, and return to the Sponsor (or disposal of the study drug, if approved by the 
Sponsor) will be maintained by the clinical site. These records will adequately document that 
the patients were provided the study drug as specified in the protocol and should reconcile all 
study drug received from the Sponsor. Accountability records will include dates, quantities, 
batch/serial numbers, expiration dates (if applicable), and patient numbers. The Sponsor (or 
designee) will review drug accountability at the site during monitoring visits. 
All unused study drug will be retained at the site until inventoried by the monitor. All unused or 
expired study drug will be returned to the Sponsor or, if authorized, disposed of at the study site 
and documented. 
5.5. 
Assessment of Treatment Compliance 
All study drug will be administered IV at the investigational site, under the direction of the 
Investigator. As a result, a patient’s compliance with study drug administration is ensured. Any 
deviation(s) from the prescribed dosage regimen or problems with administering the IV infusion 
should be recorded in the eCRF.  
Patients should attend scheduled clinic visits and must comply with study criteria under their 
control. Deviation(s) from the prescribed dosage regimen should be recorded in the eCRF.  
5.6. 
Administration of Study Drug(s) 
The Investigator or designee is responsible for: 
• Explaining the correct use of the investigational agent(s) and planned duration of each 
individual’s treatment to the site personnel, 
• Verifying that instructions are followed properly,  
• Maintaining accurate records of study drug dispensation, destruction, and collection, and  
• Returning or destroying all unused medication to Leap or its designee at the end of the 
study. 

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Patients will be instructed to contact the Investigator as soon as possible if they have an issue 
with the study drug(s) so that the situation can be assessed. 
5.6.1. 
DKN-01 Administration 
DKN-01 is a large molecular weight protein that will be administered at a dose of 300 mg 
(Groups 1-4) and 600 mg (Groups 5 and 6) as an IV infusion over a minimum of 30 minutes 
and up to a maximum of 2 hours on D1 and 15 of each 28-day cycle without interruption.  
5.6.2. 
Paclitaxel Administration 
For patients receiving combination therapy, paclitaxel will be administered at a dose of 
80 mg/m2 via IV infusion over 1 hour on D1, 8, and 15 of each 28-day cycle according to 
standard clinical practice and as per the prescribing information (Bristol-Myers Squibb 
Company, 2011).  
Standard of care premedication for paclitaxel will be given prior to each paclitaxel infusion 
(e.g., dexamethasone 20 mg PO 12 to 6 hours prior; diphenhydramine 50 mg IV 30 to 
60 minutes prior; and cimetidine or ranitidine 50 mg IV 30 to 60 minutes prior) (Bristol-Myers 
Squibb Company, 2011). 
On D1 and 15 of each cycle, DKN-01 will be administered first followed by paclitaxel as 
separate infusions. 
For Groups 5 and 6, 3 patients in each group will initially be enrolled in a safety run-in phase. If 
the first 2 of 3 patients in a group have a DLT (see Section 5.6.2.1), the MTD will have been 
exceeded (see Section 5.6.2.1) and a cohort will be enrolled to evaluate DKN-01 at a dose of 
300 mg (±paclitaxel, depending on group assignment). If none of the 3 treated patients in a 
group develop a DLT after a minimum of one cycle of treatment, enrollment into the group will 
proceed according to the planned schedule. If a DLT is observed in 1 of the 3 patients in a 
group, up to an additional 3 patients will be enrolled and treated. If no further DLTs are 
observed within the expanded group of 6, enrollment into the group will proceed. If ≥2 of 6 
patients within a group experience a DLT, the MTD will have been exceeded and a cohort will 
be enrolled to evaluate DKN-01 at a dose of 300 mg (±paclitaxel, depending on group 
assignment). 
5.6.2.1. 
Dose-Limiting 
Toxicity 
Determination 
and 
Maximum 
Tolerated 
Dose/ 
Recommended Phase 2 Dose Definition 
A DLT is defined as an AE during C1 that is possibly related to the study drug(s) and fulfills 
any one of the following criterion using the NCI CTCAE version 5.0. 
• Grade 4 neutropenia lasting ≥ 5 days or Grade 3 or 4 neutropenia with fever and/or 
infection 
• Grade 4 thrombocytopenia (or Grade 3 with bleeding) 
• Grade 4 anemia 
• Grade 3 or 4 non-hematological toxicity (excluding Grade 3 vomiting and Grade 3 
diarrhea including the clinical sequelae [e.g., electrolyte abnormalities] despite optimal 
supportive care and excluding alopecia) 

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• Dosing delay greater than 14 days due to treatment-emergent AEs or related severe 
laboratory abnormalities 
• Grade 3 hypersensitivity reaction to DKN-01 with premedication (Grade 3 
hypersensitivity reaction to DKN-01 without premedication is not considered a DLT) 
• Grade 4 hypersensitivity reaction to DKN-01 with or without premedication 
• Any Grade 5 AE 
• Any treatment-related AE that causes the patient to discontinue treatment during C1. 
A drug-related fever ≤ Grade 3 will not be considered a DLT. 
Patients in Group 6 must have completed 100% of the DKN-01 doses and 75% of the paclitaxel 
doses in C1 to be evaluable for DLT. 
Furthermore, in any study part, if a patient experiences a TEAE meeting the definition of DLT 
in the first cycle of treatment, he/she will be discontinued from study treatment. 
The MTD is defined as the highest tested dose level below the dose level at which a DLT is 
seen in 2 or more patients. 
The RP2D is defined as the MTD or up to the highest planned dose level evaluated in 
Groups 5-6 without identification of the MTD. 
5.6.3. 
Rollover Treatment Phase 
The dose and schedule of study drug(s) will remain the same as per the previous study part. 

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6. 
TREATMENT OF PATIENTS 
6.1. 
Criteria for Initiation of a New Treatment Cycle 
A new cycle may be initiated for patients meeting the following criteria:  
• Absolute neutrophil count (ANC) resolved to baseline grade or ≤Grade 1 (≥1500/mm3). 
• Platelet count ≥75×109/L. 
• Liver associated enzymes/function (e.g., AST, ALT, alkaline phosphatase [ALP], 
bilirubin) ≤Grade 1 or resolved to baseline grade. 
• Any other drug-related AEs that may have occurred resolved to ≤Grade 1 severity or 
baseline grade. 
If these conditions are not met on D1 of a new cycle, the patient will be evaluated weekly and a 
new cycle of treatment will not be initiated until the toxicity has resolved as described above. 
The maximum treatment delay is 28 days prior to necessitating withdrawal from study. 
If, in the opinion of the Investigator, a patient is receiving clinical benefit from continued 
treatment with DKN-01 alone or in combination with paclitaxel, patients may continue therapy 
until developing documented PD or otherwise meeting criteria for treatment discontinuation 
(Section 6.4.1).  
Patients for whom the Investigator decides it is in their best interest to stop DKN-01 treatment 
are discontinued and complete the EOT procedures. 
6.1.1. 
Criteria for Treatment on Days 8 and 15 of a Treatment Cycle 
Treatment may be administered on D8 and 15 for patients meeting the following criteria: 
• ANC ≥1000 cells/mm3. 
• Platelet count ≥75×109/L. 
• Liver associated biochemical abnormalities must resolve to ≤Grade 1 or baseline grade. 
Refer to Section 6.2.2 for instructions for paclitaxel dose modifications for the management of 
peripheral neuropathy as well as neutropenia and thrombocytopenia within a cycle. 
6.2. 
Dosing Modifications, Reductions and Re-escalations, and Delays 
6.2.1. 
DKN-01 Dosing and Dose Adjustments 
DKN-01 will be administered via IV infusion on D1 and 15 in each 28-day treatment cycle.  
After the first occurrence of a toxicity necessitating withholding of study treatment, the 
Investigator may elect to restart DKN-01 treatment for the patient at the previously received 
dose once the toxicity resolves to ≤Grade 1 or baseline grade. For subsequent recurrence of the 
toxicity, DKN-01 treatment, per Investigator discretion, may be resumed at the next lower dose 
after the toxicity resolves to ≤Grade 1 or baseline grade (see Table 1).  

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Table 1 
DKN-01 Dose Adjustments for Groups 1-4 
Toxicity 
Occurrence 
DKN-01 
First*  
Restart at 300 mg after toxicity resolves to ≤Grade 1 or baseline grade. 
Second  
Restart at reduced dose of 150 mg after toxicity resolves to ≤Grade 1 or baseline grade. 
Third  
Restart at reduced dose of 75 mg after toxicity resolves to ≤Grade 1 or baseline grade. 
Fourth 
Discontinue 
*If the toxicity is judged to be significant in the opinion of the Investigator or the Investigator does not wish to dose at the same 
dosing level, he/she may contact the Medical Monitor to consider a one dose reduction level with the first occurrence of 
toxicity. 
Table 2  
DKN-01 Dose Adjustments for Groups 5 and 6 
Toxicity 
Occurrence 
DKN-01 
First*  
Restart at 600 mg after toxicity resolves to ≤Grade 1 or baseline grade. 
Second  
Restart at reduced dose of 300 mg after toxicity resolves to ≤Grade 1 or baseline grade. 
Third  
Restart at reduced dose of 150 mg after toxicity resolves to ≤Grade 1 or baseline grade. 
Fourth 
Discontinue 
*If the toxicity is judged to be significant in the opinion of the Investigator or the Investigator does not wish to dose at the same 
dosing level, he/she may contact the Medical Monitor to consider a one dose reduction level with the first occurrence of 
toxicity. 
Once a patient’s DKN-01 dose has been reduced, no re-escalation to a previously received dose 
is allowed at any time during the study. Intra-patient dose escalation is not permitted at any time 
during the study.  
For patients who experience an infusion reaction to DKN-01, all attempts should be made to 
obtain blood samples for determination of anti-DKN-01 antibody (immunogenicity sample) and 
serum DKN-01 levels as close to the onset of the event as possible, at the resolution of the 
event, and 30 days following the event or just prior to the start of new therapy, whichever 
comes first. In addition, these samples may be used for determination of PcD markers.  
DKN-01-related adverse reactions and infusion reactions are to be managed as described in 
Appendix 12.5 and Appendix 12.4, respectively.  
6.2.2. 
Paclitaxel Dosing and Dose Adjustments 
For patients receiving combination therapy, paclitaxel is administered via IV infusion on D1, 8, 
and 15 of each treatment cycle. The paclitaxel dose is to be modified for peripheral neuropathy 
and for neutropenia and thrombocytopenia as described in Table 3 and Table 4, respectively. 

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Table 3 
Paclitaxel Dose Modifications for Peripheral Neuropathy 
Grade 
Mgmt/Next Dose Paclitaxel 
Grade 1-2, tolerable 
No change in dose. 
Grade 2, intolerable 
Hold until ≤ tolerable Grade 2. Resume at reduced dose. 
Grade 3-4 
Hold until <Grade 2. Resume at reduced dose. 
Recommended management: consider medications for neuropathy. 
 
Table 4 
Paclitaxel Dose Modifications for Neutropenia and Thrombocytopenia 
Laboratory Value 
Management/Next Dose Paclitaxel 
Neutropenia 
Day 8 or 15 of cycle:  
Hold until ≥1000 cells/mm3, 
no change in dose. 
 
The use of growth factors is permitted 
Thrombocytopenia 
Day 8 and 15 of cycle:  
 
Hold until ≥75×109/L, no 
change in dose. 
 
Grade 3-4 
Hold until ≥75×109/L. Resume 
at reduced dose, if indicated. 
 
A platelet goal of 50×109/L should be considered for those on anticoagulation. 
 
Recommendations for the management of other toxicities considered to be paclitaxel-related are 
summarized in Table 5. 
Table 5 
Paclitaxel Dose Adjustments  
Toxicity Occurrence 
Paclitaxel 
First* 
Restart at 80 mg/m2 after toxicity resolves to ≤Grade 1 or baseline grade 
(Days 1, 8, and 15 per cycle) 
Second 
Restart at 70 mg/m2 after toxicity resolves to ≤Grade 1 or baseline grade 
(Days 1, 8, and 15 per cycle) 
Third 
Restart at 60 mg/m2 after toxicity resolves to ≤Grade 1 or baseline grade 
(Days 1, 8, and 15 per cycle) 
Fourth 
Discontinue 
*If the toxicity is judged to be significant in the opinion of the Investigator and the Investigator does not wish to dose at the 
same dosing level, he/she may contact the Medical Monitor to consider a 1 dose reduction level with the first occurrence of 
toxicity. 
If, in the opinion of the Investigator, a patient is receiving clinical benefit from treatment with 
the combination of DKN-01 plus paclitaxel but has a compelling clinical reason after C2 to 
discontinue treatment with paclitaxel, the patient will be permitted to continue in the study with 
DKN-01 monotherapy at the discretion of the treating clinician. Patients can continue therapy 
until they meet criteria for discontinuation (Section 6.4.1). 
6.2.3. 
Dose Delays 
The start of a new cycle may be delayed up to 28 days (for toxicities only) to allow sufficient 
time for recovery from the previous cycle. Patients who do not recover from toxicity within 
28 days will be discontinued from the study and undergo EOT procedures.  

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Missed doses will not be made up.  
Supportive care use of transfusion for symptomatic anemia or hemoglobin <8 g/dL and of 
colony-stimulating factors for neutropenia is encouraged per established guidelines. 
A treatment delay at the start of a cycle (Day 1) of no more than 7 days, because of holidays, 
weekends, inclement weather, or other justifiable events, will be permitted and not considered 
as a protocol violation. If a delay of therapy is ≥28 days is necessary, the patient must be 
removed from the study. 
6.3. 
Duration of Study Participation and Treatment 
A patient’s duration of study participation will include a Screening Period, a Treatment Period 
of repeating 28-day cycles, and a Post-Treatment Follow-up Period. The total duration of 
participation for a patient is dependent upon the patient’s response to treatment as well as 
toxicity to study drugs. If, in the opinion of the Investigator, a patient is receiving clinical 
benefit from treatment with the combination of DKN-01 plus paclitaxel but has a compelling 
clinical reason after C2 to discontinue treatment with paclitaxel, the patient will be permitted to 
continue in the study with DKN-01 monotherapy at the discretion of the treating clinician. 
Patients can continue therapy until they meet criteria for discontinuation (Section 6.4.1). 
Patients enrolled in the rollover treatment phase will continue to receive the same dose and 
schedule of study drug(s) as per the previous study part. 
Upon discontinuing DKN-01, patients undergo EOT assessments and are followed up for AEs 
for 30 days after the last DKN-01 dose.  
After completion of the EOT visit, patients without radiographically-documented PD will 
continue to be followed up in the PD follow-up phase until radiographically documented PD. 
During this PD follow-up period, efficacy assessments for disease response and PD per RECIST 
1.1 will be performed every 8 weeks [see Table 6 or Table 7 (Rollover Treatment Phase only)]. 
Patients are expected not to start any other anti-cancer therapy during the PD follow-up phase 
prior to radiographically documented PD; however, if alternate therapy is started, patients will 
continue to be followed for radiologic progression even after starting subsequent therapy.  
After discontinuation of treatment and documentation of PD, all patients will be followed in the 
Survival Follow-up Phase for survival until death, withdrawal of consent, loss to follow-up, or 
closure of the study by the Sponsor. Survival follow-up will occur 4 times per year (every 12 
weeks [±14 days]) after the 30 days post treatment discontinuation visit or end of PD follow-up 
phase, as applicable, and may be conducted via telephone or office visit. During survival 
follow-up, the following information will be collected: survival and subsequent anti-cancer 
therapies. 
6.4. 
Withdrawal and Replacement of Patients 
6.4.1. 
Withdrawal from Treatment or the Study 
Patients will be informed that they have the right to withdraw from the study at any time for any 
reason without prejudice to their medical care. The Sponsor and Investigators also have the 
right to withdraw patients from the study.  

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All patients who withdraw from the study prematurely will undergo all EOT assessments. 
Regardless of the reason for withdrawal, efforts should be made to follow safety events from the 
time of withdrawal through resolution or until the event stabilizes.  
Study drug should be discontinued for any of the following reasons: 
• AEs/unacceptable toxicity justifying treatment or study withdrawal. 
• Non-adherence to the study drug regimen or protocol requirements. 
• Non-compliance with instructions or failure to return for follow-up. 
• Investigator decides that study termination is in the patient’s best medical interest. 
• Lost to follow-up. 
• Enrollment in any other clinical study involving use of an investigational drug or device 
or enrollment in any other type of medical research judged not to be scientifically or 
medically compatible with this study. 
• Availability of an open label extension study of DKN-01 trials, under which patients, 
who are participating in a study with DKN-01 and who in the opinion of the investigator 
are receiving clinical benefit could continue to receive access to DKN-01 as a 
monotherapy or in combination 
• Dosing delay of ≥28 days. 
• Development of radiographically-documented PD, as determined by the Investigator 
using RECIST 1.1 (Appendix 12.2). 
• With the consent of the patient or the legally authorized representative the Investigator 
may determine that limited data collection may be continued (e.g., through medical 
record review) for the duration of the study after a patient has withdrawn. 
6.4.2. 
Replacement of Study Patients 
Patients who discontinue from the study will not be replaced.  
6.5. 
Concomitant Medications, Therapies and Supportive Care 
No other chemotherapy, immunotherapy, hormone therapy, or any other type of therapy 
(including herbal or natural supplements) for treatment of cancer or experimental drugs will be 
permitted while the patients are on this study. In addition, any disease progression requiring 
other forms of specific antitumor therapy will also necessitate discontinuation from the study. 
Appropriate documentation for all forms of premedications, supportive care, and concomitant 
medications must be captured on the case report form.  
Necessary supportive measures for optimal medical care will be given throughout the study, 
including IV antibiotics to treat infections, growth factor support and blood components, etc. 
Additional care, including palliative radiotherapy (excluding target lesions and lesions 
representing progressive disease), may be administered as indicated by the treating physician, 
patient’s medical need, and after discussion with the Medical Monitor. 

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All concomitant medications should be recorded in the eCRF throughout the patient’s 
participation in the study, from the time of provision of informed consent through the EOT visit. 

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7. 
STUDY ASSESSMENTS 
The Schedule of Assessments for the study is provided in Table 6 in Appendix 12.1. For the 
Rollover Treatment Phase of the study assessments are outlined in Table 7 in Appendix 12.1. 
Detailed descriptions of the study assessments to be conducted during this study are described 
in the following sub-sections.  
7.1. 
Clinical Procedures and Safety Assessments 
7.1.1. 
Informed Consent 
A complete description of the study is to be presented to each potential study patient. Signed 
and dated informed consent is to be obtained before any study-specific procedures are 
performed. 
7.1.2. 
Inclusion / Exclusion Criteria Review 
The inclusion and exclusion criteria will be reviewed during the Screening Period as 
assessments are performed to confirm patient eligibility for the study. The criteria will be 
reviewed prior to administration of the first dose of study drug on C1D1 to confirm continued 
study eligibility. 
7.1.3. 
Demographics, Medical and Disease History 
Demographic data and medical and disease histories will be obtained for all patients during the 
Screening Period. Demographic data to be recorded in the source document/eCRF includes 
gender, race, and date of birth. Information on significant medical and surgical history including 
dates, outcome, and whether or not ongoing or currently treated will be recorded. The date of 
original cancer diagnosis will be recorded along with any known cancer genomics profile 
results and previous treatments, including chemotherapy, radiation therapy, surgery, and use of 
blood products, including red cell and platelet transfusions and growth factors, within the 
previous 3 months. In addition, all other medications taken within 28 days of the initial 
Screening visit will be recorded.  
The medical history will be reviewed prior to dosing on C1D1 to assess continued study 
eligibility and adherence to final inclusion/exclusion criteria. This recent medical history 
includes a review for changes from Screening as well as a review of the patient’s recent 
medication use to assess whether or not any changes have occurred since the previous study 
visit. 
7.1.4. 
Physical Examination 
A complete physical examination (general appearance, head/ears/eyes/nose/throat [HEENT], 
lungs/chest, heart, abdomen, lymph nodes, musculoskeletal, extremities, and neurological 
examination) will be conducted at the time points designated in Table 6, (see Table 7 for 
Rollover Treatment Phase). During Screening, the physical examination is to include 
measurement of height. 
Abbreviated (i.e., symptom-directed) physical examinations will be conducted at the time points 
designated in Table 6 (see Table 7 for Rollover Treatment Phase) to address any complaints or 
concerns verbalized by the patient at all other study visits. 

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7.1.5. 
Vital Signs and Weight 
Vital signs are to be measured at the time points designated in Table 6, (see Table 7 for 
Rollover Treatment Phase). Vital signs to be measured include systolic and diastolic blood 
pressure (mmHg; measured in the same arm), oral temperature (°C), pulse (bpm), and 
respiration rate (breaths/minute). 
Weight will be measured on Day 1 of each treatment cycle and at the EOT visit. Body surface 
area (BSA) is to be calculated on Day 1 of each treatment cycle using the weight from that cycle 
and the Screening height measurement. 
7.1.6. 
Electrocardiograms 
A 12-lead ECG will be obtained at the time points designated in Table 6, (see Table 7 for 
Rollover Treatment Phase). Additional ECGs may be obtained as clinically warranted and 
judged by the Investigator.  
Patients must be supine for approximately 5 to 10 minutes before ECG collection and remain 
supine but awake during ECG collection.  
ECGs will be interpreted by a qualified physician (the Investigator or qualified designee) at the 
site as soon after the time of ECG collection as possible, and ideally while the patient is still 
present, to determine whether the patient meets entry criteria at the relevant visit(s) and for 
immediate patient management, should any clinically relevant findings be identified.  
If a clinically significant quantitative or qualitative change from baseline is identified after 
enrollment, the Investigator will assess the patient for symptoms (for example, palpitations, near 
syncope, syncope) to determine whether the patient can continue in the study. The Investigator 
or qualified designee is responsible for determining if any change in patient management is 
needed and must document his/her review of the ECG printed at the time of evaluation. 
The machine-read ECG intervals and heart rate may be used for data analysis and report writing 
purposes.  
7.1.7. 
Eastern Cooperative Oncology Group Performance Status (ECOG PS) 
The ECOG PS (Oken et al. 1982) will be determined at the time points designated in Table 6, 
(see Table 7 for Rollover Treatment Phase). Patients must have an ECOG PS of 0-1 to be 
enrolled into the study. Patients with an ECOG PS of 2 may be entered upon review and 
approval for study participation by the Medical Monitor. 
7.1.8. 
Clinical Laboratory Evaluations 
Routine clinical laboratory evaluations will be performed locally by a certified laboratory 
selected for the study. Prior to starting the study, the Investigator will provide copies of all 
laboratory certifications and normal ranges for all laboratory parameters to be assessed by the 
local laboratory. 
Refer to Section 6.1 and Section 6.1.1 for laboratory criteria required to initiate a new treatment 
cycle and for subsequent study drug doses within a cycles. 

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Clinical laboratory evaluations are to be performed at the time points designated in Table 6 (see 
Table 7 for Rollover Treatment Phase). Final clinical laboratories are to be performed at the 
EOT visit. 
All clinically significant laboratory abnormalities noted on testing will be followed up by repeat 
testing and further investigated according to the judgment of the Investigator. 
The Investigator must review all the patient’s laboratory reports in a timely manner. 
Investigators must document their review of each laboratory report and must assess whether or 
not any abnormal test results are clinically significant. The Investigator must complete an 
appropriate AE form for any abnormal test results that are identified as clinically significant. 
Specific tests to be performed are described below: 
Hematology 
Hemoglobin, hematocrit, erythrocyte count (RBC), mean cell volume (MCV), mean cell 
hemoglobin concentration (MVHC), platelets, leukocytes (WBC) and differential [absolute 
counts of] neutrophils (segmented and banded), lymphocytes, monocytes, eosinophils, and 
basophils. Neutrophil-to-lymphocyte ratio (NLR) also is to be determined. It is acceptable to 
use the automated differential for complete blood count (CBC). 
Chemistry 
Sodium, potassium, total bilirubin, direct bilirubin, lactate dehydrogenase (LDH), ALP, ALT, 
AST, blood urea nitrogen (BUN), creatinine, creatine kinase (CK), uric acid, calcium, glucose 
(random), albumin, cholesterol, serum chloride, phosphorus, carbon dioxide, and total protein. 
Urinalysis 
Specific gravity, pH, protein, glucose, ketones, blood, and urine leukocyte esterase.  
Coagulation Studies 
PT, PTT, and INR. 
Pregnancy Testing 
Serum or urine pregnancy testing is to be performed for women of childbearing potential. If a 
urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be 
required. On C1D1, the pregnancy test may be performed within 72 hours before the study drug 
dose; the results must be available and confirmed to be negative before administration of the 
first study drug dose. Pregnancy testing is to be repeated during the study any time pregnancy is 
suspected. 
Pregnant and breastfeeding women must not take DKN-01; hence the study investigator may 
need to test to confirm that a patient is postmenopausal. A woman of childbearing potential is 
defined as any female who has experienced menarche and who has not undergone successful 
surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not 
postmenopausal (defined as amenorrhea >12 consecutive months; or women with documented 
plasma follicle-stimulating hormone level >35µlU/mL). Women who are using oral, implanted 
or injectable contraceptive hormones, an intrauterine device, barrier methods (diaphragm, 

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condoms, spermicidal) to prevent pregnancy, practicing abstinence or where partner is sterile 
(e.g., vasectomy), should be considered to be of childbearing potential. 
CA 125 
Blood samples for measurement of CA125 are to be collected at the time points designated in 
Table 6. 
Other Clinical Laboratory Tests 
Blood samples for measurement of vitamin D and thyroid-stimulating hormone are to be 
collected at the time points designated in Table 6. 
7.1.9. 
Concomitant Medications / Procedures Review 
A review of concomitant medications and procedures will be conducted at each study visit. Any 
medications taken by study patients or concomitant procedures (e.g., transfusions, radiation, 
surgery, or other palliative care) are to be recorded in the eCRF and reviewed for compliance 
with protocol requirements.  
7.1.10. 
Adverse Event Monitoring 
Each patient must be carefully monitored for the development of any AEs, including infusion-
related AEs (see Section 7.1.11), throughout the study from signing of the informed consent 
through 30 days after the last dose of DKN-01, when EOT procedures are performed. This 
information should be obtained in the form of non-leading questions (e.g., “How are you 
feeling?”), and from signs and symptoms detected during each examination, from laboratory 
evaluation, observations of study personnel, patient diary, and spontaneous reports from 
patients. 
During post-treatment follow-up, any SAEs that the Investigator considers related to study 
treatment are to be reported. 
All AEs will be graded using the NCI CTCAE, version 5.0, grading system (available at:  
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_
Reference_8.5x11.pdf). The Investigator will assess and grade all AEs. Details of AE 
monitoring and reporting are provided in Section 8 of this protocol. 
7.1.11. 
Medical Events of Interest 
The following sections describe the assessment and management of DKN-01 infusion-related 
AEs. Details for the management and assessment of these events are found in Appendix 12.3 
and Appendix 12.4.  
7.1.11.1. Infusion-related Reactions 
The NCI CTCAE, version 5.0, definition of infusion-related reactions will be used in this study 
(see Appendix 12.3), and any reactions will be graded using these same criteria. The Sponsor or 
designee should be contacted immediately if questions arise concerning the grade of the 
reaction. 
Infusion-related reactions are temporally associated with the infusion of DKN-01 (≤24 hours 
post-infusion). Symptoms occurring during or following infusion of study drug may also be 
defined according to AE categories such as allergic reaction, anaphylaxis, or cytokine release 

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syndrome. In the setting of symptoms occurring during or following infusion of investigational 
therapy, investigators are encouraged to use the AE term “Infusion-related reaction” and any 
additional terms (including those not listed in the NCI CTCAE) that best describe the event. 
For patients who experience an infusion reaction to DKN-01, all attempts should be made to 
obtain blood samples for determination of anti-DKN-01 antibody (immunogenicity sample) and 
serum DKN-01 levels as close to the onset of the event as possible, at the resolution of the 
event, and 30 days following the event or just prior to the start of new therapy, whichever 
comes first. In addition, these samples may be used for determination of PcD markers.  
Guidelines for the management of DKN-01 infusion-related reactions are summarized in 
Appendix 12.4. 
7.2. 
Blood Sample Collection for Pharmacokinetics, Pharmacodynamics, and 
Exploratory Assessments 
Blood samples are to be collected for PK, PcD, and exploratory assessments as indicated in the 
following subsections at the time points designated in Table 6. After processing of the samples 
for the protocol-specified assays, any remaining biological material (whole blood, serum, 
plasma) is to be stored for future exploratory analyses, as deemed appropriate. In the rollover 
treatment phase blood sample for pharmacokinetics, pharmacodynamics, and exploratory 
assessments will not be collected. 
7.2.1. 
Blood Sample Collection for DKK1 
Blood samples will be collected for determination of total DKK1 (includes DKK1/DKN-01 
complex) in serum at the time points designated in Table 6. Free serum DKK1 levels may be 
estimated.  
Serum levels of DKK1 will be measured using a validated Enzyme-linked Immunosorbent 
Assay (ELISA), designed to perform in the presence of DKN-01.  
7.2.2. 
Pharmacokinetic Samples 
Blood samples will be collected for the assessment of serum DKN-01 concentrations at the time 
points designated in Table 6. Instructions for the collection and handling of blood samples will 
be provided by the Sponsor. The actual date and time (24-hour clock time) of each sampling 
will be recorded.  
Serum concentrations of DKN-01 will be assayed using a validated method at a laboratory 
designated by the Sponsor.  
Prior to analysis, the samples will be stored at a facility designated by the Sponsor. 
Bioanalytical samples collected to measure investigational product concentrations will be 
retained for a maximum of 1 year following last patient visit for the study. 
Any remaining serum from the samples collected for PK may be pooled and used for 
exploratory metabolism work, as deemed appropriate.  
7.2.3. 
Samples for Immunogenicity Research 
Blood samples will be collected for assessment of antibodies to DKN-01 (i.e., ADA) at the time 
points designated in Table 6. The blood sample collected for immunogenicity will be separated 

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into serum and divided into 2 tubes, one (A) for screening assay and the other (B) for storage 
for potential evaluation in a functional/cell-based assay.  
ADA will be assessed using a validated assay (Qualitative Affinity Capture Elution [ACE] 
ELISA), which is tolerant to high concentrations of free drug (DKN-01).  
If any patient is found to be ADA-positive at the EOT visit, the patient will be monitored 
monthly (if feasible) until serum samples are determined to be ADA-negative. 
Samples may be stored for a maximum of 2 years following last patient visit for the study at a 
facility selected by the Sponsor to enable further analysis of immune responses to DKN-01. The 
duration allows the Sponsor to respond to regulatory requests related to DKN-01.   
7.2.4. 
Samples for Exploratory Biomarkers 
Blood samples for exploratory biomarkers relevant to DKN-01 and/or the study indication will 
be collected at the time points specified in Table 6. 
Samples may be stored for a maximum of 2 years following last patient visit for the study at a 
facility selected by the Sponsor.   
7.3. 
Tumor Tissue Samples 
Fresh tumor tissue samples are required to be collected from all patients during Screening for 
genomic cancer profiling (i.e., CTNNB1 mutation and Wnt-signaling mutation). Although fresh 
biopsy is preferred, an archived specimen collected within 3 months of study entry may be 
acceptable, with the prior approval of the Medical Monitor. 
Approximately 50% of all evaluable patients enrolled in each group, in Stage 1 and in Stage 1 
and 2 combined (Groups 1-4) and in Groups 5 and 6, are required to have an activating 
β-catenin mutation (CTNNB1 mutation) or other Wnt signaling alteration (e.g., LRP5/6, APC, 
AXIN1/2, GSK3B, RNF43, ZNRF3, RSPO2/3, FBXW7, ARID1A, or CBP/CREBBP; see full 
list in Appendix 12.6), based on testing of the Screening tumor tissue sample by a CLIA-
accredited laboratory. Once 50% of evaluable patients without a documented β-catenin mutation 
or other Wnt signaling alteration have been enrolled within a group in Stage 1 (or in Stage 1 and 
2 combined, or in Groups 5 and 6), then only patients with activating β-catenin mutation 
(CTNNB1 mutation) or other identified Wnt signaling alteration, based on testing of the 
Screening tumor tissue sample by a CLIA-accredited laboratory, will be eligible for enrollment 
in that group (see Section 3.1 for details). (To allow for real-time testing of Screening tumor 
tissue samples, the Screening period may be extended to 42 days in such cases, with results 
obtained and confirmed to be positive before the performance of additional Screening 
procedures. Note that all other Screening assessments must be performed within 28 days before 
C1D1.)  
Patients with prior documentation of a known activating β-catenin mutation (CTNNB1 
mutation) or other Wnt signaling alteration by a CLIA-accredited laboratory will be permitted 
to enroll based on this documentation. In such patients, a Screening tumor sample will be 
collected and analyzed centrally; however, confirmatory results are not required for study 
enrollment. 

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Fresh tumor tissue samples also will be obtained from all patients at C2D1 ±7 days. The same 
lesion biopsied during Screening is to be biopsied at C2D1 ±7. The target lesion(s) should not 
be biopsied. If a repeat biopsy is required during study participation, a sample of the biopsy will 
be submitted for evaluation.  
For patients who discontinue from the study prior to C2D1, a tumor tissue sample is to be 
obtained at the EOT visit.  
Exploratory analyses will include gene expression levels (i.e., RNA-Seq), DKK1 expression 
(e.g., RNAscope in situ hybridization), immunohistology, infiltrating immune cells and 
additional IHC staining (e.g., DKK1 and associated downstream elements, [e.g., β-catenin]) on 
tumor tissue relative to safety and efficacy outcomes. 
Tumor blocks or partial blocks will be sectioned and may be returned to the Investigator at last 
patients visit or before if requested.  
The samples will be coded with the patient number and stored for up to a maximum 15 years 
after the last patient visit for the study at a facility selected by the Sponsor. The samples and any 
data generated from them can only be linked back to the patient by Investigator site personnel. 
The duration allows the Sponsor to respond to regulatory requests related to the study drug. 
Samples will be destroyed according to a process consistent with local regulation. 
7.4. 
Efficacy and Response Assessments 
Response and evaluation of PD will be determined according to RECIST v 1.1 (Eisenhauer et al. 
2009) (Appendix 12.2). Refer to the Schedule of Assessments [Table 6, (see Table 7 for Rollover 
Treatment Phase)] for details regarding the timing of specific efficacy measures.  
For baseline tumor measurements, all sites of disease should be imaged by computed 
tomography (CT)/positron emission tomography (PET). With the approval of the Medical 
Monitor, if the anatomic region cannot be adequately imaged by CT/PET, CT or MRI may be 
used instead. Baseline imaging studies may be performed within 28 days before C1D1.  
Tumor measurements are to be repeated within ±7 days of the first study drug dose in every 
other cycle, starting in C3, and at the EOT visit (±7 days) until radiographically documented 
PD. Repeat assessments should use the same radiographic methods as used at baseline 
(Appendix 12.2).  
To confirm objective responses, all lesions should be radiologically assessed, and the same 
radiologic method used for the initial response determination should be repeated at a minimum 
of 4 weeks following the initial observation of an objective response, using the sample method 
that was used at baseline. If a patient is discontinued from the study, repeat radiology 
assessments may be omitted if clear clinical signs of progressive disease are present. 
7.5. 
Post-Treatment Follow-up and Mortality Assessments 
After completion of the EOT visit, patients without radiographically-documented PD will 
continue to be followed up in the PD follow-up phase until radiographically documented PD. 
During this PD follow-up period, efficacy assessments for disease response and PD per RECIST 
1.1 will be performed every 8 weeks [see Table 6 (see Table 7 for Rollover Treatment Phase)]. 
Patients are expected not to start any other anti-cancer therapy during the PD follow-up phase 

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prior to radiographically documented PD; however, if alternate therapy is started, patients will 
continue to be followed for radiologic progression even after starting subsequent therapy.  
After discontinuation of treatment and documentation of PD, all patients will be followed in the 
Survival Follow-up Phase for survival until death, withdrawal of consent, loss to follow-up, 
implementation of the rollover treatment phase, or closure of the study by the Sponsor. Survival 
follow-up will occur 4 times per year (every 12 weeks [±14 days]) after the 30 days post 
treatment discontinuation visit or end of PD follow-up phase, as applicable, and may be 
conducted via telephone or office visit. During survival follow-up, the following information 
will be collected: survival and subsequent anti-cancer therapies. 

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8. 
ADVERSE EVENTS 
8.1. 
Definitions, Documentation, and Reporting 
8.1.1. 
Adverse Event Definition 
An AE is any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. An adverse event (also referred to as an adverse 
experience) can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a drug, without any judgment about 
causality. An adverse event can arise from any use of the drug (e.g., off-label use, use in 
combination with another drug) and from any route of administration, formulation, or dose, 
including an overdose. 
The Investigator is required to provide appropriate information concerning any findings that 
suggest significant hazards, contraindications, side effects, or precautions pertinent to the safety 
of the drug under investigation. 
In addition to collecting the AE verbatim and the NCI CTCAE severity grade, AE verbatim text 
will also be mapped by the Sponsor or designee to corresponding terminology within the 
Medical Dictionary for Regulatory Activities (MedDRA). 
Cases of pregnancy that occur during maternal or paternal exposures to study drug should be 
reported. Data on fetal outcome and breast-feeding are collected for regulatory reporting and 
drug safety evaluation. 
8.1.2. 
Serious Adverse Event Definition 
An AE is considered to be serious if, in the view of either the Investigator or the Sponsor, it 
results in any of the following outcomes: 
• Death. 
• Life-threatening. Life-threatening means that the patient was at immediate risk of death 
from the reaction as it occurred, i.e., it does not include a reaction which hypothetically 
might have caused death had it occurred in a more severe form. 
• In-patient hospitalization or prolongation of existing hospitalization. Hospitalization 
admissions and/or surgical operations scheduled to occur during the study period, but 
planned prior to study entry are not considered AEs if the illness or disease existed 
before the patient was enrolled in the study, provided that it did not deteriorate in an 
unexpected manner during the study (e.g., surgery performed earlier than planned). 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions. 
• Congenital anomaly/birth defect. 
• Important medical event. An important medical event is an event that may not result in 
death, be life-threatening, or require hospitalization but may be considered an SAE 
when, based upon appropriate medical judgment, it may jeopardize the patient or patient 
and may require medical or surgical intervention to prevent one of the outcomes listed in 
the definitions for SAEs. Examples of such medical events include allergic 

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bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in in-patient hospitalization, or the 
development of drug dependency or drug abuse. 
Planned surgeries should not be reported as SAEs unless the underlying medical condition has 
worsened during the course of the study. 
Planned hospitalizations or elective procedures for underlying preexisting conditions that are 
already recorded in the patient’s medical history at the time of study enrollment should not be 
considered SAEs. Hospitalization or prolongation of hospitalization without a precipitating 
clinical AE (for example, for the administration of study therapy or other protocol-required 
procedure) should not be considered SAEs. 
8.2. 
Procedures for Recording and Reporting AEs and SAEs 
Each patient must be carefully monitored for the development of any AEs. This information 
should be obtained in the form of non-leading questions (e.g., “How are you feeling?”) and 
from signs and symptoms detected during each examination, observations of study personnel, 
patient diaries, and spontaneous reports from patients. 
All AEs (serious and non-serious) spontaneously reported by the patient and/or in response to 
an open question from study personnel or revealed by observation, physical examination or 
other diagnostic procedures will be recorded on the appropriate page of the eCRF. Any 
clinically relevant deterioration in laboratory assessments or other clinical findings is 
considered an AE and must be recorded on the appropriate pages of the eCRF. When possible, 
signs and symptoms indicating a common underlying pathology should be noted as one 
comprehensive event. 
Study site personnel must alert Leap or its designee of any SAE within 24 hours of Investigator 
awareness of the event via a Leap-approved method. Alerts issued via telephone are to be 
immediately followed with official notification on study-specific SAE forms. The AEs which 
are serious and unexpected, and assessed as at least possibly related to study drug (possibly or 
related) will be reported to the regulatory authority by Leap, or it’s designee in accordance with 
21 CFR § 312.32. Patients will be monitored for AEs from signing of the informed consent 
form (ICF) to 30 days after the last dose of DKN-01.  
All SAEs that occur during the course of the study must be reported by the Investigator within 
24 hours from the point in time when the Investigator becomes aware of the SAE (Contact 
information will be provided by Leap or its designee). 
All SAEs must be reported whether or not considered causally related to the study drug. SAE 
forms will be completed and the information collected will include patient number, a narrative 
description of the event and an assessment by the Investigator as to the intensity of the event 
and relatedness to study drug. Follow-up information on the SAE may be requested by the 
Sponsor or designee. 
Certain SAEs require expedited reporting to regulatory authorities and Institutional Review 
Boards (IRB)/Independent Ethics Committees (IEC). If there are serious, unexpected adverse 
drug experiences associated with the use of the study drug, Leap or designee will notify the 

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appropriate regulatory agency(ies) and all participating Investigators on an expedited basis. It is 
the responsibility of the Investigator to promptly notify the IRB/IEC of all unexpected serious 
adverse drug experiences associated with the use of the study drug. 
For both serious and non-serious AEs, the Investigator must determine both the intensity of the 
event and the relationship of the event to study drug administration. 
Intensity of all AEs, including clinically significant treatment-emergent laboratory 
abnormalities and potential systemic reactions, will be graded according to the NCI CTCAE, 
version 5.0 (available at:  
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_
Reference_8.5x11.pdf). For AEs without matching terminology within the NCI CTCAE, 
version 5.0, criteria, the Investigator will be responsible for selecting the appropriate system 
organ class and assessing severity grade based on the intensity of the event. Note that both 
CTCAE term (actual or coded) and severity grade must be selected by study site personnel and 
collected in the eCRF. This collection is in addition to verbatim text used to describe the AE.  
The CTCAE grade refers to the severity of the AE and ranges from Grade 1 (mild AE), Grade 2 
(moderate AE), Grade 3 (severe AE) and Grade 4 (life-threatening or disabling AE) to Grade 5 
(death related to AE). 
AEs not listed by the CTCAE will be graded as follows: 
• Mild: discomfort noticed but no disruption of normal daily activity. 
• Moderate: discomfort sufficient to reduce or affect daily activity. 
• Severe: inability to work or perform normal daily activity. 
• Life threatening:  represents an immediate threat to life. 
• Death 
Relationship to study drug administration will be determined by the Investigator according to the 
following criteria. 
• Not Related: No relationship can be established between the event and the 
administration of study drug. The event is related to other etiologies, such as 
concomitant medications or patient’s clinical state. 
• Possible:  A reaction that follows a plausible temporal sequence from administration of 
the study drug and follows a pattern to the suspected study drug. The event recurs on re-
challenge. The event is not commonly associated with drug exposure but is also 
uncommon in the patient population. The reaction might have been produced by the 
patient’s clinical state or other modes of therapy administered to the patient. 
• Related:  A reaction that is known to be strongly associated with drug exposure. A 
temporal relationship can be established between the administration of study drug and 
the event. The reaction cannot be reasonably explained by the known characteristics of 
the patient’s clinical state or other modes of therapy administered to the patient. 
For the purpose of safety analyses, all AEs that are classified as having a possible or related 
relationship to study drug will be considered treatment-related events. 

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SAEs occurring after a patient has received the study drug will be collected for 30 days after the 
last dose of study drug, regardless of the Investigator’s opinion of causation. Thereafter, SAEs 
are not required to be reported unless the Investigator feels the events were related to either the 
study drug or a protocol procedure. 
Progressive disease (PD) will be documented in the eCRF intended to capture tumor response 
and PD, and will be analyzed accordingly. Signs and symptoms related to PD should be 
reported in the appropriate eCRF as either an AE or SAE. Verbatim terms such as “disease 
progression” or “progressive disease” etc. should not be reported as AEs or SAEs unless the 
Investigator considers the progression to be atypical, accelerated or caused by the study drug. 
Similarly, for deaths occurring as a result of PD during the study or until 30 days after the last 
dose of study drug is administered, the sign or symptom with an outcome of death should be 
reported on the AE and SAE pages: the verbatim term of “death” should not be used on the AE 
or SAE forms as the event. Additional information pertaining to the death should be reported on 
the eCRF intended to capture death information. 
8.3. 
Monitoring of Adverse Events and Period of Observation 
AEs and SAEs will be recorded starting at time of patient consent up to and including 30 days 
after administration of the last dose of DKN-01. All AEs should be monitored until they are 
resolved or are clearly determined to be due to a patient’s stable or chronic condition or 
intercurrent illness(es).  
Any SAE that occurs at any time after the EOT procedures are performed, which the 
Investigator considers to be related to study drug, must be reported to Leap or designee. 
If a patient’s dosage is reduced or treatment is discontinued as a result of an AE, study site 
personnel must clearly report to Leap or its designee via eCRF the circumstances and data 
leading to any such dosage reduction or discontinuation of treatment. 
All AEs should be monitored until they are resolved or are clearly determined to be due to a 
patient’s stable or chronic condition or intercurrent illness(es). 
Patients will be evaluated for AEs at each visit. Each patient will be instructed to call his or her 
physician to report any AEs between visits. Study site personnel will record the occurrence and 
nature of each patient’s preexisting conditions, including clinically significant signs and 
symptoms of the disease under treatment in the study.  
After the ICF is signed, site personnel will record any change in the condition(s) and the 
occurrence and nature of any AEs. All AEs related to protocol procedures will be reported to 
Leap or designee. Any clinically significant findings from ECGs, laboratory, or vital sign 
measurements that result in a diagnosis should be reported to Leap or its designee. Investigators 
will be instructed to report to Leap or its designee their assessment of the potential relatedness 
of each AE to protocol procedure, study drug, and/or drug delivery system via designated data 
transmission methods.  

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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Sample Size Determination 
This is a proof-of-concept basket study designed primarily to seek information on the safety, 
PK, and efficacy of DKN-01 in combination with paclitaxel and as DKN-01 monotherapy in 
patients with recurrent EOC or EEC with and without activating β-catenin mutation and/or Wnt 
signaling alterations, or carcinosarcoma (MMMT). A maximum of 124 evaluable patients 
(combination regimen plus monotherapy regimen) will be enrolled in the study. This is an 
exploratory open-label study with 6 groups. Groups 1-4 employ a 2-stage study design 
conducted separately for each group. Up to 21 evaluable patients are enrolled in each of 
Groups 1, 3, and 4 and up to 31 evaluable patients in Group 2. Groups 5 and 6 are exploratory 
in nature and will have up to 10 and 20 evaluable patients enrolled and dosed at the RP2D, 
respectively. 
The sample sizes for Groups 5 and 6 are based on practical considerations and clinical 
judgement to obtain sufficient information on the safety, initial clinical effectiveness, and PK 
data in the carcinosarcoma groups at a DKN-01 dose exceeding 300 mg. 
The sample size of Groups 1 through 4 employ a 2-stage study design and were calculated as 
follows: For each monotherapy group (Groups 1 and 3) after 12 evaluable patients are enrolled 
(Stage 1), an additional 9 evaluable patients will be enrolled in that group (Stage 2) if 1 or more 
patients respond (i.e., experience CR or PR). If there are no responses in Stage 1, then 
preliminary anti-tumor activity in the group will be rejected and no further patients will be 
enrolled in that group. If the group continues to Stage 2, a total of 21 evaluable patients will be 
studied for that group. The group will be considered successful if ≥3 treated patients respond. 
This design is applied to each monotherapy group separately and is based on a 2-stage Simon 
Minimax design for a total of 21 evaluable patients (null hypothesis that ORR ≤5% versus the 
alternative hypothesis that ORR ≥20% with alpha=0.080 and power=0.803).  
For combination therapy Group 2, after 20 evaluable patients are enrolled (Stage 1), an 
additional 11 evaluable patients will be enrolled in that group (Stage 2) if 3 or more patients 
respond (i.e., experience CR or PR). If there are fewer than 3 responses in Stage 1, then 
preliminary anti-tumor activity in the group will be rejected and no further patients will be 
enrolled in that group. If the group continues to Stage 2, a total of 31 evaluable patients will be 
studied for that group. The group will be considered successful if ≥6 treated patients respond. 
This design is applied to combination therapy Group 2 separately and is based on a 2-stage 
Simon Minimax design for a total of 31 evaluable patients (null hypothesis that ORR ≤12% 
versus the alternative hypothesis that ORR ≥25% with alpha=0.150 and power=0.802). 
For combination therapy Group 4, after 16 evaluable patients are enrolled (Stage 1), an 
additional 5 evaluable patients will be enrolled in that group (Stage 2) if 2 or more patients 
respond (i.e., experience CR or PR). If there are fewer than 2 responses in Stage 1, then 
preliminary anti-tumor activity in the group will be rejected and no further patients will be 
enrolled in that group. If the group continues to Stage 2, a total of 21 evaluable patients will be 
studied for that group. The group will be considered successful if ≥4 treated patients respond. 
This design is applied to combination therapy Group 4 separately and is based on a 2-stage 
Simon Minimax (Simon 1989) design for a total of 21 evaluable patients (null hypothesis that 

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ORR ≤10% versus the alternative hypothesis that ORR ≥25% with alpha=0.149 and 
power=0.803).  
There are no formal comparisons planned between groups. Any statistical results will be 
interpreted in the perspective of the exploratory nature of the study.  
9.2. 
Randomization 
There is no randomization in this open-label Phase 2 study. 
9.3. 
Populations for Analysis 
Several study populations will be used for analysis, as follows: 
• Evaluable Analysis Set (EAS): All patients who received any amount of DKN-01 and 
have at least one evaluable post-baseline RECIST tumor response assessment or were 
discontinued due to toxicity. The EAS will be the primary population for analyses of 
ORR, ODCR, PFS, DoR, DoCR, DoCB, and TTP. 
• Full analysis set (FAS): All enrolled patients who receive any amount of DKN-01. The 
FAS will be used for analyses of OS, TTTF, sensitivity analysis of select tumor-related 
endpoints, and exploratory endpoints. 
• Safety population, defined as all enrolled patients who receive any amount of study 
treatment (either DKN-01 or paclitaxel). All safety analyses will be based on this 
population. The safety population and FAS are identical, unless a patient received 
paclitaxel but did not receive DKN-01. 
• A Per-Protocol (PP) subset may also be used to analyze select efficacy endpoints and 
will be based on study drug exposure (compliance and/or time on study drug) and major 
protocol deviations. The criteria for inclusion in the PP subset will be finalized and 
documented. The PP set will be defined and finalized separately for each group. 
• PK Analysis Set: All enrolled patients who receive at least a single dose of DKN-01 and 
have sufficient data to determine PK parameters. 
9.4. 
Procedures for Handling Missing, Unused and Spurious Data 
The procedures for handling missing, unused, or spurious data, along with the detailed method 
for analysis of each variable, transformations, and exploratory analyses will be presented in the 
Statistical Analysis Plan (SAP). 
9.5. 
Interim Analyses 
Interim analyses will be conducted after Stage 1 for Groups 1-4. No interim analyses are planned 
for Groups 5 and 6. For each monotherapy group (Groups 1 and 3), after 12 evaluable patients 
are enrolled (Stage 1), an additional 9 evaluable patients will be enrolled in that group (Stage 2) 
if 1 or more patients respond (i.e., experience CR or PR). If there are no responses, then 
preliminary anti-tumor activity in the group will be rejected and no further patients will be 
enrolled in that group. 
For combination therapy Group 2, after 20 evaluable patients are enrolled (Stage 1), an additional 
11 evaluable patients will be enrolled in that group (Stage 2) if 3 or more patients respond (i.e., 

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experience CR or PR). If there are fewer than 3 responses in Stage 1, then preliminary anti-tumor 
activity in the group will be rejected and no further patients will be enrolled in that group. 
For combination therapy Group 4, after 16 evaluable patients are enrolled (Stage 1), an additional 
5 evaluable patients will be enrolled in that group (Stage 2) if 2 or more patients respond (i.e., 
experience CR or PR). If there are fewer than 2 responses in Stage 1, then preliminary anti-tumor 
activity in the group will be rejected and no further patients will be enrolled in that group. 
9.6. 
Statistical Methods 
9.6.1. 
General Methods 
Summaries will be tabulated for each group and within each group, where applicable, by 
presence of Wnt signaling alterations and/or CTNNB1 activating mutations. Selected 
parameters may also be summarized by dose and will be detailed in the SAP. 
Descriptive statistics (N, mean, standard deviation, median, minimum, and maximum) will be 
presented for continuous variables. Frequency distributions (counts and associated percentages) 
will be presented for categorical variables. Median, 25th and 75th percentiles and standard error 
will be presented for time-to-event data. 
This study is descriptive in nature; no formal comparisons between groups will be performed. 
All confidence intervals (CIs) will be 95%, unless stated otherwise. 
Individual patient data listings will be provided to support summary tables.  
The effects of noncompliance, treatment discontinuations, premature study withdrawals, 
subsequent therapies, and covariates will be assessed to determine the impact on the general 
applicability of results from this study. 
9.6.2. 
Disposition of Patients 
All patient discontinuations will be documented, and the extent of each patient’s participation in 
the study will be reported. If known, a reason for their discontinuation will be given. The 
following information will be summarized: 
• Number enrolled 
• Number receiving treatment 
• Number and percentage who completed the protocol 
• Number and percentage of patients who discontinued treatment 
• Reason for discontinuation 
9.6.3. 
Baseline Characteristics 
Patient characteristics will include a summary/listing of the following: 
• Patient demographics 
• Baseline disease characteristics 
• Prior disease-related therapies 
• Concomitant medications 

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Other patient characteristics will be summarized as deemed appropriate. 
9.6.4. 
Efficacy Analysis 
Efficacy data will be summarized for each group. Selected summaries may also be done within 
each group, as applicable, by presence of Wnt signaling alterations and/or CTNNB1 activating 
mutations, and by subgroups as described in the SAP. 
All efficacy endpoints are secondary for Group 5 and Group 6. 
9.6.4.1. 
Primary Efficacy Endpoint and Analysis (Groups 1-4) 
For the purpose of the 2-stage design in Groups 1-4, the ORR is considered the primary efficacy 
endpoint. The ORR is defined as the proportion of patients with BOR of PR or CR according to 
RECIST 1.1. The proportion of patients with ORR in the EAS, along with a 95% CI, based on 
the Clopper-Pearson interval, will be reported. Secondary analyses of ORR described above 
may be repeated in FAS, treating missing BOR as a non-responder. ORR at each visit and best 
overall response will also be summarized using the EAS. Secondary analyses of ORR may be 
repeated in the PP set.  
9.6.4.2. 
Secondary Efficacy Endpoints and Analysis (Groups 1-4) 
Secondary efficacy variables in the study include: 
• Objective disease control rate (ODCR) is defined as the percentage of patients with 
BOR of CR, PR, or SD. The analysis of ODCR will be performed using the EAS and 
conducted in the same manner as ORR. Similar to ORR, analysis of ODCR may be 
repeated in the FAS and PP set. 
• Overall survival (OS) is defined as the time from first dose of study drug until date of 
death due to any cause. Patients without documentation of death at the time of analysis 
will be censored as of the date the patient was last known to be alive, or the data cut-off 
date, whichever is earlier. Overall survival (OS) will be performed in the FAS using 
Kaplan-Meier methods. 
• Progression-free survival (PFS) is defined as time from first dose of study drug to first 
documentation of PD (per RECIST 1.1) or death due to any cause. Analysis of PFS will 
be performed in the EAS and may be repeated in the FAS and PP set. 
Patients who do not experience PD and are alive will be censored at the time of last 
evaluable tumor assessment. Patients who do not experience PD and start new anti-
cancer therapy will be censored at the last evaluable tumor assessment on or prior to the 
time the new anti-cancer therapy. For analyses conducted in the FAS, patients with no 
evaluable post-baseline tumor assessments will be censored at the time of receipt of first 
study drug. Patients who are lost to follow-up for assessment of PD will be censored at 
their last evaluable tumor assessment. Additional details for censoring will be specified 
in the SAP and will be based on the Food and Drug Administration, Guidance for 
Industry: Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics, 
dated May 2007. The analysis of PFS will be based on Kaplan-Meier methods. 

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• Time to progression (TTP) is defined as time from first dose of study drug to first 
documentation of PD (per RECIST 1.1). Analysis of TTP will be performed in the EAS 
and may be repeated in the FAS and PP set.  
Patients who do not experience PD will be censored at the time of last evaluable tumor 
assessment. Patients who do not experience disease progression and start new anti-
cancer therapy will be censored at the last evaluable tumor assessment on or prior to the 
time the new anti-cancer therapy was begun. For analyses conducted in the FAS, 
patients with no evaluable post-baseline tumor assessments will be censored at the time 
of receipt of first study drug. Patients who are lost to follow-up for assessment of PD 
will be censored at their last evaluable tumor assessment. Additional details for 
censoring will be specified in the SAP. The analysis of TTP will be based on 
Kaplan-Meier methods. 
• Duration of response (DoR) includes patients with an objective disease response (PR or 
CR) and is defined as the time from the first tumor assessment that supports the patient’s 
objective disease response to the time of PD or death due to any cause. Patients who do 
not experience PD or death at the time of analysis will be censored using the same rules 
as described for PFS. The analysis of DOR will be performed in the EAS using Kaplan-
Meier methods. 
• Duration of CR (DoCR) includes patients with a CR and is otherwise defined and 
analyzed similarly to DoR. 
• Duration of clinical benefit (DoCB) includes patients with a BOR of CR, PR, or SD 
and is defined as the time from the first tumor assessment of CR, PR or SD to the time 
of PD or death due to any cause. Patients who do not experience PD or death at the time 
of analysis will be censored using the same rules as described for PFS. The analysis of 
DoCB will be performed in the EAS using Kaplan-Meier methods. 
• Time to treatment failure (TTTF) is defined as time from first dose of study drug to 
discontinuation of DKN-01 for any reason including PD, toxicity, and death. Patients 
without documentation of death at the time of analysis will be censored as of the date the 
patient was last known to be alive, or the data cut-off date, whichever is earlier. Time to 
treatment failure (TTTF) will be performed in the FAS using Kaplan-Meier methods. 
9.6.4.3. 
Secondary Efficacy Endpoints and Analysis (Groups 5-6) 
Secondary efficacy endpoints in each independent study group (Groups 5-6) are: 
• ORR (i.e., BOR of CR + PR), as assessed by the Investigator using RECIST 1.1. 
• ODCR (i.e., CR+PR+SD > 6 weeks), as assessed by the Investigator using RECIST 1.1. 
• OS, defined as the time from first study drug dose (i.e., C1D1) to death from any cause.  
• PFS, defined as the time from first study drug dose (C1D1) to first radiographically-
documented PD, as determined using RECIST 1.1, or death due to any cause. 
• TTP, defined as the time from first study drug dose (C1D1) until the date of first 
radiographically-documented PD, as determined using RECIST 1.1. 

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• DoR, defined as the time from initial response (≥PR) until radiographically-documented 
PD or death; PD is defined using RECIST 1.1. 
• DoCR, defined as the time from initial CR until radiographically-documented PD or 
death; PD is defined using RECIST 1.1. 
• DoCB, defined as the time from the first tumor assessment of CR, PR or SD to the time 
of PD or death due to any cause; PD is defined using RECIST 1.1. 
• 
TTTF, defined as the time from first study drug dose (C1D1) until the date of treatment 
discontinuation of DKN-01 for any reason, including PD, toxicity, and death. 
9.6.5. 
Safety Analysis 
All analysis of safety and toxicity will be conducted in the safety population. 
Adverse event terms and severity grades will be assigned by the Investigator using the NCI 
CTCAE, version 5.0. Safety parameters will be listed and summarized using standard 
descriptive statistics. 
Analyses will be conducted to characterize the safety and tolerability of DKN-01 and DKN-01 
in combination with paclitaxel by group and overall. 
Safety analyses will include presentations of the following: 
• TEAEs, including severity and possible relationship to study drug 
• Dose adjustments 
• Laboratory values 
• Vital signs 
• ECOG performance status 
• Physical examinations 
• ECG readings 
• Infusion-related reactions 
• Concomitant medication 
For Groups 5 and 6, the following analysis will be presented: 
• DLTs 
9.6.5.1. 
Study Drug Exposure 
Descriptive statistics of the amount of each drug, the number of infusions administered, and 
compliance will be tabulated by group, along with information on missed doses, dosing delays, 
and dose reductions. 
9.6.5.2. 
Adverse Events 
AEs will be coded using the current MedDRA dictionary. 
Analyses of AEs will be performed for those events that are considered treatment-emergent, 
where a TEAE is defined as any AE with onset or (worsening of a pre-existing condition) after 

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the first dose of study drug through 30 days following the last dose of study drug. AEs with 
partial dates will be assessed using the available date information to determine if treatment-
emergent; AEs with completely missing dates will be assumed to be treatment-emergent. 
Incidence of TEAEs, TEAEs leading to dose reduction/interruption, TEAEs related to study 
drug, SAEs, TEAEs leading to study drug discontinuation, and TEAEs with an outcome of 
death will be summarized by system organ class and preferred term by group. A summary of 
TEAEs of CTCAE Grade 3 or higher will also be provided by group. The number and percent 
of patients with infusion-related reactions will be summarized by group, overall, and by visit. 
No formal hypothesis-testing analysis of TEAE incidence will be performed. All TEAEs 
occurring on-study will be listed in patient data listings. By-patient listings also will be provided 
for the following:  patient deaths, SAEs, TEAEs leading to study drug discontinuation, and 
TEAEs with intensity ≥Grade 3. 
9.6.5.3. 
Clinical Laboratory Data 
Clinical laboratory values will be summarized in SI units (Système Internationale d'Unités; 
International System of Units). 
The actual value and change from baseline to each on-study evaluation will be summarized for 
each clinical laboratory parameter, including hematology and clinical chemistry. Summaries 
will be presented by group. In the event of multiple evaluations for the same parameter at the 
same visit, the last non-missing value per study day/time will be used. 
Shift tables that present changes from baseline to worst on-study values relative to NCI CTCAE 
classification ranges and incidence of treatment-emergent Grade 3 / 4 clinical laboratory 
abnormalities will be presented by group.  
All laboratory data will be provided in data listings. A subset listing will be presented for all 
clinically significant abnormal laboratory values. 
9.6.5.4. 
Other Safety Parameters 
Concomitant medications and procedures will be summarized by group. Vital signs, ECG 
results, and shifts from baseline in ECOG PS will be summarized descriptively over time by 
group. These data and physical examination results will be provided in data listings. 
9.6.6. 
Pharmacokinetic Analyses 
Pharmacokinetic analyses will be conducted on patients in the PK Analysis Set, defined as all 
enrolled patients who have received at least a single dose of DKN-01 and have sufficient data to 
determine PK parameters.  
The Cmax, Tmax, and AUCs will be reported, as feasible.  
Data may be pooled with data from other studies to refine the previously developed population 
PK and/or PK/PcD models, or to conduct further modeling activities.  
9.6.7. 
Immunogenicity Analyses 
Details regarding immunogenicity analyses will be provided in the SAP. 

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9.6.8. Analysis of Exploratory Endpoints 
Exploratory analysis will be evaluated for the following exploratory endpoints: 
• DKK1 concentration in serum and plasma. 
• Tumor genetics, gene expression levels (e.g., RNA-Seq), DKK1 expression (e.g. 
RNAscope in situ hybridization), immunohistology, infiltrating immune cells and 
additional IHC staining (DKK1 and associated downstream elements, [e.g., β-catenin]) 
on tumor tissue relative to safety and efficacy outcomes. 
Additional details will be provided in the SAP. 
9.6.9. 
Procedures for Reporting Deviations to the Original Statistical Analysis Plan 
All deviations from the original SAP will be provided in the final clinical study report. 

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10. 
ADMINISTRATIVE REQUIREMENTS 
10.1. Good Clinical Practice 
The study will be conducted in accordance with ICH GCP and the appropriate regulatory 
requirement(s). The Investigator will be thoroughly familiar with the appropriate use of the 
study drug as described in the protocol and Investigator’s Brochure. Essential clinical 
documents will be maintained to demonstrate the validity of the study and the integrity of the 
data collected. Master files should be established at the beginning of the study, maintained for 
the duration of the study and retained according to the appropriate regulations. 
10.2. Ethical Considerations 
The study will be conducted in accordance with ethical principles founded in the Declaration of 
Helsinki (see Appendix 12.7). The IRB will review all appropriate study documentation in order 
to safeguard the rights, safety, and well-being of the patients. The study will only be conducted 
at sites where IRB approval has been obtained. The protocol, Investigator’s Brochure, informed 
consent, advertisements (if applicable), written information given to the patients (including 
diary cards), safety updates, annual progress reports, and any revisions to these documents will 
be provided to the IRB by the Investigator. 
10.3. Patient Information and Informed Consent 
After the study has been fully explained, written informed consent will be obtained from either 
the patient or his/her guardian or legal representative prior to study participation. The method of 
obtaining and documenting the informed consent and the contents of the consent will comply 
with ICH-GCP and all applicable regulatory requirement(s). 
10.4. Patient Confidentiality 
In order to maintain patient privacy, all eCRFs, study drug accountability records, study reports 
and communications will identify the patient by initials and the assigned patient number. The 
Investigator will grant monitor(s) and auditor(s) from Leap or its designee and regulatory 
authority(ies) access to the patient’s original medical records for verification of data gathered on 
the eCRFs and to audit the data collection process. The patient’s confidentiality will be 
maintained and will not be made publicly available to the extent permitted by the applicable 
laws and regulations. 
10.5. Protocol Compliance 
The Investigator will conduct the study in compliance with the protocol provided by Leap, and 
given approval/favorable opinion by the IRB and the appropriate regulatory authority(ies). 
Modifications to the protocol should not be made without agreement of both the Investigator 
and Leap. Changes to the protocol will require written IRB approval/favorable opinion prior to 
implementation, except when the modification is needed to eliminate an immediate hazard(s) to 
patients. The IRB may provide, if applicable regulatory authority(ies) permit, expedited review 
and approval/favorable opinion for minor change(s) in ongoing studies that have the approval 
/favorable opinion of the IRB. Leap will submit all protocol modifications to the regulatory 
authority(ies) in accordance with the governing regulations.  

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When immediate deviation from the protocol is required to eliminate an immediate hazard(s) to 
patients, the Investigator will contact Leap, if circumstances permit, to discuss the planned 
course of action. Any departures from the protocol must be fully documented in the eCRF and 
source documentation.  
10.6. Direct Access to Source Data 
Monitoring and auditing procedures developed by Leap or designee will be followed, in order to 
comply with GCP guidelines. 
The study will be monitored by Leap or its designee. Monitoring will be done by personal visits 
from a representative of the Sponsor (site monitor) and will include on-site review of the eCRFs 
for completeness and clarity, cross-checking with source documents, and clarification of 
administrative matters will be performed. The review of medical records will be performed in a 
manner to ensure that patient confidentiality is maintained. 
The site monitor will ensure that the investigation is conducted according to protocol design and 
regulatory requirements by frequent communications (letter, telephone, and fax). 
All unused study drug and other study materials are to be returned to Leap after the clinical 
phase of the study has been completed or, if authorized, disposed of at the study site and 
documented (see Section 5.4). 
Regulatory authorities, the IEC/IRB, and/or the clinical quality assurance group of Leap or 
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. 
10.7. Case Report Form Completion 
Leap or its designee will provide the study sites with an eCRF that will be completed for each 
study patient. 
It is the Investigator’s responsibility to ensure the accuracy, completeness, and timeliness of the 
data reported in the patient’s eCRF. Source documentation supporting the eCRF data should 
indicate the patient’s participation in the study and should document the dates and details of 
study procedures, adverse events, and patient status. 
The Investigator, or designated representative, should complete the eCRF pages as soon as 
possible after information is collected, preferably on the same day that a study patient is seen 
for an examination, treatment, or any other study procedure. Any outstanding entries must be 
completed immediately after the final examination. An explanation should be given for all 
missing data. 
The Investigator must sign and date the Investigator’s Statement at the end of the eCRF to 
endorse the recorded data. 
10.8. Record Retention 
The Investigator will maintain all study records according to ICH-GCP and applicable 
regulatory requirement(s). Records will be retained until the Investigator is notified by the 
Sponsor that this is no longer required. If the Investigator withdraws from the responsibility of 

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keeping the study records, custody must be transferred to a person willing to accept the 
responsibility. Leap must be notified in writing if a custodial change occurs. 
10.9. Liability and Insurance 
Leap has subscribed to an insurance policy covering, in its terms and provisions, its legal 
liability for injuries caused to participating persons and arising out of this research performed 
strictly in accordance with the scientific protocol as well as with applicable law and professional 
standards. 
10.10. Publication of Study Findings and Use of Information 
All information regarding DKN-01 supplied by Leap to the Investigator is privileged and 
confidential information. The Investigator agrees to use this information to accomplish the 
study and will not use it for other purposes without consent from Leap. The Investigator is 
obligated to provide Leap with complete data obtained during the study. The information 
obtained from the clinical study will be used towards the development of DKN-01 and may be 
disclosed to regulatory authority(ies), other investigators, corporate partners, or consultants as 
required. 
It is anticipated that the results of this study will be presented at scientific meetings and/or 
published in a peer reviewed scientific or medical journal. A Publications Committee, 
comprised of investigators participating in the study and representatives from Leap, as 
appropriate, will be formed to oversee the publication of the study results, which will reflect the 
experience of all participating study centers. Subsequently, individual investigators may publish 
results from the study in compliance with their agreement with Leap. A pre-publication 
manuscript is to be provided to Leap at least 30 days prior to the submission of the manuscript 
to a publisher. Similarly, Leap will provide any company-prepared manuscript to the 
investigators for review at least 30 days prior to submission to a publisher. 
 

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11. 
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12. 
APPENDICES 
 

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12.1. Schedule of Assessments 
The schedule of study assessments is presented in Table 6. 
Table 6 
Schedule of Assessments 
Procedure 
Screening 
(Within 
28 Days of 
C1 D1)1 
Treatment Period 
EOT 
(30 Days 
Post Tx 
Discon-
tinuation) 
PD 
Follow-up 
(Q8 
weeks3) 
Survival 
Follow-up 
(Q12 
weeks4) 
Cycle 1 
≥Cycle 2 
C1 
D1/ 
Baseline 
C1D8 
C1D15 
D1 
D82 
D15 
Visit Window 
- 
- 
± 1D 
± 1D 
± 1D 
± 1D 
± 1D 
+ 7D 
± 7D 
± 14D 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Cancer history, including treatment 
history5 and, if available, genomics 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Tumor tissue collection/biopsy 
X6,7 
 
 
 
X8 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
Complete physical examination 
X 
 
 
 
 
 
 
X 
 
 
Abbreviated physical examination 
 
X 
 
X 
X 
 
X 
 
 
 
Weight 
X 
X 
 
 
X 
 
 
X 
 
 
Body surface area 
 
X 
 
 
X 
 
 
 
 
 
Vital signs 
X 
X 
 
 
X 
 
 
X 
 
 
Electrocardiogram 
X 
X 
 
 
X 
 
 
X 
 
 
ECOG performance status 
X 
X 
 
 
X 
 
 
X 
 
 
Laboratory sample collection 
 
 
 
 
 
 
 
 
 
 
Hematology9 
X10 
X 
 
X 
X 
 
X 
X 
 
 
Neutrophil-to-lymphocyte ratio (NLR) 
X10 
X 
 
 
 
 
 
 
 
 
Coagulation studies9 
X10 
 
 
 
 
 
 
 
 
 
Clinical chemistries11 
X10 
X 
 
X 
X 
 
X 
X 
 
 
CA125 
X10 
X 
 
 
X 
 
 
X 
 
 
Vitamin D 
X10 
X 
 
 
 
 
 
X 
 
 
TSH 
X10 
X 
 
 
X 
 
 
X 
 
 
Urinalysis12 
X10 
X 
 
 
X 
 
 
X 
 
 
Pregnancy testing13 
X10 
X 
 
 
X 
 
 
X 
 
 
PK14 
 
X 
X 
X 
X 
 
 
X 
 
 

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Procedure 
Screening 
(Within 
28 Days of 
C1 D1)1 
Treatment Period 
EOT 
(30 Days 
Post Tx 
Discon-
tinuation) 
PD 
Follow-up 
(Q8 
weeks3) 
Survival 
Follow-up 
(Q12 
weeks4) 
Cycle 1 
≥Cycle 2 
C1 
D1/ 
Baseline 
C1D8 
C1D15 
D1 
D82 
D15 
Visit Window 
- 
- 
± 1D 
± 1D 
± 1D 
± 1D 
± 1D 
+ 7D 
± 7D 
± 14D 
ADA15 
 
X 
 
 
X 
 
 
X 
 
 
Serum DKK1 
X 
X 
 
 
X 
 
 
X 
 
 
Plasma samples for exploratory 
biomarker analysis 
 
X 
 
 
X 
 
 
X 
 
 
Study drug administration16 
 
 
 
 
 
 
 
 
 
 
Pre-treatment17 
 
X 
X 
X 
X 
X 
X 
 
 
 
DKN-01 monotherapy 
 
X 
 
X 
X 
 
X 
 
 
 
Combination therapy: 
 
 
 
 
 
 
 
 
 
 
DKN-0118 
 
X 
 
X 
X 
 
X 
 
 
 
Paclitaxel18 
 
X 
X 
X 
X 
X 
X 
 
 
 
Tumor imaging19 
X 
 
 
 
X 
 
 
X 
X 
 
Disease response assessment20 
 
 
 
 
X 
 
 
X 
X 
 
Adverse events, including infusion-
related AEs  
 
X 
X 
X 
X 
X 
X 
X 
 
 
Concomitant medications 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Survival and subsequent therapies 
 
 
 
 
 
 
 
X 
X 
X 

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Table footnotes: 
1 
To allow-for real-time testing of Screening tumor tissue samples, the Screening period may be extended to 42 days in such cases, with results obtained and confirmed to be 
positive before the performance of additional Screening procedures. All other Screening assessments must be performed within 28 days before C1D1. 
2 
After completion of Cycle 2, subsequent D8 visits can be conducted over the phone with patients in the monotherapy groups. 
3 
Imaging studies, tumor assessments, and disease response assessment should be performed as scheduled every 8 weeks (± 7 days) following first dose of study therapy until 
radiographically-documented progression of disease, even if therapy is delayed. PD Follow-up phase only applies to patients who discontinue study treatment without 
documented PD. 
4 
All patients will be followed in the Survival Follow-up phase for survival until death, withdrawal of consent, loss to follow-up, implementation of the rollover treatment 
phase, or closure of the study by the Sponsor. Long-term follow-up will occur 4 times per year (every 12 weeks ±14 days) after the 30 days post treatment discontinuation 
visit or PD follow-up phase discontinuation visit, as applicable. 
5 
Cancer treatment history is to include documentation of prior chemotherapy, radiation therapy, surgery, and use of blood products, including red cell and platelet 
transfusions and growth factors within the previous 3 months. 
6 
Note that fresh tumor tissue samples are required to be collected from all patients during Screening for genomic cancer profiling. Although fresh biopsy is preferred, an 
archived specimen collected within 3 months of study entry may be acceptable, with the prior approval of the Medical Monitor.  
7 
This basket study will enrich for Wnt signaling alterations whereby approximately 50% of all patients enrolled require an activating β-catenin mutation (CTNNB1 mutation) 
or other Wnt signaling alteration (e.g., LRP5/6, APC, AXIN1/2, GSK3B, RNF43, ZNRF3, RSPO2/3, FBXW7, ARID1A, or CBP/CREBBP; see full list in Appendix 12.6). 
Once 50% of patients (i.e., 10 patients) without a documented β-catenin or other Wnt signaling alteration have been enrolled within a group, enrollment in that group will 
continue only with patients with activating β-catenin mutation (CTNNB1 mutation) or other identified Wnt signaling alteration. 
8 
Fresh tumor tissue samples will be obtained from all patients at C2D1 ±7 days. The same lesion biopsied during Screening is to be biopsied at C2D1 ±7 days. The target 
lesion(s) should not be biopsied. If a repeat biopsy is required during study participation, a sample of the biopsy will be submitted for evaluation. Patients who discontinue 
prior to the C2D1 visit are to have a biopsy performed at the EOT visit. Exploratory analyses will include tumor genetics, gene expression levels (e.g., RNA-Seq), DKK1 
expression (e.g., RNAscope in situ hybridization), immunohistology, infiltrating immune cells and additional IHC staining to evaluate DKK1 and DKK1 associated 
downstream elements (e.g., β-catenin) on tumor tissue relative to safety and efficacy outcomes. If a repeat biopsy is required during study participation, a sample of the 
biopsy will be submitted for evaluation.  
9 
Hematology includes hemoglobin, hematocrit, erythrocyte count (RBC), mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), leukocytes (WBC), 
neutrophils, segmented and banded, lymphocytes, monocytes, eosinophils, basophils, and platelets. It is acceptable to use the automated differential for complete blood count 
(CBC). Coagulation studies include prothrombin time (PT)/partial thromboplastin time (PTT) and international normalized ratio (INR).  
10 
If Screening safety laboratory tests are obtained ≤72 hours of C1D1 to confirm eligibility, safety labs should be repeated on C1D1 but do not need to be resulted prior to 
dosing. If Screening laboratory tests are obtained ≥72 hours prior to C1D1, then all safety laboratory tests need to be repeated on C1D1 to confirm eligibility. All pre-
treatment laboratory tests are to be obtained with 24- 48 hours of D1 dosing. 
11 
Clinical chemistry includes sodium, potassium, total and direct bilirubin, lactate dehydrogenase (LDH), ALP, ALT, AST, blood urea nitrogen (BUN), creatinine, creatine 
kinase, uric acid, calcium, glucose (random), albumin, cholesterol, serum chloride, phosphorus, carbon dioxide, and total protein. 
12 
Urinalysis includes specific gravity, pH, protein, glucose, ketones, blood, and leukocyte esterase. 
13 
Serum or urine pregnancy testing is to be performed for women of childbearing potential. If a urine test is positive or cannot be confirmed as negative, a serum pregnancy 
test will be required. On C1D1, the pregnancy test may be performed within 72 hours before the study drug dose; the results must be available and confirmed to be negative 
before administration of the first study drug dose. Pregnancy testing is to be repeated during the study any time pregnancy is suspected. 
14 
Blood samples for serum PK are to be collected on C1D1 pre-infusion, post-infusion, and then 24 hours (1 day), and 168 hours (7 days) post-infusion. Thereafter, such 
samples are to be collected pre- and post-infusion on D1 of each cycle and a final sample is to be collected at the EOT visit. Please use the following windows when 
scheduling blood samples for PK: C1D1 pre-infusion: - 60-minute window; C1D1 post infusion: ± 5-minute window; 24 hours (1 day): random draw during Day 2; 
168 hours (7 days): ± 1 day; C1D15 pre-infusion: -60 minute window 

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15 
Blood samples for serum ADA/immunogenicity are to be collected pre-infusion on C1D1, and then pre-infusion on D1 of every other cycle beginning with C3 (C5, C7, C9, 
etc) and at the EOT visit. If any patient is found to be ADA-positive at the EOT visit, the patient will be monitored monthly (if feasible) until serum samples are determined 
to be ADA-negative. If a patient has an infusion reaction, all attempts should be made to obtain an immunogenicity and PK sample as close to the onset of the event as 
possible, at the resolution of the event and 30 days following the event.   
16 
For patients receiving combination therapy, study drug is to be administered in the following order:  premedications DKN-01  paclitaxel. 
17 
Premedication for paclitaxel (will be given prior to each paclitaxel infusion as per local standard of care. Suggested premedications include dexamethasone 20 mg orally 
[PO] 12 to 6 hours prior; diphenhydramine 50 mg IV 30 to 60 minutes prior; and cimetidine or ranitidine 50 mg IV 30 to 60 minutes prior) or equivalents.  
18 
DKN-01 will be administered IV over a minimum of 30 minutes and up to a maximum of 2 hours given on days 1 and 15 of each cycle without interruption plus paclitaxel 
administered IV over 1 hour on Days 1, 8, and 15 of each 28-day cycle according to standard clinical practice. Standard of care premedication for paclitaxel will be given 
prior to DKN-01. For patients receiving combination therapy, DKN-01 will be administered first followed by paclitaxel. 
19 
Baseline imaging studies may be performed within 28 days before C1D1. For baseline tumor measurements, all sites of disease should be imaged by CT/PET. With the 
approval of the Medical Monitor, if the anatomic region cannot be adequately imaged by CT/PET, CT or MRI may be used instead. Tumor measurements are to be repeated 
within ±7 days of the first study drug dose in every other cycle, starting in C3, and at the EOT Visit until radiographically documented progression of disease. Repeat 
assessments should use the same radiographic methods as used at Baseline.  
20 
Disease response is to be assessed by the Investigator using RECIST 1.1 (Eisenhauer et al., 2009) within ±7 days of the first study drug dose in every other cycle, starting in 
Cycle 3 and at the EOT Visit following first dose of study therapy until radiographically documented PD. 
 
  
 
 

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The schedule of study assessments for Rollover Treatment Phase is presented in Table 7. 
Table 7 
Schedule of Assessments- Rollover Treatment Phase 
Procedure 
Treatment Period 
EOT 
(30 Days 
Post Tx 
Discon-
tinuation) 
PD Follow-up 
(Q8 weeks3) 
Survival 
Follow-up 
(Q12 weeks4) 
≥Cycle 2 
D1 
D82 
D15 
Visit Window 
± 1D 
± 1D 
± 1D 
+ 7D 
± 7D 
± 14D 
Informed consent1 
 
 
 
 
 
 
Complete physical examination 
 
 
 
X 
 
 
Abbreviated physical examination 
X 
 
X 
 
 
 
Weight 
X 
 
 
X 
 
 
Body surface area 
X 
 
 
 
 
 
Vital signs 
X 
 
 
X 
 
 
Electrocardiogram 
X 
 
 
X 
 
 
ECOG performance status 
X 
 
 
X 
 
 
Laboratory sample collection 
 
 
 
 
 
 
Hematology5 
X 
 
X 
X 
 
 
Coagulation studies5 
 
 
 
 
 
 
Clinical chemistries6 
X 
 
X 
X 
 
 
Urinalysis7 
X 
 
 
X 
 
 
Pregnancy testing8 
X 
 
 
X 
 
 
Study drug administration9 
 
 
 
 
 
 
Pre-treatment10 
X 
X 
X 
 
 
 
DKN-01 monotherapy 
X 
 
X 
 
 
 
Combination therapy: 
 
 
 
 
 
 
DKN-0111 
X 
 
X 
 
 
 
Paclitaxel11 
X 
X 
X 
 
 
 
Tumor imaging 12 
X 
 
 
X 
X 
 
Disease response assessment13 
X 
 
 
X 
X 
 
Adverse events, including infusion-related AEs  
X 
X 
X 
X 
 
 
Concomitant medications 
X 
X 
X 
X 
 
 
Survival and subsequent therapies 
 
 
 
X 
X 
X 

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Table footnotes: 
1 
Prior to starting treatment in the Rollover Treatment Phase patient are be consented to the corresponding consent form. 
2 
After completion of Cycle 2, subsequent D8 visits can be conducted over the phone with patients in the monotherapy groups. 
3 
Imaging studies, tumor assessments, and disease response assessment should be performed as scheduled every 12 weeks (± 7 days) following first dose of study therapy until 
radiographically-documented progression of disease, even if therapy is delayed. PD Follow-up phase only applies to patients who discontinue study treatment without 
documented PD. 
4 
All patients will be followed in the Survival Follow-up phase for survival until death, withdrawal of consent, loss to follow-up, or closure of the study by the Sponsor. Long-
term follow-up will occur 4 times per year (every 12 weeks ±14 days) after the 30 days post treatment discontinuation visit or PD follow-up phase discontinuation visit, as 
applicable. 
5 
Hematology includes hemoglobin, hematocrit, erythrocyte count (RBC), mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), leukocytes (WBC), 
neutrophils, segmented and banded, lymphocytes, monocytes, eosinophils, basophils, and platelets. It is acceptable to use the automated differential for complete blood count 
(CBC). Coagulation studies include prothrombin time (PT)/partial thromboplastin time (PTT) and international normalized ratio (INR). All pre-treatment laboratory tests are 
to be obtained with 24- 48 hours of D1 dosing. 
6 
Clinical chemistry includes sodium, potassium, total and direct bilirubin, lactate dehydrogenase (LDH), ALP, ALT, AST, blood urea nitrogen (BUN), creatinine, creatine 
kinase, uric acid, calcium, glucose (random), albumin, cholesterol, serum chloride, phosphorus, carbon dioxide, and total protein. All pre-treatment laboratory tests are to be 
obtained with 24- 48 hours of D1 dosing. 
7 
Urinalysis includes specific gravity, pH, protein, glucose, ketones, blood, and leukocyte esterase. All pre-treatment laboratory tests are to be obtained with 24- 48 hours of 
D1 dosing. 
8 
Serum or urine pregnancy testing is to be performed for women of childbearing potential. If a urine test is positive or cannot be confirmed as negative, a serum pregnancy 
test will be required. Pregnancy testing is to be repeated during the study any time pregnancy is suspected. 
9 
For patients receiving combination therapy, study drug is to be administered in the following order:  premedications DKN-01  paclitaxel. 
10 
Premedication for paclitaxel (will be given prior to each paclitaxel infusion as per local standard of care. Suggested premedications include dexamethasone 20 mg orally 
[PO] 12 to 6 hours prior; diphenhydramine 50 mg IV 30 to 60 minutes prior; and cimetidine or ranitidine 50 mg IV 30 to 60 minutes prior) or equivalents.  
11 
DKN-01 will be administered IV over a minimum of 30 minutes and up to a maximum of 2 hours given on days 1 and 15 of each cycle without interruption plus paclitaxel 
administered IV over 1 hour on Days 1, 8, and 15 of each 28-day cycle according to standard clinical practice. Standard of care premedication for paclitaxel will be given 
prior to DKN-01. For patients receiving combination therapy, DKN-01 will be administered first followed by paclitaxel. 
12 
Tumor measurements are to be repeated within ±7 days every 12 weeks, and at the EOT Visit until radiographically documented progression of disease. Repeat assessments 
should use the same radiographic methods as used at Baseline.  
13 
Disease response is to be assessed by the Investigator using RECIST 1.1 (Eisenhauer et al., 2009) within ±7 days every 12 weeks and at the EOT Visit following first dose of 
study therapy until radiographically documented PD. 
 
 
 

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12.2. Response Evaluation Criteria in Solid Tumors (RECIST) Quick Reference Guide 
Response and progression will be evaluated in this study using the international criteria 
proposed in:  Eisenhauer EA, Therasse P, Bogaerts J, et al. 2009. New response evaluation 
criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228-247. 
Eligibility 
Only patients with measurable disease at baseline should be included in protocols where ORR is 
the primary endpoint. Measurable disease is defined as the presence of at least one measurable 
lesion. 
Methods of Assessment 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. 
• CT is the best currently available and reproducible method to measure lesions selected 
for response assessment. MRI is also acceptable in certain situations (e.g., for body scans 
but not for lung). 
• Lesions on a chest X-ray may be considered measurable lesions if they are clearly 
defined and surrounded by aerated lung. However, CT is preferable. 
• Clinical lesions will only be considered measurable when they are superficial and 
≥10 mm in diameter as assessed using calipers. For the case of skin lesions, 
documentation by color photography, including a ruler to estimate the size of the lesion, 
is recommended. 
• Ultrasound should not be used to measure tumor lesions. 
• Tumor markers alone cannot be used to assess response. If markers are initially above 
the upper normal limit, they must normalize for a patient to be considered in complete 
response. 
• Cytology and histology can be used in rare cases (e.g., for evaluation of residual masses 
to differentiate between Partial Response [PR] and Complete Response [CR] or 
evaluation of new or enlarging effusions to differentiate between Progressive Disease 
[PD] and Response/Stable Disease [SD]).  
Use of endoscopy and laparoscopy is not advised. However, they can be used to confirm 
complete pathological response. 
Baseline Disease Assessment 
All baseline evaluations should be performed as closely as possible to the beginning of treatment 
and never more than 4 weeks before the beginning of the treatment. 
Measurable Lesions - Must be accurately measured in at least one dimension (longest diameter 
in the plane of measurement is to be recorded) with a minimum size of: 

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• 10 mm by CT scan (CT scan slice thickness no greater than 5 mm; when CT scans have 
slice thickness >5 mm, the minimum size should be twice the slice thickness). 
• 10 mm caliper measurement by clinical exam (lesions which cannot be accurately 
measured with calipers should be recorded as non- measurable). 
• 20 mm by chest X-ray 
• Malignant lymph nodes 
- 
To be considered pathologically enlarged and measurable, a lymph node must be ≥15 
mm in short axis when assessed by CT scan (CT scan slice thickness is 
recommended to be no greater than 5 mm). At baseline and in follow-up, only the 
short axis will be measured and followed. 
- 
Lytic bone lesions or mixed lytic-blastic lesions with identifiable soft tissue 
components that can be evaluated by cross-sectional imaging techniques such as CT 
or MRI can be considered measurable if the soft tissue component meets the 
definition of measurability described above. 
- 
‘Cystic lesions’ thought to represent cystic metastases can be considered measurable 
if they meet the definition of measurability described above. However, if non-cystic 
lesions are present in the same patient, these are preferred for selection as target 
lesions. 
Non-Measurable Lesions - Non-measurable lesions are all other lesions, including small 
lesions (longest diameter <10 mm or pathological lymph nodes with 10 to <15 mm short axis), 
as well as truly non-measurable lesions. Lesions considered truly non-measurable include: 
leptomeningeal disease, ascites, pleural or pericardial effusion, inflammatory breast disease, 
lymphangitic involvement of skin or lung, abdominal masses/abdominal organomegaly 
identified by physical examination that is not measurable by reproducible imaging techniques. 
Blastic bone lesions are non-measurable. 
Lesions with prior local treatment, such as those situated in a previously irradiated area or in 
an area subjected to other loco-regional therapy, are usually not considered measurable unless 
there has been demonstrated progression in the lesion. Study protocols should detail the 
conditions under which such lesions would be considered measurable. 
Target Lesions 
- 
All measurable lesions up to a maximum of two lesions per organ and five lesions in 
total, representative of all involved organs, should be identified as target lesions and 
recorded and measured at baseline. 
- 
Target lesions should be selected on the basis of their size (lesions with the longest 
diameter) and be representative of all involved organs, as well as their suitability for 
reproducible repeated measurements. 
- 
All measurements should be recorded in metric notation using calipers if clinically 
assessed. 

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A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters, which will be used as 
reference to further characterize any objective tumor regression in the measurable dimension of 
the disease. If lymph nodes are to be included in the sum, only the short axis will contribute. 
Non-Target Lesions 
All lesions (or sites of disease) not identified as target lesions, including pathological lymph 
nodes and all non-measurable lesions, should be identified as non-target lesions and be recorded 
at baseline. Measurements of these lesions are not required and they should be followed as 
‘present’, ‘absent’ or in rare cases, ‘unequivocal progression’. 
Response Criteria 
Evaluation of Target Lesions 
Complete Response (CR) 
Disappearance of all target lesions. Any pathological lymph nodes (whether 
target or non-target) must have reduction in short axis to <10 mm.  
Partial Response (PR) 
At least a 30% decrease in the sum of the diameters of target lesions, taking as 
reference the baseline sum of diameters. 
Progressive Disease (PD) 
At least a 20% increase in the sum of the LD of target lesions, taking as reference 
the smallest sum on study (this may include the baseline sum). The sum must 
also demonstrate an absolute increase of at least 5 mm. 
Stable Disease (SD) 
Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify 
for PD. 
Special Notes on the Assessment of Target Lesions 
• Lymph nodes identified as target lesions should always have the actual short axis 
measurement recorded even if the nodes regress to below 10 mm on study. When lymph 
nodes are included as target lesions, the ‘sum’ of lesions may not be zero even if 
complete response criteria are met since a normal lymph node is defined as having a 
short axis of <10 mm. 
• Target lesions that become ‘too small to measure’. While on study, all lesions (nodal and 
non-nodal) recorded at baseline should have their actual measurements recorded at each 
subsequent evaluation, even when very small. However, sometimes lesions or lymph 
nodes become so faint on a CT scan that the radiologist may not feel comfortable 
assigning an exact measure and may report them as being ‘too small to measure’, in 
which case a default value of 5 mm should be assigned. 
• Lesions that split or coalesce on treatment. When non-nodal lesions ‘fragment’, the 
longest diameters of the fragmented portions should be added together to calculate the 
target lesion sum. Similarly, as lesions coalesce, a plane between them may be 
maintained that would aid in obtaining maximal diameter measurements of each 
individual lesion. If the lesions have truly coalesced such that they are no longer 
separable, the vector of the longest diameter in this instance should be the maximal 
longest diameter for the ‘coalesced lesion’. 

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Evaluation of Non-Target Lesions 
Complete Response 
(CR) 
• 
Disappearance of all non-target lesions and normalization of tumor marker 
levels. All lymph nodes must be non-pathological in size (< 10 mm short 
axis) 
Non-CR/Non-PD 
• 
Persistence of one or more non-target lesion(s) or/and maintenance of 
tumor marker level above the normal limits 
Progressive Disease 
(PD) 
• 
Unequivocal progression of existing non-target lesions. 
• 
When patient has measurable disease. To achieve ‘unequivocal progression’ 
on the basis of the non-target disease, there must be an overall level of 
substantial worsening in non-target disease such that, even in presence of 
SD or PR in target disease, the overall tumor burden has increased 
sufficiently to merit discontinuation of therapy. A modest ‘increase’ in the 
size of one or more non-target lesions is usually not sufficient to qualify for 
unequivocal progression status 
• 
When patient has only non-measurable disease. There is no measurable 
disease assessment to factor into the interpretation of an increase in non-
measurable disease burden. Because worsening in non-target disease cannot 
be easily quantified, a useful test that can be applied is to consider if the 
increase in overall disease burden based on change in non-measurable 
disease is comparable in magnitude to the increase that would be required 
to declare PD for measurable disease. Examples include an increase in a 
pleural effusion from ‘trace’ to ‘large’ or an increase in lymphangitic 
disease from localized to widespread progression status. 
New Lesions 
The appearance of new malignant lesions denotes disease progression: 
• The finding of a new lesion should be unequivocal (i.e., not attributable to differences in 
scanning technique, change in imaging modality or findings thought to represent 
something other than tumor, especially when the patient’s baseline lesions show partial 
or complete response). 
• If a new lesion is equivocal, for example because of its small size, continued therapy and 
follow-up evaluation will clarify if it represents truly new disease. If repeat scans 
confirm there is definitely a new lesion, then progression should be declared using the 
date of the initial scan. 
• A lesion identified on a follow-up study in an anatomical location that was not scanned 
at baseline is considered a new lesion and disease progression. 
It is sometimes reasonable to incorporate the use of fludeoxyglucose-positron emission 
tomography (FDG-PET) scanning to complement CT in assessment of progression (particularly 
possible ‘new’ disease). New lesions on the basis of FDG-PET imaging can be identified 
according to the following algorithm: 
Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is PD based on a new 
lesion. 

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No FDG-PET at baseline and a positive FDG-PET at follow-up: 
• If the positive FDG-PET at follow-up corresponds to a new site of disease confirmed by 
CT, this is PD. 
• If the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT scans are needed to determine if there is truly progression 
occurring at that site (if so, the date of PD will be the date of the initial abnormal FDG-
PET scan). 
• If the positive FDG-PET at follow-up corresponds to a pre-existing site of disease on CT 
that is not progressing on the basis of the anatomic images, this is not PD. 
Time Point Response 
A summary of the overall response status calculation at each time point for patients who have 
measurable disease at baseline is presented in Table 1 below. 
Table 1 
Time Point Response: Patients with Target (+/–non-target) Disease 
Target lesions 
Non-Target lesions 
New Lesions 
Overall response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
NE 
No 
PR 
PR 
Non-PD/or not all evaluated 
No 
SD 
SD 
Non-PD/or not all evaluated 
Yes or No 
PD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
CR = complete response; PR – partial response; SD – stable disease; PD = progressive disease; NE – unevaluable 
When patients have non-measurable (therefore non-target) disease only, Table 2 is to be used. 
Table 2 
Time Point Response: Patients with Non-target Disease 
Non-Target lesions 
New Lesions 
Overall response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD1 
Not all evaluated 
No 
NE 
PD 
Yes or No 
PD 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
CR = complete response; PR – partial response; SD – stable disease; PD = progressive disease; NE – unevaluable.  
1 Non-CR / non-PD is preferred over ‘Stable Disease’ for non-target disease since SD is increasingly used as an endpoint for 
assessment of efficacy in some trials. To assign this category when no lesions can be measured is not advised. 

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Confirmation 
In non-randomized trials where response is the primary endpoint, confirmation of PR and CR is 
required to ensure responses identified are not the result of measurement error. This will also 
permit appropriate interpretation of results in the context of historical data where response has 
traditionally required confirmation in such trials.  
However, in all other circumstances, (i.e., in randomized Phase 2 or 3 trials or studies where 
stable disease or progression are the primary endpoints), confirmation of response is not 
required since it will not add value to the interpretation of trial results. However, elimination of 
the requirement for response confirmation may increase the importance of central review to 
protect against bias, in particular in studies, which are not blinded.  
In the case of SD, measurements must have met the SD criteria at least once after study entry at a 
minimum interval (in general not less than 6–8 weeks) that is defined in the study protocol. 
Missing Assessments and Unevaluable Designation 
When no imaging/measurement is done at all at a particular time point, the patient is not 
evaluable (NE) at that time point. 
If only a subset of lesion measurements are made at an assessment, usually the case is also 
considered NE at that time point, unless a convincing argument can be made that the 
contribution of the individual missing lesion(s) would not change the assigned time point 
response. This would most likely happen in the case of PD. 
Criteria for Continuing Treatment after Evidence of Progressive Disease by RECIST 1.1 
Radiologic tumor flare, which is not defined in RECIST 1.1, has been observed in patients 
undergoing treatment (Hales et al., 2010). Thus, patients who have evidence of clinical benefit 
but with PD as defined by RECIST 1.1 may be considered for continued study treatment at the 
Investigator’s discretion (after discussion with the Medical Monitor) if they meet the following 
criteria: 
• Tumor shrinkage (at least 30% decrease in diameter from baseline) of one or more 
evaluable lesions 
Improvement in one or more symptoms or signs attributable to the underlying cancer as 
assessed by the Investigator. 

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12.3. 
NCI-CTCAE v 5.0 Infusion-related Reactions 
Adverse 
Event 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Infusion-
related 
reaction 
Mild transient 
reaction; infusion 
interruption not 
indicated; 
intervention not 
indicated 
Therapy or infusion 
interruption indicated 
but responds promptly 
to symptomatic 
treatment (e.g., 
antihistamines, 
NSAIDS, narcotics, 
I.V. fluids); 
prophylactic 
medications indicated 
for ≤ 24 hrs 
Prolonged (e.g., not 
rapidly responsive to 
symptomatic 
medication and/or brief 
interruption of 
infusion); recurrence of 
symptoms following 
initial improvement; 
hospitalization 
indicated for clinical 
sequelae 
Life-threatening 
consequences; 
urgent 
intervention 
indicated 
Death 
Definition: A disorder characterized by an adverse reaction to the infusion of pharmacological or biological substances. 
Allergic 
reaction 
Systemic 
intervention not 
indicated 
Oral intervention 
indicated 
Bronchospasm; 
hospitalization 
indicated for clinical 
sequelae; intravenous 
intervention indicated 
Life-threatening 
consequences; 
urgent 
intervention 
indicated 
Death 
Definition: A disorder characterized by an adverse local or general response from exposure to an allergen. 
Anaphylaxis 
- 
- 
Symptomatic 
bronchospasm, with or 
without urticaria; 
parenteral intervention 
indicated; allergy-
related 
edema/angioedema; 
hypotension 
Life-threatening 
consequences; 
urgent 
intervention 
indicated 
Death 
Definition: A disorder characterized by an acute inflammatory reaction resulting from the release of histamine and histamine-
like substances from mast cells, causing a hypersensitivity immune response. Clinically, it presents with breathing difficulty, 
dizziness, hypotension, cyanosis, and loss of consciousness and may lead to death. 
Cytokine 
release 
syndrome 
Fever with or 
without 
constitutional 
symptoms 
Hypotension 
responding to fluids; 
hypoxia responding to 
<40% O2 
Hypotension managed 
with one pressor; 
hypoxia requiring 
≥40% O2 
Life-threatening 
consequences; 
pressor or 
ventilator support 
indicated 
Death 
Definition: A disorder characterized by fever, tachypnea, headache, tachycardia, hypotension, rash, and/or hypoxia caused by 
the release of cytokines. 
 

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12.4. 
Management of DKN-01 Infusion-related Reactions 
Grade  
Management 
Grade 1 
• 
Slow the infusion rate by 50%. 
• 
Monitor the patient for worsening of condition. 
• 
For subsequent infusions, premedicate with diphenhydramine hydrochloride 50 mg IV (or 
equivalent); additional premedication may be administered at the investigator’s discretion. 
Grade 2 
• 
Stop the infusion. 
• 
Administer diphenhydramine hydrochloride 50 mg IV (or equivalent), acetaminophen 650 mg orally 
for fever, and oxygen.  
• 
Resume the infusion at 50% of the prior rate once the infusion reaction has resolved or decreased to 
Grade 1. 
• 
Monitor for worsening of condition. 
• 
For subsequent infusions, premedicate with diphenhydramine hydrochloride 50 mg IV (or 
equivalent); additional premedication may be administered at the investigator’s discretion. 
• 
For a second Grade 1 or 2 infusion reaction, administer dexamethasone 10 mg IV (or equivalent); 
then, for subsequent infusions, premedicate with diphenhydramine hydrochloride 50 mg IV (or 
equivalent), acetaminophen 650 mg orally, and dexamethasone 10 mg IV (or equivalent). 
Grade 3 
• 
Stop the infusion and disconnect the infusion tubing from the patient. 
• 
Administer diphenhydramine hydrochloride 50 mg IV (or equivalent), dexamethasone 10 mg IV (or 
equivalent), bronchodilators for bronchospasm, and other medications/treatment as medically 
indicated. 
• 
Patients who have a Grade 3 infusion reaction with premedication will not receive further DKN-01 
treatment, but will continue to be followed on the protocol. 
Grade 4 
• 
Stop the infusion and disconnect the infusion tubing from the patient. 
• 
Administer diphenhydramine hydrochloride 50 mg IV (or equivalent), dexamethasone 10 mg IV (or 
equivalent), and other medications/treatment as medically indicated. 
• 
Give epinephrine or bronchodilators as indicated. 
• 
Hospital admission for observation may be indicated. 
• 
Patients who have a Grade 4 infusion reaction with or without premedication will not receive further 
DKN-01 treatment, but will continue to be followed on the protocol. 
 

Clinical Study Protocol DEK-DKK1-P204_ 01 July 2020 
page 74 
CONFIDENTIAL 
Leap Therapeutics, Inc. 
12.5. 
Management of DKN-01-related Adverse Reactions 
System Monitoring 
Severity 
Management 
Follow-up 
Gastrointestinal 
Any changes in normal 
bowel habits or changes 
from BL: 
• 
Diarrhea 
• 
Abdominal pain 
• 
Blood or mucus in 
stool with or 
without fever 
• 
Peritoneal signs 
consistent with 
bowel perforation 
• 
Ileus 
 
Moderate: 
• 
4 to 6 stools/day over 
baseline 
• 
Abdominal pain 
• 
Blood or mucus in 
stool 
• 
Withhold DKN-01 
• 
Administer 
antidiarrheal 
treatment while 
etiology is 
investigated. 
Symptoms Resolve to 
≤Grade 1 or baseline 
(Section 6.2): 
• 
Resume DKN-01 as 
per Table 1 if 
symptoms have 
improved to mild 
severity or 
resolution. 
 
Severe or life-threatening: 
• 
7 stools/day over 
baseline 
• 
Peritoneal signs 
consistent with bowel 
perforation 
• 
Ileus 
• 
Fever 
• 
Permanently 
discontinue DKN-01 
• 
Rule out bowel 
perforation 
• 
Consider endoscopic 
evaluation 
 
 
Liver 
 
 
 
Elevations in liver 
function tests: 
• 
AST >2.5 x ULN 
• 
ALT >2.5 x ULN 
• 
Total bilirubin >1.5 
x ULN 
 
Moderate: 
• 
AST or ALT >2.5 to 
<5.0 x ULN and/or 
• 
Total bilirubin >1.5 to 
<3.0 x ULN 
• 
Withhold DKN-01 
• 
Rule out infectious or 
malignant causes 
• 
Increase frequency of 
liver function test 
monitoring until 
resolution 
Symptoms Resolve to 
≤Grade 1 or baseline 
(Section 6.2): 
• 
Resume DKN-
01 as per Table 
1 if liver 
function tests 
are <2.5 x ULN 
or return to BL 
and bilirubin is 
<1.5 x ULN or 
returns to BL. 
Symptoms Ongoing: 
• 
If AST or ALT 
elevation continues 
to be >5 x ULN OR 
total bilirubin > 3 x 
ULN, see below. 
Severe or life-threatening 
• 
AST or ALT >5.0 x 
ULN and/or 
• 
Total bilirubin >3.0 x 
ULN 
• 
Permanently 
discontinue DKN-01 
• 
Rule out infectious or 
malignant causes 
• 
Increase frequency of 
liver function test 
monitoring until 
resolution 
 
 

Clinical Study Protocol DEK-DKK1-P204_ 01 July 2020 
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Leap Therapeutics, Inc. 
System Monitoring 
Severity 
Management 
Follow-up 
Skin 
• 
Pruritus 
• 
Rash 
 
Moderate 
• 
Non-localized rash 
(diffuse, <50% of skin 
surface 
• 
Withhold DKN-01 
• 
Administer topical 
corticosteroids if 
there is no 
improvement of 
symptoms within 1 
week. 
Symptoms Resolve to 
≤Grade 1 or baseline 
(Section 6.2): 
• 
Resume DKN-01 as 
per Table 1 if 
dermatitis resolves 
or improves to mild 
(localized) 
symptoms. 
Symptoms Ongoing: 
• 
If symptoms 
worsen, see below. 
Severe or life-threatening 
• 
Stevens-Johnson 
syndrome, toxic 
epidermal necrolysis, 
or rash complicated by 
full thickness dermal 
ulceration, or necrotic, 
bullous or hemorrhagic 
manifestations 
• 
Permanently 
discontinue DKN-01 
• 
Administer systemic 
corticosteroid therapy 
 
Neurologic 
Monitor for symptoms 
of motor or sensory 
neuropathy 
• 
Unilateral or 
bilateral weakness 
• 
Sensory alterations 
• 
Paresthesia 
. 
Moderate 
• 
Moderate symptoms, 
clinically detectable 
with no impact on 
ADLs 
• 
Withhold DKN-01 
• 
Introduce appropriate 
medical intervention 
Symptoms Resolve to 
≤Grade 1 or baseline 
(Section 6.2): 
• 
Resume DKN-01 as 
per Table 1 when 
symptoms resolve or 
return to BL 
Symptoms Ongoing: 
• 
If symptoms 
worsen, see below 
Severe or life-threatening 
• 
Severe symptoms 
(impact on ADLs) or 
life threatening 
• 
Permanently 
discontinue DKN-01 
• 
Institute appropriate 
medical intervention 
 
Endocrine 
• 
Fatigue 
• 
Headache 
• 
Mental status 
changes 
• 
Abdominal pain 
• 
Unusual bowel 
habits 
• 
Hypotension 
• 
Abnormal thyroid 
function tests and/or 
serum chemistries 
 
Moderate to life-
threatening 
• 
Document signs and/or 
symptoms of 
dysfunction 
• 
Endocrinopathies 
requiring hormone 
replacement or medical 
intervention 
• 
AEs requiring 
hospitalization, urgent 
medical intervention or 
interfering with ADLs 
• 
Withhold DKN-01 
• 
Evaluate endocrine 
function 
• 
Consider 
radiographic pituitary 
gland imaging 
• 
Continue to assess as 
indicated 
• 
Initiate appropriate 
hormone-
replacement therapy 
Symptoms Resolve to 
≤Grade 1 or baseline 
(Section 6.2): 
• 
Resume DKN-01 as 
per Table 1 when: 
• 
Patient is stable on 
hormone-
replacement therapy 
(as indicated) 
Symptoms Ongoing: 
• 
Permanently 
discontinue DKN-01  

Clinical Study Protocol DEK-DKK1-P204_ 01 July 2020 
page 76 
CONFIDENTIAL 
Leap Therapeutics, Inc. 
 
 

Clinical Study Protocol DEK-DKK1-P204_ 01 July 2020 
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Leap Therapeutics, Inc. 
12.6. 
Wnt Signaling Alterations 
ZNRF3  
RSPO2  
RNF43  
CTNNB1 
AXIN1  
APC  
WISP3  
TNKS2  
TNKS  
TERT  
SOX9  
SOX2  
SLIT2  
PAX5  
NOTCH1  
MLL2  
LTK  
LRP1B  
LRP  
GSK3B  
GREM1  
FOXP1  
FBXW7  
FAM123B  
CREB  
CDH20  
CDC73  
ARID1A  
APCDD1 

Clinical Study Protocol DEK-DKK1-P204_ 01 July 2020 
page 78 
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Leap Therapeutics, Inc. 
12.7. Declaration of Helsinki 
World Medical Association Declaration of Helsinki: 
Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects 
Adopted by the 18th World Medical Association (WMA) General Assembly, Helsinki, Finland, 
June 1964 and amended by the 29th WMA General Assembly, Tokyo, Japan, October 1975, 35th 
WMA General Assembly, Venice, Italy, October 1983, and the 41st WMA General Assembly, 
Hong Kong, September 1989, the 48th WMA General Assembly, Somerset West, Republic of 
South Africa, October 1996; 52nd WMA General Assembly, Edinburgh, Scotland, October 2000; 
53rd WMA General Assembly, Washington 2002 (Note of Clarification on paragraph 29 added); 
55th WMA General Assembly, Tokyo 2004 (Note of Clarification on Paragraph 30 added); and 
59th WMA General Assembly, Seoul, October 2008. 
A. 
INTRODUCTION  
1. The World Medical Association (WMA) has developed the Declaration of Helsinki as a 
statement of ethical principles for medical research involving human subjects, including 
research 
on 
identifiable 
human 
material 
and 
data.  
The Declaration is intended to be read as a whole and each of its constituent paragraphs 
should not be applied without consideration of all other relevant paragraphs.  
2. Although the Declaration is addressed primarily to physicians, the WMA encourages other 
participants in medical research involving human subjects to adopt these principles.  
3. It is the duty of the physician to promote and safeguard the health of patients, including 
those who are involved in medical research. The physician's knowledge and conscience 
are dedicated to the fulfilment of this duty.  
4. The Declaration of Geneva of the WMA binds the physician with the words, "The health 
of my patient will be my first consideration," and the International Code of Medical Ethics 
declares that, "A physician shall act in the patient's best interest when providing medical 
care."  
5. Medical progress is based on research that ultimately must include studies involving 
human subjects. Populations that are underrepresented in medical research should be 
provided appropriate access to participation in research.  
6. In medical research involving human subjects, the well-being of the individual research 
subject must take precedence over all other interests.  
7. The primary purpose of medical research involving human subjects is to understand the 
causes, development and effects of diseases and improve preventive, diagnostic and 
therapeutic interventions (methods, procedures and treatments). Even the best current 
interventions must be evaluated continually through research for their safety, 
effectiveness, efficiency, accessibility and quality.  
8. In medical practice and in medical research, most interventions involve risks and burdens.  

Clinical Study Protocol DEK-DKK1-P204_ 01 July 2020 
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Leap Therapeutics, Inc. 
9. Medical research is subject to ethical standards that promote respect for all human subjects 
and protect their health and rights. Some research populations are particularly vulnerable 
and need special protection. These include those who cannot give or refuse consent for 
themselves and those who may be vulnerable to coercion or undue influence.  
10. Physicians should consider the ethical, legal and regulatory norms and standards for 
research involving human subjects in their own countries as well as applicable 
international norms and standards. No national or international ethical, legal or regulatory 
requirement should reduce or eliminate any of the protections for research subjects set 
forth in this Declaration.  
B. 
BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH  
11. It is the duty of physicians who participate in medical research to protect the life, health, 
dignity, integrity, right to self-determination, privacy, and confidentiality of personal 
information of research subjects.  
12. Medical research involving human subjects must conform to generally accepted scientific 
principles, be based on a thorough knowledge of the scientific literature, other relevant 
sources of information, and adequate laboratory and, as appropriate, animal 
experimentation. The welfare of animals used for research must be respected.  
13. Appropriate caution must be exercised in the conduct of medical research that may harm 
the environment.  
14. The design and performance of each research study involving human subjects must be 
clearly described in a research protocol. The protocol should contain a statement of the 
ethical considerations involved and should indicate how the principles in this Declaration 
have been addressed. The protocol should include information regarding funding, 
Sponsors, institutional affiliations, other potential conflicts of interest, incentives for 
subjects and provisions for treating and/or compensating subjects who are harmed as a 
consequence of participation in the research study. The protocol should describe 
arrangements for post-study access by study subjects to interventions identified as 
beneficial in the study or access to other appropriate care or benefits.  
15. The research protocol must be submitted for consideration, comment, guidance and 
approval to a research ethics committee before the study begins. This committee must be 
independent of the researcher, the Sponsor and any other undue influence. It must take 
into consideration the laws and regulations of the country or countries in which the 
research is to be performed as well as applicable international norms and standards but 
these must not be allowed to reduce or eliminate any of the protections for research 
subjects set forth in this Declaration. The committee must have the right to monitor 
ongoing studies. The researcher must provide monitoring information to the committee, 
especially information about any serious adverse events. No change to the protocol may 
be made without consideration and approval by the committee.  
16. Medical research involving human subjects must be conducted only by individuals with 
the appropriate scientific training and qualifications. Research on patients or healthy 

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Leap Therapeutics, Inc. 
volunteers requires the supervision of a competent and appropriately qualified physician 
or other health care professional. The responsibility for the protection of research subjects 
must always rest with the physician or other health care professional and never the 
research subjects, even though they have given consent.  
17. Medical research involving a disadvantaged or vulnerable population or community is 
only justified if the research is responsive to the health needs and priorities of this 
population or community and if there is a reasonable likelihood that this population or 
community stands to benefit from the results of the research.  
18. Every medical research study involving human subjects must be preceded by careful 
assessment of predictable risks and burdens to the individuals and communities involved 
in the research in comparison with foreseeable benefits to them and to other individuals 
or communities affected by the condition under investigation.  
19. Every clinical trial must be registered in a publicly accessible database before recruitment 
of the first subject.  
20. Physicians may not participate in a research study involving human subjects unless they 
are confident that the risks involved have been adequately assessed and can be 
satisfactorily managed. Physicians must immediately stop a study when the risks are found 
to outweigh the potential benefits or when there is conclusive proof of positive and 
beneficial results.  
21. Medical research involving human subjects may only be conducted if the importance of 
the objective outweighs the inherent risks and burdens to the research subjects.  
22. Participation by competent individuals as subjects in medical research must be voluntary. 
Although it may be appropriate to consult family members or community leaders, no 
competent individual may be enrolled in a research study unless he or she freely agrees.  
23. Every precaution must be taken to protect the privacy of research subjects and the 
confidentiality of their personal information and to minimize the impact of the study on 
their physical, mental and social integrity.  
24. In medical research involving competent human subjects, each potential subject must be 
adequately informed of the aims, methods, sources of funding, any possible conflicts of 
interest, institutional affiliations of the researcher, the anticipated benefits and potential 
risks of the study and the discomfort it may entail, and any other relevant aspects of the 
study. The potential subject must be informed of the right to refuse to participate in the 
study or to withdraw consent to participate at any time without reprisal. Special attention 
should be given to the specific information needs of individual potential subjects as well 
as to the methods used to deliver the information. After ensuring that the potential subject 
has understood the information, the physician or another appropriately qualified individual 
must then seek the potential subject's freely-given informed consent, preferably in writing. 
If the consent cannot be expressed in writing, the non-written consent must be formally 
documented and witnessed.  

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Leap Therapeutics, Inc. 
25. For medical research using identifiable human material or data, physicians must normally 
seek consent for the collection, analysis, storage and/or reuse. There may be situations 
where consent would be impossible or impractical to obtain for such research or would 
pose a threat to the validity of the research. In such situations the research may be done 
only after consideration and approval of a research ethics committee.  
26. When seeking informed consent for participation in a research study the physician should 
be particularly cautious if the potential subject is in a dependent relationship with the 
physician or may consent under duress. In such situations the informed consent should be 
sought by an appropriately qualified individual who is completely independent of this 
relationship.  
27. For a potential research subject who is incompetent, the physician must seek informed 
consent from the legally authorized representative. These individuals must not be included 
in a research study that has no likelihood of benefit for them unless it is intended to 
promote the health of the population represented by the potential subject, the research 
cannot instead be performed with competent persons, and the research entails only 
minimal risk and minimal burden.  
28. When a potential research subject who is deemed incompetent is able to give assent to 
decisions about participation in research, the physician must seek that assent in addition 
to the consent of the legally authorized representative. The potential subject's dissent 
should be respected.  
29. Research involving subjects who are physically or mentally incapable of giving consent, 
for example, unconscious patients, may be done only if the physical or mental condition 
that prevents giving informed consent is a necessary characteristic of the research 
population. In such circumstances the physician should seek informed consent from the 
legally authorized representative. If no such representative is available and if the research 
cannot be delayed, the study may proceed without informed consent provided that the 
specific reasons for involving subjects with a condition that renders them unable to give 
informed consent have been stated in the research protocol and the study has been 
approved by a research ethics committee. Consent to remain in the research should be 
obtained as soon as possible from the subject or a legally authorized representative.  
30. Authors, editors and publishers all have ethical obligations with regard to the publication 
of the results of research. Authors have a duty to make publicly available the results of 
their research on human subjects and are accountable for the completeness and accuracy 
of their reports. They should adhere to accepted guidelines for ethical reporting. Negative 
and inconclusive as well as positive results should be published or otherwise made 
publicly available. Sources of funding, institutional affiliations and conflicts of interest 
should be declared in the publication. Reports of research not in accordance with the 
principles of this Declaration should not be accepted for publication.  

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Leap Therapeutics, Inc. 
C 
ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH 
MEDICAL CARE  
31. The physician may combine medical research with medical care only to the extent that the 
research is justified by its potential preventive, diagnostic or therapeutic value and if the 
physician has good reason to believe that participation in the research study will not 
adversely affect the health of the patients who serve as research subjects.  
32. The benefits, risks, burdens and effectiveness of a new intervention must be tested against 
those of the best current proven intervention, except in the following circumstances:  
• The use of placebo, or no treatment, is acceptable in studies where no current proven 
intervention exists; or  
• Where for compelling and scientifically sound methodological reasons the use of 
placebo is necessary to determine the efficacy or safety of an intervention and the 
patients who receive placebo or no treatment will not be subject to any risk of serious 
or irreversible harm. Extreme care must be taken to avoid abuse of this option.  
33. At the conclusion of the study, patients entered into the study are entitled to be informed 
about the outcome of the study and to share any benefits that result from it, for example, 
access to interventions identified as beneficial in the study or to other appropriate care or 
benefits.  
34. The physician must fully inform the patient which aspects of the care are related to the 
research. The refusal of a patient to participate in a study or the patient's decision to 
withdraw from the study must never interfere with the patient-physician relationship.  
35. In the treatment of a patient, where proven interventions do not exist or have been 
ineffective, the physician, after seeking expert advice, with informed consent from the 
patient or a legally authorized representative, may use an unproven intervention if in the 
physician's judgement it offers hope of saving life, re-establishing health or alleviating 
suffering. Where possible, this intervention should be made the object of research, 
designed to evaluate its safety and efficacy. In all cases, new information should be 
recorded and, where appropriate, made publicly available.  

DKN_01_P204_Rollover Amendment V.6_Final
063020
Final Audit Report
2020-07-01
Created:
2020-07-01
By:
Katie Woolford (kwoolford@leaptx.com)
Status:
Signed
Transaction ID:
CBJCHBCAABAA-6A4EWxjoyX2PRDhqAVP6Rzffk9zyE9d
"DKN_01_P204_Rollover Amendment V.6_Final 063020" History
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