Phase 2, Single-arm, Open-label Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations and Progressed On or After Applicable Targeted Therapy and Platinum Based Chemotherapy (TROPION-Lung05)
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Sponsor: Daiichi Sankyo

CLINICAL STUDY PROTOCOL 
Phase 2, Single-arm, Open-label Study of DS-1062a in 
Advanced or Metastatic Non-small Cell Lung Cancer with 
Actionable Genomic Alterations and Progressed on or After 
Applicable Targeted Therapy and Platinum-based 
Chemotherapy (TROPION-Lung05) 
(Phase 2 Study of DS-1062a in Advanced or Metastatic Non-small 
Cell Lung Cancer with Actionable Genomic Alterations) 
 
PROTOCOL NUMBER: DS1062-A-U202 
 
IND Number 136626/  
EudraCT Number 2020-002774-27 
 
Version 5.0, 25 Sep 2023 
 
Daiichi Sankyo, Inc.  
211 Mt. Airy Road 
Basking Ridge, NJ 07920, United States  
 
CONFIDENTIALITY STATEMENT 
Information contained in this document is proprietary to Daiichi Sankyo, Inc.  The information is 
provided to you in confidence which is requested under an agreed upon and signed 
Confidentiality and Disclosure Agreement.  Do not give this document or any copy of it or reveal 
any proprietary information contained in it to any third party (other than those in your 
organization who are assisting you in this work and are bound by the Confidentiality and 
Disclosure Agreement) without the prior written permission of an authorized representative of 
Daiichi Sankyo, Inc. 

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INVESTIGATOR AGREEMENT 
Phase 2, Single-arm, Open-label Study of DS-1062a in Advanced or Metastatic Non-small 
Cell Lung Cancer with Actionable Genomic Alterations and Progressed on or After 
Applicable Targeted Therapy and Platinum-based Chemotherapy (TROPION-Lung05) 
Investigator’s Signature: 
I have fully discussed the objectives of this study and the contents of this protocol with the Sponsor’s 
representative. 
I understand that information contained in or pertaining to this protocol is confidential and should not be 
disclosed, other than to those directly involved in the execution or the ethical review of the study, without 
written authorization from the Sponsor.  It is, however, permissible to provide information to a subject in 
order to obtain consent. 
I agree to conduct this study according to this protocol and to comply with its requirements, subject to 
ethical and safety considerations and guidelines, and to conduct the study in accordance with International 
Council for Harmonisation for Technical Requirements for Pharmaceuticals for Human Use (ICH) 
Guideline for Good Clinical Practice (ICH E6[R2]), which has its foundations in the Declaration of 
Helsinki, and applicable regional regulatory requirements. 
I agree to make available to Sponsor personnel, their representatives and relevant regulatory authorities, 
my subjects’ study records in order to verify the data that I have entered into the case report forms.  I am 
aware of my responsibilities as a Principal Investigator as provided by the Sponsor. 
I understand that the Sponsor may decide to suspend or prematurely terminate the study at any time for 
whatever reason; such a decision will be communicated to me in writing. 
Conversely, should I decide to withdraw from execution of the study, I will communicate my intention 
immediately in writing to the Sponsor. 
 
 
Print Name 
Signature 
 
 
Title 
Date (DD MMM YYYY) 

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DOCUMENT HISTORY 
Version Number 
Version Date 
5.0 
25 Sep 2023 
4.0 
17 May 2022 
3.0  
14 Jul 2021 
2.0 
23 Sep 2020 
1.0 
23 Jun 2020 
 

Protocol DS1062-A-U202 
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SUMMARY OF CHANGES 
Please refer to the comparison document for protocol Version 5.0 (dated 25 Sep 2023) vs. 
protocol Version 4.0 (dated 17 May 2022) for actual changes in text.  The summary of changes 
below is a top-line summary of major changes in the current DS1062-A-U202 clinical study 
protocol (Version 5.0) by section. 
Amendment Rationale: 
The main purpose of this amendment to Study DS1062-A-U202 is to update safety information 
based on a review of the emerging data across the Dato-DXd clinical development program.  
Additional changes are made to add clarity to the protocol language and to ensure consistency 
with other studies in the development program. 
Conventions Used in This Summary of Changes 
All locations (section numbers and/or paragraph/bullet numbers) refer to the current protocol 
version, which incorporates the items specified in this Summary of Changes document.  
Minor edits, such as updates to language that do not alter original meaning, updates to version 
numbering, formatting, changes in font color, corrections to typographical errors, use of 
abbreviations, moving verbiage within a section or table, changes in style, or changes in case, are 
not noted in the table below. 
Section # and Title 
Description of Change 
Brief Rationale 
Section 1.1. Protocol 
Synopsis 
Section 6.5. Guidelines for 
Dose Modification 
Section 9.5.2. Safety 
Analyses 
Section 10.5.5. Action Taken 
Regarding Study Drug 
Section 10.7. Appendix 7: 
Instructions Related to 
Coronavirus Disease 2019 
(COVID-19) 
Replaced the term “dose interruption” with 
“dose delay”; and added the term “infusion 
interruption.”  
To clarify whether a subject 
had an interruption of an 
infused dose versus having an 
upcoming dose delayed. 
Section 1.3. Schedules of 
Events 
Table 1.2: Schedule of Events 
for Cycle 4 and Subsequent 
Cycles of the Treatment 
Period, End of Treatment, 
and Follow-up Period 
Removed the text “For subjects with a positive 
ADA at the Follow-up visit, an additional 
plasma ADA sample must be collected every 
3 months (±1 month) up to 1 year from the last 
dose of DS-1062a, or until the ADA becomes 
negative, or the ADA titer becomes less than 
baseline, or the subject starts another therapy 
for cancer, or the subject withdraws consent 
from the study, whichever occurs first.” and the 
“X” in the “Long-term Survival Follow-up 
(Every 3 Months)” column 
Because of the updated 
understanding of ADA and 
for consistency with other 
studies of Dato-DXd. 
Section 2.2. Study Rationale 
Section 2.3. Benefit and Risk 
Added IRR to the list of identified risks and 
removed it from the list of important identified 
To reflect the most recent 
safety information. 

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Section # and Title 
Description of Change 
Brief Rationale 
Assessment 
Section 8.4.1.2. Adverse 
Events of Special Interest 
risks. 
Section 1.3. Schedules of 
Events 
Table 1.1: Schedule of Events 
for Screening and Cycles 1 
through 3 of the Treatment 
Period  
Table 1.2: Schedule of Events 
for Cycle 4 and Subsequent 
Cycles of the Treatment 
Period, End of Treatment, 
and Follow-up Period 
Section 6.5. Guidelines for 
Dose Modification 
Table 6.3: Dose 
Modifications for 
Non-hematologic and 
Hematologic Toxicity 
Related to DS-1062a 
Added “It should be strongly recommended 
that subjects avoid the use of contact lenses 
starting on the day of the first DS-1062a dose 
and to use artificial tears (preferably 
preservative free) 4 times per day as a 
preventative measure and up to 8 times per day 
as clinically needed.” 
To reflect the most recent 
safety information. 
Section 1.3. Schedules of 
Events 
Table 1.1: Schedule of Events 
for Screening and Cycles 1 
through 3 of the Treatment 
Period  
Table 1.2: Schedule of Events 
for Cycle 4 and Subsequent 
Cycles of the Treatment 
Period, End of Treatment, 
and Follow-up Period 
Updated the following statement: 
“Subjects will be provided an oral care plan 
prior and during study treatment: daily before 
dosing, throughout treatment, and up to the 
first follow-up visit.” 
To reflect the most recent 
safety information. 
Added the following footnotes: 
“For prevention of oral mucositis/stomatitis, 
initiate a daily oral care plan (see 
Section 8.4.4). The importance of multiple 
daily mouth rinses during treatment (eg, prior 
to dosing) and up to the first follow-up visit 
should be emphasized. 
For prevention of ocular surface toxicity, it 
should be strongly recommended that subjects 
avoid the use of contact lenses starting on the 
day of the first DS-1062a dose and to use 
artificial tears (preferably preservative free) 
4 times per day as a preventative measure and 
up to 8 times per day as clinically needed. 
Ophthalmologic assessments, including, but not 
limited to, visual acuity testing, slit lamp 
examination, intraocular pressure measurement, 
fundoscopy, and fluorescein staining, will be 
performed at screening, as clinically indicated, 
and at the EOT visit by an ophthalmologist or, 
if unavailable, another licensed eye care 
For added clarity. 

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Section # and Title 
Description of Change 
Brief Rationale 
provider.” 
Section 1.1. Protocol 
Synopsis 
Section 6.5. Guidelines for 
Dose Modification 
Section 10.7. Appendix 7: 
Instructions Related to 
Coronavirus Disease 2019 
(COVID-19) 
 
Updated the following statement: 
“The dose may be interrupted delayed for up to 
4 9 weeks (28 63 days) from the planned date 
of the next cycle administration (ie, up to 
12 weeks or 84 days from the last infusion).  
If a subject is assessed as requiring a dose 
interruption delay longer than 4 12 weeks (28 
84 days) from the last infusion, the subject 
must be withdrawn from the study discontinue 
study treatment. unless discussed with and 
agreed upon by the Sponsor’s Medical 
Monitor.”  
The duration of a dose delay 
period was revised to allow 
subjects receiving clinical 
benefit but requiring more 
recovery time to continue to 
receive treatment without 
being discontinued.   
The requirement to 
discontinue the subject with 
an extended dose delay from 
the study was revised to the 
requirement to discontinue the 
subject from treatment while 
remaining in the study. 
The language regarding the 
discussion with the Medical 
Monitor was revised for 
readability. 
Section 1.3. Schedules of 
Events  
Table 1.1: Schedule of Events 
for Screening and Cycles 1 
through 3 of the Treatment 
Period 
Table 1.2: Schedule of Events 
for Cycle 4 and Subsequent 
Cycles of the Treatment 
Period, End of Treatment, 
and Follow-up Period 
Section 6.1. Study Drug 
Description 
Table 6.1: Study Drug 
Dosing Information 
Section 6.2. Preparation, 
Handling, Storage, and 
Accountability for Study 
Drug 
Section 6.5. Guidelines for 
Dose Modification 
Table 6.3: Dose 
Modifications for 
Non-hematologic and 
Hematologic Toxicity 
Related to DS-1062a 
Section 8.4.4. Other Safety 
Added the following text: 
“If a subject does not experience any IRR 
during or after the first 2 cycles, the 
post-infusion observation period can be 
shortened to at least 30 minutes for subsequent 
cycles.  Subjects with identified IRR related to 
the study drug should be observed 
post-infusion for at least 1 hour for the 2 cycles 
after the IRR event and for at least 30 minutes 
at each subsequent cycle.” 
To shorten the 1-hour 
observation period after 
infusion, if appropriate. 

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Section # and Title 
Description of Change 
Brief Rationale 
Section 1.3. Schedules of 
Events 
Table 1.1: Schedule of Events 
for Screening and Cycles 1 
through 3 of the Treatment 
Period 
Table 1.2: Schedule of Events 
for Cycle 4 and Subsequent 
Cycles of the Treatment 
Period, End of Treatment, 
and Follow-up Period 
Section 6.5. Guidelines for 
Dose Modification 
Table 6.3: Dose 
Modifications for 
Non-hematologic and 
Hematologic Toxicity 
Related to DS-1062a 
Section 8.4.1.2. Adverse 
Events of Special Interest 
Section 8.4.4. Other Safety 
For suspected ILD/pneumonitis events, made 
the following changes in evaluations: 
“For suspected ILD/pneumonitis, treatment 
with study drug should be interrupted delayed 
pending evaluation. Evaluations should include 
the following: 
 
High-resolution CT  
 
Pulmonologist consultation (infectious 
disease consultation as clinically 
indicated)  
 
Blood culture and complete blood 
count. Other blood tests could be 
considered as needed. 
 
Consider Bronchoscopy and 
bronchoalveolar lavage if clinically 
indicated and feasible 
 
Pulmonary function tests (including 
FVC and CO diffusing capacity) and 
pulse oximetry (SpO2)  
 
Arterial Clinical laboratory tests 
(arterial blood gases if clinically 
indicated, blood culture, blood cell 
count, differential white blood cell 
count, C-reactive protein, and a 
COVID-19 test). 
 
One blood sample collection for PK 
analysis as soon as ILD/pneumonitis is 
suspected, if feasible. 
To reflect the most recent 
safety information. 
Section 2.2. Study Rationale 
Split the AESI of mucositis/stomatitis into 
2 AESIs of oral mucositis/stomatitis and 
mucosal inflammation other than oral 
mucositis/stomatitis. 
To reflect the most recent 
safety information. 
Section 2.2. Study Rationale 
Section 8.4.1.2. Adverse 
Events of Special Interest 
Added ocular surface toxicity to the list of 
AESIs. 
To accurately reflect the 
safety information. 
Section 2.3. Benefit and Risk 
Assessment 
Removed the language “As of 04 Sep 2020,” in 
the paragraph discussing the important 
identified risks and identified risks for the study 
drug. 
For accuracy, because the 
changes to the list of 
identified risks were made 
after 04 Sep 2020. 
Section 4.1.1. Design 
Overview 
Section 8.3. Efficacy 
Assessments 
Added “To ensure accurate survival data are 
available at the time of any database lock, 
updated survival status may be requested 
during the study by the Sponsor.  For example, 
updated survival status may be requested prior 
to, but not limited to, the planned DCO and 
database lock for the primary analysis and final 
analysis.  Upon Sponsor notification, all 
To ensure survival data are 
accurately documented. 

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Section # and Title 
Description of Change 
Brief Rationale 
subjects who do not/will not have a scheduled 
study visit or study contact during the 
Sponsor-defined period will be contacted for 
their survival status (excluding subjects who 
have discontinued from the entire study or with 
a previously reported death event).” 
Section 6.1. Study Drug 
Description 
Table 6.1: Study Drug 
Dosing Information 
Section 6.2. Preparation, 
Handling, Storage, and 
Accountability for Study 
Drug 
Revised the following statement: “In case of 
IRR at any time during treatment, subsequent 
doses will be infused over 90 minutes. 
Additional please refer to details provided in 
Table 6.3.” 
For accuracy, as instructions 
for IRR may vary as indicated 
in Table 6.3: Dose 
Modifications for 
Non-hematologic and 
Hematologic Toxicity Related 
to DS-1062a. 
Section 6.2. Preparation, 
Handling, Storage, and 
Accountability for Study 
Drug 
Added “For prevention of oral 
mucositis/stomatitis, subjects are advised to 
initiate a daily oral care plan (OCP; see 
Section 8.4.4 for details) before study 
intervention initiation and maintain it 
throughout the study.  An OCP should include 
daily inert, bland mouth rinses (eg, with a 
nonalcoholic, bicarbonate-containing 
mouthwash 4 to 6 times a day), although other 
prophylaxis regimens (eg, dexamethasone oral 
solution 0.1 mg/mL 10 mL 3 to 4 times daily 
swish for 1 to 2 minutes then spit out, as well 
as cryotherapy throughout the infusion) 
advocated by institutional/local guidelines are 
permitted.  An OCP should also include 
educating subjects on the importance of oral 
hygiene, tooth brushing, flossing, and hydration 
and lubrication of the oral mucosa, and on the 
benefits of adhering to their recommended 
OCP.  Per the investigator’s judgment, a 
professional dental evaluation before study 
drug initiation and dental treatment, if 
indicated, may reduce the risk of local and 
systemic infections from odontogenic sources.” 
For added clarity of 
instructions for oral care. 
Section 6.5. Guidelines for 
Dose Modification 
Added “If a subject cannot restart study 
treatment for other reasons (eg, intercurrent 
conditions not related to disease progression or 
toxicity), the case should be discussed with the 
Sponsor’s Medical Monitor.  Study treatment 
dose delay for conditions other than toxicity 
resolution should be kept as short as possible.” 
For added clarity. 
Section 6.5. Guidelines for 
Dose Modification 
Table 6.3: Dose 
Modifications for 
Removed the statement “If there are any signs 
or symptoms of a Grade 1 or Grade 2 IRR, the 
infusion of DS-1062a infusion must be either 
slowed down or interrupted based on the 
severity of the IRR.  If the IRR is Grade 3 or 
To reflect the most recent 
safety information. 

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Section # and Title 
Description of Change 
Brief Rationale 
Non-hematologic and 
Hematologic Toxicity 
Related to DS-1062a 
Grade 4 or if there are any signs of 
anaphylaxis, the infusion of DS-1062a must be 
discontinued” 
For Grade 1 IRR, modified the guidelines as 
follows: 
“If IRR (such as fever and chills, with and 
without nausea/vomiting, pain, headache, 
dizziness, dyspnea, and Grade 1 or 2 
hypotension) is observed during administration, 
the infusion rate should be reduced by 50% of 
the initial infusion rate, and subjects should 
be closely monitored.  
If no other reactions appear upon resumption of 
the study drug at the above reduced infusion 
speed rate, then the infusion rate for 
subsequent infusion speed for next treatment 
cycles may be resumed at the initial planned 
speed infusion rate.” 
For Grade 2 IRR, modified the guidelines as 
follows: 
“Administration of Dato-DXd should be 
interrupted briefly.  Symptomatic treatment 
should be started. (eg, antihistamines, 
NSAIDs, narcotics, IV fluids). 
 
If the event resolves or improves to 
Grade 1, infusion can be restarted at a 
50% reduced infusion rate (ie, 
180 minutes for a 90-minute 
infusion and 60 minutes for a 
30-minute infusion). 
 
Subsequent administrations should be 
conducted at the reduced rate. If an 
IRR recurs upon rechallenge of 
Dato-DXd while it is being infused 
at a reduced rate during the same 
cycle, then treat as Grade 3 and 
follow the Grade 3 toxicity 
management guideline (TMG). 
If there is no recurrence, the subsequent 
infusion should be administered at a 
reduced rate. 
 
If there is no new IRR, then 
Dato-DXd can be administered at 
the initial planned infusion rate 
(90 or 30 minutes) for subsequent 
treatment cycles. 
For Grade 3 IRR, modified the guidelines as 

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Section # and Title 
Description of Change 
Brief Rationale 
follows: 
“Administration of Dato-DXd should be 
stopped immediately for that cycle and initiate 
treatment of the IRR symptoms. 
 
If the IRR does not resolve within the 
same day, recurrence of symptoms 
occurs following initial improvement, 
or hospitalization is necessary for 
clinical sequelae, then permanently 
discontinue Dato-DXd.  
 
If the IRR resolves within the same 
day of Dato-DXd infusion, no 
recurrence of symptoms occurs 
following initial improvement, and no 
hospitalization is necessary for clinical 
sequelae, then for the next cycle, 
administer Dato-DXd at a 50% 
reduced infusion rate (ie, 180 minutes 
for a 90-minute infusion; 60 minutes 
for a 30-minute infusion). 
o 
If there is no new IRR, then 
for the subsequent cycle, 
administer Dato-DXd at the 
initial infusion rate (90 or 
30 minutes).  If the subject 
tolerates that initial infusion 
rate with no new IRR, then 
for the subsequent cycles, 
administer Dato-DXd at the 
same infusion rate (90 or 
30 minutes). 
o 
If a new IRR occurs that is 
Grade 2 or greater with 
subsequent cycles, 
permanently discontinue 
Dato-DXd and initiate 
treatment of the IRR 
symptoms.” 
Administration of DS-1062a must be 
discontinued immediately and permanently. 
Urgent intervention indicated.  Antihistamines, 
steroids, epinephrine, bronchodilators, 
vasopressors, IV fluid therapy, oxygen 
inhalation etc, should be administered. 
IV antihistamines (H1 or H2 blocker), 
supplemental oxygenation, and volume 
resuscitation (IV fluid therapy) should also be 
considered as clinically indicated.” 

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Section # and Title 
Description of Change 
Brief Rationale 
For Grade 4 IRR, added the following 
guidelines: 
“Administration of DS-1062a must be 
discontinued immediately and permanently.  
Urgent intervention is indicated. Epinephrine, 
antihistamines, steroids, bronchodilators, 
vasopressors, IV fluid therapy, supplemental 
oxygen, etc. should be considered as clinically 
indicated.” 
For febrile neutropenia, added “Grade 3 and 
Grade 4: Discontinue subject from study 
treatment.” 
For Grade 1 pulmonary toxicity, added  
“b. 
Grade 0 refers to full resolution of 
ILD/pneumonitis, including the disappearance 
of radiological findings associated with active 
ILD/pneumonitis.  Residual scarring or fibrosis 
following recovery of ILD/pneumonitis is not 
considered to be active disease.” 
For general considerations for ocular surface 
toxicity, added the following statement: 
“The following grading scale replaces the 
CTCAE 5.0 grades for triggering the toxicity 
management guidelines for cornea-related AEs: 
Corneal Toxicity Severity Grading Scale 
Normal = Clear cornea, no epithelial defects 
Grade 1 = Nonconfluent superficial keratitis 
Grade 2 = Confluent superficial keratitis, a 
cornea defect, or 3-line or more loss in best 
corrected distance visual acuity 
Grade 3 = Corneal ulcer or stromal opacity, or 
best corrected distance visual acuity 20/200 or 
worse 
Grade 4 = Corneal perforation” 
For Grade 4, replaced “ophthalmological 
assessments” to “urgent ophthalmological 
assessments.” 
For gastrointestinal events, added “Grade 4 
Vomiting: Discontinue subject from study 
treatment.” 
For oral mucositis/stomatitis, modified the 
guidelines as follows: 
“As soon as oral pain, inflammation, and/or 
ulceration develops, strongly consider 

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Section # and Title 
Description of Change 
Brief Rationale 
steroid-containing mouth rinses (eg, 
dexamethasone 0.1 mg/mL, 10 mL 3 to 4 times 
daily swish for 1 to 2 minutes then spit out, or 
local alternative).  
May consider oral nystatin suspension or 
other topical antifungal agents at least 
15 minutes after the steroid-containing 
mouthwash according to clinician preference 
based on institutional/local guidelines.” 
For Grade 3 diarrhea, modified the guidelines 
as follows: 
“If prophylaxis and supportive medications per 
institutional guidelines have NOT YET been 
optimized:” 
Section 6.7. Prior and 
Concomitant Medications 
Added 2 bullet points in the Permitted 
Therapies/Products: 
 
“Neurokinin-1 (NK1) receptor antagonists 
can be used, if needed. 
 
Subjects with bronchopulmonary disorders 
who require intermittent use of 
bronchodilators (eg, albuterol) will be 
included in this study.” 
Updated the following statement in the 
Permitted Therapies/Products: 
 
“Based on the currently available clinical 
safety data, it is highly recommended that 
subjects receive prophylactic antiemetic 
agents prior to infusion of Dato-DXd and 
on subsequent days as needed.  
Antiemetics such as 5-hydroxytryptamine 
receptor 3 antagonists (5-HT3) or 
neurokinin 1 receptor antagonists, and 
steroids (eg, dexamethasone) should be 
considered and administered in accordance 
with the prescribing information or 
institutional guidelines.” 
Updated the following statement in the 
Prohibited Therapies/Products: 
 
“Concomitant use of chronic systemic (IV 
or oral) corticosteroids or other 
immunosuppressive medications 
>10 mg/day of prednisone or equivalent 
except for managing AEs; inhaled steroids, 
intra-articular steroid injections, and other 
topical steroid formulations are permitted 
in this study.  Corticosteroid mouthwash 
formulations are permitted to prevent and 
To reflect the most recent 
safety information. 

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Section # and Title 
Description of Change 
Brief Rationale 
manage certain AEs. 
Subjects with bronchopulmonary disorders 
who require intermittent use of bronchodilators 
(such as albuterol) will not be excluded from 
this study.” 
Section 6.7. Prior and 
Concomitant Medications 
Added “All concomitant medications 
administered during the study should be 
recorded in eCRF until the end of the Safety 
Follow-up Period.  Concomitant medications 
administered as treatment for drug-related 
AESIs should be recorded until event 
resolution, end of study including any 
post-treatment follow-up (if applicable), study 
termination, withdrawal of consent, or subject 
death.” 
To reflect the most recent 
safety information. 
Section 7.2. Subject 
Withdrawal/Discontinuation 
from the Study 
Updated the following text: 
"If the subject refuses declines all of the above 
methods of follow-up, the investigator should 
personally speak to the subject to ensure the 
subject understands all of the potential methods 
of follow-up. If the subject continues to refuse 
If the subject declines routine follow-up, the 
Investigator should discuss with the subject 
if sparse survival follow-up by telephone or 
verification of medical records is permitted 
prior to database locks. If the subject 
continues to decline all potential methods of 
follow-up, the investigator will document this 
as a withdrawal of consent (from the 
interventional portion and follow-up).” 
To clarify the option of sparse 
contacts for survival 
follow-up only. 
Section 7.2. Subject 
Withdrawal/Discontinuation 
from the Study 
Section 7.3. Lost to 
Follow-up 
Added “Knowledge of the vital status at study 
end in all subjects is crucial for the integrity of 
the study.” 
To emphasize the necessity of 
accurate documentation of 
survival data. 
Section 8.1. Eligibility 
Assessment 
Added the following statements: 
“Informed consent should be obtained ≤28 days 
prior to initiation of treatment and before any 
protocol-specific procedures are performed, 
except scans that might be done prior to 
consent per SoC.  Imaging studies 
(CT/MRI/bone scans) should be performed 
≤28 days prior to initiation of treatment.  If 
these scans are performed per SoC prior to 
consenting, as long as they are within 28 days 
of the planned dosing and from the same 
facility where follow-up scans during the study 
will be performed, they can be used as part of 
the screening assessments and do not need to 
For added clarity. 

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Section # and Title 
Description of Change 
Brief Rationale 
be repeated.” 
Section 8.4.1. Adverse Event 
Added “All ILD/pneumonitis events regardless 
of severity should be reported beyond the 
28-day Safety Follow-up Period.” 
To reflect the most recent 
safety information. 
Section 8.4.1. Adverse Event 
Section 8.4.1.2. Adverse 
Events of Special Interest 
Added “All AESIs, regardless of severity or 
seriousness, must be followed until event 
resolution, end of study including any 
post-treatment follow-up (if applicable), study 
termination, withdrawal of consent, or subject’s 
death.” 
To ensure all AESIs are 
followed to resolution. 
Section 8.4.1.2. Adverse 
Events of Special Interest 
Section 8.4.4. Other Safety 
Updated the following statement: 
“Ophthalmologic assessments, including, but 
not limited to, visual acuity testing, slit lamp 
examination, intraocular pressure measurement, 
fundoscopy, and fluorescein staining, will be 
performed at screening, as clinically indicated, 
and at the EOT visit by an ophthalmologist or, 
if unavailable, another licensed eye care 
provider.” 
Because the ophthalmological 
assessment form is mandatory 
and all tests are 
recommended. 
Section 8.4.1.3. Hepatic 
Events 
Removed “within a 3-week interval or 
simultaneously at any time” for adverse event 
reporting requirements for hepatic events. 
To reflect the most recent 
safety information. 
Section 8.4.4. Other Safety 
Updated the following statement: 
“Subjects should be advised to use artificial 
tears 4 times daily as a preventative measure 
and up to 8 times daily as clinically needed 
and to avoid the use of contact lenses.” 
To reflect the most recent 
safety information. 
Section 10.5.5. Action Taken 
Regarding Study Drug 
Revised text as follows: 
 
“Drug Infusion Interrupted: The study 
drug administration was started and 
then temporarily stopped. 
 
Dose Delayed: The study drug was 
not administered at the next 
scheduled cycle/dosing visit but was 
administered at a later date.” 
To clarify the meaning of the 
terms “dose delay” and 
“infusion interruption.” 

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TABLE OF CONTENTS 
INVESTIGATOR AGREEMENT...................................................................................................2 
DOCUMENT HISTORY.................................................................................................................3 
SUMMARY OF CHANGES ...........................................................................................................4 
1. 
PROTOCOL SUMMARY ............................................................................................21 
1.1. 
Protocol Synopsis ..........................................................................................................21 
1.2. 
Study Schema ................................................................................................................31 
1.3. 
Schedules of Events ......................................................................................................32 
2. 
INTRODUCTION ........................................................................................................47 
2.1. 
Background ...................................................................................................................47 
2.1.1. 
Non-small Cell Lung Cancer ........................................................................................47 
2.1.2. 
DS-1062a ......................................................................................................................47 
2.2. 
Study Rationale .............................................................................................................48 
2.3. 
Benefit and Risk Assessment ........................................................................................50 
2.3.1. 
Benefit and Risk with Regard to COVID-19 ................................................................50 
3. 
OBJECTIVES, OUTCOME MEASURES, AND ENDPOINTS .................................51 
3.1. 
Rationale for Selection of Primary and Secondary Endpoints ......................................55 
4. 
STUDY DESIGN ..........................................................................................................56 
4.1. 
Overall Design ..............................................................................................................56 
4.1.1. 
Design Overview ...........................................................................................................56 
4.1.2. 
End of Study ..................................................................................................................58 
4.1.3. 
Dose Regimen ...............................................................................................................58 
4.1.4. 
Duration.........................................................................................................................58 
4.2. 
Rationale for Study Design ...........................................................................................59 
4.3. 
Justification for Dose ....................................................................................................59 
5. 
STUDY POPULATION ...............................................................................................61 
5.1. 
Inclusion Criteria ...........................................................................................................61 
5.2. 
Exclusion Criteria..........................................................................................................64 
5.3. 
Screening Failures, Rescreening, and Subject Replacement ........................................67 
6. 
STUDY TREATMENT ................................................................................................68 
6.1. 
Study Drug Description ................................................................................................68 
6.2. 
Preparation, Handling, Storage, and Accountability for Study Drug ...........................68 

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6.3. 
Measure to Minimize Bias: Randomization and Blinding ............................................70 
6.4. 
Treatment Compliance ..................................................................................................70 
6.5. 
Guidelines for Dose Modification .................................................................................70 
6.6. 
Emergency Unblinding .................................................................................................78 
6.7. 
Prior and Concomitant Medications..............................................................................78 
7. 
STUDY DRUG DISCONTINUATION AND DISCONTINUATION FROM 
THE STUDY .................................................................................................................81 
7.1. 
Discontinuation of Study Drug .....................................................................................81 
7.2. 
Subject Withdrawal/Discontinuation From the Study ..................................................82 
7.3. 
Lost to Follow-up ..........................................................................................................84 
8. 
STUDY PROCEDURES ..............................................................................................85 
8.1. 
Eligibility Assessment ...................................................................................................85 
8.2. 
Randomization ..............................................................................................................87 
8.3. 
Efficacy Assessments ....................................................................................................87 
8.4. 
Safety Assessments .......................................................................................................89 
8.4.1. 
Adverse Event ...............................................................................................................89 
8.4.1.1. 
Adverse Events Reporting.............................................................................................91 
8.4.1.2. 
Adverse Events of Special Interest ...............................................................................92 
8.4.1.3. 
Hepatic Events ..............................................................................................................95 
8.4.2. 
Pregnancy ......................................................................................................................95 
8.4.3. 
Clinical Laboratory Evaluations ...................................................................................96 
8.4.4. 
Other Safety ..................................................................................................................96 
8.5. 
Pharmacokinetic Assessments ......................................................................................99 
8.6. 
Biomarker and Pharmacodynamic Assessments .........................................................100 
8.6.1. 
Exploratory Biomarker Assessments in Blood Samples .............................................101 
8.6.2. 
Exploratory Biomarker Assessments in Tumor Tissues .............................................101 
8.6.3. 
Additional Exploratory Biomarker Assessments ........................................................102 
8.6.4. 
TROP2 Immunohistochemistry Analysis ...................................................................102 
8.6.5. 
Pharmacogenomic (Inherited Genetic) Analysis ........................................................102 
8.6.5.1. 
Banking of Specimens for Inherited Genetic Analysis ...............................................103 
8.6.6. 
Immunogenicity ..........................................................................................................103 
9. 
STATISTICAL CONSIDERATIONS ........................................................................104 
9.1. 
General Statistical Considerations ..............................................................................104 

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9.2. 
Statistical Hypothesis ..................................................................................................104 
9.3. 
Sample Size Determination .........................................................................................104 
9.4. 
Population for Analysis Sets .......................................................................................105 
9.5. 
Statistical Analysis ......................................................................................................105 
9.5.1. 
Efficacy Analyses........................................................................................................106 
9.5.1.1. 
Primary Efficacy Analyses ..........................................................................................106 
9.5.1.2. 
Secondary Efficacy Analyses ......................................................................................106 
9.5.1.3. 
Multiplicity Adjustment ..............................................................................................107 
9.5.2. 
Safety Analyses ...........................................................................................................107 
9.5.3. 
Other Analyses ............................................................................................................109 
9.5.4. 
Interim Analysis ..........................................................................................................109 
10. 
APPENDICES – SUPPORTING DOCUMENTATION AND 
OPERATIONAL CONSIDERATIONS .....................................................................110 
10.1. 
Appendix 1 Regulatory and Ethical Considerations ...................................................110 
10.1.1. 
Regulatory Compliance ...............................................................................................110 
10.1.2. 
Informed Consent ........................................................................................................111 
10.1.3. 
Subject Confidentiality................................................................................................112 
10.1.4. 
Data Integrity and Quality Assurance .........................................................................112 
10.1.5. 
Committees .................................................................................................................114 
10.1.6. 
Study Documentation and Storage ..............................................................................114 
10.1.7. 
Finances.......................................................................................................................115 
10.1.8. 
Publication, Public Disclosure Policy, and Data Sharing ...........................................116 
10.1.9. 
Protocol Deviations .....................................................................................................116 
10.1.10. Study and Site Closure ................................................................................................116 
10.1.11. Product Complaints .....................................................................................................117 
10.2. 
Appendix 2: Laboratory Tests .....................................................................................118 
10.3. 
Appendix 3: Reference Standards ...............................................................................119 
10.3.1. 
Cockcroft-Gault Equation ...........................................................................................119 
10.3.2. 
New York Heart Association ......................................................................................119 
10.3.3. 
Eastern Cooperative Oncology Group Performance Status ........................................120 
10.3.4. 
Highly Effective Contraception ..................................................................................120 
10.4. 
Appendix 4: Response Evaluation Criteria in Solid Tumors (Version 1.1) ................121 
10.5. 
Appendix 5: General Information – Adverse Events ..................................................129 

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10.5.1. 
Definition of Adverse Event .......................................................................................129 
10.5.2. 
Serious Adverse Event ................................................................................................130 
10.5.3. 
Grade Assessment .......................................................................................................131 
10.5.4. 
Causality Assessment ..................................................................................................131 
10.5.5. 
Action Taken Regarding Study Drug ..........................................................................132 
10.5.6. 
Other Action Taken for Event .....................................................................................132 
10.5.7. 
Adverse Event Outcome .............................................................................................132 
10.6. 
Appendix 6: Key Data Analysis Requirements ..........................................................133 
10.7. 
Appendix 7: Instructions Related to COVID-19 .........................................................134 
11. 
REFERENCES ............................................................................................................136 
12. 
LIST OF ABBREVIATIONS .....................................................................................138 
 

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LIST OF TABLES 
Table 1: 
Dose Reduction Levels for DS-1062a ........................................................................29 
Table 1.1: Schedule of Events for Screening and Cycles 1 through 3 of the Treatment 
Period ..........................................................................................................................32 
Table 1.2: Schedule of Events for Cycle 4 and Subsequent Cycles of the Treatment 
Period, End of Treatment, and Follow-up Period .......................................................41 
Table 3.1: Description of Objectives, Outcome Measures, and Endpoints .................................51 
Table 6.1: Study Drug Dosing Information .................................................................................68 
Table 6.2: Dose Reduction Levels for DS-1062a ........................................................................71 
Table 6.3: Dose Modifications for Non-hematologic and Hematologic Toxicity Related 
to DS-1062a ................................................................................................................72 
Table 8.1: Schedule of Pharmacokinetic Sample Collection .......................................................99 
Table 9.1: Exact 95% Confidence Intervals for Sample Size of All Subjects and 
Subjects with EGFR Genomic Alterations at Various Observed Objective 
Response Rates .........................................................................................................105 
Table 10.1: Clinical Laboratory Tests .........................................................................................118 
Table 10.2: New York Heart Association Classifications ...........................................................119 
Table 10.3: Eastern Cooperative Oncology Group Performance Status ......................................120 
Table 10.4: Time Point Response: Subjects with Target (± Non-target) Disease .......................126 
Table 10.5: Objective Response: Subjects with Non-target Disease Only ..................................126 
Table 10.6: Best Overall Response When Confirmation of CR and PR Required ......................127 
Table 10.7: COVID-19 Dose Modification Criteria ....................................................................134 
 

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LIST OF FIGURES 
Figure 1.1: Study Level Flow Diagram .........................................................................................31 
 

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BICR and by 
investigator per 
RECIST v1.1.  
Time frame:  
At the time of the 
primary analysis.  
earlier of the dates of 
the first documentation 
of PD or death due to 
any cause.  
Title: TTR 
Description:  
TTR as assessed by 
BICR and by 
investigator per 
RECIST v1.1.  
Time frame:  
At the time of the 
primary analysis.  
TTR is defined as the 
time from the start of 
study treatment to the 
date of the first 
documentation of 
objective response 
(confirmed CR or 
confirmed PR) in 
responding subjects. 
Efficacy 
Title: ORR  
Description: ORR as 
assessed by investigator 
per RECIST v1.1.  
Time frame:  
At the time of the 
primary analysis. 
ORR is defined as the 
proportion of subjects 
who achieved a BOR 
of confirmed CR or 
confirmed PR.   
Efficacy 
Title: OS 
Description:  
OS. 
Time frame:  
At the time of the 
primary analysis. 
OS is defined as the 
time from the start of 
study treatment to the 
date of death due to 
any cause.  
Efficacy 
To further evaluate the 
safety of DS-1062a 
Title: TEAEs and other 
safety parameters 
during the study* 
Description:  
Descriptive statistics of 
safety endpoints.  
Time frame:  
Continuous monitoring 
and reported at the time 
of the primary analysis. 
*Though this is a 
secondary objective, 
this is a primary 
outcome measure. 
TEAEs, SAEs, AESIs, 
ECOG PS, vital sign 
measurements, 
standard clinical 
laboratory parameters 
(hematology, serum 
chemistry, and 
urinalysis), ECG 
parameters, 
ECHO/MUGA scan 
findings, and 
ophthalmologic 
findings.  AEs will be 
coded using the most 
current version of 
MedDRA.  AEs and 
laboratory test results 
will be graded using 
the NCI CTCAE v5.0. 
Safety 

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Genomic Alterations 
Applicable Targeted Agents 
EGFR 
erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib 
EGFR exon20 insertion 
amivantamab, mobocertinib  
EGFR T790M 
osimertinib 
ALK fusion 
crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib 
ROS-1 fusion 
entrectinib, lorlatinib, ceritinib, and crizotinib 
NTRK fusion 
entrectinib and larotrectinib 
BRAF V600E 
dabrafenib, alone or in combination with trametinib  
MET exon 14 skipping 
capmatinib and tepotinib 
RET rearrangement 
selpercatinib and pralsetinib  
ALK = anaplastic lymphoma kinase; BRAF = proto-oncogene B-raf; EGFR = epidermal growth 
factor receptor; MET = mesenchymal-epithelial transition; NTRK = neurotrophic tyrosine 
receptor kinase; RET = rearranged during transfection; ROS-1 = ROS proto-oncogene 1; TKI = 
tyrosine kinase inhibitor 
 
 
Must undergo a mandatory pre-treatment tumor biopsy procedure. 
OR 
If available, a tumor biopsy that was recently collected (within 3 months of screening) after 
completion of the most recent anticancer treatment regimen and that has a minimum of 
10 × 4 micron sections or a tissue block equivalent of 10 × 4 micron sections may be substituted for 
the mandatory biopsy collected during screening.   
Note: Results from this biopsy will not be used to determine eligibility for the study. 
 
Archival tumor tissue from initial diagnosis is required, to the extent that archival tumor tissue is 
available. 
 
Measurable disease based on local imaging assessment using RECIST v1.1. 
 
Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 – 1 at screening.  
 
Within 7 days before Cycle 1 Day 1, has adequate bone marrow function defined as: 
 
Platelet count ≥100,000/mm3 (platelet transfusion is not allowed within 1 week prior to 
screening assessment). 
 
Hemoglobin ≥9.0 g/dL (red blood cell/plasma transfusion is not allowed within 1 week prior to 
screening assessment). 
 
Absolute neutrophil count ≥1500/mm3 (granulocyte-colony stimulating factor [G-CSF] 
administration is not allowed within 1 week prior to screening assessment). 
(See Section 6.5 and Section 6.7 for use of G-CSF and erythropoietin) 
 
Within 7 days before Cycle 1 Day 1, has adequate organ function: 
 
Adequate hepatic function defined as: 
▪ 
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5 × upper limit of 
normal (ULN) or AST/ALT ≤5.0 × ULN if transferase elevation is due to liver metastases); 
AND 
▪ 
Total bilirubin (TBL) ≤1.5 × ULN (or <3.0 mg/dL in the presence of documented Gilbert’s 
Syndrome [unconjugated hyperbilirubinemia]).   
OR 
 
Moderate hepatic dysfunction (a maximum of 9 subjects): TBL >1.5 × ULN and ≤3 × ULN and 
any AST.   

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▪ 
Note: After a maximum of 9 subjects with moderate hepatic dysfunction have been 
enrolled, subsequent subjects with moderate hepatic dysfunction will be excluded. 
 
Within 7 days before Cycle 1 Day 1, has adequate renal function, including mild or moderate renal 
function, defined as: 
 
Creatinine clearance ≥30 mL/min, as calculated using the Cockcroft-Gault equation.  
 
Has a left ventricular ejection fraction (LVEF) ≥50% by either an echocardiogram (ECHO) or 
multiple gated acquisition (MUGA) scan within 28 days before Cycle 1 Day 1. 
 
Has adequate blood clotting function defined as international normalized ratio/prothrombin time and 
either partial thromboplastin or activated partial thromboplastin time ≤1.5 × ULN within 7 days 
before enrollment. 
 
Has an adequate treatment washout period before Cycle 1 Day 1 defined as: 
Treatment 
Washout Period 
Major surgery 
≥3 weeks 
Radiation therapy (curative) and palliative 
radiation to the chest 
≥4 weeks  
≥2 weeks (palliative radiation therapy to other 
areas [ie, limited field and 10 or fewer days or 
fractions] including whole brain radiotherapy) 
Anticancer chemotherapy (immunotherapy 
[non-antibody-based therapy]), retinoid 
therapy 
≥2 weeks or 5 times the t1/2 of the 
chemotherapeutic agent, whichever is longer; 
≥6 weeks for nitrosoureas or mitomycin C, 
≥1 week for TKIs approved for the treatment 
of NSCLC - baseline CT scan should be 
completed after discontinuation of TKI 
Antibody-based anticancer therapy 
≥4 weeks 
Chloroquine/Hydroxychloroquine 
>14 days 
CT = computed tomography; NSCLC = non-small cell lung cancer; t1/2; terminal elimination half-
life; TKI = tyrosine kinase inhibitor 
Key Exclusion Criteria: 
Subjects meeting any exclusion criteria for this study will be excluded from this study.  Below is a list limited to 
the key criteria: 
 
Has spinal cord compression or clinically active central nervous system metastases, defined as 
untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control 
associated symptoms.  Subjects with clinically inactive brain metastases may be included in the 
study.  Subjects with treated brain metastases that are no longer symptomatic and who require no 
treatment with corticosteroids or anticonvulsants may be included in the study if they have 
recovered from the acute toxic effect of radiotherapy.  A minimum of 2 weeks must have elapsed 
between the end of whole brain radiotherapy and study enrollment.  Note: A computed tomography 
(CT) or magnetic resonance imaging (MRI) scan of the brain at baseline is required for all subjects.  
For those subjects in whom central nervous system (CNS) metastases are first discovered at the time 
of screening, the treating investigator should consider delay of study treatment to document stability 
of CNS metastases with repeat imaging at least 4 weeks later (in which case, repeat of all screening 
activity may be required). 
 
Has leptomeningeal carcinomatosis. 
 
Had prior treatment with:  
 
Any chemotherapeutic agent targeting topoisomerase I, including antibody-drug conjugate 
(ADC) containing such agent.  
 
TROP2-targeted therapy. 

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1.2. 
Study Schema 
Figure 1.1: 
Study Level Flow Diagram 
 
ALK = anaplastic lymphoma kinase; BICR = blinded independent central review; BRAF = proto-oncogene braf; 
CBR = clinical benefit rate; CPI = checkpoint inhibitor; Dato-DXd = datopotamab deruxtecan; DCR = disease 
control rate; DoR = duration of response; ECOG PS = Eastern Cooperative Oncology Group performance status; 
EGFR = epidermal growth factor receptor; MET = mesenchymal-epithelial transition; NSCLC = non-small cell lung 
cancer; NTRK = neurotrophic tyrosine receptor kinase; ORR = objective response rate; OS = overall survival; 
PFS = progression-free survival; Q3W = every 3 weeks; RECIST v1.1 = Response Evaluation Criteria in Solid 
Tumors version 1.1; RET = rearranged during transfection; ROS1 = ROS proto-oncogene 1; SoD = sum of 
diameters; TTR = time to response; TROP2 = trophoblast cell surface protein 2; w/ = with; w/o = without 
a Only protocol deviations that are deemed significant by the investigator, with or without consultation with the 
Sponsor, may lead to permanent study drug discontinuation. 
b Subjects who discontinue study treatment without radiographic disease progression will continue to undergo tumor 
assessments every 6 weeks (± 7 days) during follow-up until documented radiographic disease progression by 
BICR, death, lost to follow-up, or withdrawal of consent (regardless of discontinuing study treatment or starting 
new anticancer therapy).  
Notes: Primary endpoint: ORR as assessed by BICR per RECIST v1.1  
Secondary endpoints: DoR, SoD, DCR, CBR, PFS and TTR, each as assessed by BICR and investigator per 
RECIST v1.1; ORR as assessed by investigator per RECIST v1.1; OS; safety; PK; and immunogenicity. 
The pharmacokinetics (PK) of DS-1062a will be evaluated in all subjects.  Full PK sampling will 
be collected from the first approximately 30 subjects with adequate hepatic function and up to 
9 subjects with moderate hepatic dysfunction.  The remaining subjects will undergo sparse PK 
sampling (Section 8.5).  
The overall end of study (EOS) will occur after the last treated subject’s last visit has occurred; 
or after all subjects have discontinued treatment and discontinued from the study or have died; or 
an alternative study becomes available for subjects continuing to derive benefit from treatment 
with DS-1062a where the drug is offered to these subjects; or the study is discontinued by the 
Sponsor for other reasons.  
The primary completion date will occur when all subjects have had either a minimum of 
9 months of follow-up after start of study treatment or have discontinued from the study, 
whichever occurs first. 

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2. 
INTRODUCTION 
2.1. 
Background 
2.1.1. 
Non-small Cell Lung Cancer 
Lung cancer is the most common cancer and the leading cause of cancer-related mortality 
worldwide, with an estimated 2.1 million new cases of lung cancer in 2018 (11.6% of all new 
cases) and 1.8 million deaths (18.4% of all cancer deaths) globally based on GLOBOCAN data.3  
Advances in early detection of lung cancer have been slow, and more than half of lung cancers 
are still diagnosed at an advanced stage.4  Only 18% of all patients with lung cancer are alive 
5 years or more after diagnosis.5  Non-small cell lung cancer (NSCLC) accounts for 80% to 85% 
of all lung cancers.6 
The introduction of targeted therapies and checkpoint inhibitors in recent years has improved the 
treatment landscape and patients with metastatic NSCLC are now surviving longer.7,8  A number 
of genomic alterations have been identified in NSCLC that have an impact on therapy selection 
and molecular testing is part of the standard of care (SoC) in the evaluation of NSCLC.8  These 
genomic alterations include epidermal growth factor receptor (EGFR) gene mutations, which are 
associated with responsiveness to EGFR-tyrosine kinase inhibitors (TKIs); anaplastic lymphoma 
kinase (ALK) gene rearrangements, associated with response to ALK TKIs; and more rarely, 
ROS proto-oncogene 1 (ROS1) gene rearrangements (associated with responsiveness to ROS1 
TKIs), neurotrophic tyrosine receptor kinase (NTRK) gene fusions (associated with 
responsiveness to NTRK inhibitors), and proto-oncogene B-raf (BRAF) point mutations 
(associated with responsiveness to combined therapy with inhibitors of BRAF and MEK).8  
Targeted therapies (eg, EGFR, ALK, ROS1, BRAF, MET exon 14 skipping, or RET kinase 
inhibitors) are recommended during the course of treatment as systemic treatments for a subset 
of patients with NSCLC whose tumors have driver genomic alterations.  However, once subjects 
have developed acquired resistance to the various kinase inhibitors, there are limited treatment 
options.  Hence, there is a significant unmet medical need for patients with advanced or 
metastatic NSCLC with actionable genomic alterations. 
2.1.2. 
DS-1062a 
Trophoblast cell surface protein 2 (TROP2), also known as tumor-associated calcium signal 
transducer 2, is a 36-kDa single-pass transmembrane protein expressed primarily in a variety of 
epithelial cells.  TROP2 has several binding partners, including claudin 1, claudin 7, cyclin D1, 
protein kinase C, phosphatidylinositol 4,5-biphosphate, and insulin-like growth factor 1.  TROP2 
is highly expressed in various epithelial tumors, including NSCLC.9 
DS-1062a (datopotamab deruxtecan; Dato-DXd) is an antibody-drug conjugate (ADC) that 
comprises a recombinant humanized anti-TROP2 immunoglobulin 1 (IgG1) monoclonal 
antibody (mAb), MAAP-9001a, that is covalently conjugated to a drug linker, MAAA-1162a, via 
thioether bonds.  The released drug, MAAA-1181a, inhibits deoxyribonucleic acid (DNA) 
topoisomerase I and leads to apoptosis of the target cells.  

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2.2. 
Study Rationale 
DS-1062a is a TROP2-targeted antibody and topoisomerase I inhibitor conjugate.  High 
expression levels of TROP2 have been reported in NSCLC10,11 and other solid tumors.12  TROP2 
high expression in tumors has been shown to be indicative of poor prognosis.9  
DS-1062a showed antitumor activity in both in vitro and in vivo nonclinical studies.  The mean 
terminal half-life (t1/2) of DS-1062a is 4.62 days (6.0 mg/kg) in humans, which allows a once 
every 3-week (Q3W) dosing schedule.11 
Clinical data are available from the ongoing Phase 1 first-in-human (FIH) study, 
DS1062-A-J101, evaluating escalating doses of DS-1062a (0.27 mg/kg to 10.0 mg/kg) 
in unselected subjects with unresectable advanced NSCLC relapsed or refractory to SoC therapy.  
As described in the Investigator’s Brochure (IB),13 DLTs occurred in 3 subjects: 2 subjects at 
10.0 mg/kg (1 subject with Grade 3 stomatitis and 1 subject with Grade 3 mucosal inflammation) 
and 1 subject at 6.0 mg/kg (Grade 3 maculopapular rash).  The maximum tolerated dose (MTD) 
was determined at 8.0 mg/kg.13  
As of the data cutoff (DCO) date of 04 Sep 2020, data are available for 208 subjects 
(204 NSCLC, 1 large-cell neuroendocrine carcinoma, and 3 breast cancer subjects) treated with 
DS-1062a in the 0.27 mg/kg to 10.0 mg/kg Q3W cohorts, including 50 subjects treated at 
4.0 mg/kg, 46 subjects at 6.0 mg/kg, and 82 subjects at 8.0 mg/kg doses.13  The median duration 
of treatment was 2.76 months (range: 0.7 to 20.0) across all doses; 2.09 months (range: 0.7 to 
20.0) in the 4.0 mg/kg dose group; 2.07 months (range: 0.7 to 19.7 months) in the 6.0 mg/kg 
dose group; and 3.19 months (range: 0.7 to 13.5 months) in the 8.0 mg/kg dose group.  As of the 
DCO, study treatment was ongoing in 72 subjects at the 4 mg/kg, 6 mg/kg, and 8 mg/kg dose 
levels. 
As of the DCO date of 04 Sep 2020, 189 subjects were evaluable for tumor assessments, defined 
as subjects who received at least 1 dose of DS-1062a and had pre-treatment and at least 
1 post-treatment tumor assessment or discontinued from study treatment.13  The ORR by blinded 
independent central review (BICR) was 17.5% (7 partial responses [PRs] in 40 subjects) in the 
4 mg/kg dose group, 15.4% (6 PRs in 39 subjects) in the 6 mg/kg dose group, and 23.8% 
(19 PRs in 80 subjects) in the 8 mg/kg dose group.  The DCR was 72.5% (7 PRs and 21 stable 
diseases [SDs] in 40 subjects) in the 4 mg/kg dose group, 66.7% (6 PRs and 18 SDs in 
39 subjects) in the 6 mg/kg dose group, and 80.0% (19 PRs and 43 SDs in 80 subjects) in the 
8 mg/kg dose group.  
As of 04 Sep 2020, treatment-emergent adverse events (TEAEs) regardless of causality were 
reported in 199 (95.7%) of 208 subjects, including 48 (96.0%) of 50 subjects in the 4 mg/kg dose 
group, 42 (91.3%) of 46 subjects in the 6 mg/kg dose group, and 81 (98.8%) of 82 subjects in the 
8 mg/kg dose group.13  The most frequent (≥20% of subjects) TEAEs across all doses, all grades, 
regardless of dose and causality were nausea (46.6%), stomatitis (38.9%), fatigue (34.1%), 
alopecia (33.7%), decreased appetite (24.5%), vomiting (23.1%), and constipation (20.7%).   
A total of 89 (42.8%) of 208 subjects experienced at least 1 ≥Grade 3 TEAE regardless of 
causality including 11 (22.0%) of 50 subjects in the 4 mg/kg dose group, 17 (37.0%) of 
46 subjects in the 6 mg/kg dose group, and 46 (56.1%) of 82 subjects in the 8 mg/kg dose group.  
The frequency of ≥Grade 3 TEAEs appears to be dose-related.   

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Forty two (20.2%) of 208 subjects experienced ≥Grade 3 TEAEs assessed by the investigator as 
study drug-related, including 5 (10.0%) of 50 subjects in the 4 mg/kg dose group, 7 (15.2%) of 
46 subjects in the 6 mg/kg dose group, and 27 (32.9%) of 82 subjects in the 8 mg/kg dose 
group.13  The most frequently reported ≥Grade 3 TEAE (≥5 subjects) assessed by the 
investigator as study drug-related across all doses was mucosal inflammation (6 subjects [2.9%]). 
Numerically higher rates of drug-related TEAEs, TEAEs ≥Grade 3, drug-related TEAEs 
≥Grade 3, serious TEAEs, drug-related serious TEAEs, TEAEs associated with drug 
discontinuation, drug-related TEAEs associated with study drug discontinuation, TEAEs 
associated with dose reduction, and TEAEs associated with death were observed in the 8 mg/kg 
cohort compared to the 4 mg/kg and/or 6 mg/kg cohorts.  A total of 20 (9.6%) of 208 subjects 
experienced TEAEs associated with study drug withdrawal, including 4 (8.0%) of 50 subjects in 
the 4 mg/kg dose group, 4 (8.7%) of 46 subjects in the 6 mg/kg dose group, and 12 (14.6%) of 
82 subjects in the 8 mg/kg dose group.  The most frequent TEAE across all doses leading to 
study drug withdrawal was pneumonitis (8 subjects [3.8%]).  A total of 35 (16.8%) of 208 
subjects experienced TEAEs associated with dose reduction, including 1 (2.0%) of 50 subjects in 
the 4 mg/kg dose group, 4 (8.7%) of 46 subjects in the 6 mg/kg dose group, and 25 (30.5%) of 
82 subjects in the 8 mg/kg dose group.  The most frequent (≥5 subjects) TEAEs associated with 
dose reduction across all doses were stomatitis (12 subjects [5.8%]) and mucosal inflammation 
(7 subjects [3.4%]).  A total of 28 (13.5%) of 208 subjects experienced TEAEs associated with 
dose interruption, including 2 (4.0%) of 50 subjects in the 4 mg/kg dose group, 9 (19.6%) of 
46 subjects in the 6 mg/kg dose group, and 16 (19.5%) of 82 subjects in the 8 mg/kg dose group.  
The most frequent (≥4 subjects) TEAEs across all doses associated with dose interruption were 
lung infection and pneumonitis (4 subjects [1.9%] each).   
As of 04 Sep 2020 across all doses, there were 14 subjects (6.7%) with interstitial lung disease 
(ILD)/pneumonitis events that were independently adjudicated as drug-related: 12 subjects 
(14.6%) on 8.0 mg/kg, 1 subject (2.2%) on 6.0 mg/kg, and 1 subject (2.0%) on 4.0 mg/kg. Of the 
14 subjects with events adjudicated as drug-related ILD, 3 (1.4%) subjects experienced Grade 5 
events; these 3 subjects were in the 8.0 mg/kg dose group.  
Across all doses, 40 (19.2%) of 208 subjects treated have experienced TEAEs of infusion-related 
reaction (IRR).13  All events of IRR were Grade 1 or Grade 2 except for 2 Grade 3 events (1 at 
4 mg/kg and 1 at 6 mg/kg).  All occurred during Cycle 1 or 2 of study treatment and were 
manageable.  
ILD/pneumonitis is an important identified risk for DS-1062a.  Other identified risks include 
IRR, fatigue, anemia, stomatitis/mucosal inflammation, diarrhea, nausea, decreased appetite, 
alopecia, vomiting, dry eye, and rash/maculopapular rash.  Potential risks include keratitis, skin 
pigmentation, AST increased, ALT increased, and constipation.  Adverse events of special 
interest (AESIs) include ILD/pneumonitis, oral mucositis/stomatitis, mucosal inflammation other 
than oral mucositis/stomatitis, ocular surface toxicity, and IRR.  Established treatment guidelines 
are in place to manage these and other toxicities associated with DS-1062a. 
Refer to the most recent IB for additional information.13 
There is a significant unmet medical need for patients with advanced or metastatic NSCLC with 
actionable genomic alterations after having received kinase inhibitors and platinum-based 
chemotherapy.  DS-1062a has the potential to offer a treatment option for patients with advanced 

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or metastatic NSCLC with genomic alterations.  This study will further evaluate the efficacy and 
safety of DS-1062a at a dose of 6.0 mg/kg in this population.  
2.3. 
Benefit and Risk Assessment 
DS-1062a is being developed for the treatment of TROP2-expressing malignant tumors. 
Nonclinical studies have demonstrated the antitumor activity of DS-1062a in TROP2 
tumor-bearing mouse models.  Thus, DS-1062a is expected to demonstrate efficacy in treating 
TROP2-expressing tumors in patients. 
In nonclinical toxicology studies, lung toxicity, corneal toxicity, skin toxicity, intestinal toxicity, 
lymphatic/hematopoietic system toxicity, reproductive and accessory organ toxicities, hepatic 
toxicity, renal toxicity, and joint cartilage toxicity were found in association with the 
administration of DS-1062a.  As with any therapeutic antibodies, there is a possibility of IRRs 
and immune responses causing allergic or anaphylactic reactions to DS-1062a. 
In vitro studies indicate that DS-1062a exhibits TROP2 expression-dependent cell growth 
inhibitory activity, and in vivo studies using a tumor-bearing mouse model indicate that 
administration of DS-1062a results in the regression of TROP2-expressing tumors. 
As of the DCO date of 04 Sep 2020, a total of 208 subjects have been treated with DS-1062a in 
the ongoing DS1062-A-J101 Phase 1 study.13  Data from this study show antitumor activity 
across dose groups with tumor responses observed at starting doses of 4.0, 6.0, and 8.0 mg/kg 
with an acceptable and manageable toxicity profile.  As of the DCO date of 04 Sep 2020, 
DS-1062a has demonstrated response rates across these 3 dose cohorts with confirmed and 
durable responses as described in Section 2.2.  
Based on cumulative review, an important identified risk for DS-1062a is ILD/pneumonitis.  
Other identified risks include IRR, fatigue, anemia, stomatitis/mucosal inflammation, diarrhea, 
nausea, decreased appetite, alopecia, vomiting, dry eye, and rash/ rash maculopapular.  The 
potential risks include keratitis, skin pigmentation, AST increased, ALT increased, and 
constipation.  DS-1062a exhibits an acceptable and generally manageable safety profile with 
adequate mitigation measures for the important identified risks and other risks mentioned above. 
In summary, aggregate safety and efficacy data from the DCO date of 04 Sep 2020 suggest a 
more favorable benefit/risk profile for 6 mg/kg relative to those of the 8 mg/kg and 4 mg/kg 
doses supporting the selection of 6 mg/kg for further development of DS-1062a. 
For additional information on justification for dose selected in this study, see Section 4.3.  
2.3.1. 
Benefit and Risk with Regard to COVID-19 
With the emergence of coronavirus disease 2019 (COVID-19), there is a potential safety risk due 
to the impact of COVID-19 on the lung.  The Sponsor has developed a monitoring plan to limit 
and manage the potential risk of COVID-19 to DS-1062a study subjects.  For details regarding 
the assessment and management of confirmed or suspected COVID-19, see Section 10.7. 

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3.1. 
Rationale for Selection of Primary and Secondary Endpoints 
The primary efficacy endpoint of the study will be the ORR, defined as the proportion of 
subjects who achieve a confirmed best overall response (BOR) of confirmed CR or PR as 
assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.  The ORR 
is a direct measure of the drug antitumor activity.  Because ORR is directly attributable to drug 
effect, it is an appropriate measure of efficacy in studies without comparator.14  
Duration of response in subjects with confirmed response of CR or PR is an important secondary 
endpoint of the study.  A durable response is clinically meaningful in subjects with advanced or 
metastatic NSCLC who have received 1 platinum-containing therapy and 1 or more lines of 
targeted therapy to the applicable genomic alterations in the study, in which there remains an 
unmet medical need.  

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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a global, multicenter, single-arm, open-label, Phase 2 study designed to evaluate the 
efficacy, PK, and safety of DS-1062a in subjects with advanced or metastatic NSCLC with 
actionable genomic alterations specified in Section 5.1 and who have been previously been 
treated with 1 platinum-containing therapy and 1 or more lines of targeted therapy to the 
applicable genomic alterations in the study.  The study population is described in Section 5.   
The study will be conducted at approximately 85 study sites located in North America, Europe, 
and the Asia Pacific region.  
The study start date is the date when the first subject has signed informed consent.  A subject is 
eligible to be enrolled into the study when the investigator or designee has obtained written 
consent, has confirmed all eligibility criteria have been met by the subject, and all screening 
procedures have been completed.   
4.1.1. 
Design Overview 
This study will enroll approximately 150 subjects with advanced or metastatic NSCLC with 
known genomic alterations in EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or 
RET who had previously received treatment with progressed on or after 1 platinum-containing 
therapy and 1 or more lines of targeted therapy to the applicable genomic alterations in the study.  
Patients with tumors expressing mutations in KRAS are not eligible for this study.  The rationale 
for this exclusion is that KRAS mutations are rarely found in conjunction with the genomic 
alterations listed above and as such do not typically receive targeted kinase inhibitors.  In 
addition, and in contrast to patients with the above listed genomic alterations, patients with 
KRAS mutant tumors respond to treatment with checkpoint inhibitors, and thus represent a 
population distinct from the kinase mutant populations included in this study.   
Subjects whose tumors harbor EGFR mutations should comprise approximately 50% of subjects 
enrolled in the study, among those, 80% should have received osimertinib (regardless of T790M 
status) as a prior line of therapy.  Subjects who meet these prior therapy requirements for 
advanced or metastatic NSCLC are eligible.  See the washout period for prior treatments in 
Section 5.1. 
The PK of DS-1062a will be evaluated in all subjects; see Section 8.5.  Full PK sampling will be 
collected from the first approximately 30 subjects with adequate hepatic function and up to 
9 subjects with moderate hepatic dysfunction.  The remaining subjects will have sparse PK 
sampling.  
Up to 9 subjects with moderate hepatic dysfunction, as defined by the National Cancer Institute 
Organ Dysfunction Working Group (NCI-ODWG),15 will be allowed in the study.  After a 
maximum of 9 subjects with moderate hepatic dysfunction have been enrolled, subsequent 
subjects with moderate hepatic dysfunction will be excluded. 
The schedules of events are presented in Table 1.1 (Screening and Cycles 1 through 3 of the 
Treatment Period) and Table 1.2 (Cycle 4 onwards, End of Treatment [EOT], and the Follow-up 
Period).   

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The study will be divided into 3 periods: Screening Period, Treatment Period, and Follow-up 
Period (which includes the Long-term Survival Follow-up [LTSFU]):   
 The Screening Period will start on the day of signing the informed consent form (ICF) 
and will have a maximum duration of 28 days.  Rescreening is permitted 1 time for any 
subject who did not meet reversible or transient eligibility criteria upon initial screening.  
During the 28-day Screening Period, subjects’ eligibility will be confirmed.  Subjects will 
undergo medical history evaluation, physical examination, vital signs determination, 
laboratory tests, electrocardiogram (ECG), echocardiogram (ECHO) or multigated 
acquisition (MUGA) scan, ophthalmologic assessment, and tumor biopsy procedure.  A 
tumor biopsy previously obtained within 3 months of signing the ICF, and with no 
anticancer treatment administered in the 3 months, may be substituted for the mandatory 
pre-treatment biopsy procedure during screening.  Biopsies may be collected from a 
lesion that has been irradiated, provided that it can be documented that the lesion has 
increased/appeared since radiation occurred and that the biopsy is collected at least 
3 months after radiation.  Documented results for genomic alterations in EGFR, ALK, 
ROS1, NTRK, BRAF, MET exon 14 skipping, or RET must be obtained for inclusion in 
the study and the previously known tumor genomic alteration status will be used. 
 Eligible subjects will enter the Treatment Period.  The Treatment Period starts on Cycle 1 
Day 1 and continues until a subject permanently discontinues DS-1062a.  During the 
Treatment Period, eligible subjects will receive DS-1062a until they meet one of the 
discontinuation criteria (see Section 7.1).  Subjects will undergo radiographic assessment 
of tumor response based on RECIST v1.1 every 6 weeks (±7 days) from Cycle 1 Day 1 
until radiographic disease progression as assessed by BICR, death, lost to follow-up, or 
withdrawal of consent, regardless of treatment discontinuation or start of new anticancer 
therapy (tumor assessment is not restricted to Treatment Period).  Subjects who 
experience clinical benefit will continue to receive DS-1062a until radiographic disease 
progression, clinical progression, unacceptable toxicity, withdrawal of consent by 
subject, physician decision, protocol deviation, pregnancy, lost to follow-up, study 
termination by the Sponsor, death, or other reasons (see Section 7.1). 
 The Follow-up Period will start upon permanent discontinuation of DS-1062a.  During 
the Follow-up Period, subjects will be followed for 28 days (+7 days) for safety.  After 
discontinuation of study drug, subjects will then enter the LTSFU Period, during which 
they will be followed every 3 months for collection of information on subsequent 
anticancer treatment and survival, including the cause and date of death.  During the 
Follow-up Period, subjects who discontinued treatment without radiographic disease 
progression as assessed by BICR will continue to undergo tumor assessments every 
6 weeks (± 7 days) until radiographic disease progression as assessed by BICR, death, 
lost to follow-up, or withdrawal of consent.  
To ensure accurate survival data are available at the time of any database lock, updated survival 
status may be requested during the study by the Sponsor.  For example, updated survival status 
may be requested prior to, but not limited to, the planned data cut and database lock for the 
primary analysis and final analysis.  Upon Sponsor notification, all subjects who do not/will not 
have a scheduled study visit or study contact during the Sponsor-defined period will be contacted 
for their survival status (excluding subjects who have discontinued from the entire study or with 

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a previously reported death event).  A potential companion diagnostic (CDx) assay to analyze 
TROP2 expression may be developed as part of the DS-1062 program.  Depending on the results 
of biomarker association with clinical benefit, a CDx may be developed in the course of this 
study.  
The primary analysis of ORR by BICR will be conducted after all subjects either have been 
followed for at least 9 months after the start of study treatment or have discontinued from the 
study, whichever occurs first.  The final analysis will occur after all subjects have discontinued 
from the study (see definition of overall EOS in Section 4.1.2).  
The study population is described in Section 5.  A study level flow diagram is presented in 
Figure 1.1.  
4.1.2. 
End of Study 
The primary completion date will occur when all subjects have had either a minimum of 
9 months of follow-up after start of study treatment or have discontinued from the study, 
whichever occurs first.  This date is used as the DCO date for the primary analysis.  All subjects 
still on treatment and continuing to derive benefit from DS-1062a at the primary completion date 
will continue to follow the study Schedule of Events (SoE) until the overall EOS is reached.  All 
subjects who have not had disease progression at the time of the primary completion date will 
continue to be followed for tumor assessments and survival.   
The subject’s EOS is the date of their last study visit/contact. 
The overall EOS will occur after the last subject last visit has occurred; or after all subjects have 
discontinued treatment and discontinued from the study, or have died; or an alternative study 
becomes available for subjects continuing to derive benefit from treatment with DS-1062a where 
the drug is offered to these subjects; or the study is discontinued by the Sponsor for other 
reasons. 
4.1.3. 
Dose Regimen 
DS-1062a will be administered as an intravenous (IV) infusion at a dose of 6.0 mg/kg Q3W on 
Day 1 of each 21-day cycle.  The study will use the DS-1062a drug product (lyophilized-drug 
product [Lyo-DP]).  
Subjects who experience clinical benefit will continue to receive DS-1062a until radiographic 
disease progression, clinical progression, death, pregnancy, withdrawal of subject consent, the 
subject becomes lost to follow-up, study termination by the Sponsor, physician decision, adverse 
event (AE), protocol deviation, or other reasons (see Section 7.1).  See Table 6.1 for complete 
details on dose regimen. 
Up to 3 dose reductions will be permitted for subjects.  The adjustment for reduced dosing of 
DS-1062a is shown in Table 6.2.  Once the dose of DS-1062a is reduced, no dose escalation is 
permitted.   
4.1.4. 
Duration 
Study duration is inclusive of 3 periods: Screening Period, Treatment Period, and Follow-up 
Period (which includes the LTSFU) as shown in Figure 1.1. 

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Duration of Treatment and Subject Participation 
Subjects who experience clinical benefit will continue to receive DS-1062a until radiographic 
disease progression, clinical progression, unacceptable toxicity, withdrawal of consent by 
subject, physician decision, protocol deviation, pregnancy, lost to follow-up, study termination 
by the Sponsor, death, or other reasons (see details in Section 7.1). 
Note: Only protocol deviations that are deemed significant by the investigator, with or without 
consultation with the Sponsor, may lead to permanent study drug discontinuation. 
In the event of early termination of the study, the Sponsor will consider providing DS-1062a to 
subjects who benefit from treatment according to legal regulations in the corresponding 
countries.  Alternatively, these subjects may also be treated with SoC per investigator’s decision. 
Overall Study Duration 
Enrollment is planned to occur over a period of approximately 19 months, with treatment and 
follow-up (28-day Safety Follow-up and Long-term Survival Follow-up) projected to continue 
for approximately 24 months after the last subject receives the first dose of DS-1062a.  The study 
will continue until the overall EOS is reached.  Thus, the anticipated total duration of the study is 
approximately 43 months.   
See Section 4.1 for the definition of study start and Section 4.1.2 for the definition of the overall 
EOS. 
Study Drug Continuation After the End of Study 
Not applicable. 
4.2. 
Rationale for Study Design 
There is significant unmet medical need for patients with advanced or metastatic NSCLC with 
actionable genomic alterations after they have received platinum-based chemotherapy.  This 
Phase 2 study is to further evaluate the efficacy, PK, and safety of 6.0 mg/kg DS-1062a as 
monotherapy. 
The primary efficacy endpoint, ORR, will be based on BICR and represents an additional 
measure to minimize bias in the assessment of the efficacy endpoints in the study. 
The rationale for dose selection is presented in Section 4.3 and the rationale for selection of the 
primary efficacy endpoint is presented in Section 3.1. 
4.3. 
Justification for Dose 
The 6.0-mg/kg dose of DS-1062a was selected based on preliminary results of the ongoing FIH 
Phase 1 study DS1062-A-J101, which enrolled 208 subjects with NSCLC across a DS-1062a 
dose range of 0.27 mg/kg to 10 mg/kg.  In this study, DS-1062a has shown a generally tolerable 
safety profile in subjects with NSCLC across a DS-1062a dose range of 0.27 mg/kg to 8.0 
mg/kg.  The non-tolerated dose for DS-1062a was 10.0 mg/kg, at which 2 subjects had Grade 3 
DLTs of mucosal inflammation and stomatitis.  In addition, 1 subject at 6.0 mg/kg had a 
dose-limiting toxicity of Grade 3 maculopapular rash.  The MTD was reached at 8.0 mg/kg.  
Enrollment was expanded to include 50, 50, and 80 subjects at doses of 4.0, 6.0, and 8.0 mg/kg, 

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respectively, to enrich the data for the part of the dose-response relationship where benefit-risk 
balance is most delicate.  
As noted in Section 2.2, the ORR was 17.5% (7 PRs in 40 subjects) in the 4 mg/kg dose group, 
15.4% (6 PRs in 39 subjects) in the 6 mg/kg dose group, and 23.8% (19 PRs in 80 subjects) in 
the 8 mg/kg dose group.  Numerically higher rates of drug-related TEAEs, TEAEs ≥Grade 3, 
drug-related TEAEs ≥Grade 3, serious TEAEs, drug-related serious TEAEs, TEAEs associated 
with drug discontinuation, drug-related TEAEs associated with study drug discontinuation, 
TEAEs associated with dose reduction, and TEAEs associated with death were observed in the 
8 mg/kg cohort compared to the 4 mg/kg and/or 6 mg/kg cohorts (Section 2.2).  DS-1062a was 
less tolerated at 8.0 mg/kg compared to 4.0 mg/kg and 6.0 mg/kg, and based on overall safety 
and efficacy data, 8.0 mg/kg was not considered an optimal dose for further evaluation.  
The Phase 1 study DS1062-A-J101 is ongoing, and data are continually emerging.  Barring any 
substantial changes in the efficacy and safety profiles of the 4.0-mg/kg and 6.0-mg/kg doses with 
more mature data, 6.0 mg/kg is considered to be the optimal dose for DS-1062a monotherapy 
studies in NSCLC. 
With respect to the dosing schedule, the mean terminal half-life of DS-1062a is 4.62 days at the 
6.0-mg/kg dose in clinical studies, thus supporting a Q3W dosing schedule. 

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5. 
STUDY POPULATION 
The study population includes adult subjects with a diagnosis of advanced or metastatic NSCLC 
with actionable genomic alterations specified below that have progressed on or after 
1 platinum-containing therapy and 1 or more lines of targeted therapy to the applicable genomic 
alterations in the study.  
5.1. 
Inclusion Criteria 
Subjects must meet all of the following criteria to be eligible for enrollment into the study: 
1. Sign and date the ICF prior to the start of any study-specific qualification procedures. 
1. Adults ≥18 years (if the legal age of consent is >18 years old, then follow local regulatory 
requirements).16 
2. Has pathologically documented NSCLC that  
a. Is stage IIIB, IIIC or stage IV NSCLC disease at the time of enrollment (based on the 
American Joint Committee on Cancer, Eighth Edition). 
b. Has 1 or more of the following documented activating tumor genomic alterations*: 
EGFR**, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.  
* Those whose tumors harbor KRAS mutations, in the absence of any of the 
genomic alterations specified above, will be excluded. 
** Overexpression of EGFR, in the absence of activating mutations, is NOT 
sufficient for enrollment.  Subjects who have not received osimertinib should be 
evaluated for presence of EGFR T790M mutation after relapse/progression 
on/after most recent EGFR TKI, unless the subject is already known to be positive 
with documented results for this mutation or unless osimertinib is not locally 
approved.   
3. Has documentation of radiographic disease progression while on or after receiving the 
most recent treatment regimen for advanced or metastatic NSCLC. 
4. Subject must meet the following for advanced or metastatic NSCLC: 
a. Has been treated with at least 1 but no more than 2 cytotoxic agent-containing therapy 
in the metastatic setting: 
i. 
One platinum-containing regimen (either as monotherapy or combination 
therapy); 
ii. 
May have received up to one additional line of cytotoxic agent-containing 
therapy; 
iii. 
Those who received a platinum-containing regimen as adjuvant therapy for 
early-stage disease must have relapsed or progressed while on the treatment or 
within 6 months of the last dose OR received at least one additional course of 
platinum-containing therapy (which may or may not be same as in the 
adjuvant setting) for relapsed/progressive disease; 

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b. May have received up to one checkpoint inhibitor (CPI)-containing regimen (may be 
in combination with a cytotoxic agent as part of a regimen described in 5a above or as 
an additional CPI regimen without a cytotoxic agent); 
c. Has been treated with one or more lines of non-CPI targeted therapy that is locally 
approved for the subject’s applicable genomic alteration at the time of screening; OR 
one or more of the agents specified in the table below; 
i. 
Those who received a targeted agent as adjuvant therapy for early stage 
disease must have relapsed or progressed while on the treatment or within 
6 months of the last dose OR received at least one additional course of 
targeted therapy for the same genomic alterations (which may or may not be 
same agent used in the adjuvant setting) for relapsed/progressive disease. 
ii. 
Subjects who have been treated with a prior TKI must receive additional 
targeted therapy, if clinically appropriate, for the applicable genomic 
alterations, or the subject will not be allowed in the study. 
Genomic Alterations 
Applicable Targeted Agents 
EGFR 
erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib 
EGFR exon20 insertion 
amivantamab, mobocertinib 
EGFR T790M 
osimertinib 
ALK fusion 
crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib 
ROS-1 fusion 
entrectinib, lorlatinib, ceritinib, and crizotinib 
NTRK fusion 
entrectinib and larotrectinib 
BRAF V600E 
dabrafenib, alone or in combination with trametinib 
MET exon 14 skipping 
capmatinib and tepotinib 
RET rearrangement 
selpercatinib and pralsetinib  
ALK = anaplastic lymphoma kinase; BRAF = proto-oncogene B-raf; EGFR = epidermal growth 
factor receptor; MET = mesenchymal-epithelial transition; NTRK = neurotrophic tyrosine receptor 
kinase; RET = rearranged during transfection; ROS-1 = ROS proto-oncogene 1; TKI = tyrosine 
kinase inhibitor 
5. Must undergo a mandatory pre-treatment tumor biopsy procedure. 
OR 
If available, a tumor biopsy that was recently collected (within 3 months of screening) 
after completion of the most recent anticancer treatment regimen and that has a minimum 
of 10 × 4 micron sections or a tissue block equivalent of 10 × 4 micron sections may be 
substituted for the mandatory biopsy collected during screening.   
Note: Results from this biopsy will not be used to determine eligibility for the study. 
6. Archival tumor tissue from initial diagnosis is required, to the extent that archival tumor 
tissue is available.  
7. Has measurable disease based on local imaging assessment using RECIST v1.1 (see 
criteria in Section 10.4). 
8. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at 
screening (see criteria in Section 10.3.3). 

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9. Within 7 days before Cycle 1 Day 1, has adequate bone marrow function defined as: 
a. Platelet count ≥100,000/mm3 (platelet transfusion is not allowed within 1 week prior 
to screening assessment). 
b. Hemoglobin ≥9.0 g/dL (red blood cell/plasma transfusion is not allowed within 
1 week prior to screening assessment). 
c. Absolute neutrophil count ≥1500/mm3 (granulocyte-colony stimulating factor 
[G-CSF] administration is not allowed within 1 week prior to screening assessment). 
(See Section 6.5 and Section 6.7 for use of G-CSF and erythropoietin) 
10. Within 7 days before Cycle 1 Day 1, has 
 Adequate hepatic function, defined as:  
▪ Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) 
≤2.5 × upper limit of normal (ULN) or AST/ALT ≤5.0 × ULN if transferase 
elevation is due to liver metastases) AND 
▪ Total bilirubin (TBL) ≤1.5 × ULN or (<3.0 mg/dL in the presence of 
documented Gilbert’s Syndrome [unconjugated hyperbilirubinemia]). 
OR 
 Moderate hepatic dysfunction (a maximum of 9 subjects): TBL >1.5 × ULN and 
≤3 × ULN and any AST.   
▪ Note: After a maximum of 9 subjects with moderate hepatic dysfunction have 
been enrolled, subsequent subjects with moderate hepatic dysfunction will be 
excluded. 
11. Within 7 days before Cycle 1 Day 1, has adequate renal function, including mild or 
moderate renal function, defined as:  
 Creatinine clearance ≥30 mL/min, as calculated using the Cockcroft-Gault equation 
(see Section 10.3.1).  
12. Has a left ventricular ejection fraction (LVEF) ≥50% by either an ECHO or MUGA scan 
within 28 days before Cycle 1 Day 1.  
13. Has adequate blood clotting function defined as international normalized 
ratio/prothrombin time and either partial thromboplastin or activated partial 
thromboplastin ≤1.5 × ULN within 7 days before enrollment. 
14. Has an adequate treatment washout period before Cycle 1 Day 1 defined as:  
Treatment 
Washout Period 
Major surgery 
≥3 weeks 
Radiation therapy (curative) and palliative 
radiation to the chest 
≥4 weeks  
≥2 weeks (palliative radiation therapy to other areas [ie, 
limited field and 10 or fewer days or fractions] including 
whole brain radiotherapy)  
Anticancer chemotherapy (immunotherapy 
[non-antibody-based therapy]), retinoid 
therapy 
≥2 weeks or 5 times the t1/2 of the chemotherapeutic 
agent, whichever is longer; ≥6 weeks for nitrosoureas or 
mitomycin C, ≥1 week for TKIs approved for the 
treatment of NSCLC - baseline CT scan should be 
completed after discontinuation of TKI 
Antibody-based anticancer therapy 
≥4 weeks 
Chloroquine/Hydroxychloroquine 
>14 days 

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CT = computed tomography; NSCLC = non-small cell lung cancer; t1/2; terminal elimination half-life; 
TKI = tyrosine kinase inhibitor 
15. If the subject is a female of childbearing potential, she must have a negative serum 
pregnancy test at screening and must be willing to use highly effective birth control (as 
detailed in Section 10.3.4) upon enrollment, during the Treatment Period, and for 
7 months following the last dose of study drug.  Females of non-childbearing potential 
are defined as pre-menopausal females with a documented tubal ligation or hysterectomy, 
or postmenopausal (defined as 12 months of spontaneous amenorrhea [in questionable 
cases, a blood sample with simultaneous follicle stimulating hormone (FSH) 
>40 mIU/mL and estradiol <40 pg/mL/147 pmol/L is confirmatory]).  Females on 
hormone replacement therapy (HRT) and whose menopausal status is in doubt will be 
required to use 1 of the contraception methods outlined for women of childbearing 
potential if they wish to continue their HRT during the study.  Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status prior to study 
enrollment.  For most forms of HRT, at least 2 to 4 weeks will elapse between the 
cessation of therapy and the blood draw; this interval depends on the type and dosage of 
HRT.  Following confirmation of their postmenopausal status, they can resume use of 
HRT during the study without use of a contraceptive method.  
16. If male, the subject must be surgically sterile or must use a condom in addition to highly 
effective birth control (as detailed in Section 10.3.4) if their partners are of reproductive 
potential upon enrollment, during the Treatment Period, and for 4 months after the final 
dose of study drug administration. 
17. Male subjects must not freeze or donate sperm starting at Screening and throughout the 
study period, and at least 4 months after the final study drug administration.  Preservation 
of sperm should be considered before enrollment in the study.  
18. Female subjects must not donate, or retrieve for their own use, ova from the time of 
screening and throughout the study treatment period, and for at least 7 months after the 
final study drug administration.  Preservation of ova should be considered prior to 
enrollment in the study. 
19. Be willing and able to comply with scheduled visits, drug administration plan, laboratory 
tests, other study procedures, and study restrictions. 
20. Has a life expectancy ≥3 months based on investigator’s opinion. 
5.2. 
Exclusion Criteria 
Subjects who meet any of the following criteria will be disqualified from entering the study: 
1. Has spinal cord compression or clinically active central nervous system metastases, 
defined as untreated and symptomatic, or requiring therapy with corticosteroids or 
anticonvulsants to control associated symptoms.  Subjects with clinically inactive brain 
metastases may be included in the study.  Subjects with treated brain metastases that are 
no longer symptomatic and who require no treatment with corticosteroids or 
anticonvulsants may be included in the study if they have recovered from the acute toxic 
effect of radiotherapy.  A minimum of 2 weeks must have elapsed between the end of 

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whole brain radiotherapy and study enrollment.  Note: A computed tomography (CT) or 
magnetic resonance imaging (MRI) scan of the brain at baseline is required for all 
subjects.  For those subjects in whom central nervous system (CNS) metastases are first 
discovered at the time of screening, the treating investigator should consider delay of 
study treatment to document stability of CNS metastases with repeat imaging at least 
4 weeks later (in which case, repeat of all screening activity may be required). 
2. Has leptomeningeal carcinomatosis.  
3. Prior treatment with: 
a. Any chemotherapeutic agent targeting topoisomerase I, including ADC containing 
such agent. 
b. TROP2-targeted therapy. 
4. Uncontrolled or significant cardiovascular disease, including: 
a. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) 
>470 milliseconds (msec) (based on the average of screening triplicate 12-lead ECG 
determinations). 
b. History of myocardial infarction within 6 months prior to Cycle 1 Day 1. 
c. History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1. 
d. Symptomatic congestive heart failure (CHF) (New York Heart Association Class II to 
IV) at screening.  Subjects with a history of Class II to IV CHF prior to screening 
must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO or 
MUGA scan within 28 days of Cycle 1 Day 1) in order to be eligible (see criteria in 
Section 10.3.2). 
e. History of serious cardiac arrhythmia requiring treatment. 
f. LVEF <50% by ECHO or MUGA scan within 28 days before Cycle 1 Day 1. 
g. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic 
blood pressure >110 mmHg) within 28 days before Cycle 1 Day 1. 
5. Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current 
ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at 
screening. 
6. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses 
including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli 
within 3 months of the study Cycle 1 Day 1, severe asthma, severe chronic obstructive 
pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.), or any 
autoimmune, connective tissue or inflammatory disorders with pulmonary involvement 
(ie, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.), or prior pneumonectomy. 
7. Clinically significant corneal disease. 
8. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.  Note: Subjects 
with localized fungal infections of skin or nails are eligible.  
9. Has known HIV infection that is not well controlled.  All of the following criteria are 
required to define an HIV infection that is well controlled: undetectable viral RNA load, 

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CD4+ counts/levels >250, no history of AIDs-defining opportunistic infection within the 
past 12 months, and stable for at least 4 weeks on same anti-HIV retroviral medications.  
If an HIV infection meets the above criteria, monitoring of the subjects’ viral RNA load 
as well as the CD4+ count levels would be important.  Subjects should be tested for HIV 
prior to Cycle 1 Day 1 if acceptable by local regulations or Institutional Review Board 
(IRB)/Ethics Committee (EC).  
10. Has an active or uncontrolled hepatitis B and/or hepatitis C infection, is positive for 
hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (hepatitis 
B surface antigen [HBsAg], anti-hepatitis B surface antigen [anti-HBs], anti-hepatitis B 
core antibody [anti-HBc], or hepatitis B virus [HBV] DNA) and/or hepatitis C infection 
(as per HCV RNA) within 28 days of Cycle 1 Day 1.  
Subjects are eligible if:  
a. Subjects have received hepatitis B vaccination with only anti-HBs positivity and no 
clinical signs of hepatitis. 
b. Subjects who are HBsAg+, with HBV infection for more than 6 months (ie, chronic 
HBV infection) must meet the following conditions: 
i. HBV DNA viral load <2000 IU/mL. 
ii. Have normal transaminase values, or, if liver metastases are present, abnormal 
transaminases with a result of AST/ALT <3 × ULN which are not attributable to 
HBV infection.  
iii. Start or maintain antiviral treatment if clinically indicated as per the investigator.  
c. Subjects have been curatively treated for hepatitis C infection as demonstrated 
clinically and by viral serology.  
11. Has other primary malignancies, except adequately resected non-melanoma skin cancer, 
curatively treated in situ disease, or other solid tumors curatively treated, with no 
evidence of disease for ≥3 years. 
12. Concomitant medical condition that would increase the risk of toxicity in the opinion of 
the investigator. 
13. Toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) 
not yet improved to NCI CTCAE version 5.0 Grade ≤1 or baseline. 
Note: Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no 
worsening to >Grade 2 for at least 3 months prior to Cycle 1 Day 1 and managed with 
SoC treatment) that the investigator deems related to previous anticancer therapy, 
comprised of (including, but not limited to): 
a. Chemotherapy-induced neuropathy 
b. Fatigue 
c. Residual toxicities from prior immunotherapy treatment: Grade 1 or Grade 2 
endocrinopathies, which may include: 
 Hypothyroidism/hyperthyroidism 
 Type I diabetes 

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 Hyperglycemia 
 Adrenal insufficiency 
 Adrenalitis 
 Skin hypopigmentation (vitiligo)  
14. Has a history of severe hypersensitivity reactions to either the drug substances or inactive 
ingredients (including but not limited to polysorbate 80). 
15. History of severe hypersensitivity reactions to other monoclonal antibodies. 
16. Is pregnant or breastfeeding or planning to become pregnant. 
17. Has substance abuse or any other medical conditions such as clinically significant cardiac 
or psychological conditions, that may, in the opinion of the investigator, interfere with the 
subject’s participation in the clinical study or evaluation of the clinical study results. 
18. Psychological, social, familial, or geographical factors that would prevent regular 
follow-up.  Adults under guardianship, curatorship, safeguard of justice, or family 
empowerment measure are not eligible. 
19. Otherwise considered inappropriate for the study by the investigator. 
5.3. 
Screening Failures, Rescreening, and Subject Replacement 
For subjects who do not meet the criteria for participation in the study (screen failures), the 
reason for screen failure must be recorded in the Screening Log.   
Subjects who have dropped out will not be replaced. 
Rescreening is permitted 1 time for any subject who did not meet reversible or transient 
eligibility criteria upon initial screening.  The Screening Period for subjects who are rescreened 
is 28 days.  A new subject identification number must be provided at the time of rescreening.   

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6. 
STUDY TREATMENT 
See Figure 1.1 for treatment sequence. 
6.1. 
Study Drug Description 
Table 6.1 describes the formulation, dose, regimen, duration, packaging, and labeling of 
DS-1062a. 
Table 6.1: 
Study Drug Dosing Information 
Study Drug Name 
DS-1062a (Datopotamab Deruxtecan; Dato-DXd) 
Dosage Formulation 
DS-1062a DP will be provided as sterile lyophilized-DP consisting of 
100 mg of lyophilized powder in a single-use amber glass vial to be 
reconstituted with water for injection and further diluted with 5% 
dextrose injection prior to use.  
Dosage Level 
6.0 mg/kg 
Route of Administration 
IV 
Dosing Instructions/Regimen 
One IV infusion every 3 weeks on Day 1 of each 21-day cycle.  
Premedication is required prior to any dose of DS-1062a that must 
include antihistamines and acetaminophen with or without 
glucocorticoids.  Subjects should remain at the site for at least 1-h post-
infusion of every dose of DS-1062a for close observation for possible 
allergic reaction. 
If a subject does not experience any IRR during or after the first 2 cycles, 
the post-infusion observation period can be shortened to at least 
30 minutes for subsequent cycles. Subjects with identified IRR related to 
the study drug should be observed post-infusion for at least 1 hour for the 
2 cycles after the IRR event and for at least 30 minutes at each 
subsequent cycle. 
Duration 
The initial dose will be infused over approximately 90 min on Cycle 1 
Day 1.  In the absence of an IRR, the subsequent doses will be infused 
over approximately 30 min.  In case of IRR at any time during treatment, 
please refer to details provided in Table 6.3. 
Packaging 
DS-1062a will be supplied by the Sponsor.  The packaging will be 
clearly labeled “For Clinical Study Use Only,” and will show the display 
name of the study drug, the lot number, storage condition, protocol 
number and other required information in accordance with local 
regulations. 
Labeling 
DS-1062a glass vials will be labeled as required per local regulatory 
requirement. 
DP = drug product; IRR = infusion-related reaction; IV = intravenous 
6.2. 
Preparation, Handling, Storage, and Accountability for Study Drug 
Preparation, Handling, and Disposal 
The preparation of study drug will be conducted in accordance with the Pharmacy Manual 
provided by the Sponsor.  The drug for IV infusion is prepared by dilution of the required 
volume of the DP calculated based on the subject’s baseline body weight, defined as the last 

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measurement on or before the first dose.  Prepared medicinal solutions should be used 
immediately.  Refer to the Pharmacy Manual for detailed information about preparation and 
administration of DS-1062a. 
Procedures for proper handling and disposal should be followed in compliance with the standard 
operating procedures (SOPs) or other institutional guidelines of the site. 
Administration 
DS-1062a will be administered as a 6.0 mg/kg IV infusion Q3W on Day 1 of each 21-day cycle.  
Premedication is required prior to any dose of DS-1062a that must include antihistamines and 
acetaminophen with or without glucocorticoids. 
The initial dose of DS-1062a will be infused over approximately 90 minutes.  If there is no IRR 
after the initial dose, the next dose of DS-1062a will be infused over approximately 30 minutes.  
In case of IRR at any time during treatment, refer to details provided in Table 6.3.  Subjects 
should remain at the site for at least 1-hour post-infusion of every DS-1062a dose for close 
observation for possible allergic reaction.  If a subject does not experience any IRR during or 
after the first 2 cycles, the post-infusion observation period can be shortened to at least 
30 minutes for subsequent cycles. Subjects with identified IRR related to the study drug should 
be observed post-infusion for at least 1 hour for the 2 cycles after the IRR event and for at least 
30 minutes at each subsequent cycle. 
For prevention of oral mucositis/stomatitis, subjects are advised to initiate a daily oral care plan 
(OCP; see Section 8.4.4 for details) before study intervention initiation and maintain it 
throughout the study.  An OCP should include daily inert, bland mouth rinses (eg, with a 
nonalcoholic, bicarbonate-containing mouthwash 4 to 6 times a day), although other prophylaxis 
regimens (eg, dexamethasone oral solution 0.1 mg/mL 10 mL 3 to 4 times daily swish for 1 to 
2 minutes then spit out, as well as cryotherapy throughout the infusion) advocated by 
institutional/local guidelines are permitted.  An OCP should also include educating subjects on 
the importance of oral hygiene, tooth brushing, flossing, and hydration and lubrication of the oral 
mucosa, and on the benefits of adhering to their recommended OCP.  Per the investigator’s 
judgment, a professional dental evaluation before study drug initiation and dental treatment, if 
indicated, may reduce the risk of local and systemic infections from odontogenic sources. 
The subject’s weight at baseline (ie, the last weight measurement taken prior to the first dose) 
will be used to calculate the initial dose.  If during the treatment the subject’s weight changes by 
± 10% of the baseline weight, the subject’s dose must be recalculated based on the subject’s 
updated weight.  After the recalculation, the updated subject’s weight will be used as the new 
baseline weight.  The site may follow local institutional policy for recalculating dose based on 
weight changes less than 10%. 
The drug formulation used in this study will be Lyo-DP.   
Storage 
Drug supplies must be stored in a secure, limited access storage area under the recommended 
storage conditions as noted on the label: Lyo-DP should be stored between 2°C and 8°C, 
protected from light.   

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If storage conditions are not maintained per specified requirements, then the Sponsor or contract 
research organization (CRO) should be contacted.  See the Pharmacy Manual for additional 
information on storage conditions of study drug/storage conditions of the infusion solution. 
Drug Accountability 
When a drug shipment is received, the pharmacist or designee will check the amount and 
condition of the drug against the shipping documentation.  The pharmacist or designee shall 
contact the Sponsor as soon as possible if there is a problem with the shipment. 
The Receipt of Shipment Form should be faxed as instructed on the form unless receipt is 
controlled by IRT.  The original will be retained at the study site.   
The pharmacist is responsible for study drug accountability, reconciliation and record 
maintenance (ie, Receipt of Shipment Form, dispensation/return record, and certificate of 
destruction/return receipt). 
At the end of the study, all unused DS-1062a will be returned or destroyed as per local laws or 
site policy and only after the CRO’s study monitor has completed a final inventory.  As 
applicable, the study site must file a copy of the appropriate institution policy within their 
investigator site file and provide a copy to the Sponsor.  See the Pharmacy Manual for details. 
6.3. 
Measure to Minimize Bias: Randomization and Blinding 
Not applicable.  
6.4. 
Treatment Compliance 
DS-1062a will be administered as an IV infusion to subjects under the supervision of study site 
personnel.  Therefore, treatment compliance will be guaranteed as long as the subject attends 
each visit for administration of study drug.  Start and stop date/time of infusion must be recorded 
in the electronic case report form (eCRF).  
6.5. 
Guidelines for Dose Modification 
All dose modifications (ie, infusion interruptions, dose delays, dose reduction, and/or treatment 
discontinuation) should be based on the worst preceding toxicity (NCI CTCAE v5.0).  Possible 
exceptions to the dose modification criteria may be allowed on a case-by-case basis after 
discussion and agreement between the investigator and Sponsor.  The agreement must be 
documented.  Dose modification decisions may be based on local laboratory results. 
All infusion interruptions, dose delays, or other modifications must be recorded in the eCRF.  If 
study drug is delayed, missed doses will not be made up.   
In the event of an infusion interruption or a dose delay occurring prior to completion of a 
PK/pharmacodynamic blood sampling in the study, investigators should contact the Sponsor’s 
Medical Monitor for guidance regarding scheduling of these procedures. 

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Dose Reduction Guidelines 
Up to 3 dose reductions will be permitted for subjects (Table 6.2).  If toxicity continues after the 
permitted dose reductions, the subject will be withdrawn from the study treatment if further 
toxicity meeting the requirement for dose reduction occurs. 
Once the dose of DS-1062a has been reduced because of toxicity, all subsequent cycles should 
be administered at that lower dose level unless further dose reduction is required.  Once the dose 
of DS-1062a is reduced, no escalation is permitted. 
Table 6.2: 
Dose Reduction Levels for DS-1062a 
Starting Dose 
Dose Reduction 1 
Dose Reduction 2 
Dose Reduction 3 
6.0 mg/kg 
4.0 mg/kg 
3.0 mg/kg 
2.0 mg/kg 
 
Dose Modification – Toxicity Management Guidelines 
Dose modification criteria for subjects with suspected or confirmed COVID-19 are presented in 
Section 10.7.  
Specific criteria for DS-1062a infusion interruption, dose delay, dose reduction, and/or 
discontinuation in case of TEAEs that are considered related to the use of DS-1062a by the 
investigator are presented in Table 6.3, which is applicable only to TEAEs that are assessed as 
related to use of DS-1062a by the investigator(s).  For non-drug-related TEAEs or if nothing is 
noted in Table 6.3, standard practice should be followed.  Appropriate experts should be 
consulted as deemed necessary.  The investigator may consider infusion interruption, dose delay, 
or study treatment discontinuation based on other events not listed in Table 6.3 according to the 
subject’s condition.  
There will be no dose modifications for Grade 1 or Grade 2 TEAEs unless specified in Table 6.3.  
For Grade 3 or Grade 4 events, monitoring (including local laboratory tests when appropriate) 
should be performed frequently and at an interval no greater than 7 days.  The dose may be 
delayed for up to 9 weeks (63 days) from the planned date of the next cycle administration (ie, 
up to 12 weeks or 84 days from the last infusion).  If a subject is assessed as requiring a dose 
delay longer than 12 weeks (84 days) from the last infusion, the subject must discontinue study 
treatment. Study treatment dose delay for conditions other than toxicity resolution should be kept 
as short as possible. 
If a subject cannot restart study treatment for other reasons (eg, intercurrent conditions not 
related to disease progression or toxicity), the case should be discussed with the Sponsor’s 
Medical Monitor. 
A subject for whom DS-1062a dosing is temporarily withheld for any reason may have future 
cycles scheduled based on the date of the last DS-1062a dose. 

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Table 6.3: 
Dose Modifications for Non-hematologic and Hematologic Toxicity Related 
to DS-1062a 
Worst NCI CTCAE v5.0 Grade 
Toxicity (unless otherwise 
specified) 
Management Guidelines for DS-1062a 
Infusion-related Reaction 
Premedication is required prior to any dose of Dato-DXd that must include antihistamines and acetaminophen 
with or without glucocorticoids. Subjects should remain at the site for at least 1-hour post-infusion of every dose 
of Dato-DXd for close observation for possible allergic reaction.  If a subject does not experience any IRR during 
or after the first 2 cycles, the post-infusion observation period can be shortened to at least 30 minutes for 
subsequent cycles. Subjects with identified IRR related to the study drug should be observed post-infusion for at 
least 1 hour for the 2 cycles after the IRR event and for at least 30 minutes at each subsequent cycle.  
Grade 1 
If IRR (such as fever and chills, with and without nausea/vomiting, pain, 
headache, dizziness, dyspnea, and Grade 1 or 2 hypotension) is observed 
during administration, the infusion rate should be reduced by 50% of the 
initial infusion rate, and subjects should be closely monitored.  
If no other reactions appear upon resumption of the study drug at the 
above reduced infusion rate, then the infusion rate for subsequent 
treatment cycles may be resumed at the initial infusion rate. 
Grade 2 
Administration of Dato-DXd should be interrupted.  Symptomatic 
treatment should be started.  
 
If the event resolves or improves to Grade 1, infusion can be 
restarted at a 50% reduced infusion rate (ie, 180 minutes for a 
90-minute infusion and 60 minutes for a 30-minute infusion). 
 
If an IRR recurs upon rechallenge of Dato-DXd while it is 
being infused at a reduced rate during the same cycle, then treat 
as Grade 3 and follow the Grade 3 TMG. 
If there is no recurrence, the subsequent infusion should be 
administered at a reduced rate. 
 
If there is no new IRR, then Dato-DXd can be administered at 
the initial planned infusion rate (90 or 30 minutes) for 
subsequent treatment cycles. 
Grade 3 
Administration of Dato-DXd should be stopped immediately for that 
cycle and initiate treatment of the IRR symptoms. 
 
If the IRR does not resolve within the same day, recurrence of 
symptoms occurs following initial improvement, or 
hospitalization is necessary for clinical sequelae, then 
permanently discontinue Dato-DXd.  
 
If the IRR resolves within the same day of Dato-DXd infusion, 
no recurrence of symptoms occurs following initial 
improvement, and no hospitalization is necessary for clinical 
sequelae, then for the next cycle, administer Dato-DXd at a 
50% reduced infusion rate (ie, 180 minutes for a 90-minute 
infusion; 60 minutes for a 30-minute infusion). 
o 
If there is no new IRR, then for the subsequent cycle, 
administer Dato-DXd at the initial infusion rate (90 or 
30 minutes).  If the subject tolerates that initial 
infusion rate with no new IRR, then for the subsequent 
cycles, administer Dato-DXd at the same infusion rate 

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Worst NCI CTCAE v5.0 Grade 
Toxicity (unless otherwise 
specified) 
Management Guidelines for DS-1062a 
(90 or 30 minutes). 
o 
If a new IRR occurs that is Grade 2 or greater with 
subsequent cycles, permanently discontinue Dato-DXd 
and initiate treatment of the IRR symptoms. 
Grade 4 
Administration of Dato-DXd must be discontinued immediately and 
permanently.  
Urgent intervention is indicated. Epinephrine, antihistamines, steroids, 
bronchodilators, vasopressors, IV fluid therapy, supplemental oxygen, 
etc. should be considered as clinically indicated. 
Hematologic Toxicity 
Neutrophil Count Decreased and/or White Blood Cell Count Decreased 
Grade 3 (ANC defined as <1.0-0.5 × 
109/L; WBC defined as <2.0-1.0 × 
109/L) 
Delay dose until resolved to ≤Grade 2, then maintain dose 
Grade 4 (ANC defined as <0.5 × 
109/L; WBC defined as <1.0 × 109/L) 
Delay dose until resolved to ≤Grade 2: 
 
If resolved in ≤14 days from day of onset, maintain dose. 
 
If resolved in >14 days from day of onset, reduce dose by 1 level. 
Febrile neutropenia 
Grade 3  
(ANC <1 × 109/L, fever >38.3°C or a 
sustained temperature of ≥38 °C for 
more than 1 hour) 
Delay dose until resolved, then reduce dose by 1 level. 
Grade 4 
Discontinue subject from study treatment. 
Lymphocyte Count Decreased 
Grade 4  
(<0.2 × 109/L) 
Delay dose until resolved to ≤Grade 2: 
 
If resolved in ≤14 days from day of onset, maintain dose. 
 
If resolved in >14 days from day of onset, reduce dose by 1 level. 
Anemia 
Grade 3  
(Hb <8.0 g/dL; transfusion indicated) 
Delay dose until resolved to ≤Grade 2, then maintain dose. 
Grade 4  
(Life-threatening consequences; 
urgent intervention indicated) 
Delay dose until resolved to ≤Grade 2, then reduce dose by 1 level. 
Platelet Count Decreased 
Grade 3  
(platelets <50 – 25 × 109/L) 
Delay dose until resolved to ≤Grade 1: 
 
If resolved in ≤7 days from day of onset, maintain dose. 
 
If resolved in >7 days from day of onset, reduce dose by 1 level. 
Grade 4  
(platelets <25 × 109/L) 
Delay dose until resolved to ≤Grade 1, then reduce dose by 1 level. 
Non-hematologic Toxicities 
Pulmonary Toxicity 
If a subject develops radiographic changes potentially consistent with ILD/pneumonitis or develops an acute 
onset of new or worsening pulmonary or other related signs/symptoms such as dyspnea, cough or fever, rule out 
ILD/pneumonitis.  

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Worst NCI CTCAE v5.0 Grade 
Toxicity (unless otherwise 
specified) 
Management Guidelines for DS-1062a 
If the AE is confirmed to have an etiology other than treatment related ILD/pneumonitis, follow the management 
guidance outlined in the “Other Non-Laboratory Adverse Events” dose modification section below. 
If the AE is suspected to be ILD/pneumonitis, treatment with DS-1062a should be delayed pending further 
evaluations.  
Evaluations should include the following: 
 
High-resolution CT  
 
Pulmonologist consultation (infectious disease consultation, as clinically indicated) 
 
Bronchoscopy and BAL if clinically indicated and feasible 
 
Pulmonary function tests (including force vital capacity and CO diffusing capacity) and pulse oximetry 
(SpO2)  
 
Clinical laboratory tests (arterial blood gases if clinically indicated, blood culture, blood cell count, 
differential white blood cell count, C-reactive protein, and a COVID-19 test) 
 
One blood sample collection for PK analysis as soon as ILD/pneumonitis is suspected, if feasible 
Other tests could be considered, as needed. 
If the AE is confirmed to be ILD/pneumonitis as per the above evaluations, follow the ILD/pneumonitis 
management guidance as outlined below. 
All events of ILD/pneumonitis regardless of severity or seriousness must be followed until resolution including 
after Dato-DXd discontinuation. 
Grade 1 
The administration of Dato-DXd must be delayed for any 
ILD/pneumonitis events regardless of grade.  
 
Monitor and closely follow-up in 2 to 7 days for onset of 
clinical symptoms and pulse oximetry (SpO2) 
 
Consider follow-up imaging in 1-2 weeks (or as clinically 
indicated). 
 
Consider starting systemic steroids (eg, at least 0.5 mg/kg/day 
prednisone or equivalent) until improvement, followed by 
gradual taper over at least 4 weeks. 
 
If the event worsens despite initiation of corticosteroids, then 
follow Grade 2 guidelinesa. 
For Grade 1 events, Dato-DXd can be restarted only if the event is fully 
resolved to Grade 0:b 
 
If resolved in ≤28 days from day of onset, maintain dose 
 
If resolved in >28 days from day of onset, reduce dose by 
1 level  
However, if the Grade 1 ILD/pneumonitis has not resolved within 
84 days from the last infusion, the drug should be permanently 
discontinued. 
a. 
If the subject is asymptomatic, then the subject should still be 
considered as Grade 1 even if steroid treatment is given. 
b. Grade 0 refers to full resolution of ILD/pneumonitis, including 
the disappearance of radiological findings associated with 
active ILD/pneumonitis.  Residual scarring or fibrosis 
following recovery of ILD/pneumonitis is not considered to be 
active disease. 
Grade 2 
Permanently discontinue subject from study treatment. 

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Worst NCI CTCAE v5.0 Grade 
Toxicity (unless otherwise 
specified) 
Management Guidelines for DS-1062a 
 
Promptly start and treat with systemic steroids (eg, at least 
1 mg/kg/day prednisone or equivalent) for at least 14 days or 
until complete resolution of clinical and chest CT findings, 
then followed by gradual taper over at least 4 weeks. 
 
Monitor symptoms closely. 
 
Re-image as clinically indicated. 
 
If worsening or no improvement in clinical or diagnostic 
observations in 5 days,  
 
Consider increasing dose of steroids (eg, 2 mg/kg/day 
prednisone or equivalent) and administration may be 
switched to IV (eg, methylprednisolone). 
 
Re-consider additional workup for alternative 
etiologies as described above. 
 
Escalate care as clinically indicated. 
Grade 3 and 4 
Permanently discontinue subject from study treatment. 
 
Hospitalization required. 
 
Promptly initiate empiric high-dose methylprednisolone IV 
treatment (eg, 500-1000 mg/day for 3 days), followed by at 
least 1 mg/kg/day of prednisone (or equivalent) for at least 
14 days or until complete resolution of clinical and chest CT 
findings, then followed by gradual taper over at least 4 weeks. 
 
Re-image as clinically indicated. 
 
If still no improvement within 3 to 5 days,  
 
Re-consider additional workup for alternative 
etiologies as described above. 
 
Consider other immuno-suppressants and/or treat per 
local practice. 
Ocular Surface Toxicity (eg, dry eye, decreased or blurred vision, photophobia, keratitis, corneal ulcer) 
General considerations 
Consider obtaining an ophthalmological assessment to ensure accurate 
diagnosis, event grading, appropriate treatment, and event resolution, as 
appropriate.  
It should be strongly recommended that subjects avoid the use of contact 
lenses starting on the day of the first DS-1062a dose and to use artificial 
tears (preferably preservative free) 4 times per day as a preventative 
measure and up to 8 times per day as clinically needed. 
Use of eye medications (eg, topical corticosteroids) other than artificial 
tears should be at the discretion of an ophthalmologist or if unavailable, 
another licensed eye care provider. 
The following grading scale replaces the CTCAE 5.0 grades for 
triggering the TMGs for cornea-related AEs: 
Corneal Toxicity Severity Grading Scale 
Normal = Clear cornea, no epithelial defects 
Grade 1 = Nonconfluent superficial keratitis 
Grade 2 = Confluent superficial keratitis, a cornea defect, or 3-line or 

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Worst NCI CTCAE v5.0 Grade 
Toxicity (unless otherwise 
specified) 
Management Guidelines for DS-1062a 
more loss in best corrected distance visual acuity 
Grade 3 = Corneal ulcer or stromal opacity, or best corrected distance 
visual acuity 20/200 or worse 
Grade 4 = Corneal perforation 
Grade 1 
Consider obtaining an ophthalmological assessment. 
Grade 2 
Obtain an ophthalmological assessment.  
Delay dose until resolved to ≤Grade 1, then maintain dose. 
Grade 3 
Obtain an ophthalmological assessment.  
Delay dose until resolved to ≤Grade 1, then reduce dose by 1 level. 
Grade 4 
Obtain an urgent ophthalmological assessment.  
Discontinue subject from study treatment. 
Hepatic Toxicity 
AST or ALT with simultaneous TBL increased 
AST/ALT >3.0 × ULN with 
simultaneous TBL >2.0 × ULN 
Delay study medication until drug-induced liver injury can be ruled out.  
If drug-induced liver injury is ruled out, the subject should be treated 
accordingly, and resumption of study drug may occur after discussion 
between the investigator and Sponsor.  
If drug-induced liver injury cannot be ruled out from diagnostic workup, 
permanently discontinue study treatment. 
Monitor AST/ALT and TBL twice weekly until resolution or return to 
baseline. 
AST or ALT 
Grade 2 (>3.0 - 5.0 × ULN if baseline 
was normal; >3.0 - 5.0 × baseline if 
baseline was abnormal) 
No action for Grade 2 AST/ALT.  
Grade 3 (>5.0 - 20.0 × ULN if 
baseline was normal; >5.0 - 20.0 × 
baseline if baseline was abnormal) 
In subjects without liver metastases 
and subjects with liver metastases and 
baseline level ≤3 × ULN 
Repeat testing within 3 days.  Delay dose until resolved to ≤Grade 1 if 
baseline ≤3 × ULN, otherwise delay dose until resolved to ≤baseline, 
then: 
 
If resolved in ≤7 days from day of onset, maintain dose. 
 
If resolved in >7 days from day of onset, reduce dose by 1 level. 
Grade 3: (>8.0 - 20.0 × ULN if 
baseline was normal; >8.0 - 20.0 × 
baseline if baseline was abnormal) 
In subjects with liver metastases, if 
the baseline level was >3 × ULN 
Repeat testing within 3 days.  Delay dose until resolved to ≤baseline 
level, then: 
 
If resolved in ≤7 days from day of onset, maintain dose. 
 
If resolved in >7 days from day of onset, reduce dose by 1 level. 
Grade 4 (>20.0 × ULN if baseline 
was normal; >20.0 × baseline if 
baseline was abnormal) 
Discontinue subject from study treatment. 
TBL 
Grade 2 (>1.5 - 3.0 × ULN if baseline 
was normal; >1.5 - 3.0 × baseline if 
baseline was abnormal) 
If no documented Gilbert’s syndrome or liver metastases at baseline, 
delay dose until resolved to ≤Grade 1: 
 
If resolved in ≤7 days from day of onset, maintain dose. 
 
If resolved in >7 days from day of onset, reduce dose by 1 level. 
If documented Gilbert’s syndrome or liver metastases at baseline, 
continue study treatment. 

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Worst NCI CTCAE v5.0 Grade 
Toxicity (unless otherwise 
specified) 
Management Guidelines for DS-1062a 
Grade 3 (>3.0 - 10.0 × ULN if 
baseline was normal; >3.0 - 10.0 × 
baseline if baseline was abnormal) 
If no documented Gilbert’s syndrome or liver metastases at baseline, 
repeat testing within 3 days.  Delay dose until resolved to ≤Grade 1: 
 
If resolved in ≤7 days from day of onset, reduce dose by 1 level. 
 
If resolved in >7 days from day of onset, discontinue DS-1062a.   
 
If documented Gilbert’s syndrome or liver metastases at baseline, repeat 
testing within 3 days.  Delay dose until resolved to <Grade 2: 
 
If resolved in ≤7 days from day of onset, reduce dose by 1 level. 
 
If resolved in >7 days from day of onset, discontinue Dato-DXd. 
Grade 4 (>10.0 × ULN if baseline 
was normal; >10.0 × baseline if 
baseline was abnormal) 
Discontinue subject from study treatment. 
Gastrointestinal 
Nausea/Vomiting 
Grade 3  
If prophylaxis and supportive medications have NOT YET been 
optimized: 
- Delay dose until resolved to ≤Grade 1 or baseline, optimize 
medications, and then maintain dose. 
If prophylaxis and supportive medications have ALREADY been 
optimized: 
- Delay dose until resolved to ≤Grade 1 or baseline, and then reduce 
dose by 1 level. 
Grade 4 Vomiting 
Discontinue subject from study treatment 
Oral Mucositis/Stomatitis 
General considerations 
Increase the frequency of bland mouth rinses up to every hour, if 
necessary, and applicable. 
Provide adequate pain management (eg, doxepin 0.5%, viscous lidocaine 
2%). 
As soon as oral pain, inflammation, and/or ulceration develops, strongly 
consider steroid-containing mouth rinses (eg, dexamethasone 
0.1 mg/mL, 10 mL 4 times daily swish for 1 to 2 minutes then spit out, 
or local alternative).  
May consider oral nystatin suspension or other topical antifungal agents 
at least 15 minutes after the steroid-containing mouthwash according to 
clinician preference based on institutional/local guidelines. 
Consider cryotherapy (ice chips or ice water held in the mouth) 
throughout the infusion. 
For severe and/or persistent events, consider referral to a dentist or oral 
surgeon. 
Grade 1 
Maintain dose.  Optimize prophylactic and supportive medications. 
Grade 2 
Optimize prophylactic and supportive medications.  Consider a dose 
delay or reduction if clinically indicated. 
Grade 3 
If prophylaxis and supportive medications have NOT YET been 
optimized: 

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Worst NCI CTCAE v5.0 Grade 
Toxicity (unless otherwise 
specified) 
Management Guidelines for DS-1062a 
- Delay dose until resolved to ≤Grade 1 or baseline, optimize 
medications, and then maintain dose. 
If prophylaxis and supportive medications have ALREADY been 
optimized: 
- Delay dose until resolved to ≤Grade 1 or baseline, then reduce dose by 
1 level. 
Grade 4 
Discontinue subject from study treatment 
Diarrhoea 
Grade 3 
If prophylaxis and supportive medications per institutional guidelines 
have NOT YET been optimized: 
- Delay dose until resolved to ≤Grade 1 or baseline, optimize 
medications, and then maintain dose. 
If prophylaxis and supportive medications have ALREADY been 
optimized: 
- Delay dose until resolved to ≤Grade 1 or baseline, then reduce dose by 
1 level. 
Grade 4 
Discontinue subject from study treatment. 
Other Laboratory Adverse Events 
Grade 3 
Delay dose until resolved to ≤Grade 1 or baseline level, if determined by 
the investigator to be clinically significant. 
Grade 4 
Discontinue subject from study treatment. 
Other Non-Laboratory Adverse Events 
Grade 3 
Delay dose until resolved to ≤Grade 1 or baseline level, if determined by 
the investigator to be clinically significant  
Grade 4 
Discontinue subject from study treatment. 
AE = adverse event; ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; BAL 
= bronchoalveolar lavage; CHF = congestive heart failure; COVID-19 = coronavirus disease 2019; CT = computed tomography; 
CTCAE = Common Terminology Criteria for Adverse Events; Dato-DXd = datopotamab deruxtecan; Hb = hemoglobin; 
ILD = interstitial lung disease; IRR = infusion-related reaction; IV = intravenous; LVEF = left ventricular ejection fraction; 
NCI = National Cancer Institute; PK = pharmacokinetic; TBL = total bilirubin; TMG = toxicity management guideline; 
ULN = upper limit of normal; WBC = white blood cell. 
All dose modifications should be based on the worst preceding toxicity. 
6.6. 
Emergency Unblinding 
Not applicable.  
6.7. 
Prior and Concomitant Medications 
Therapies used from the time the subject signs the ICF for study participation to the 28-Day 
Follow-up Visit (+ 7 days) after the last administration of DS-1062a will be recorded in the 
eCRF.  Prophylactic therapies (including any required premedication), prior therapies, and all 
concomitant therapies will be recorded in the eCRF. 
All therapies received by subjects within 28 days prior to the first dose of DS-1062a will be 
recorded as prior therapies.  Concomitant therapies include all prescription, over-the-counter, and 
herbal remedies. 

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All concomitant medications administered during the study should be recorded in eCRF until the 
end of the Safety Follow-up Period.  Concomitant medications administered as treatment for 
drug-related AESIs should be recorded until event resolution, end of study including any 
post-treatment follow-up (if applicable), study termination, withdrawal of consent, or subject 
death. 
Prohibited Therapies/Products 
With the exception of medications that are under investigation in the study (eg, SoC, 
comparators, or combination therapies), the following medications, treatment and procedures 
will be prohibited during the treatment period.  The Sponsor must be notified if a subject 
receives any of these during the study: 
 Other anticancer therapy, including cytotoxic, targeted agents, immunotherapy, antibody, 
retinoid, transplant, or anticancer hormonal treatment (concurrent use of hormones for 
noncancer-related conditions [eg, insulin for diabetes and HRT] is acceptable). 
 Live vaccines.  
 Other investigational therapeutic agents. 
 Radiotherapy (except for palliative radiation to known metastatic sites as long as it does 
not affect assessment of response or delay treatment for more than the maximum time 
specified in the dose modification section [see Section 6.5]). 
 Radiotherapy to the thorax. 
 Concomitant use of chronic systemic (IV or oral) corticosteroids or other 
immunosuppressive medications >10 mg/day of prednisone or equivalent except for 
managing AEs; inhaled steroids, intra-articular steroid injections, and other topical 
steroid formulations are permitted in this study.  Corticosteroid mouthwash formulations 
are permitted to prevent and manage certain AEs. 
 Concomitant treatment with chloroquine or hydroxychloroquine is not allowed during the 
study treatment.  If chloroquine or hydroxychloroquine is administered per local clinical 
practice and regulations, then a washout period of no less than 14 days is required before 
resumption of DS-1062a. 
Restricted Therapies/Products 
 The use of tobacco products, e-cigarettes, and vaping is strongly discouraged but not 
prohibited. 
 Subjects should be closely monitored when DS-1062a is concomitantly used with drugs 
that inhibit CYP3A, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, 
multidrug and toxin extrusion transporter (MATE) 2-K, P-glycoprotein, breast cancer 
resistance protein, and multidrug resistance-associated protein (MRP) 1.  For a list of 
inhibitor drugs, refer to the United States (US) Food and Drug Administration (FDA) 
Table of Substrates, Inhibitors and Inducers17 or locally available sources. 

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Permitted Therapies/Products 
 Hematopoietic growth factors may be used for prophylaxis or treatment based on the 
clinical judgment of the investigator. 
 Concomitant use of dietary supplements, medications not prescribed by the investigator, 
and alternative/complementary treatments is discouraged, but not prohibited.  
 Prophylactic or supportive treatment of study drug-induced AEs will be otherwise as per 
investigator’s discretion and institutional guidelines. 
 Based on the currently available clinical safety data, it is highly recommended that 
subjects receive prophylactic antiemetic agents prior to infusion of Dato-DXd and on 
subsequent days as needed.  Antiemetics such as 5-hydroxytryptamine 3 antagonists 
(5-HT3) and steroids (eg, dexamethasone) should be considered and administered in 
accordance with the prescribing information or institutional guidelines. 
 Inhaled intranasal, intraocular, intra-articular or topical steroids, and adrenal replacement 
steroid doses are permitted in the absence of active autoimmune disease.  
 Neurokinin-1 (NK1) receptor antagonists can be used, if needed. 
 Subjects with bronchopulmonary disorders who require intermittent use of 
bronchodilators (eg, albuterol) will be included in this study.  
 The use of approved bone-modifying agents (eg, bisphosphonates or receptor activator of 
nuclear factor kappa B ligand [RANKL] targeting agents) to treat or control bone disease 
is allowed on study if a subject had initiated treatment with such agents at least 4 weeks 
prior to baseline tumor assessment.  Subjects who started the study without receiving 
bisphosphonates or RANKL targeted agents are not allowed to begin treatment with those 
medications while receiving study treatment unless otherwise allowed by the protocol to 
be used for the treatment of AEs or SAEs. 

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7. 
STUDY DRUG DISCONTINUATION AND DISCONTINUATION 
FROM THE STUDY 
7.1. 
Discontinuation of Study Drug 
The primary reason for the permanent discontinuation of DS-1062a treatment administration 
must be recorded.  Reasons for treatment discontinuation include: 
 Death 
 AE 
 Disease progression 
 Clinical progression 
 Withdrawal by subject (to discontinue study drug)  
o Note: This section only refers to withdrawal from treatment with study drug, 
which is NOT the same thing as a complete withdrawal from the study.  Discuss 
with the subject that they will remain in the study (ie, continue with study visits 
and assessments, including survival follow-up). 
 Physician decision 
 Lost to follow-up (see Section 7.3 for details on when a subject is considered Lost to 
Follow-up) 
 Pregnancy 
 Protocol deviation (Note: Only protocol deviations that are deemed significant by the 
investigator, with or without consultation with the Sponsor, may lead to permanent study 
drug discontinuation) 
 Study termination by the Sponsor 
 Other 
After study drug is permanently discontinued for any reason other than death or lost to 
follow-up, the subject will be treated as clinically indicated by the investigator or referring 
physician. 
The investigator must discuss with the subject that their decision to permanently discontinue the 
study drug means the subject may still agree to continue into the Follow-up Period for onsite or 
modified follow-up visits.  Subjects will be followed for disease progression, if applicable, and 
survival at regularly scheduled intervals (see Table 1.2). 
Subjects who discontinue study treatment for reasons other than disease progression as assessed 
by BICR, including clinical progression or the initiation of new anticancer treatment, will 
continue to undergo tumor assessments every 6 weeks during the Follow-up Period until 
radiographic disease progression as assessed by BICR, death, lost to follow-up, or withdrawal of 
consent. 

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Procedures for Discontinuation from Study Drug 
The subject should be instructed to contact the investigator or study site staff before or at the 
time study drug is discontinued. 
If a subject is discontinued from the study drug: 
 The reason(s) for discontinuation and the last dose date should be documented in the 
subject’s medical record and eCRF. 
 Due to an AE, the investigator will follow the subject until the AE has resolved or 
stabilized. 
 An EOT evaluation should be performed as described in the SoE (Table 1.2). 
 A safety follow-up evaluation should be performed approximately 28 days (+7 days) after 
the last dose of study drug as described in the SoE (Table 1.2). 
 If subject has discontinued without disease progression, continue tumor assessments until 
disease progression, if applicable, and survival as described in the SoE (Table 1.2). 
 LTSFU evaluations will be performed to assess survival as described in the SoE 
(Table 1.2). 
The investigator will complete and report the observations as thoroughly as possible up to the 
date of discontinuation, including the date of last dose.  All procedures and tumor assessments 
specified for the EOT visit will be conducted.  See Table 1.2 for specific EOT procedures. 
If a subject does not agree to continue to come to the study site, then a modified follow-up must 
be arranged to ensure the continued collection of endpoints and safety information.  Options for 
modified follow-up are noted below. 
Modified Follow-up Options 
The following modified follow-up options can be offered to the subject who does not agree to 
study visits at the study site.  If a subject does not come back to the study site, every effort 
should be made to contact the subject to gain required information, such as the approaches listed 
below.  
 Study personnel contacting the subject by telephone (may be quarterly, bi-annually, 
annually, or only at EOS). 
 Study personnel contacting an alternative person (eg, family member, spouse, partner, 
legal representative, physician or other healthcare provider). 
 Study personnel accessing and reviewing the subject’s medical information from 
alternative sources (eg, doctor’s notes, hospital records). 
Dates of the modified follow-up contact(s) should be recorded.  See Section 7.2 for definition of 
withdrawal by subject from the study (ie, withdrawal of consent). 
7.2. 
Subject Withdrawal/Discontinuation From the Study 
Subjects may discontinue from the study for any of the following reasons: 

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 Death 
 Withdrawal by subject (from the study)  
o NOTE: This indicates that the subject withdraws consent and decides to not 
undergo any further study procedures or be followed for long-term survival. 
 Lost to follow-up (see Section 7.3 for details on when a subject is considered lost to 
follow-up). 
 Study termination by Sponsor. 
 Other. 
Reason for study discontinuation and date of last contact will be recorded on the eCRF.   
If the reason for study discontinuation is the death of the subject, the options for categorizing the 
primary cause of death are progressive disease or an AE.  If the reason of death is unknown, 
every effort should be made to obtain the primary cause of death.  Only 1 AE will be recognized 
as the primary cause of death. 
Only subjects who decline all of the following methods of follow-up will be considered to have 
withdrawn consent from study participation (ie, from the interventional portion and follow-up): 
 Attendance at study visits per protocol. 
 Study personnel contacting the subject by telephone. 
 Study personnel contacting an alternative person. 
 Study personnel accessing and reviewing the subject’s medical information from 
alternative sources. 
If the subject declines all of the above methods of follow-up, the investigator should personally 
speak to the subject to ensure the subject understands all of the potential methods of follow-up.  
If the subject declines routine follow-up, the investigator should discuss with the subject if sparse 
survival follow-up by telephone or verification of medical records is permitted prior to database 
locks.  If the subject continues to decline all potential methods of follow-up, the investigator will 
document this as a withdrawal of consent (from the interventional portion and follow-up). 
Withdrawal Procedures 
If a subject is withdrawn from both the interventional and follow-up portions of the study: 
 The investigator will complete and report the observations as thoroughly as possible up to 
the date of withdrawal including the date of last dose, date of last contact, and the reason 
for withdrawal. 
 Any disclosure of future information is also withdrawn; the Sponsor may retain and 
continue to use any data collected before such a withdrawal of consent. 
 The subject may request destruction of any samples taken and not tested, and the 
investigator must document this in the site study records. 

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 Study site personnel may use local, regional, and national public records (in accordance 
with local law) to monitor vital status.  Knowledge of the vital status at study end in all 
subjects is crucial for the integrity of the study. 
See SoE (Table 1.2) for data to be collected at the time of study discontinuation and follow-up 
and for any further evaluations that need to be completed. 
7.3. 
Lost to Follow-up 
A subject will be considered lost to follow-up if he/she does not return for 2 consecutive 
scheduled visits per the Schedules of Events and is unable to be contacted by the study site staff.  
Before a subject is deemed lost to follow-up, the investigator or designee will make every effort 
to regain contact with the subject (where possible, 3 telephone calls, texts, or emails, and if 
necessary, a certified letter to the subject’s last known mailing address or local equivalent 
methods).  These contact attempts should be documented. 
If direct contact with the subject is not possible the site must make every effort to collect survival 
status from public records (eg, obituaries, death certificates, etc.) in accordance with local laws.  
Knowledge of the vital status at study end in all subjects is crucial for the integrity of the study. 

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8. 
STUDY PROCEDURES 
See SoE in Table 1.1 for study procedures during the Screening Period and the first 3 cycles of 
the Treatment Period, and Table 1.2 for study procedures during Cycle 4 and the subsequent 
cycles of the Treatment Period, EOT, and the Follow-up Period. 
8.1. 
Eligibility Assessment 
Review the subject’s demographics, medical and NSCLC history, prior medications, non-drug 
therapies and radiotherapy, vital signs, and results of tests (physical examination, height, weight, 
peripheral oxygen saturation (SpO2), ECOG PS, ophthalmologic assessment, 12-lead ECG in 
triplicate, ECHO/MUGA scan, laboratory assessments) and compare against the eligibility 
criteria (Section 5.1 and Section 5.2).  See Section 5.3 for rescreening/subject replacement. 
Informed Consent 
Before a subject’s participation in the study, it is the investigator’s responsibility to obtain freely 
given consent, in writing, from the subject after adequate explanation of the aims, methods, 
anticipated benefits, and potential hazards of the study and before any protocol-specific 
procedures or any study drugs are administered.  Subjects should be given the opportunity to ask 
questions and receive responses to their inquiries and should have adequate time to decide 
whether or not to participate in the study.  The written ICF should be prepared in the local 
language(s) of the potential subject population. 
Informed consent should be obtained ≤28 days prior to initiation of treatment and before any 
protocol-specific procedures are performed, except scans that might be done prior to consent per 
SoC.  Imaging studies (CT/MRI/bone scans) should be performed ≤28 days prior to initiation of 
treatment.  If these scans are performed per SoC prior to consenting, as long as they are within 
28 days of the planned dosing and from the same facility where follow-up scans during the study 
will be performed, they can be used as part of the screening assessments and do not need to be 
repeated. 
See Section 10.1.2 for additional details. 
Qualifying Tumor Tissue Specimen 
A baseline biopsy procedure to collect fresh tumor tissue from the primary or metastatic lesions 
performed after termination of the most recent anticancer treatment is mandatory for all subjects.  
If available, a tumor biopsy that was recently collected (within 3 months of screening) and after 
the most recent anticancer treatment regimen and that has a minimum of 10 × 4 micron sections 
or a tissue block equivalent of 10 × 4 micron sections may be substituted for the mandatory 
pre-treatment biopsy procedure during screening.  Results from the TROP2 testing of the 
pre-treatment tumor biopsy will not be used to determine eligibility for the study.  Although 
baseline fresh biopsies taken from metastatic lesions prior to the date of ICF are acceptable, 
collection during the Screening Period using Sponsor-provided neutral-buffered formalin in kits 
is preferred to standardize tissue fixation for subsequent analysis.  On-treatment biopsy is 
optional at Cycle 2 Days 2 to 8 (if clinically feasible and not contraindicated).  Biopsies may be 
collected from a lesion that has been irradiated, provided that it can be documented that the 
lesion has increased/appeared since radiation occurred and that the biopsy is collected at least 

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3 months after radiation.  Any SAE directly related to the new biopsy should be reported as 
outlined in Section 8.4.1.1.  It is recommended, if possible, that the optional Cycle 2 biopsy be 
taken from a lesion in the same anatomical location as the pre-treatment biopsy and fixed in 
Sponsor-provided neutral buffered formalin. 
Additionally, archival tumor tissue samples from the initial diagnosis are required, to the extent 
that the archival tumor tissue is available, for measurement of TROP2 expression level or for the 
assessment of other biomarkers.  Archived tissue samples from surgery, endoscopy, or core 
needle biopsy already collected and formalin-fixed paraffin-embedded (FFPE) will be used.  
Archival samples can be FFPE tissue block(s), prepared by the standard procedure at the study 
site.  Additional information on tumor tissue collection, processing and immediate shipping 
procedures is included in the Study Laboratory Manual. 
Non-Small Cell Lung Cancer History 
Subject’s NSCLC history will be obtained by the investigator or a qualified designee. 
Actionable Mutation Status 
Subjects must have documented results for genomic alterations in EGFR, ALK, ROS1, NTRK, 
BRAF, MET exon 14 skipping, or RET to be enrolled in the study.  
General Medical History and Baseline Conditions 
Subject’s medical history will be obtained by the investigator or a qualified designee. 
Untoward medical occurrence (including clinically relevant laboratory values that are not 
symptoms of NSCLC/vital signs that are out of range) that were diagnosed or known to exist 
prior to signing the ICF will be recorded on the General Medical History and Baseline 
Conditions eCRF, not the Adverse Event eCRF.  Record the start date of any medical occurrence 
that started after the ICF was signed and is ongoing at the time of the first dose of DS-1062a on 
the General Medical History and Baseline Conditions eCRF. 
Demographics 
Review the subject’s demographics against the eligibility criteria. 
Human Immunodeficiency Virus Antibody Test 
Perform an HIV antibody test as acceptable by local regulations or independent IRB/EC. 
Hepatitis Screening 
Hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCV Ab) must be 
performed prior to enrollment (if HCV Ab is positive, test HCV RNA). Subjects with known 
active hepatitis or uncontrolled hepatitis B and/or hepatitis C infection, is positive for hepatitis B 
or C virus based on the evaluation of results of tests for hepatitis B (HBsAg, anti-HBs, anti-HBc, 
or HBV DNA) and/or hepatitis C infection (as per HCV RNA) will be excluded except those 
meeting certain conditions specified under exclusion criterion 10 (Section 5.2). 

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8.2. 
Randomization 
Not applicable.  
8.3. 
Efficacy Assessments 
Radiographic Tumor Assessments 
Radiographic tumor assessments will include all known or suspected sites of disease, as per 
RECIST v1.1 (Section 10.4).  Imaging must include CT or MRI scans of the chest, abdomen, and 
any other sites of disease; as well as brain CT or MRI scan at baseline (screening) for all 
subjects.  Subjects with brain metastases at baseline should have brain MRI or CT scan 
performed every 6 weeks (± 7 days) from Cycle 1 Day 1.  Additional brain imaging may be 
performed as needed clinically. 
The CT scans should be performed with contrast agents unless contraindicated for medical 
reasons; follow the local label/package insert/Summary of Product Characteristics or institutional 
guidelines for allergic reactions to contrast agents.  
Baseline tumor assessment must be performed within 28 days of Cycle 1 Day 1.  A tumor 
assessment performed for the assessment of disease progression on the prior therapy will be 
acceptable as baseline if performed within 28 days of Cycle 1 Day 1.   
A complete set of the scans is required in this study (see Section 8.3).  All scans during the 
subjects’ participation in the study must be sent to BICR.  Perform radiographic tumor 
assessments using spiral CT or MRI with ≤5 mm cuts unless another modality of disease 
assessment is necessary for the lesions.  
Antitumor activity will be assessed at baseline (screening), and every 6 weeks (± 7 days) from 
Cycle 1 Day 1, independent of treatment cycle, until radiographic disease progression as 
assessed by BICR, death, lost to follow-up, or withdrawal of consent regardless of 
discontinuation of study treatment or initiation of new anticancer therapy (Table 1.1 and 
Table 1.2).  Subjects who discontinue study treatment for reasons other than disease progression 
per BICR will continue to undergo tumor assessments every 6 weeks during the Follow-up 
Period until radiographic disease progression as assessed by BICR, death, lost to follow-up, or 
withdrawal of consent.  Imaging timing should follow calendar days.  In addition, radiographic 
tumor assessments will also be conducted whenever disease progression is suspected (eg, 
symptomatic deterioration) and at the time of withdrawal from the treatment (if not done in the 
previous 6 weeks).  Tumor measurements will be performed as per RECIST v1.1 (see 
Section 10.4).  
The same imaging technique used to characterize each identified and reported lesion at baseline 
will be employed in the subsequent tumor assessments.  
Bone scan (bone scintigraphy) or 18F-fluorodeoxyglucose-positron emission tomography 
(PET)/CT is required at baseline and follow-up bone imaging is required only if new bone 
metastases are suspected. When disease progression in the bone or new lesion (NL) in the bone 
is suspected, 18F FDG PET/CT should be used to determine disease progression. 

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When tumor assessments at a visit are performed over multiple days, the date of response (CR, 
PR, SD, Non-CR/Non-PD [subjects with non-target lesions {NTL} only] or not evaluable [NE]) 
should be recorded as the date of the last radiographic evaluation included in the series for that 
assessment, and the date of progression should be recorded as the date of the earliest 
radiographic evaluation included in the series for that assessment.  
Measurable or evaluable lesions that have been previously irradiated will not be considered 
target lesions (TLs) unless increase in size has been observed after completion of radiation 
therapy.  
Response Assessment 
Assessment of response will be made by BICR based on RECIST v1.1 (Section 10.4).  
Assessment of response will also be made by the investigator based on RECIST v1.1.  Objective 
responses (CR or PR) must be confirmed at the next tumor assessment time point at least 
4 weeks (28 days) apart.  Tumor assessments will continue until disease progression is confirmed 
by BICR.  The results of BICR assessment of the subject scans will not be shared with the site or 
investigator.  The investigator will manage the subject and make treatment decisions based solely 
on investigator/local assessment and will be completely independent of BICR. 
Subsequent Anticancer Treatments 
Subsequent anticancer treatments, radiation therapy received, and surgeries performed since the 
EOT must be monitored and recorded in the eCRF until the end of the study.   
Disease Progression 
Subjects who discontinue study treatment for reasons other than disease progression as assessed 
by BICR, including clinical progression, or subjects who start new anticancer treatment will 
continue to undergo tumor assessments every 6 weeks during the Follow-up Period until 
radiographic disease progression as assessed by BICR, death, lost to follow-up, or withdrawal of 
consent. 
The date of disease progression on subsequent therapies will be recorded in the eCRF regardless 
of subsequent anti-NSCLC treatments. 
Survival Follow-up 
All subjects should be followed for survival at least every 3 months after discontinuing study 
drug (see Table 1.2).  Survival monitoring will continue until the end of the study. 
To ensure accurate survival data are available at the time of any database lock, updated survival 
status may be requested during the study by the Sponsor. For example, updated survival status 
may be requested prior to, but not limited to, the planned data cut and database lock for the 
primary analysis and final analysis. Upon Sponsor notification, all subjects who do not/will not 
have a scheduled study visit or study contact during the Sponsor-defined period will be contacted 
for their survival status (excluding subjects who have discontinued from the entire study or with 
a previously reported death event). 

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8.4. 
Safety Assessments 
8.4.1. 
Adverse Event 
Method to Detect Adverse Events 
The definitions of an AE or SAE can be found in Section 10.5.  AEs may be directly observed, 
reported spontaneously by the subject or by questioning the subject (or, when appropriate, by a 
caregiver, surrogate, or the subject’s legally authorized representative) at each study visit.  
Subjects should be questioned in a general way, without asking about the occurrence of any 
specific symptoms.  The investigator must assess all AEs to determine seriousness, severity, and 
causality.  The investigator and any qualified designees are responsible for detecting, 
documenting, and recording events that meet the definition of an AE or SAE and remain 
responsible for following AEs that are serious, considered related to the study drug or study 
procedures, or that caused the subject to discontinue DS-1062a. 
All clinical laboratory results, vital signs, and ECG results or findings should be appraised by the 
investigator to determine their clinical significance.  Isolated abnormal laboratory results, vital 
sign findings, or ECG findings (ie, not part of a reported diagnosis) should be reported as AEs if 
they are symptomatic, lead to study drug discontinuation, lead to dose reduction, require 
corrective treatment, or constitute an AE in the investigator’s clinical judgment. 
Time Period for Collecting Adverse Events, Including Adverse Events of Special Interest 
and Serious Adverse Events 
All SAEs occurring after the subject signs the ICF and up to 35 days (ie, 28 days + 7 days) after 
the last dose of study medication (ie, the Follow-up Period), whether observed by the 
investigator or reported by the subject, will be recorded on the Adverse Event eCRF.  All SAEs 
will be followed until resolution, stabilization, the event is otherwise explained, or the subject is 
lost to follow-up.  After the 28-day Safety Follow-up visit, only SAEs considered to be related to 
study drug by the investigators should be reported. 
All ILD/pneumonitis events regardless of severity should be reported beyond the 28-day Safety 
Follow-up Period. All events of ILD regardless of severity or seriousness will be followed until 
resolution including after study drug discontinuation. 
All AESIs, regardless of severity or seriousness, must be followed until event resolution, end of 
study including any post-treatment follow-up (if applicable), study termination, withdrawal of 
consent, or subject’s death. 
All non-serious AEs occurring after the subject has taken the first dose of DS-1062a until 
35 days (ie, 28 days + 7 days) after the last dose of DS-1062a will be recorded on the Adverse 
Event eCRF. 
Exacerbation of a pre-existing medical condition and symptom after the first dose of DS-1062a 
including increase in severity of the symptom will be recorded as an AE on the Adverse Event 
eCRF, unless it is a condition of NSCLC. 

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Reporting Procedure for Investigators 
All AEs (including AESIs and SAEs) will be reported in AE eCRF.  All AEs (serious and non-
serious) must be reported with the investigator’s assessment of seriousness, severity, and 
causality to DS-1062a. 
Always report the diagnosis as the AE or SAE term.  When a diagnosis is unavailable, report the 
primary sign or symptom as the AE or SAE term with additional details included in the narrative 
until the diagnosis becomes available.  If the signs and symptoms are distinct and do not suggest 
a common diagnosis, report them as individual entries of AE or SAE. 
Disease-specific Adverse Events and Serious Adverse Events 
Disease progression/worsening of NSCLC will not be recorded as an AE on the AE eCRF.  
However, events associated with disease progression, such as events that are assessed by 
investigator as unequivocally associated with worsening of underlying NSCLC (such as events 
related to brain metastases, spinal cord compression, bone pain, liver metastases, hepatomegaly, 
and tumor growth), may be recorded as AEs. 
Death due to disease progression should be recorded on the Death eCRF.  

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8.4.1.1. 
Adverse Events Reporting 
The following types of events should be reported by the investigator in the electronic data 
capture (EDC) within 24 hours of awareness: 
 SAEs (Section 10.5.2). 
 Hepatic events (both serious and non-serious) that meet the potential Hy’s Law 
criteria (as defined in Section 8.4.1.3).  A targeted questionnaire is built within the 
eCRF to collect relevant additional information for these potential cases. 
 All potential ILD/pneumonitis cases should be reported within 24 hours, including 
both serious and non-serious potential ILD/pneumonitis cases (potential 
ILD/pneumonitis is defined by the Event Adjudication Site Manual List of Preferred 
Terms). 
 Grade ≥3 IRR events. 
 Grade ≥3 ocular surface toxicity events.  
 Grade ≥2 keratitis events (includes keratitis, punctate keratitis, and ulcerative 
keratitis)  
Details summarizing the course of the SAE, including its evaluation, treatment, and outcome 
should be provided.  Specific or estimated dates of AE onset, treatment, and resolution should be 
included.  Medical history, concomitant medications, and laboratory data that are relevant to the 
event should also be summarized in the SAE report.  For fatal events, the SAE report should 
state whether an autopsy was or will be performed and should include the results if available.  
Source documents (including medical reports) will be retained at the study site and should not be 
submitted to the Sponsor for SAE reporting purposes. 
If using EDC for SAE reporting: Complete the eCRF or Serious Adverse Event Report Form 
within 24 hours of awareness.  If the eCRF is unavailable, report SAEs by faxing or emailing the 
Serious Adverse Event Report Form to the Sponsor/CRO using the provided fax transmittal form 
and the appropriate fax number provided for your country or email address.  Once EDC becomes 
available, please enter SAEs reported on the Serious Adverse Event Report Form into the eCRF 
as soon as possible.  Please refer to the eCRF Completion Guide for additional instructions. 
Call the local SAE Hotline (see Study Site Manual) or your study monitor for any questions on 
SAE reporting. 
See Section 8.4.1 for details on the time period for collecting SAEs. 
Reporting Requirement to Sites and Regulatory Authorities 
The Sponsor or CRO will inform investigators and regulatory authorities of any suspected 
unexpected serious adverse reactions (SUSARs) occurring in study sites or other studies of 
DS-1062a, as appropriate per institutional and/or local reporting requirements. 
The Sponsor and CRO will comply with any additional local safety reporting requirements.  The 
investigator will assess if an AE is to be considered “unexpected” based on the Reference Safety 
Information section in the current IB.13  

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Follow-up for Adverse Events and Serious Adverse Events 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated to elucidate the nature and/or causality 
of the AE or SAE as fully as possible.  This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other health care 
professionals. 
Urgent safety queries and follow-up information, such as an event upgraded to a 
fatal/life-threatening case, must be followed and addressed promptly.  The investigator will 
submit any important and updated SAE data, as noted above, to the Sponsor/CRO within 
24 hours of receipt of the information.  Other follow-up information and response to non-urgent 
safety queries should be combined for reporting to provide the most complete data possible 
within each follow-up report. 
8.4.1.1.1. Overdose 
An overdose is defined as the accidental or intentional administration of any dose of a product 
that is considered both excessive and medically important.  All occurrences of overdose must be 
reported to (CRO or Sponsor) within 24 hours of awareness.  Overdose will be reported via the 
Serious Adverse Event Report /Overdose Form or eCRF. 
An “excessive and medically important” overdose includes any overdose in which either an SAE 
or a non-serious AE (Section 10.5.1), or no AE occurs and is considered by the investigator as 
clinically relevant, ie, poses an actual or potential risk to the subject. 
8.4.1.2. 
Adverse Events of Special Interest  
For the Dato-DXd clinical program, based on the available preclinical data, current clinical 
developmental program, review of the cumulative literature, reported toxicities for drugs with 
similar monoclonal antibody and payload of Dato-DXd, and biological plausibility, 
ILD/pneumonitis, IRR, oral mucositis/stomatitis, mucosal inflammation other than oral 
mucositis/stomatitis, and ocular surface toxicity are considered to be AESIs. 
All AESIs, regardless of severity or seriousness, must be followed until event resolution, end of 
study including any post-treatment follow-up (if applicable), study termination, withdrawal of 
consent, or subject’s death. 
Additional relevant information regarding the AESIs for the Dato-DXd clinical program 
regardless of seriousness is to be collected through the targeted questionnaires (TQs) within the 
clinical study database. 
Interstitial Lung Disease/Pneumonitis 
ILD/pneumonitis is considered an important identified risk based on a comprehensive 
cumulative review of the available safety data from the clinical development program as well as 
the results of potential ILD/pneumonitis cases reviewed by the independent ILD Adjudication 
Committee (AC), available data from recent epidemiology/literature, biological plausibility, and 
safety information from drugs with similar monoclonal antibody and payload as DS-1062a.  
Refer to the current IB for a summary of preliminary clinical study data. 

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ILD/pneumonitis should be ruled out if a subject develops radiographic changes potentially 
consistent with ILD/pneumonitis or develops an acute onset of new or worsening pulmonary or 
other related signs/symptoms such as dyspnea, cough or fever. If the AE is confirmed to have an 
etiology other than ILD/pneumonitis, follow the management guidance outlined in “Other 
Non-Laboratory Adverse Events” in Table 6.3.  
If the AE is suspected to be ILD/pneumonitis, treatment with Dato-DXd should be delayed 
pending further evaluations. Evaluations should include high-resolution CT, pulmonologist 
consultation (infectious disease consultation as clinically indicated), bronchoscopy and 
bronchoalveolar lavage if clinically indicated and feasible, pulmonary function tests (including 
FVC and CO diffusing capacity) and pulse oximetry (SpO2), and clinical laboratory tests (arterial 
blood gases if clinically indicated, blood culture, blood cell count, differential white blood cell 
count, C-reactive protein, and a COVID-19 test), and one blood sample collection for PK 
analysis as soon as ILD/pneumonitis is suspected, if feasible. Other tests could be considered, as 
needed.  
If the AE is confirmed to be ILD/pneumonitis, follow the management guidance outlined in 
“Pulmonary Toxicity” in Table 6.3.  
All events of ILD/pneumonitis, regardless of severity or seriousness, will be followed until 
resolution including after Dato-DXd discontinuation. An autopsy in cases of Grade 5 
ILD/pneumonitis is encouraged. 
For broad surveillance of ILD/pneumonitis, a predefined list of PTs eligible for adjudication as 
described in the Event Adjudication Site Manual are included for enhanced data collections; 
additional data for these AEs will be collected via TQs of pulmonary toxicity. 
Interstitial Lung Disease Adjudication Committee 
An independent ILD/pneumonitis AC for the DS-1062a program is responsible for reviewing all 
cases of potential ILD/pneumonitis.  To ensure adequate and relevant independent evaluation, 
systematic additional data collection will be conducted for all cases that will be brought for 
adjudication.  This additional data collection will cover a more in-depth relevant medical history 
(eg, smoking, radiation, COPD, and other chronic lung conditions), diagnostic evaluation, 
treatment, and outcome of the event.  This data collection will be triggered based on a predefined 
list of preferred terms eligible for adjudication as described in the Event Adjudication Site 
Manual.  
Infusion-related Reaction 
IRR is an identified risk.  A targeted questionnaire will be available as an eCRF to collect 
relevant additional information.  All ≥Grade 3 events of IRR, regardless of seriousness, must be 
reported in EDC within 24 hours.  Refer to the current IB for a summary of preliminary clinical 
study data.13 
Premedication is required prior to any dose of Dato-DXd and must include antihistamines and 
acetaminophen with or without glucocorticoids.  
Monitoring/management of vital signs and clinical symptoms, response to symptomatic 
treatment, and clinical course are outlined in management guidelines in Section 6.5.  Further 
details of the management of DS-1062a IRRs are outlined in Section 6.5.  

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For broad surveillance of IRR, selected PTs from Hypersensitivity SMQ and narrow and selected 
broad PTs from Anaphylactic Reaction SMQ are included for enhanced data collection.  
Additional data for these ≥Grade 3 AEs will be collected via TQs of IRR. 
Oral Mucositis/Stomatitis 
Oral mucositis/stomatitis AEs are considered as identified risks associated with Dato-DXd 
treatment. Mucosal inflammation other than oral mucositis/stomatitis is also an identified risk 
but is considered as a separate AESI.  Refer to Section 8.4.4 for the OCP. 
Recommendations for preventing and treating oral mucositis/stomatitis are available in the SoE, 
Other Safety (Section 8.4.4), and Toxicity Management Guidelines (Table 6.3).  
For broad surveillance of oral mucositis/stomatitis, selected PTs under the MedDRA SMQs of 
Oropharyngeal conditions (Select Narrow PTs) and Drug reaction with eosinophilia and systemic 
symptoms syndrome (Select Broad PTs) are included for enhanced data collections; additional 
data for these AEs regardless of CTCAE grading will be collected via TQs of oral 
mucositis/stomatitis.  
Mucosal Inflammation Other than Oral Mucositis/Stomatitis 
Mucosal inflammation AEs are considered as identified risks associated with Dato-DXd 
treatment. The category of “mucosal inflammation other than oral mucositis/stomatitis” is also 
an identified risk and an AESI. 
For broad surveillance of mucosal inflammation other than oral mucositis/stomatitis, the mucosal 
inflammation PT is included for enhanced data collections; additional data for this AE 
regardless of CTCAE grading will be collected via TQs of mucosal inflammation other than 
oral mucositis/stomatitis.  
Ocular Surface Toxicity 
Ocular surface toxicity (eg, dry eye, keratitis) is considered as an AESI associated with 
Dato-DXd treatment. Dry eye is considered as an identified risk and keratitis as a potential risk 
within this AESI. 
Subjects are advised to use artificial tears 4 times daily as a preventative measure and up to 8 
times daily as clinically needed and to avoid the use of contact lenses. The use of other eye 
medications (eg, topical corticosteroids) for prophylaxis should be at the discretion of an 
ophthalmologist or, if unavailable, another licensed eye care provider.  
Recommendations for preventing and treating ocular surface toxicity are available in the SoE, 
Other Safety (Section 8.4.4), and Toxicity Management Guidelines (Table 6.3). 
For broad surveillance of ocular surface toxicity, selected PTs under the MedDRA Selected PTs 
from Corneal disorder SMQ and select relevant PTs from Eye disorder system organ class 
(SOC); additional data for these AEs regardless of CTCAE grading will be collected via TQs 
of ocular surface toxicity. 

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8.4.1.3. 
Hepatic Events 
Hepatic events (both serious and non-serious) which meet the potential Hy’s Law criteria defined 
as an elevated (ALT and/or AST) ≥3 × ULN and an elevated TBL ≥2 × ULN, regardless if it is 
due to disease progression per investigator assessment, that may occur at different time points 
during this study, should always be reported to the Sponsor.18  These events must be reported 
either by a Serious Adverse Event Report Form or eCRF, with the investigator’s assessment of 
seriousness, severity, causality, and a detailed narrative. These events should be reported within 
24 hours of investigator’s awareness of the event regardless of seriousness.  A targeted 
questionnaire is in-built as an eCRF to collect relevant additional information for these potential 
cases.  
If the subject discontinues study drug due to liver enzyme abnormalities, the subject will have 
additional clinical laboratory evaluations as described in Section 10.2 in order to determine the 
nature and severity of the potential liver injury.  
8.4.2. 
Pregnancy 
The Sponsor must be immediately notified of any female subject who becomes pregnant while 
receiving or within 7 months of the last dose of DS-1062a.  Additionally, the Sponsor must be 
immediately notified of any partner of a male subject who becomes pregnant while receiving or 
within 4 months of the last dose of DS-1062a. 
Although pregnancy is not technically an AE, all pregnancies must be followed to conclusion to 
determine their outcome.  If a pregnancy is reported, the investigator must inform the Sponsor 
within 24 hours of learning of the pregnancy. 
This information is important for both drug safety and public health concerns.  It is the 
responsibility of the investigator, or designee, to report any pregnancy in a female subject or 
partner of a male subject using the Exposure In Utero (EIU) Reporting Form.  Please contact 
your study monitor to receive the EIU Reporting Form upon learning of a pregnancy.  The 
investigator should make every effort to follow the female subject or partner of a male subject 
(upon obtaining written consent from the partner) until completion of the pregnancy and 
complete the EIU Reporting Form with complete pregnancy outcome information, including 
normal delivery and induced abortion.  Any adverse pregnancy outcome, either serious or 
non-serious, should be reported in accordance with study procedures.  If the outcome of the 
pregnancy meets the criteria for immediate classification as an SAE (ie, postpartum 
complications, spontaneous or induced abortion, stillbirth, neonatal death, or congenital 
anomaly, including that in an aborted fetus), the investigator should follow the procedures for 
reporting SAEs. 
Pregnancy Test 
For women of childbearing potential (as defined in Section 5.1): document the results of a 
negative serum pregnancy test.  For eligibility, if not performed as a part of routine care, a serum 
pregnancy test (within 28 days prior to Cycle 1 Day 1) must be performed.  Within 3 days before 
Cycle 1 Day 1, a pregnancy test (urine/serum per institutional guideline) must be done for all 
female subjects of childbearing potential (see Table 1.1).  Repeat pregnancy tests (urine or serum 
per institutional guidelines) must be performed within 3 days before infusion at each cycle, at 

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EOT visit, and at the 28-day Safety Follow-up visit.  A positive urine pregnancy test must 
immediately be confirmed using a serum test. 
8.4.3. 
Clinical Laboratory Evaluations 
Clinical laboratory tests including hematology, blood chemistry, and pregnancy tests will be 
performed as per the SoE by the local laboratory (Table 1.1 and Table 1.2).  Urinalysis and 
coagulation will be performed at screening only.  Refer to Section 10.2 for the complete list of 
laboratory parameters. 
All laboratory values must be appraised by the investigator as to clinical significance and used to 
take appropriate clinical management measures.  All abnormal laboratory values considered 
clinically significant by the investigator should be recorded on the AE page of the eCRF.  If the 
abnormal laboratory value constitutes an SAE, an SAE should be reported in the eCRF and other 
relevant procedures must be followed (see Section 8.4.1.1). 
Abnormal laboratory values (NCI CTCAE Grade 3 or 4) occurring during the clinical study will 
be followed until repeat test results return to normal (or baseline), stabilize, or are no longer 
clinically relevant.  New or worsened clinically relevant abnormalities should be recorded as 
AEs on the Adverse Event eCRF. 
8.4.4. 
Other Safety 
Physical Examinations, Weight, and Height 
Physical examinations should be performed as per the SoE (Table 1.1 and Table 1.2).  A 
complete physical examination should include a weight measurement and an evaluation of the 
head, eyes, ears, nose, and throat and the cardiovascular, dermatological, musculoskeletal, 
respiratory, gastrointestinal, genitourinary, and neurological systems.  Any abnormality 
identified at baseline should be recorded on the General Medical History and Baseline 
Conditions eCRF.  At subsequent visits (or as clinically indicated), limited, symptom-directed 
physical examinations should be performed.  Changes from baseline abnormalities should be 
collected in the subject’s study record.  New or worsened clinically relevant abnormalities should 
be recorded as AEs on the Adverse Event eCRF.  Height will be obtained once, prior to Cycle 1 
Day 1 dosing. 
Vital Signs 
Vital signs will be measured and recorded as per the SoE (Table 1.1 and Table 1.2).  Vital signs 
will include the measurements of respiratory rate, pulse rate, systolic and diastolic blood 
pressures, and temperature.  Blood pressure and pulse rate will be measured after the subject has 
rested in a preferably recumbent position or if recumbent position is not possible, then sitting for 
5 minutes or more and prior to laboratory draws. 
Pulse Oximetry 
Peripheral oxygen saturation (SpO2) will be measured by pulse oximeter and at the same time 
vital signs are measured. 

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Electrocardiograms 
12-lead ECGs will be performed and recorded for every subject as per the Schedules of Events 
(Table 1.1 and Table 1.2).  The ECG will be measured after the subject has rested in a recumbent 
position for 5 minutes or more.  At Screening only, ECGs will be taken in triplicate in close 
succession, no more than approximately 5 minutes apart, and after at least 5 minutes of quiet rest 
in the supine position.   
Single ECGs will be performed as clinically indicated for all subsequent treatment cycles.  If an 
ECG abnormality is detected, ECGs will be performed in triplicate. 
At any visit during which a subject exhibits a heart rate ≤50 bpm or other clinical indications for 
ECG, the ECG will be repeated.  Abnormal, clinically relevant findings occurring post-baseline 
will be reported as AEs.  Electrocardiograms will be transmitted electronically to a central reader 
for determination of heart rate, PR interval, RR interval, QRS amplitude, QT interval, QTcF 
interval, and any other results. 
Multigated Acquisition Scan or Echocardiogram 
MUGA/ECHO must be performed as per the Schedules of Events (Table 1.1 and Table 1.2).  
Subjects must have an LVEF ≥50% to be eligible for the study.  The same test must be used 
throughout the study. 
ECOG Performance Status 
Assess and record the subject’s ECOG PS as per the Schedules of Events (Table 1.1 and 
Table 1.2). 
Ophthalmologic Assessments 
Ophthalmologic assessments (OAs), including, but not limited to, visual acuity testing, slit lamp 
examination, intraocular pressure measurement, fundoscopy, and fluorescein staining, will be 
performed at screening, as clinically indicated, and at the EOT visit by an ophthalmologist or, if 
unavailable, another licensed eye care provider. A suitable alternative to fluorescein staining of 
the cornea may be used in exceptional circumstances where fluorescein is not available. An 
ophthalmologic assessment should be considered for any ocular symptoms including, but not 
limited to, dry eye, decreased or blurred vision, foreign-body sensation, photophobia, tearing, 
pain, and eye redness. All OAs (baseline, as clinically indicated, EOT) should be documented on 
worksheets in the eCRF, and copies of all consultation reports should be enclosed in the eCRF as 
applicable.  
Subjects should be advised to use artificial tears 4 times daily as a preventative measure and up 
to 8 times daily as clinically needed and to avoid the use of contact lenses. The use of other eye 
medications (eg, topical corticosteroids) for prophylaxis should be at the discretion of an 
ophthalmologist or, if unavailable, another licensed eye care provider.  

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ILD/Pneumonitis Investigation 
For suspected ILD/pneumonitis, treatment with Dato-DXd should be delayed pending the 
following evaluations: 
 High-resolution CT 
 Pulmonologist consultation (infectious diseases consultation as clinically indicated)  
 Bronchoscopy and bronchoalveolar lavage if clinically indicated and feasible 
 Pulmonary function tests (including force vital capacity and CO diffusing capacity) and 
pulse oximetry (SpO2) 
 Clinical laboratory tests (arterial blood gases if clinically indicated, blood culture, blood 
cell count, differential white blood cell count, C-reactive protein, and a COVID-19 test)  
 One blood sample collection for PK analysis as soon as ILD/ pneumonitis is suspected, if 
feasible. 
Other tests could be considered, as needed. 
IRR 
Premedication is required prior to any dose of Dato-DXd and must include antihistamines and 
acetaminophen with or without glucocorticoids. Subjects/participants should remain at the site 
for at least 1 hour post infusion of every dose of Dato-DXd for close observation for possible 
allergic reaction.  
If a subject does not experience any IRR during or after the first 2 cycles, the post-infusion 
observation period can be shortened to at least 30 minutes for subsequent cycles. Subjects with 
identified IRR related to the study drug should be observed post-infusion for at least 1 hour for 
the 2 cycles after the IRR event and for at least 30 minutes at each subsequent cycle. 
Oral Care Plan (Stomatitis/Oral Mucositis) 
Subjects/participants should adhere to the following guidance: 
 Gently brush their teeth after meals and at bedtime using a soft or ultra-soft toothbrush 
(or swab) and a bland-flavored fluoride-containing toothpaste, 
 Floss their teeth every day, if able to do so without pain or causing gingival bleeding. 
 Daily use of prophylaxis with a steroid-containing mouthwash (eg, dexamethasone oral 
solution 0.1 mg/mL 10 mL 4 times daily swish for 1 to 2 minutes then spit out; or a 
similar mouthwash regimen using an alternative steroid advocated by institutional/local 
guidelines) is highly recommended. 
o Note: Subjects/participants are allowed to take oral nystatin suspension or other 
topical antifungal agents after the steroid-containing mouthwash according to 
clinician preference based on institutional/local guidelines. 
 In the absence of a prophylactic steroid-containing mouthwash, daily use of inert, bland 
mouth rinses (eg, with a non-alcoholic and/or bicarbonate-containing mouthwash, 4 to 6 
times a day) is recommended. 
 Prophylactic cryotherapy (ice chips or ice water held in the mouth throughout the 
infusion) should also be considered. 

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The following algorithm, to be followed from steps 1 to 4, may be used as a guidance to select an 
appropriate prophylaxis mouthwash: 
20. Dexamethasone mouthwash formulated at 0.5 mg/5mL. If not available, then use→ 
21. Dexamethasone mouthwash compounded at site/locally. If not available, then use→ 
22. Other steroid-based mouthwash available at site/locally. If not available, then use→ 
23. Non-steroid mouthwash or other local mouthwash 
Nausea and Vomiting  
Based on the currently available clinical safety data, it is highly recommended that subjects 
receive prophylactic antiemetic agents prior to infusion of Dato-DXd and on subsequent days as 
needed (see Section 6.7). 
8.5. 
Pharmacokinetic Assessments 
Blood samples for PK analyses will be obtained based on the SoE (Table 1.1 and Table 1.2) at 
time points outlined in Table 8.1.  Details on the analysis of PK assessments are provided in the 
Statistical Analysis Plan (SAP). 
Plasma concentration-time profiles of the 3 analytes (DS-1062a, total anti-TROP2 antibody, and 
MAAA-1181a) will be established from blood PK samples collected from Cycle 1 Day 1 to 
Cycle 8 Day 1 for the following cohorts: 
 Full PK cohort: Approximately the first 30 subjects with adequate hepatic function in 
the study and additional subjects (up to 9) with moderate hepatic dysfunction will 
undergo full PK sampling. 
 Sparse PK cohort: All other subjects will undergo sparse PK sampling.  
In addition, a blood sample for PK analysis will be collected as soon as ILD/pneumonitis is 
suspected in a subject.  
Table 8.1: 
Schedule of Pharmacokinetic Sample Collection 
Cycles 
Days 
Full Sampling Pharmacokinetic 
Cohort  
Sparse Sampling Pharmacokinetic 
Cohort 
1 
1 
Predose: 
Within 8 hours before infusion  
Postdose:  
 
Within 30 minutes after end of 
infusion  
 
3 hours (± 15 minutes) after 
infusion start 
 
5 hours (± 15 minutes) after 
infusion start 
 
7 hours (± 15 minutes) after 
infusion start  
Predose: 
Within 8 hours before infusion 
Postdose:  
 
Within 30 minutes after end of 
infusion 
 
5 hours (± 1 hour) after infusion 
start 
2 
24 hours (± 2 hours) after Day 1 infusion start 
4  
3 days (± 1 day) after Day 1 infusion start 

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Cycles 
Days 
Full Sampling Pharmacokinetic 
Cohort  
Sparse Sampling Pharmacokinetic 
Cohort 
8  
7 days (± 1 day) after Day 1 infusion start 
15  
14 days (± 1 day) after Day 1 infusion 
start 
None 
2 
1 (±2) 
Predose: Within 8 hours before infusion 
Postdose: Within 1 hour after end of infusion 
3  
1 (±2) 
Predose:  
Within 8 hours before infusion 
Postdose:  
Within 1 hour after end of infusion 
None 
4 
1 (± 2) 
Predose: Within 8 hours before infusion 
Postdose: Within 1 hour after end of infusion 
6 
1 (± 2) 
Predose: Within 8 hours before infusion 
Postdose: Within 1 hour after end of infusion 
8 
1 (± 2) 
Predose: Within 8 hours before infusion 
Postdose: Within 1 hour after end of infusion 
Plasma concentrations of DS-1062a, total anti-TROP2 antibody, and MAAA-1181a will be 
measured using validated assays at the bioanalytical laboratory. 
Instructions for the collection and handling of biological samples will be included in the 
Laboratory Manual.  The actual date and time (24-hour clock time) of each sample collection 
should be recorded.   
The following PK parameters will be calculated for the subjects in the full PK cohort using 
non-compartmental analysis of concentration–time data of DS-1062a, total anti-TROP2 
antibody, and MAAA-1181a in plasma: maximum plasma concentration (Cmax), time to reach 
maximum plasma concentration (Tmax), area under the plasma concentration-time curve up to 
the last quantifiable time (AUClast), area under the plasma concentration-time curve during 
dosing interval (AUCtau), and if data permit, area under the plasma concentration-time curve up 
to infinity (AUCinf), t1/2, total body clearance (CL), volume of distribution at steady-state (Vss), 
volume of distribution based on the terminal phase (Vz), and elimination rate constant associated 
with the terminal phase (Kel). 
Population PK and exposure-response (ER) analyses may be performed to characterize the 
relationships between dose and exposure and between exposure and efficacy/safety endpoints.  If 
performed, the results of the PopPK and ER analyses will be reported separately from the clinical 
study report (CSR).  
8.6. 
Biomarker and Pharmacodynamic Assessments 
Note: Unless restricted by local/site policies or country-specific regulations, blood and tissue 
collections for exploratory biomarker and pharmacogenomic analyses as described below must 
be followed, and any deviations from the protocol should be reported as protocol deviations.  
The Sponsor must be notified of the specific local or country-specific restriction or regulation 
that applies, and the restriction or regulation must be documented appropriately in the applicable 
study files. 

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Biomarker Analysis for Potential In Vitro Assay 
Collected samples may be assessed for the purpose of analytical validation and/or bridging 
studies of diagnostic tests (including for the detection of TROP2), which may be proposed as an 
in vitro diagnostic (IVD).  The results of these studies will determine the ability of the 
companion diagnostic test(s) to classify subjects as positive for the biomarker with a proposed 
threshold in relation to clinical efficacy.  Data obtained from biomarker analysis may be used to 
perform clinical efficacy analysis as described in the SAP. 
8.6.1. 
Exploratory Biomarker Assessments in Blood Samples 
Cell-free DNA (cfDNA) from blood samples collected during the study to assess changes in 
tumor mutations or other genomic alterations in response to treatment will be analyzed with the 
intent of monitoring the biological or antitumor impact of treatment with DS-1062a. Additional 
candidate blood-based biomarkers may be considered as suggested by updated literature.  
Biomarkers will be assessed using validated assays in blood collected at the time points specified 
in the Schedules of Events in Table 1.1 and Table 1.2. 
One or more of the biomarkers may also be assessed for correlation with efficacy.  
A blood sample will be collected at the time point specified in Table 1.1 to serve as a liquid 
biopsy to identify subjects who are likely to derive clinical benefit. 
A whole blood sample will be collected at the time point specified in Table 1.1 to serve as a 
control for whole exome sequence/whole genome sequence tissue analysis.  
Plasma and serum samples will be collected at timepoints specified in the SoE (Table 1.1 and 
Table 1.2) and at the time of suspected ILD onset.  Samples may be analyzed to look for 
biomarkers predictive of ILD. 
Biomarker samples will be shipped to a central laboratory.  Sample collection, preparation, 
handling, storage, and shipping instructions are provided in the Laboratory Manual. 
8.6.2. 
Exploratory Biomarker Assessments in Tumor Tissues 
Biomarker analyses will be used to investigate the effect of DS-1062a at the molecular and 
cellular level as well as to determine how changes in the biomarkers may relate to exposure and 
clinical outcomes.  Biopsies may be collected from a lesion that has been irradiated, provided 
that it can be documented that the lesion has increased/appeared since radiation occurred and that 
the biopsy is collected at least 3 months after radiation.  The following samples for biomarker 
research are required and will be collected from all subjects in this study as specified in Table 1.1 
and Table 1.2: 
 Mandatory biopsy procedure to collect fresh tumor biopsy tissue before study entry 
(see inclusion criterion 6; Section 5.1).  If available, a tumor biopsy that was collected 
(within 3 months of Screening) after completion of the most recent anticancer 
treatment regimen and that has a minimum of 10 × 4 micron sections or a tissue block 
equivalent to 10 × 4 micron sections, may be substituted for the mandatory 
pre-treatment biopsy procedure before study entry. 
 Archival tumor tissue (if available; see inclusion criterion 6; Section 5.1).  

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In addition to the biomarkers specified above, exploratory biomarker research may be conducted 
on any samples.  The following optional samples for biomarker research should be collected 
from study subjects where possible:  
 Optional on-study Cycle 2 biopsy if clinically feasible and not contraindicated at the 
time of on-treatment biopsy. 
 Optional EOT biopsy. 
The sample collection information as required should be recorded on the eCRF pages and central 
laboratory requisition forms.  Detailed instructions for the collection, handling, and shipping of 
biomarker samples are outlined in the Laboratory Manual. 
8.6.3. 
Additional Exploratory Biomarker Assessments 
During the study, in addition to the biomarkers specified above, exploratory research may be 
conducted on these collected samples.  Biomarker assessments may include but are not limited to 
IHC or other analyses of proteins and whole exome/whole genome or targeted genetic analysis of 
DNA/RNA in tumor and blood samples.  These studies would extend the search for other 
potential biomarkers relevant to the effects of DS-1062a, cancer, and/or the response/resistance 
to the study treatment.  This may include the development of ways to detect, monitor, or treat 
NSCLC.  These additional investigations would be dependent upon clinical outcome, reagent, 
and sample availability.  
If the subject agrees, remaining samples (tumor, blood, or other specimen obtained during the 
study) may be stored for a maximum of 15 years (or according to local regulations) following 
finalization of the CSR at a facility selected by the Sponsor to enable further analysis and address 
scientific questions of biomarkers relevant to DS-1062a and/or malignancies.  The banked 
samples may be analyzed to design or improve methods for analyzing the development of 
diagnostic tests, characteristics of cancer, and, possibly, research related to other diseases that 
may lead to new treatments or the development of a diagnostic test that could be commercialized 
in the future to benefit other patients, or in response to a Health Authority request.  If performed, 
the results of the biomarker analyses will be reported separately from the CSR. 
8.6.4. 
TROP2 Immunohistochemistry Analysis 
TROP2 expression levels may be measured using an IHC assay on all tumor biopsy samples 
collected during this study, including archival tumor material.   
8.6.5. 
Pharmacogenomic (Inherited Genetic) Analysis 
A single blood sample for pharmacogenetic analysis will be collected from each subject.  The 
pharmacogenomic blood sample will be scheduled for Cycle 1 Day 1 predose (see Table 1.1) but 
may be collected at any time after the first dose of DS-1062a.  Detailed instructions for the 
collection, handling, and shipping of samples are outlined in the Laboratory Manual.   
Pharmacogenomic samples may be analyzed for genes involved in absorption, metabolism, 
elimination, safety, and efficacy of the study drug.  Additionally, samples may be analyzed for 
genes involved in study drug-related signaling pathways, or to examine diseases or physiological 
processes or safety related to the study drug, such as ILD/pneumonitis.  

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Genetic analyses will not be performed on blood samples collected for PK or safety assessments.  
Subject confidentiality will be maintained.   
If subjects agree, the remaining DNA will be stored, as outlined in Section 8.6.5.1 for performing 
future pharmacogenetic analysis.  Otherwise, all remaining DNA samples will be destroyed.  
8.6.5.1. 
Banking of Specimens for Inherited Genetic Analysis 
Procedures for the long-term preservation (banking) of blood and/or DNA specimens extracted 
from subjects’ blood samples for each subject who consented are described in the Laboratory 
Manual. 
The banked samples may be analyzed for genes involved in absorption, distribution, metabolism, 
elimination, safety, and efficacy of DS-1062a.  Additionally, samples may be analyzed for genes 
involved in DS-1062a related signaling pathways, or to examine diseases or physiologic 
processes related to DS-1062a.  DNA samples will not be immortalized or sold to anyone.  This 
information may be useful in increasing the knowledge of differences among individuals in the 
way they respond to the study drug, as well as helping in the development of new drugs or 
improvement of existing drugs. 
Storage and Disposal of Specimens 
Banked DNA samples will be stored for a maximum of 15 years after the finalization of the CSR 
for this protocol.  These specimens will be kept for pharmacogenetic analysis in case new 
genomic or genetic information is obtained in the future regarding the response (PK or 
pharmacodynamic) to DS-1062a, or in case serious adverse drug reactions (ADRs) are noted in a 
clinical study and pharmacogenetic analysis is to be conducted for investigation into the cause. 
During the storage period, the samples will be coded with labels having no personal information 
and will not be immortalized or sold to anyone.  Subjects will have the right to withdraw consent 
and have their sample destroyed at any time.  However, the data will not be discarded if analysis 
has been completed before the subject withdraws consent. 
Disclosure of the Results of Future Pharmacogenetic Analysis 
Because the nature and value of future pharmacogenetic analysis cannot be known at this time, 
any results obtained from research involving pharmacogenetic samples will not be disclosed to 
the subject or investigators now or in the future. 
8.6.6. 
Immunogenicity 
Blood samples for plasma antidrug antibody (ADA) analyses will be collected in all subjects as 
at the time points specified in the Schedules of Events (Table 1.1 and Table 1.2). 
Details for ADA plasma sampling, processing, and storage will be provided in the Laboratory 
Manual.  
The ADA testing will be performed using a validated ADA assay following tiered assay steps 
including screening, confirmatory as well as titer determination.  If ADA is confirmed, further 
analysis to profile the immunogenicity of DS-1062a (eg, neutralizing antibody assay) will be 
conducted.  Plasma concentrations of DS-1062a, total anti-TROP2 antibody, and MAAA-1181a 
may also be measured using the same ADA samples for purpose of ADA assessment.  

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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
General Statistical Considerations 
The DCO date for the primary analysis will occur when all subjects have had either a minimum 
of 9 months of follow-up after the start of study treatment or have discontinued from the study, 
whichever occurs first.  All data collected up to the DCO date will be included in the primary 
analysis.  Data from all sites will be pooled for analyses. 
The final analysis of the study will occur after all subjects have discontinued from the study.  
Data collected beyond the primary analysis DCO may be presented as appropriate in a CSR 
addendum if deemed necessary.  
Descriptive statistics on continuous data will include mean, median, standard deviation, and 
range (as well as geometric mean and geometric coefficient of variation for PK data).  
Categorical data will be summarized using frequency counts and percentages.  Graphical 
summaries of the data may be presented.  Time-to-event endpoints except for time to response 
(TTR) will be reported using Kaplan-Meier estimates.  
Assessments of change from baseline to post-treatment or the ratio of post-treatment to baseline 
will include only those subjects with both baseline and post-treatment measurements.  The last 
non-missing value of a variable taken before the first dose of study drug will be used as the 
baseline value, unless otherwise specified.  In general, missing data will not be imputed for the 
purpose of data analysis, unless otherwise specified.  
9.2. 
Statistical Hypothesis 
The primary objective of this study is to estimate the antitumor activity of DS-1062a among 
subjects with advanced or metastatic NSCLC with actionable genomic alterations specified in 
Section 5.1 that has progressed on or after 1 platinum-containing therapy and 1 or more lines of 
targeted therapy, as measured by the ORR as assessed by BICR per RECIST v1.1.  Confirmation 
of response (CR/PR) is required for ORR.  
9.3. 
Sample Size Determination 
A sample size of approximately 150 subjects, including approximately 50% (75 subjects) with 
EGFR genomic alterations, will provide sufficient statistical precision for the estimate of the 
ORR.  The exact 95% CIs based on the Clopper-Pearson method at various ORRs is provided in 
Table 9.1.  When the observed ORR is greater than or equal to 30%, the lower bound of the 95% 
CI is greater than 20% for all subjects and for the EGFR gene mutation subgroup, if there are 
75 subjects with EGFR genomic alterations.1,2  If there are 60 subjects with EGFR genomic 
alterations, then the lower bound of the 95% CI is greater than 20% when the observed ORR is 
greater than or equal to 32%. 

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Table 9.1: 
Exact 95% Confidence Intervals for Sample Size of All Subjects and Subjects 
with EGFR Genomic Alterations at Various Observed Objective Response 
Rates 
Sample Size 
Number of Responders 
Observed ORR (%) 
Exact 95% CI 
N=150 
(All Subjects) 
38 
25 
18.6, 33.1 
45 
30 
22.8, 38.0 
53 
35 
27.7, 43.6 
60 
40 
32.1, 48.3 
68 
45 
37.2, 53.7 
75 
50 
41.7, 58.3 
N=75 
(Subjects with EGFR Genomic 
Alteration) 
19 
25 
16.0, 36.7 
23 
31 
20.5, 42.4 
26 
35 
24.0, 46.5 
30 
40 
28.9, 52.0 
34 
45 
33.8, 57.3 
38 
51 
38.9, 62.4 
CI = confidence interval; EGFR = epidermal growth factor receptor; ORR = objective response rate 
The exact 95% CIs for the observed ORRs are based on binomial distribution and calculated 
using SAS® version 9.4. 
9.4. 
Population for Analysis Sets 
Analysis Sets 
 The Safety Analysis Set will include subjects who received at least 1 dose of study 
drug.   
 The Full Analysis Set (FAS) will include all subjects who received at least 1 dose of 
study drug.  The FAS is the same as the Safety Analysis Set in this study. 
 The PK Analysis Set will include all subjects in the Safety Analysis Set who had at 
least 1 PK sample with measurable plasma concentration of DS-1062a, total 
anti-TROP2 antibody, or MAAA-1181a. 
9.5. 
Statistical Analysis 
The SAP will be developed and finalized before database lock and will describe the subject 
populations to be included in the analyses, and procedures for accounting for missing, unused, 
and spurious data.  This section is a summary of the planned statistical analyses of the primary 
and secondary endpoints.  Additional analytical conventions and details will be described in the 
SAP. 

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9.5.1. 
Efficacy Analyses 
Table 3.1 lists the primary and secondary endpoints and their corresponding definitions.  
Additional details for the analysis and censoring rules are noted in the following sections.  
Detailed censoring rules for the primary and applicable secondary efficacy endpoints will be 
specified in the SAP.   
The FAS will be used for all efficacy analyses, unless otherwise specified.  
9.5.1.1. 
Primary Efficacy Analyses 
The primary efficacy endpoint, ORR, is defined as the proportion of subjects who achieve a 
BOR of confirmed CR or confirmed PR as assessed by BICR.  CR/PR will be confirmed with a 
follow-up tumor assessment at least 4 weeks (28 days) apart.   
The BOR will be determined using tumor assessments at different evaluation time points from 
the date of first dose of study treatment until radiographic disease progression as assessed by 
BICR or start of any further non-palliative anticancer treatment, whichever is earlier.  Clinical 
deterioration will not be considered as radiographic disease progression.   
The estimate of ORR and its 2-sided 95% exact (Clopper-Pearson)19 CI will be provided. 
9.5.1.2. 
Secondary Efficacy Analyses 
Secondary efficacy endpoints include: DoR, best percentage change in the sum of diameters 
(SoD) of measurable tumors, DCR, clinical benefit rate (CBR), progression-free survival (PFS), 
and TTR, as assessed by BICR and by investigator per RECIST v1.1; ORR as assessed by the 
investigator per RECIST v1.1; and overall survival (OS).  
A brief description of each endpoint is provided below:  
 DoR is defined as the time from the date of the first documentation of response 
(confirmed CR or confirmed PR) to the date of the first documentation of PD or death 
due to any cause.  Duration of response will be measured for responding subjects 
(subjects with confirmed CR or confirmed PR) only.  Detailed censoring rules for DoR 
will be specified in the SAP.   
 Best percentage change in the SoD of measurable tumors is defined as the percentage 
change in the smallest SoD from all post-baseline tumor assessments, taking as reference 
the baseline SoD. 
 DCR is defined as the proportion of subjects with a BOR of confirmed CR, confirmed 
PR, or SD.  
 CBR is defined as the proportion of subjects with confirmed CR, confirmed PR, or SD 
that lasts for at least 180 days.  
 PFS is defined as the time from the start of study treatment to the earlier of the dates of 
the first documentation of PD or death due to any cause.  Detailed censoring rules for 
PFS will be specified in the SAP. 

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 TTR is defined as the time from the start of study treatment to the date of the first 
documentation of response (confirmed CR or confirmed PR).  The TTR will be measured 
for responding subjects (confirmed CR or confirmed PR) only. 
 OS is defined as the time from the start of study treatment to the date of death due to any 
cause.  If there is no death reported for a subject before the DCO for the OS analysis, OS 
will be censored at the last contact date at which the subject is known to be alive. 
For DoR, PFS, and OS, the survival distribution of these endpoints will be summarized and 
presented graphically using the Kaplan-Meier method; median event times and their 2-sided 95% 
CIs will be presented using Brookmeyer and Crowley methods.  In addition, the event-free 
probability at different time points (eg, 3, 6, 9, 12 months) will be estimated with corresponding 
2-sided 95% CIs using the Greenwood formula for variance derivation.  TTR will be 
summarized descriptively.   
Descriptive statistics for the best percentage change from baseline in the SoD of measurable 
tumors will be provided.  A waterfall plot of the best percent change in the SoD for each subject 
will be presented. 
ORR, DCR, and CBR, as assessed by investigator, will be analyzed in the same manner as the 
primary efficacy endpoint. 
9.5.1.3. 
Multiplicity Adjustment 
Not applicable. 
9.5.2. 
Safety Analyses 
Safety analyses in general will be descriptive and will be presented in tabular format with the 
appropriate summary statistics.  Safety analyses will be performed using the Safety Analysis Set. 
The overall study period will be divided into 3 mutually exclusive segments for statistical 
analysis and reporting purposes:  
 Pre-treatment period: from date of informed consent (inclusive) to the start of study 
treatment − 1. 
 On-treatment period: from the start of study treatment (inclusive) to 35 days (ie, 28 days 
+ 7 days) after the last dose date of study treatment (inclusive). 
 Post-treatment period: starting from 36 days after the last dose date of study treatment. 
Only data from the on-treatment period will be summarized, unless otherwise specified, except 
in cases where data from the pre-treatment period will be used for baseline calculation. 
Adverse Events 
Adverse events will be coded using MedDRA and graded using NCI CTCAE v5.0.   
A TEAE is defined as an AE with a start or worsening date on or after the start date of study 
treatment until 35 days since date of last dose (ie, on-treatment period).  The AE summary will 
only include TEAEs.  However, SAEs starting or worsening after the on-treatment period, if 
reported as related to the study treatment, will also be summarized. 

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The TEAEs will be summarized using MedDRA SOC and preferred term.  Additional summaries 
will be provided by the worst NCI CTCAE grade and relationship to the study treatment (ie, 
regardless of relationship to study drug, study drug related).   
Treatment-emergent AEs associated with study drug reduction, infusion interruption, dose delay, 
study treatment discontinuation, or death will also be summarized.  
If the subjects reported more than 1 AE with the same PT, the AE with the greatest severity will 
be presented.  If the subjects reported more than 1 AE with the same primary SOC, the subject 
will be counted only once with the greatest severity at the SOC level, where applicable.   
Adverse events of special interest will also be summarized. 
All AEs will be listed including, but not limited to, verbatim term, PT, SOC, NCI CTCAE grade, 
relationship to study drug, start and end dates, and outcome.  Non-TEAEs will be flagged in the 
listing.  
Clinical Laboratory Evaluation 
Descriptive statistics will be provided for the clinical laboratory results by scheduled time of 
evaluation including the EOT visit, as well as for the change from baseline.  
Abnormal clinical laboratory results will be graded according to NCI CTCAE v5.0, if applicable, 
and the grade will be presented in a by-subject data listing.  A shift table, presenting the 2-way 
frequency tabulation for baseline and the worst on-treatment value according to the CTCAE 
grade, will be provided for clinical laboratory tests.  A listing of abnormal clinical laboratory test 
results deemed of clinical significance or of Grade 3 or above will be generated. 
Electrocardiogram 
Descriptive statistics will be provided for the ECG measurements by scheduled time of 
evaluation including the EOT visit, as well as for the change from baseline.  In addition, the 
number and percentage of subjects with ECG interval values meeting the criteria will be 
tabulated for QT and QTcF (eg, QTc ≤450 msec, >450 to ≤480 msec, >480 msec to ≤500 msec, 
and >500 msec; and change from baseline ≥30 msec and ≥60 msec). 
A listing of ECG data will be generated. 
Vital Signs 
Descriptive statistics will be provided for the vital sign measurements by scheduled time of 
evaluation including the EOT visit, as well as for the change from baseline.  A listing of vital 
sign data will be generated. 
Other 
All other safety endpoints (eg, physical examination findings including ECOG PS, 
ECHO/MUGA, and ophthalmologic findings) will be listed and summary tables will be 
generated. 

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9.5.3. 
Other Analyses 
Biomarkers 
Biomarkers (eg, tumor and/or blood gene expression, genomic alteration, gene signatures, and 
TROP2 expression) may be summarized using descriptive statistics.  Association between 
biomarkers, efficacy, and safety from DS-1062a may also be explored as appropriate. 
Pharmacokinetics/Pharmacodynamics 
Pharmacokinetic analyses will be performed using the PK Analysis Set.  Plasma concentrations 
for DS-1062a, total anti-TROP2 antibody, and MAAA-1181a will be listed, plotted, and 
summarized using descriptive statistics at each study day and time point for the full and sparse 
PK cohorts.  PK parameters will be calculated for the full PK cohort using non-compartmental 
analysis and will be listed and summarized using descriptive statistics. 
Immunogenicity 
ADA prevalence, which is the percentage of subjects who were ADA positive at any time point 
(baseline or post-baseline), will be summarized.  ADA incidence, which is the proportion of 
subjects having treatment-emergent ADA will also be reported.  This includes subjects who were 
ADA negative at baseline and became ADA positive post-baseline (treatment-induced ADA); 
subjects who were ADA positive at baseline and post-baseline but had an increase in ADA titer 
of at least 4-fold from baseline to post-baseline (treatment-boosted ADA); or subjects who had 
missing ADA data at baseline and were ADA positive post-baseline.   
Titer and neutralizing antibodies will be determined when ADA is positive.  The number of 
subjects with neutralizing antibodies will be summarized. 
9.5.4. 
Interim Analysis 
Not applicable. 

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10. 
APPENDICES – SUPPORTING DOCUMENTATION AND 
OPERATIONAL CONSIDERATIONS 
10.1. 
Appendix 1 Regulatory and Ethical Considerations 
10.1.1. 
Regulatory Compliance 
The study protocol, the IB, available safety information, recruitment procedures 
(eg, advertisements), subject information and consent form, any subject written instructions to be 
given to the subject, information about payments and compensation available to the subjects, and 
documentation evidencing the investigator’s qualifications should be submitted to the 
independent IRB or EC for ethical review and approval according to local regulations, prior to 
the study start.  The written approval should identify all documents reviewed by name and 
version. 
Changes in the conduct of the study or planned analysis will be documented in a protocol 
amendment and/or the SAP.  Written approval of all protocol amendments and changes to any of 
the above listed documents must be obtained from the IRB or EC. 
The investigator should notify the IRB or EC of deviations from the protocol or SAEs occurring 
at the study site and other AE reports received from the Sponsor/CRO, in accordance with local 
procedures. 
The Sponsor will appoint a coordinating investigator.  Among other possible duties, the 
coordinating investigator will be responsible for reviewing the final CSR and testifying to the 
accuracy of the description of the study conduct.  Because the coordinating investigator should 
have personal knowledge of the conduct of the study, he or she will normally be chosen from 
among those investigators who have enrolled and treated at least 1 subject.  However, where an 
investigator has special knowledge of the field or of the study, the coordinating investigator can 
be chosen prior to enrollment of the first subject.  In all cases, the coordinating investigator must 
be chosen prior to locking the database. 
Compliance Statement, Ethics, and Regulatory Compliance 
This study will be conducted in compliance with the protocol, the ethical principles that have 
their origin in the Declaration of Helsinki, the International Council for Harmonisation (ICH) 
consolidated Guideline E6 for Good Clinical Practice (GCP) (CPMP/ICH/135/95), and 
applicable regulatory requirement(s) including the following: 
 European Commission Directive and/or; 
 US FDA GCP Regulations: Code of Federal Regulations Title 21, parts 11, 50, 54, 56 
and 312 as appropriate and/or; 
 Japanese Ministry of Health, Labor and Welfare Ordinance No. 28 (27 Mar 1997) and/or; 
 The Act on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, 
Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics No. 
1 (25 Nov 2014); 
 Other applicable local regulations. 

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In addition, the investigator will inform the Sponsor in writing within 24 hours of any urgent 
safety measures taken by the investigator to protect the study subjects against any immediate 
hazard, and of any suspected/actual serious GCP non-compliance that the investigator becomes 
aware of. 
Supply of New Information Affecting the Conduct of the Study 
When new information becomes available that may adversely affect the safety of subjects or the 
conduct of the study, the Sponsor will inform all investigators involved in the clinical study, 
Independent Ethics Committees (IECs)/IRBs, and regulatory authorities of such information, and 
when needed, will amend the protocol and/or subject information. 
The investigator should immediately inform the subject whenever new information becomes 
available that may be relevant to the subject’s consent or may influence the subject’s willingness 
to continue participation in the study.  The communication should be documented on medical 
records, for example, and it should be confirmed whether the subject is willing to remain in the 
study. 
If the subject information is revised, it must be re-approved by the EC/IRB.  The investigator 
should obtain written informed consent to continue participation with the revised written 
information even if subjects were already informed of the relevant information.  The investigator 
or other responsible personnel who provided explanations and the subject should sign and date 
the revised ICF. 
10.1.2. 
Informed Consent 
In obtaining and documenting informed consent, the investigator should comply with the 
applicable regulatory requirements, and should adhere to GCP and to the ethical principles that 
have their origin in the Declaration of Helsinki.  The ICF and any revision(s) should be approved 
by the EC/IRB prior to being provided to potential subjects. 
The subject’s written informed consent should be documented in the subject’s medical records.  
The ICF should be signed and personally dated by the subject and by the person who conducted 
the informed consent discussion (not necessarily the investigator).  The original signed ICF 
should be retained in accordance with institutional policy, and a copy of the signed ICF should 
be provided to the subject.  The date and time (if applicable) that informed consent was given 
must be recorded in the eCRF. 
If the subject cannot read, then according to ICH GCP Guideline, Section 4.8.9, an impartial 
witness should be present during the entire informed consent discussion.  This witness should 
sign the ICF after the subject has consented to their participation.  By signing the ICF, the 
witness attests that the information in the ICF and any other written information was adequately 
explained to and apparently understood by the subject and that informed consent was freely 
given by the subject. 
A separate special consent for inherited genetic analysis will be obtained from subjects in 
accordance with health authorities in their particular region/country. 
Suggested model text for the ICF for the study and any applicable subparts (PK, 
pharmacodynamic, etc.) is provided in the Sponsor’s ICF template for the investigator to prepare 

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the documents to be used at his or her study site.  Updates to applicable forms will be 
communicated via letter from the Sponsor. 
For study sites in the US, an additional consent is required for the Health Insurance Portability 
and Accountability Act (HIPAA). 
10.1.3. 
Subject Confidentiality 
The investigators and the Sponsor will preserve the confidentiality of all subjects taking part in 
the study, in accordance with GCP and local regulations. 
For European study sites, the Sponsor will observe the rules laid down in the General Data 
Protection Regulation 2016/679/EU on the protection of individuals with regard to the 
processing of personal data and the free movement of such data. 
The investigator must ensure that the subject’s anonymity is maintained.  On the eCRFs or other 
documents submitted to the Sponsor or the CRO, subjects should be identified by a unique 
subject identification (SID) as designated by the Sponsor.  Documents that are not for 
submission to the Sponsor or the CRO (eg, signed ICF) should be kept in strict confidence by the 
investigator. 
In compliance with ICH GCP Guidelines, it is required that the investigator and institution 
permit authorized representatives of the company, of the regulatory agency(s), and the 
independent IRB/EC direct access to review the subject’s original medical records for 
verification of study-related procedures and data.  The investigator is obligated to inform the 
subject that his/her study-related records will be reviewed by the above-named representatives 
without violating the confidentiality of the subject. 
10.1.4. 
Data Integrity and Quality Assurance 
Monitoring and Inspections 
The CRO monitor and regulatory authority inspectors are responsible for contacting and visiting 
the investigator for the purpose of inspecting the facilities and, upon request, inspecting the 
various records of the study (eg, eCRFs, source data, and other pertinent documents). 
The verification of adherence to the protocol; completeness, accuracy, and consistency of the 
data; and adherence to ICH GCP and local regulations on the conduct of clinical research will be 
accomplished through a combination of onsite visits by the monitor and review of study data 
remotely.  The frequency of the monitoring visits will vary based on the activity at each study 
site.  The monitor is responsible for inspecting the eCRFs and ensuring completeness of the 
study essential documents.  The monitor should have access to subject medical records and other 
study-related records needed to verify the entries on the eCRFs.  Detailed information is 
provided in the monitoring plan. 
The monitor will communicate deviations from the protocol, SOPs, GCP and applicable 
regulations to the investigator and will ensure that appropriate action(s) designed to prevent 
recurrence of the detected deviations is taken and documented. 

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The investigator agrees to cooperate with the monitor to ensure that any problems detected in the 
course of these monitoring visits are addressed to the satisfaction of the Sponsor and 
documented. 
In accordance with ICH GCP and the Sponsor’s audit plans, this study may be selected for audit 
by representatives from the Sponsor.  Audit of study site facilities (eg, pharmacy, drug storage 
areas, laboratories) and review of study-related records will occur in order to evaluate the study 
conduct and compliance with the protocol, ICH GCP, and applicable regulatory requirements.  
The investigator should respond to audit findings. 
In the event that a regulatory authority informs the investigator that it intends to conduct an 
inspection, the Sponsor shall be notified immediately. 
Data Collection 
An eCRF must be completed for each subject who signs an ICF and undergoes any screening 
procedure.  If a subject is not treated, the reason must be recorded on the eCRF.  All data 
collected during the study will be recorded in this individual, subject-specific eCRF.  Instructions 
will be provided for the completion of the eCRF and any corrections made will be automatically 
documented via an “audit trail.” 
The eCRF should be kept current to enable the study monitor to review the subject’s status 
throughout the course of the study.  Upon completion of the subject’s eCRF, it will be reviewed 
and signed off by the investigator via the EDC system’s electronic signature.  This signature will 
indicate that the investigator reviewed the data in the subject-specific eCRF, the data queries, and 
the site notifications and agrees with the eCRF content. 
Data Management 
Each subject will be identified in the database by a unique SID. 
To ensure the quality of clinical data across all study sites and subjects, a review will be 
performed by the CRO according to specifications approved by the Sponsor.  Data will be vetted 
both electronically by programmed data rules within the application and manually.  Queries 
generated by rules and raised by reviewers will be generated within the EDC application.  During 
this review, subject data will be checked for consistency, completeness and any apparent 
discrepancies. 
Data received from external sources such as central laboratories will be reconciled to the clinical 
database. 
All AEs will be coded using MedDRA.  Serious AEs in the clinical database will be reconciled 
with the safety database. 
All concomitant medications and prior cancer therapies will be coded using the World Health 
Organization Drug Reference (WHODRUG) Dictionary. 

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10.1.5. 
Committees 
Interstitial Lung Disease Adjudication Committee 
An external ILD AC will be used for this study.  Details on the membership, responsibilities, and 
working procedures of the external ILD AC will be described in its own charter, provided as a 
separate document.  The ILD AC will adjudicate all cases of potential ILD/pneumonitis on an 
ongoing basis.  
Adjudication of ILD/pneumonitis cases will be based on evaluation of eCRFs and source 
documents including, but not limited to, chest high-resolution CT, arterial blood gases, and 
carbon monoxide diffusing capacity.  The ILD AC will review ongoing cases of 
ILD/pneumonitis to make the final determination of ILD/pneumonitis diagnoses to guide 
Sponsor decisions regarding trial suspension or trial discontinuation and to provide assessment of 
ILD/pneumonitis prevalence at the end of the study.  Findings of the ILD AC with its 
recommendations will be provided to the Sponsor. 
10.1.6. 
Study Documentation and Storage 
The investigator will maintain a Signature List of appropriately qualified persons to whom 
he/she has delegated study duties.  All persons authorized to obtain informed consent and make 
entries and/or corrections on eCRFs will be included on the Signature List. 
Investigators will maintain a confidential Screening Log of all potential study candidates that 
includes limited information of the subjects, date, and outcome of the screening process. 
Investigators will be expected to maintain an Enrollment Log of all subjects enrolled in the study 
indicating their assigned study number. 
Investigators will maintain a confidential Subject Identification Code list.  This confidential list 
of names of all subjects allocated to study numbers on enrolling in the study allows the 
investigator to reveal the identity of any subject when necessary. 
Source documents are original documents, data, and records from which the subject’s eCRF data 
are obtained.  These include but are not limited to hospital records, clinical and office charts, 
laboratory and pharmacy records, diaries, microfiches, X-rays, and correspondence. 
Records of subjects, source documents, monitoring visit logs, data correction forms, eCRFs, 
inventory of study drug, regulatory documents (eg, protocol and amendments, EC/IRB 
correspondence and approvals, approved and signed ICFs, Investigator’s Agreement, clinical 
supplies receipts, distribution and return records), and other Sponsor correspondence pertaining 
to the study must be kept in appropriate study files at the study site (site-specific Trial Master 
File).  Source documents include all recordings and observations or notations of clinical 
activities and all reports and records necessary for the evaluation and reconstruction of the 
clinical study.  These records will be retained in a secure file for the period required by local 
laws or regulations or study site policy.  Prior to transfer or destruction of these records, the 
Sponsor must be notified in writing and be given the opportunity to provide further instruction. 

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Record Keeping 
The investigator and study staff are responsible for maintaining a comprehensive and centralized 
filing system (site-specific Trial Master File) of all study-related (essential) documentation, 
suitable for inspection at any time by representatives from the Sponsor and/or applicable 
regulatory authorities.  Essential documents include: 
 Subject files containing completed eCRFs, ICFs, and supporting source documentation. 
 Study files containing the protocol with all amendments, IB, copies of relevant essential 
documents required prior to commencing a clinical study, and all correspondence to and 
from the independent IRB/EC and the Sponsor. 
 Records related to the study drug including acknowledgment of receipt at study site, 
accountability records and final reconciliation and applicable correspondence. 
In addition, all original source documents supporting entries in the eCRFs must be maintained 
and be readily available. 
All essential documentation will be retained by the investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least 2 years have lapsed since the 
formal discontinuation of clinical development of the investigational drug.  These documents 
should be retained for a longer period, however, if required by the applicable laws or regulatory 
requirements or by an agreement with the Sponsor.  It is the responsibility of the Sponsor to 
inform the investigator/institution as to when these documents no longer need to be retained. 
Subjects’ medical files should be retained in accordance with applicable legislation and in 
accordance with the maximum period of time permitted by the hospital, institution or private 
practice.  
No study document should be destroyed without prior written agreement between the Sponsor 
and the investigator.  Should the investigator wish to assign the study records to another party or 
move them to another location, he/she must notify the Sponsor in writing of the new responsible 
person and/or the new location. 
10.1.7. 
Finances 
Prior to starting the study, the Principal Investigator and/or institution will sign a clinical study 
agreement with the CRO.  This agreement will include the financial information agreed upon by 
the parties. 
Reimbursement, Indemnity, and Insurance 
The Sponsor provides insurance for study subjects to make available compensation in case of 
study-related injury. 
Reimbursement, indemnity and insurance shall be addressed in a separate agreement on terms 
agreed upon by the parties. 

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10.1.8. 
Publication, Public Disclosure Policy, and Data Sharing 
The Sponsor is committed to meeting the highest standards of publication and public disclosure 
of information arising from clinical studies sponsored by the company.  The Sponsor will 
comply with US, EU, and Japanese policies for public disclosure of the clinical study protocol 
and clinical study results, and for sharing of clinical study data.  The Sponsor will follow the 
principles set forward in “Good Publication Practice for Communicating Company-sponsored 
Medical Research (GPP3)”, and publications will adhere to the “Recommendations for the 
Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals” 
established by the International Council of Medical Journal Editors (ICMJE). 
In order to ensure compliance with the public disclosure policies and the ICMJE 
recommendations, and to protect proprietary information generated during the study, all 
publications (manuscripts, abstracts, or other public disclosure) based on data generated in this 
study must be reviewed and approved in writing by the Sponsor prior to submission. 
The data from this study may be shared with or used by third parties, including commercial 
partners. 
10.1.9. 
Protocol Deviations 
The investigator must conduct the study in compliance with the protocol agreed to by the 
Sponsor and, if required, by the regulatory authority(ies), and which was given 
approval/favorable opinion by the ECs/IRBs. 
A deviation to any protocol procedure or waiver to any stated criteria will not be allowed in this 
study except where necessary to eliminate immediate hazard(s) to the subject. 
The Sponsor must be notified of all major deviations to the protocol (eg, inclusion/exclusion 
criteria, dosing, or missed study visits) in accordance with the clinical study agreement between 
the parties on an expedited basis. 
The investigator, or person designated by the investigator, should document and explain any 
deviation from the approved protocol. 
If a subject was ineligible or received the incorrect dose or study treatment, and had at least 
1 administration of study drug, data should be collected for safety purposes. 
If applicable, the investigator should notify the EC/IRB of deviations from the protocol in 
accordance with local procedures. 
10.1.10. 
Study and Site Closure 
The Sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the Sponsor.  Study sites will be closed upon study completion.  A 
study site is considered closed when all required documents and study supplies have been 
collected and a study site closure visit has been performed. 
The investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or investigator may include but are 
not limited to: 

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 Failure of the investigator to comply with the protocol, the requirements of the EC/IRB 
or local health authorities, the Sponsor’s procedures, or GCP guidelines. 
 Inadequate recruitment of subjects by the investigator. 
 Discontinuation of further study intervention development. 
Study termination may also be requested by (a) competent authority/ies. 
In the event of early termination of the study, the Sponsor will consider providing DS-1062a to 
subjects who benefit from treatment according to legal regulations in the corresponding 
countries.  Alternatively, these subjects may also be treated with SoC per investigator’s decision. 
10.1.11. 
Product Complaints 
A product complaint is any dissatisfaction with a product that may be attributed to the identity, 
quality, durability, reliability, or safety of the product.  Individuals who identify a potential 
product complaint situation should immediately report the event.  Whenever possible, the 
associated product should be maintained in accordance with the label instructions pending 
further guidance from a quality representative form the Sponsor. 
For product complaints, refer to the Pharmacy Manual for instructions and details. 

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10.2. 
Appendix 2: Laboratory Tests 
The clinical laboratory tests listed in Table 10.1 are to be performed by local laboratory in this 
study. 
Table 10.1: 
Clinical Laboratory Tests 
Test 
Analytes 
 
Blood Chemistry 
albumin 
alanine aminotransferase (ALT) 
alkaline phosphatase (ALP) 
aspartate aminotransferase (AST) 
bilirubin (total) 
blood urea nitrogen (BUN) 
Urea (if BUN is not available) 
calcium (Ca) 
chloride (Cl) 
creatinine 
cholesterol (total) 
creatine phosphokinase 
lactate dehydrogenase (LDH) 
magnesium (Mg) 
potassium (K) 
protein (total) 
sodium (Na) 
uric acid 
Hematology 
hemoglobin 
hematocrit 
platelet count 
red blood cell (RBC) count 
white blood cell (WBC) count 
differential WBC count: 
basophils  
eosinophils 
lymphocytes 
monocytes 
neutrophils 
Coagulation 
prothrombin time - international normalized ratio (INR) 
partial thromboplastin time or/and 
activated partial thromboplastin time 
Urinalysis 
(abbreviated) 
Urine dipstick testing: 
bilirubin 
protein 
glucose 
nitrites 
blood 
white blood cells 
pH 
specific gravity  
color 
clarity 
microscopic analyses: to be performed if 
clinically indicated or based on significant 
abnormal findings from the urine dipstick 
testing 
RBC 
WBC 
bacteria 
crystals 
other 
 
Pregnancy test (serum or urine) 

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10.3. 
Appendix 3: Reference Standards 
10.3.1. 
Cockcroft-Gault Equation 
The estimated creatinine clearance (CrCl; mL/min) will be calculated using the Cockcroft-Gault 
equation based on actual weight in kilograms (1 kilogram = 2.2 pounds):20  
Conventional – serum creatinine in mg/dL: 
Male: 
CrCl (mL/min) =  
Female: 
CrCl (mL/min) = 
× 0.85 
 
International System of Units (SI) – serum creatinine in μmol/L: 
Male: 
CrCl (mL/min) =  
Female: 
CrCl (mL/min) = 
× 0.85 
10.3.2. 
New York Heart Association  
The NYHA classification is summarized in Table 10.2.21  
Table 10.2: 
New York Heart Association Classifications 
Class 
Functional Capacity 
Objective Assessment 
I 
Subjects with cardiac disease but without resulting 
limitation of physical activity.  Ordinary physical activity 
does not cause undue fatigue, palpitation, dyspnea, or 
anginal pain. 
A. No objective evidence of 
cardiovascular disease. 
II 
Subjects with cardiac disease resulting in slight limitation 
of physical activity.  They are comfortable at rest.  
Ordinary physical activity results in fatigue, palpitation, 
dyspnea, or anginal pain. 
B. Objective evidence of minimal 
cardiovascular disease. 
III 
Subjects with cardiac disease resulting in marked 
limitation of physical activity.  They are comfortable at 
rest.  Less than ordinary activity causes fatigue, 
palpitation, dyspnea, or anginal pain. 
C. Objective evidence of moderately 
severe cardiovascular disease. 
IV 
Subjects with cardiac disease resulting in inability to carry 
on any physical activity without discomfort.  Symptoms of 
heart failure or anginal syndrome may be present even at 
rest.  If any physical activity is undertaken, discomfort is 
increased. 
D. Objective evidence of severe 
cardiovascular disease. 
Source: American Heart Association. Classification of Functional Capacity and Objective Assessment, Ninth edition 
March 14, 1994.  
 
[140 - age (in years)] × weight (in kg) 
serum creatinine (in mg/dL) × 72 
[140 - age (in years)] × weight (in kg) 
serum creatinine (in mg/dL) × 72 
[140 - age (in years)] × weight (in kg) 
serum creatinine (in µmol/L) × 72 × 0.0113 
[140 - age (in years)] × weight (in kg) 
serum creatinine (in µmol/L) × 72 × 0.0113 

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10.3.3. 
Eastern Cooperative Oncology Group Performance Status 
The ECOG PS scale scores are summarized in Table 10.3.22  
Table 10.3: 
Eastern Cooperative Oncology Group Performance Status 
Score 
Performance Status 
0 
Fully active, able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or 
sedentary nature (eg, light housework, office work). 
2 
Ambulatory and capable of all self-care, but unable to carry out any work activities.  Up and about 
more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or chair. 
5 
Dead 
Source: Oken MM, Creech RH, Tormey DC, et al. Toxicity and Response Criteria of the Eastern Cooperative 
Oncology Group. Am J Clin Oncol. 1982;5:649 55. 
10.3.4. 
Highly Effective Contraception 
Methods considered to be highly effective contraception include:23  
 Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation: 
o Oral 
o Intravaginal 
o Transdermal 
 Progestogen-only hormonal contraception associated with inhibition of ovulation: 
o Oral 
o Injectable 
o Implantable 
 Intrauterine device 
 Intrauterine hormone-releasing system 
 Bilateral tubal occlusion 
 Vasectomized partner 
 Complete sexual abstinence, defined as refraining from heterosexual intercourse during 
and upon completion of the study and for at least 7 months for females and for at least 
4 months for males after the last dose of DS-1062a.  Periodic abstinence (calendar, 
symptothermal, post-ovulation methods) is not an acceptable method of contraception.  
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the subject. 

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10.4. 
Appendix 4: Response Evaluation Criteria in Solid Tumors 
(Version 1.1) 
Assessment of tumor responses will be performed according to revised RECIST guidelines, 
Version 1.1.24  Some of these definitions and criteria are highlighted below. 
Measurability of Tumor at Baseline Definitions 
At baseline, tumor lesions/lymph nodes will be categorized as measurable or non-measurable as 
follows: 
 Measurable 
Tumor lesions: Must be accurately measured in at least 1 dimension (longest diameter in 
the plane of measurement is to be recorded) with a minimum size of: 
 10 mm by CT scan (CT scan slice thickness no greater than 5 mm). 
 10 mm caliper measurement by clinical examination (lesions which cannot be 
accurately measured with calipers should be recorded as non-measurable). 
 20 mm by chest X-ray. 
Measurable malignant lymph nodes: To be considered pathologically enlarged and 
measurable, a lymph node must be ≥15 mm in the 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.  See also notes below on 
“Baseline documentation of target and non-target lesions” for information on lymph node 
measurement. 
 Non-measurable 
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. 
 Special Considerations Regarding Lesion Measurability 
Bone lesions, cystic lesions, and lesions previously treated with local therapy require 
particular comment: 
Bone lesions: 
 Bone scan, PET scan or plain films are not considered adequate imaging 
techniques to measure bone lesions.  However, these techniques can be used to 
confirm the presence or disappearance of bone lesions. 
 Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue 
components, that can be evaluated by cross sectional imaging techniques such as 

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CT or MRI can be considered as measurable lesions if the soft tissue component 
meets the definition of measurability described above. 
 Blastic bone lesions are non-measurable. 
 Cystic lesions: 
 Lesions that meet the criteria for radiographically defined simple cysts should not 
be considered as malignant lesions (neither measurable nor non-measurable) since 
they are, by definition, simple cysts. 
 ‘Cystic lesions’ thought to represent cystic metastases can be considered as 
measurable lesions, if they meet the definition of measurability described above.  
However, if non-cystic lesions are present in the same subject, these are preferred 
for selection as TLs. 
 Lesions with prior local treatment: 
 Tumor lesions situated in a previously irradiated area, or in an area subjected to 
other loco-regional therapy, are not considered measurable unless there has been 
demonstrated progression in the lesion since the therapy. 
Specifications by Methods of Measurements 
 Measurement of Lesions 
All measurements should be recorded in metric notation, using calipers if clinically 
assessed.  All baseline evaluations should NEVER be performed more than 4 weeks 
(28 days) before the beginning of the treatment. 
 Method 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.  Imaging-based 
evaluation should always be done rather than clinical examination unless the lesion(s) 
being followed cannot be imaged but are assessable by clinical examination. 
CT, MRI: CT is the best currently available and reproducible method to measure lesions 
selected for response assessment.  This guideline has defined measurability of lesions on 
CT scan based on the assumption that CT slice thickness is 5 mm or less.  When CT 
scans have slice thickness greater than 5 mm, the minimum size for a measurable lesion 
should be twice the slice thickness.  MRI is also acceptable in certain situations (eg, for 
body scans). 
Tumor Response Evaluation 
 Assessment of Overall Tumor Burden and Measurable Disease 
To assess objective response or future progression, it is necessary to estimate the overall 
tumor burden at baseline and use this as a comparator for subsequent measurements. 
In this study, only subjects with measurable disease at baseline should be included in the 
study. 

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 Baseline Documentation of Target and Non-Target Lesions 
When more than 1 measurable lesion is present at baseline all lesions, up to a total of 
2 lesions per organ and a maximum of 5 lesions total representative of all involved 
organs should be identified as TLs and will be recorded and measured at baseline (this 
means in instances where subjects have only 1 or 2 organ sites involved a maximum of 2 
and 4 lesions, respectively, will be recorded). 
Target lesions should be selected on the basis of their size (lesions with the longest 
diameter), be representative of all involved organs, but in addition should be those that 
lend themselves to reproducible repeated measurements.  It may be the case that, on 
occasion, the largest lesion does not lend itself to reproducible measurement in which 
circumstance the next largest lesion which can be measured reproducibly should be 
selected. 
Lymph nodes merit special mention since they are normal anatomical structures which 
may be visible by imaging even if not involved by tumor.  As noted above, pathological 
nodes which are defined as measurable and may be identified as TLs must meet the 
criterion of a short axis of ≥15 mm by CT scan.  Only the short axis of these nodes will 
contribute to the baseline sum.  The short axis of the node is the diameter normally used 
by radiologists to judge if a node is involved by solid tumor.  Nodal size is normally 
reported as 2 dimensions in the plane in which the image is obtained (for CT scan this is 
almost always the axial plane; for MRI the plane of acquisition may be axial, sagittal, or 
coronal).  The smaller of these measures is the short axis.  For example, an abdominal 
node which is reported as being 20 mm × 30 mm has a short axis of 20 mm and qualifies 
as a malignant, measurable node.  In this example, 20 mm should be recorded as the node 
measurement.  All other pathological nodes (those with short axis ≥10 mm but <15 mm) 
should be considered NTLs.  Nodes that have a short axis <10 mm are considered 
non-pathological and should not be recorded or followed. 
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all 
TLs will be calculated and reported as the baseline SoD.  If lymph nodes are to be 
included in the sum, then as noted above, only the short axis is added into the sum.  The 
baseline SoD will be used as reference to further characterize any objective tumor 
regression in the measurable dimension of the disease. 
All other lesions (or sites of disease) including pathological lymph nodes should be 
identified as NTLs and should also be recorded at baseline.  Measurements are not 
required, and these lesions should be followed as ‘present’, ‘absent’, or in rare cases 
‘unequivocal progression.’  In addition, it is possible to record multiple NTLs involving 
the same organ as a single item on the eCRF (eg, ‘multiple enlarged pelvic lymph nodes’ 
or ‘multiple liver metastases’). 
 Evaluation of Target Lesions 
 Complete Response (CR): Disappearance of all TLs.  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 SoD of TLs, taking as 
reference the baseline SoD. 

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 PD: At least a 20% increase in the SoD of TLs, taking as reference the smallest 
sum on study (this includes the baseline sum if that is the smallest on study).  In 
addition to the relative increase of 20%, the sum must also demonstrate an 
absolute increase of at least 5 mm. (Note: The appearance of 1 or more NLs is 
also considered progression). 
 Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD, taking as reference the smallest SoD while on study. 
 Special Notes on the Assessment of Target Lesions (TLs) 
 Lymph nodes: Lymph nodes identified as TLs should always have the actual 
short axis measurement recorded (measured in the same anatomical plane as the 
baseline examination), even if the nodes regress to below 10 mm on study.  This 
means that when lymph nodes are included as TLs, the ‘sum’ of lesions may not 
be zero even if CR criteria are met, since a normal lymph node is defined as 
having a short axis of <10 mm.  For PR, SD, and PD, the actual short axis 
measurement of the nodes is to be included in the sum of TLs. 
 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 (eg, 2 mm).  
However, sometimes lesions or lymph nodes which are recorded as TLs at 
baseline become so faint on CT scan that the radiologist may not feel comfortable 
assigning an exact measure and may report them as being ‘too small to measure’.  
When this occurs, it is important that a value be recorded on the eCRF.  If it is the 
opinion of the radiologist that the lesion has likely disappeared, the measurement 
should be recorded as 0 mm.  If the lesion is believed to be present and is faintly 
seen but too small to measure, a default value of 5 mm should be assigned.  
(Note: It is unlikely that this rule will be used for lymph nodes since they usually 
have a definable size when normal and are frequently surrounded by fat such as in 
the retro-peritoneum).  This default value is derived from the 5 mm CT slice 
thickness (but should not be changed with varying CT slice thickness).  The 
measurement of these lesions is potentially non-reproducible; therefore, providing 
this default value will prevent false responses or progressions based upon 
measurement error. 
If the radiologist is able to provide an actual measurement, that should be 
recorded, even if it is below 5 mm. 
 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 TL 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 
 CR: Disappearance of all NTLs and normalization of tumor marker level.  All 
lymph nodes must be non-pathological in size (<10 mm short axis). 
 Non-CR/Non-PD: Persistence of 1 or more NTL(s) and/or maintenance of tumor 
marker level above the normal limits. 
 PD: Unequivocal progression (see comments below) of existing NTLs.  (Note: 
The appearance of 1 or more NLs is also considered progression). 
 Special Notes on Assessment of Progression of Non-target Disease 
The concept of progression of non-target disease requires additional explanation as 
follows, when the subject also has measurable disease.  In this setting, 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 1 or more NTLs is usually 
not sufficient to qualify for unequivocal progression status.  The designation of overall 
progression solely on the basis of change in non-target disease in the face of SD or PR of 
target disease will, therefore, be extremely rare. 
 New Lesions 
The appearance of new malignant lesions denotes disease progression; therefore, some 
comments on detection of NLs are important.  There are no specific criteria for the 
identification of new radiographic lesions; however, the finding of a NL should be 
unequivocal: ie, not attributable to differences in scanning technique, change in imaging 
modality, or findings thought to represent something other than tumor (for example, some 
‘new’ bone lesions may be simply healing or flare of pre-existing lesions).  This is 
particularly important when the subject’s baseline lesions show PR or CR.  For example, 
necrosis of a liver lesion may be reported on a CT scan report as a ‘new’ cystic lesion, 
which it is not. 
A lesion identified on a follow-up study in an anatomical location that was not scanned at 
baseline is considered a NL and will indicate disease progression.  An example of this is 
the subject who has visceral disease at baseline and while on study has a CT or MRI of 
the brain which reveals metastases.  The subject’s brain metastases are considered to be 
evidence of PD even if he/she did not have brain imaging at baseline. 
If a NL 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 NL, then progression should be declared using the date of the 
initial scan that indicated its presence. 
Evaluation of Best Overall Response 
The BOR is the best response recorded from the start of the study treatment until the EOT.  
Confirmatory measurement for CR or PR is required in this study.  The subject’s BOR 

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assignment will depend on the findings of both target and non-target disease and will also take 
into consideration the appearance of NLs. 
Time Point Response 
It is assumed that at each protocol-specified time point, a response assessment occurs.  
Table 10.4 provides a summary of the overall response status calculation at each time point for 
subjects who have measurable disease at baseline. 
All post-baseline scans must be compared with the baseline (Cycle 1 Day 1) scan. 
When subjects have non-measurable, therefore non-target, disease only, is to be used.   
Table 10.4: 
Time Point Response: Subjects with Target (± Non-target) Disease 
Target Lesions 
Non-target Lesions 
New Lesions 
Objective Response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all evaluated 
No 
PR 
SD 
Non-PD or not all evaluated 
No 
SD 
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; NE = not evaluable; PD = progressive disease; PR = partial response; SD = stable disease 
  
Table 10.5: 
Objective Response: Subjects with Non-target Disease Only 
Non-target Lesions 
New Lesions 
Objective Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/Non-PD 
Not all evaluated 
No 
NE 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
CR = complete response; NE = not evaluable; PD = progressive disease  
Missing Assessments and In-evaluable Designation 
When no imaging/measurement is done at all at a particular time point, the subject is NE at that 
time point.  If only a subset of lesion measurements is 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 be most likely to happen in the case of PD.  For example, if a subject had a 
baseline sum of 50 mm with 3 measured lesions and at follow-up only 2 lesions were assessed, 

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but those gave a sum of 80 mm, the subject will have achieved PD status, regardless of the 
contribution of the missing lesion. 
Best Overall Response: All Time Points 
The BOR is determined once all the data for the subject are known.  The BOR when 
confirmation of CR or PR is required is displayed in Table 10.6. 
Table 10.6: 
Best Overall Response When Confirmation of CR and PR Required 
Overall response 
 
Overall response 
First time point 
Subsequent time point 
Best 
CR 
CR 
CR 
CR 
PR 
SD, PD, or PR
a 
CR 
SD 
SD provided minimum criteria for SD duration met, 
otherwise, PD 
CR 
PD 
SD provided minimum criteria for SD duration met, 
otherwise, PD 
CR 
NE 
SD provided minimum criteria for SD duration met, 
otherwise, NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD provided minimum criteria for SD duration met, 
otherwise, PD 
PR 
NE 
SD provided minimum criteria for SD duration met, 
otherwise, NE 
NE 
NE 
NE 
CR = complete response; NE = not evaluable; PD = progressive disease; PR = partial response; SD = stable disease 
a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR 
criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR).  
Best response would depend on whether minimum duration for SD was met.  However, sometimes ‘CR’ may be 
claimed when subsequent scans suggest small lesions were likely still present and in fact the patient had PR, not 
CR at the first time point.  Under these circumstances, the original CR should be changed to PR and the best 
response is PR. 
Source: Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised 
RECIST guideline (version 1.1). Table 3. Euro J of Can. 2009:45;228-47 
Special Notes on Response Assessment 
When nodal disease is included in the sum of TLs and the nodes decrease to ‘normal’ size 
(<10 mm), they may still have a measurement reported on scans.  This measurement should be 
recorded even though the nodes are normal in order not to overstate progression should it be 
based on increase in size of the nodes.  As noted earlier, this means that subjects with CR might 
not have a total sum of ‘0’ on the eCRF. 

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Subjects with a global deterioration of health status requiring discontinuation of DS-1062a 
without objective evidence of disease progression at that time should be reported as ‘clinical 
progression.’  Every effort should be made to document objective progression even after 
discontinuation of treatment.  Symptomatic deterioration is not a descriptor of an objective 
response: it is a reason for stopping study drug.  The objective response status of such subjects is 
to be determined by evaluation of target and non-target disease.  If a radiographic tumor 
assessment has not been performed within 4 weeks (28 days) of the time of clinical progression, 
then another radiographic assessment should be performed without waiting for the next regularly 
scheduled scan. 
For equivocal findings of progression (eg, very small and uncertain NLs; cystic changes or 
necrosis in existing lesions), treatment may continue until the next scheduled assessment.  If at 
the next scheduled assessment, progression is confirmed, the date of progression should be the 
earlier date when progression was suspected. 
Frequency of Tumor Re-evaluation 
In this study, tumor measurement will be conducted at Screening, and every 6 weeks (± 7 days) 
from Cycle 1 Day 1, independent of treatment cycle, until radiographic disease progression as 
assessed by BICR, death, lost to follow-up, or withdrawal of consent regardless of 
discontinuation of study treatment or initiation of new anticancer therapy as specified in the 
Schedule of Events (see Table 1.1 and Table 1.2).  Subjects who discontinue study treatment for 
reasons other than disease progression per BICR will continue to undergo tumor assessments 
every 6 weeks during the Follow-up Period until radiographic disease progression as assessed by 
BICR, death, lost to follow-up, or withdrawal of consent.  Tumor measurement will be 
performed during the EOT visit if it was not done within the previous 6 weeks or the previous 
assessment demonstrated disease progression.  When tumor assessments at a visit are performed 
over multiple days, the date of response (CR, PR, SD, Non-CR/Non-PD [subjects with NTLs 
only] or NE) should be recorded as the date of the last radiographic evaluation included in the 
series for that assessment, and the date of progression (PD) should be recorded as the date of the 
earliest radiographic evaluation included in the series for that assessment. 
Baseline tumor assessments must be performed within the Screening Period of 28 days prior to 
the start of study treatment. 
All efforts should be made to ensure consistency between the baseline measurements and all 
subsequent measurements in reference to utilization of scanning method, equipment, technique 
(including slice thickness and field of view), and radiographic interpreter. 
The radiographic evaluation must include CT or MRI scanning of the chest and abdomen.  Any 
additional suspected sites of disease should also be imaged.  All evaluations should meet the SoC 
for imaging of lesions in the respective organ(s) and should conform to the image acquisition 
guidelines according to institutional standards. 
All target and non-target sites are evaluated at each time point of tumor assessment. 

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10.5. 
Appendix 5: General Information – Adverse Events 
10.5.1. 
Definition of Adverse Event 
An AE is any untoward medical occurrence in a subject administered a pharmaceutical product 
and that does not necessarily have to have a causal relationship with this treatment.  An AE can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for 
example), symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product.25  
It is the responsibility of investigators, based on their knowledge and experience, to determine 
those circumstances or abnormal laboratory findings which should be considered AEs. 
Events Meeting the AE Definition 
 Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (eg, ECG, radiographic scans, vital signs measurements), 
including those that worsen from baseline, considered clinically relevant in the 
medical and scientific judgment of the investigator (ie, not related to progression of 
underlying disease). 
 Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
 New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
Events NOT Meeting the AE Definition 
Any clinically relevant abnormal laboratory findings or other abnormal safety assessments which 
are associated with the underlying disease, unless judged by the investigator to be more severe 
than expected for the subject’s condition. 
 The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the subject’s 
condition. 
 Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
 Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 “Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an AE or SAE.  Such instances will be captured in the efficacy 
assessments.  However, the signs, symptoms, and/or clinical sequelae resulting from 
lack of efficacy will be reported as AE or SAE if they fulfill the definition of an AE 
or SAE. 
 Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 

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10.5.2. 
Serious Adverse Event 
An SAE is any untoward medical occurrence that at any dose: 
 Results in death 
 Is life-threatening 
 The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in 
which the subject was at risk of death at the time of the event.  It does not refer to 
an event, which hypothetically might have caused death, if it were more severe 
 Requires inpatient hospitalization or prolongation of existing hospitalization 
 In general, hospitalization signifies that the subject has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting.  Complications that occur during 
hospitalization are AEs.  If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious.  When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
 Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline or for administration of anticancer therapy after 
discontinuation of study drug is not considered an AE. 
 Results in persistent or significant disability/incapacity 
 The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
 This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
 Is a congenital anomaly/birth defect 
 Is an important medical event 
 Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that may 
not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the subject or may require medical or surgical intervention to prevent one 
of the other outcomes listed in the above definition.  These events should usually be 
considered serious. 
 Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 

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Events Exempted from SAE Reporting 
Serious events that are also efficacy endpoints, including death for OS, will be exempted from 
SAE processing and expedited reporting.25  These events are clinically anticipated events in the 
target treatment population and will be periodically reviewed in an unblinded manner to ensure 
prompt identification of any clinically concerning safety issues. 
10.5.3. 
Grade Assessment 
The severity of AEs will be graded using NCI CTCAE version 5.0.  For each episode, the highest 
severity grade attained should be reported. 
The NCI CTCAE guidelines do not allow certain grades for certain AEs.  For example, pain can 
be Grade 1 to 3 only (ie, cannot be life-threatening or fatal), whereas sepsis can only be Grade 4 
or 5 (ie, can only be life-threatening or fatal).  In addition, alopecia can only be Grade 1 or 2.  
The NCI CTCAE guidelines should be followed closely. 
 Grade 1: Mild AE 
 Grade 2: Moderate AE 
 Grade 3: Severe AE 
 Grade 4: Life-threatening consequences; urgent intervention indicated 
 Grade 5: Death related to AE 
Difference Between Severity and Seriousness 
The term “severe” is often used to describe the intensity (severity) of a specific event (as in mild, 
moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor 
medical significance (such as severe headache).  This is not the same as “serious,” which is 
based on subject/event outcome or action criteria usually associated with events that pose a threat 
to a subject’s life or functioning.  Seriousness (not severity) serves as a guide for defining 
regulatory reporting obligations. 
10.5.4. 
Causality Assessment 
The investigator should assess causal relationship between an AE and the study drug based on 
his/her clinical judgment and the following definitions.  The causality assessment must be made 
based on the available information and can be updated as new information becomes available. 
 Related: 
 The AE follows a reasonable temporal sequence from study drug administration 
and cannot be reasonably explained by the subject’s clinical state or other factors 
(eg, disease under study, concurrent diseases, and concomitant medications). 
or 
 The AE follows a reasonable temporal sequence from study drug administration 
and is a known reaction to the drug under study (or its chemical group) or is 
predicted by known pharmacology. 

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 Not Related: 
 The AE does not follow a reasonable sequence from study drug administration or 
can be reasonably explained by the subject’s clinical state or other factors 
(eg, disease under study, concurrent diseases, and concomitant medications). 
10.5.5. 
Action Taken Regarding Study Drug 
 Dose Not Changed: No change in study drug dosage was made. 
 Drug Withdrawn: The study drug was permanently stopped. 
 Dose Reduced: The dosage of study drug was reduced. 
 Infusion Interrupted: The study drug administration was started and then temporarily 
stopped. 
 Dose Delayed: The study drug was not administered at the next scheduled cycle/dosing 
visit but was administered at a later date. 
 Not Applicable: Subject died, study drug completed/permanently discontinued prior to 
reaction/event, or reaction/event occurred prior to start of treatment. 
 Unknown: Subject is lost to follow-up 
10.5.6. 
Other Action Taken for Event 
 None. 
 No treatment was required. 
 Medication required. 
 Prescription and/or over-the-counter medication was required to treat the AE. 
 Hospitalization or prolongation of hospitalization required. 
 Hospitalization was required or prolonged due to the AE, whether or not 
medication was required. 
 Other. 
10.5.7. 
Adverse Event Outcome 
 Recovered/Resolved 
 The subject fully recovered from the AE with no sequelae observed. 
 Recovered/Resolved with Sequelae 
 The subject fully recovered from the AE but with sequelae. 
 Recovering/Resolving 
 The AE is improving but not recovered 
 Not Recovered/Not Resolved 
 The AE continues without improving. 
 Fatal 
 Fatal should be used when death is a direct outcome of the AE 
 Unknown 

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10.6. 
Appendix 6: Key Data Analysis Requirements 
Endpoint/Analysis 
Key Data Requirements 
Primary Analysis 
All eCRF collected data and key external source data (eg, tumor data as assessed 
by BICR, ILD, PK data, TROP2 expression data) collected up to the DCO date 
are required for the primary analysis. 
Primary Endpoint - ORR 
All tumor assessment data (eg, target, non-target, new lesion, overall response) 
as assessed by BICR and investigator per RECIST v1.1 is required. 
BICR = blinded independent central review; DCO = data cutoff; eCRF = electronic case report form; 
ILD = interstitial lung disease; ORR = objective response rate; PK = pharmacokinetic; RECIST v1.1 = Response 
Evaluation Criteria in Solid Tumors version 1.1; TROP2 = trophoblast cell surface protein 2 

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10.7. 
Appendix 7: Instructions Related to COVID-19 
Due to the potential impact of COVID-19 (due to severe respiratory syndrome coronavirus 2 
[SARS-CoV-2]), on subject safety, the Sponsor recommends the following dose modification 
and management plan for subjects with confirmed or suspected COVID-19 while being treated 
with DS-1062a.  Dose modifications will be based on the worst CTCAE grade.  Use CTCAE 
version 5.0 general grading criteria to evaluate COVID-19.  All dose modifications 
(discontinuation, delay, infusion interruptions, or reductions) must be recorded on the AE and 
drug administration eCRFs. 
Dose Modification Criteria for Suspected or Confirmed COVID-19 
If COVID-19 infection is suspected, delay DS-1062a and rule out COVID-19 per local guidance. 
 If COVID-19 is ruled out, follow dose modification and management guidance as 
outlined in Table 6.3. 
 If COVID-19 is confirmed or is still suspected after evaluation, follow dose 
modification as outlined in Table 10.7 below and manage COVID-19 per local 
guidance until recovery of COVID-19.  COVID-19 recovery is defined as no 
signs/symptoms of COVID-19, at least 1 negative real-time reverse transcription 
polymerase chain reaction (RT-PCR) test result, and nearly or completely 
resolved chest CT findings. 
Table 10.7: 
COVID-19 Dose Modification Criteria 
COVID-19 Worst Toxicity NCI CTCAE 
Version 5.0 Grade (unless otherwise specified) 
Schedule Modification for DS-1062a 
Grade 1 
Resume study drug at the same dosea 
Grade 2 
Resume study drug at the same dose if chest CT 
findings are completely resolveda 
Reduce by 1 dose level if chest CT findings are 
nearly resolved 
Grade 3 
Reduce by 1 dose level if chest CT findings are 
completely resolved 
Discontinue study drug if chest CT findings are 
not completely resolved 
Grade 4 
Discontinue study drug 
COVID-19 = coronavirus disease 2019; CT = computed tomography 
a Closely monitor signs/symptoms after resuming DS-1062a, initially with a phone call every 3 days for the first 
week, and then with a weekly phone call thereafter, for a total of 6 weeks. 
In addition to the recommendations outlined in Table 10.7, investigators may consider dose 
modifications of the study drug according to the subject’s condition and after discussion with the 
study Medical Monitor or designee. 
If an event is suspected to be drug-related ILD/pneumonitis, manage per protocol 
ILD/pneumonitis management guideline (Table 6.3). 

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Dosing of DS-1062a may be delayed for up to 9 weeks (63 days) from the planned date of the 
next cycle administration (ie, up to 12 weeks or 84 days from the last infusion).  If a subject is 
assessed as requiring a dose delay longer than 12 weeks (84 days) from the last infusion, the 
subject must discontinue study treatment. 
Before resuming study treatment with DS-1062a, a tumor assessment should be performed if the 
subject’s last scheduled tumor assessment was missed. 
Prior and Concomitant Medications - Prohibited Therapies/Products 
 Concomitant treatment with chloroquine or hydroxychloroquine is not allowed during 
the study treatment (Section 6.7).  If chloroquine or hydroxychloroquine is 
administered per local clinical practice and regulations, then a washout period of no 
less than 14 days is required before resumption of DS-1062a. 
COVID-19 Assessment(s) 
All confirmed or suspected COVID-19 infection events must be recorded in the eCRF.  If a 
subject presents to the clinic with symptoms suggestive of COVID-19, but the real-time RT-PCR 
test is not available at the site, a sample kit will be provided for sample collection to be tested at 
a central laboratory.  The results will be provided to the site from the central laboratory. 
Serum samples will be used for COVID-19 testing from each subject who provides consent, 
unless prohibited by local restrictions.  Samples will be collected prior to the study drug infusion, 
at the time points specified in the Schedule of Events (Table 1.1 and Table 1.2), shipped to a 
central laboratory, and stored there until the tests become available. 
If subject consents, the remaining serum samples will also be stored for future analysis. 
Unless prohibited by local restrictions, sample collection, preparation, handling, storage, and 
shipping instructions are provided in the Study Laboratory Manual. 
Statistical Analysis - Assessment of the Impact of COVID-19 
If deemed appropriate, analyses will be performed to explore the impact of COVID-19 on the 
safety, efficacy, and any other endpoints, as appropriate, reported for the study. 
As a result of the impact of COVID-19 on study conduct, adjustments to the statistical analysis 
and interpretation will be made, if required.  These will be described in the SAP.  

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24. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumours: Revised RECIST guideline (version 1.1). Euro J Can. 2009: 45;228–47. 
25. ICH E2A Guideline. Clinical Safety Data Management: Definitions and Standards for 
Expedited Reporting, Oct 1994. 

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12. 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
5-HT3 
5-hydroxytryptamine 3 antagonists 
AC 
Adjudication Committee 
ADA 
antidrug antibody 
ADC 
antibody-drug conjugate 
ADR 
adverse drug reaction 
AE 
adverse event 
AESI 
adverse event of special interest 
ALK 
anaplastic lymphoma kinase 
ALT 
alanine aminotransferase 
anti-HBc 
anti-hepatitis B core antibody 
anti-HBs 
anti-hepatitis B surface antigen 
AST 
aspartate aminotransferase 
AUCinf 
area under the plasma concentration-time curve up to infinity 
AUClast 
area under the plasma concentration-time curve up to the last quantifiable time 
AUCtau 
area under the plasma concentration-time curve during dosing interval 
BICR 
blinded independent central review 
BOR 
best overall response 
BRAF 
proto-oncogene B-raf 
C1D1 
Cycle 1 Day 1 
CBR 
clinical benefit rate 
CDx 
companion diagnostic 
cfDNA 
cell-free deoxyribonucleic acid 
CHF 
congestive heart failure 
CI 
confidence interval 
CL 
total body clearance 
Cmax 
maximum plasma concentration 
CNS 
central nervous system 
COPD 
chronic obstructive pulmonary disease 
COVID-19 
coronavirus disease 2019 
CPI 
Checkpoint inhibitor 
CR 
complete response 
CRO 
contract research organization 
CSR 
clinical study report 
CT 
computed tomography 

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Abbreviation 
Definition 
CTCAE 
Common Terminology Criteria for Adverse Events 
Dato-Dxd 
Datopotamab deruxtecan 
DCO 
data cutoff 
DCR 
disease control rate 
DLT 
dose-limiting toxicity 
DoR 
duration of response 
DP 
drug product 
EC 
Ethics Committee 
ECG 
electrocardiogram 
ECHO 
echocardiogram 
ECOG PS 
Eastern Cooperative Oncology Group performance status 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EGFR 
epidermal growth factor receptor 
EIU 
Exposure In Utero 
EOS 
end of study 
EOT 
end of treatment 
ER 
exposure-response 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FFPE 
formalin-fixed paraffin-embedded 
FIH 
first-in-human 
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 
G-CSF 
granulocyte-colony stimulating factor 
Hb 
hemoglobin 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HRT 
hormone replacement therapy 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 

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Abbreviation 
Definition 
IEC 
Independent Ethics Committee 
IgG1 
immunoglobulin 1 
IHC 
immunohistochemistry 
ILD 
interstitial lung disease 
INN 
International Nonproprietary Name 
IRB 
Institutional Review Board 
IRR 
infusion-related reaction 
IRT 
Interactive Response Technology 
IV 
intravenous 
Kel 
elimination rate constant associated with the terminal phase 
LTSFU 
Long-term Survival Follow-up 
LVEF 
left ventricular ejection fraction 
Lyo-DP 
lyophilized powder drug product 
MAAA-1162a 
drug linker 
MAAA-1181a 
released drug 
MAAP-9001a 
anti-TROP2 monoclonal antibody 
mAb 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
MET 
mesenchymal-epithelial transition 
MRI 
magnetic resonance imaging 
msec 
millisecond 
MTD 
maximum tolerated dose 
MUGA 
multigated acquisition 
NCI 
National Cancer Institute 
NE 
not evaluable 
NK1 
neurokinin-1 
NL 
new lesion 
NSCLC 
non-small cell lung cancer 
NTL 
non-target lesion 
NTRK 
neurotrophic tyrosine receptor kinase 
NYHA 
New York Heart Association 
OCP 
oral care plan  
ORR 
objective response rate 
OS 
overall survival 
PD 
progressive disease (disease progression) 

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Abbreviation 
Definition 
PET 
positron emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PopPK 
population pharmacokinetics 
PR 
partial response 
PT 
preferred term 
Q3W 
every 3 weeks 
QTcF 
QT interval corrected for heart rate using Fridericia’s formula 
RANKL 
receptor activator of nuclear factor kappa B ligand 
RBC 
red blood cell 
RECIST v1.1 
Response Evaluation Criteria in Solid Tumors version 1.1 
RET 
rearranged during transfection 
ROS1 
ROS proto-oncogene 1 
RT-PCR 
reverse transcription polymerase chain reaction 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SID 
subject identification 
SMQ 
standardized MedDRA query 
SoC 
standard of care 
SOC 
system organ class 
SoD 
sum of diameters 
SoE 
Schedule of Events 
SOP 
Standard Operating Procedure 
SpO2 
peripheral oxygen saturation 
t1/2 
terminal half-life 
TBL 
total bilirubin 
TEAE 
treatment-emergent adverse event 
TKI 
tyrosine kinase inhibitor 
TL 
target lesion 
TMG 
toxicity management guideline 
Tmax 
time to reach the maximum plasma concentration 
TROP2 
trophoblast cell surface protein 2 
TTR 
time to response 
ULN 
upper limit of normal 
US 
United States 

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Abbreviation 
Definition 
Vss 
volume of distribution at steady-state 
Vz 
volume of distribution based on the terminal phase 
WBC 
white blood cell 
WHODRUG 
World Health Organization Drug Reference Dictionary 
 

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