Exchanging Ideas on How to Navigate Patient-Centric Clinical Decisions in Integration of TROP2-Targeted Therapy in TNBC and HR+, HER2- Breast Cancer

Chair and Presenter Hope S. Rugo, MD, FASCO, and Sarah Donahue, MPH, NP, AOCNP, discuss breast cancer in this CME/MOC/NCPD/CE/AAPA/IPCE activity titled “Exchanging Ideas on How to Navigate Patient-Centric Clinical Decisions in Integration of TROP2-Targeted Therapy in TNBC and HR+, HER2- Breast Cancer.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/CE/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/47QsVwg. CME/MOC/NCPD/CE/AAPA/IPCE credit will be available until August 28, 2025.

1. Exchanging Ideas on How to Navigate Patient-Centric
Clinical Decisions in Integration of TROP2-Targeted
Therapy in TNBC and HR+, HER2- Breast Cancer

Hope S. Rugo, MD, FASCO

Professor of Medicine and Winterhof Family Professor of Breast Oncology
Director, Breast Oncology and Clinical Trials Education

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California

Sarah Donahue, MPH, NP, AOCNP
Carol Franc Buck Breast Cancer Center
Helen Diller Family Comprehensive Cancer Center
University of California, San Francisco
San Francisco, California
Go online to access full CME/MOC/NCPD/CE/AAPA/IPCE information, including faculty disclosures.

Copyright © 200!

2. Our Goals for Today

Augment your knowledge of the evolving clinical role and latest
evidence on TROP2-targeting agents in the treatment of TNBC
and HR+, HER2- breast cancer

Improve your skills in integrating TROP2-targeting ADCs into

treatment plans for appropriately selected patients with TNBC
and HR+, HER2- breast cancer

Enhance your abilities in implementing best practices for
provision of team-based, patient-centric, equitable care to all
patients with TNBC and HR+, HER2- breast cancer

3. Introducing Holly, a Patient and Advocate

With TNBC

4. Harnessing TROP2-Targeting

ADC Therapy in TNBC

5. ASCENT Study Design: Sacituzumab Govitecan in
Previously Treated TNBC (NCT02574455)!

Metastatic TNBC Sacituzumab govitecan (SG)

r ASCO/CAP) 10 mg/kg N |
en Days 1 and 8, eve lay cycle m Endpoints
i (n= 267) rimary
Bern Continue treatment] |» PFS (brain
Lise LING until progression metastasis-negative)

required regimens could
be from progression that Sn ae prs

‘occurred within a 12-mo. Treatment of physician’s choice + OS, ORR, DOR, TTR,
period after completion (capecitabine, eribulin, safety, QOL
on vinorelbine, or gemcitabine)

Stratification factors

+ Number of prior chemotherapies (2-3 vs >3)

+ Geographic region (North America vs Europe)

+ Presence/absence of known brain metastases (yes/no)

1. Bardia A et a. N Engl J Med. 2021:384:1528-1641 PeerView.com

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6. ASCENT: PFS and OS Wit

h Sacituzumab Govitecan in

Previously Treated TNBC'

PFS os
10 Patents 0 mPFS,% Patents. PFS,
da CIC] events)” (osm ch
202 7 09 22 es
e Lo em 1525) os Te ea ern
ar
2 Soctvauned su 45 or Saciuzune 287 ne
2 os Genese coy att Es gonocan em wos)
30 au re
Sous rales nese cysoarsossoasin E 05 the UR PW CN OSH EEE ES)
= a 04
ÿ 03
É ét go
BE ‘govitecan >
at
3 6 8 & 6 8 À À 2 % dd =
Time, mo Time, mo
No. at Risk No. at Risk
wee m0 2 8 1 0 0 0 0 Tee we m2 1 em mM mM 7 3 Oo
Sectuzumab 67 145 82 3% 23 14 8 3 o Sacturumab 267 242 209 169 125 m 62 42 25 1 2
Gone gore
1. Barca À et a Jin Oncol 2024:42:1738-1744 PeerView.com

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7. ASCENT: Treatment Emergent AEs (Safety Population;
All Grade, 210%; Grade 23, 25% of Patients)!

SG (n = 258) TPC (n= 224)
All Grade, n(%) | Grade 23,n All Grade, n (%)
Neutropenia 165 (64) 135 (62) 98 (44) 76 (34)
Anemia 103 (40) 24,9) 62 (28) 136)
Leukopenias 4307) zum 27(12) 136)
Hematologic
Lymphopenias 26 (10) 5@) 136) 5@)
Thrombocytopenia! 170) 40) 28 (13) 5@)
Febrile neutropenia 15(6) 15(6) 5) 6@)
‘Aspartate aminotransferase increased 30(12) 16 27(12) 6@)
Hepatic
‘Alanine aminotransferase increased 28(11) 34) 22(10) 3(1)

+ Trestmentomergont AEs defined as an adverso ever mi start date on or alter Po dato ol fat dos of stay ealment and up lo 30 days ar dala ls! dose of tay Leatment
Patents are counted once il eıporancing mulile adverse evens. AES wore casos accrcng to the NedDRA systems of prefere terms (version 22 1)-* Combined nouropania and

reropha count decreased, * Combined anemia, hemoglobin deceased, and red Mood col count decreased. Combined lukoponia and we oo ca count decreases, * Combined
Iymphopenia and mpnoce court decreased. Combined Ivomtocjiopena and platelet oun! decreased 7

1. Bardı At al J Chin Oncol 2024 42:1738-1744. PeerView.com

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8. ASCENT: Treatment Emergent AEs (Safety Population;
All Grade, 210%; Grade 23, 25% of Patients)!

SG (n = 258)
All Grade, n(%) | Grade 23, n (% All Grade, n(%) | Grade 23, n (%)
Diarrhea 168 (65) 30 (12) 38 (17) 2m
Nausea 161 (62) 8(3) 68 (30) 1)
Vomiting 87 (34) 5(2) 36 (16) 3
Gastrointestinal
Constipation 96 (37) 4 (<1) 52 (23) o
Abdominal pain 54(21) 703) 18(8) 3
Stomatit 27 (11) 2(1) 14 (6) o

2 Treaimentomergent AE ls defined as an acverse event wi sia dat on or aer e dat st dose au treatment and up to 30 days ar cate last dose of suey coment
Patent are eauned nos expo mute acue events. AS wore cased ag tot MeGORA Systems ul reed ema oi 22.1) =
1.Bardia A tal J Clin Oncol 2024:42:1738-1744, PeerView.com

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9. Other Trials Assessing TROP2-Targeting ADCs
in Advanced TNBC

1 Phase Drug Indication Treatment Primary Endpoint

ASCENT-03 a SG vs treatment of physician's

RECENT CS 3 SG TNBG, 1L (PDA negative) m PFS by BICR

ASCENT-04 ;

en 3 sc TNBC, AL (PO-L1 positive) SG + pembrolizumab vs TPC PFS by BICR

TROPION-Breast02 5 ae a Dato-DX vs investigator's choice of 0 and PFS by BICR

(NCTOS374512) | inaligible) ‘chemotherapy (ICC)

TROPION-Breasi05 Dato-DX + durvalumab vs IGC +

ee 3 DawDXé TNEC,1L(PDAA positive) er PFS by BICR

BEGONIA Incidence of adverse
12 Dato-Dxd TNBC, AL Dato-DXd + durvalumad events and laboratory

(NCTOS742102) a

MORPHEUS-panBC Multiple MBCILABC (diferent Multiple options, including

(NCTO3424005) 10/2 combinations subtypes) alezolizumab + SG RE

OptiTROP-Broasto1 3 Sacituzumab Sacituzumab tiumotecan

(NCTOS347134) tirumotecan TEC ot vs ICO PFS by BICR

Sacituzumab Sacituzumab tnumolecan
NCTO6278364 a ou TNBC, AL nat Be OS and PFS by BICR

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10. Ongoing Trials Assessing TROP2-Targeting ADCs
in Early TNBC

Phase Drug Indication Treatment Primary Endp
ASCENT-05 . SG + pembrolizumab Invasive disease-free survival
(NCTOS633654) > Se en vs TPC (DFS)

TROPION- Dato-DXd + durvalumab iDFS for datopotamab
Breast03 3 Dato-DXd TNBC, adjuvant vs ICT (capecitabine deruxtecan + durvalumab
(NCTOS629585) and/or pembrolizumab) vs ICT
TROPION- a Pathologic complete response
Breast04 3 DatoDXd © neoadiuvam and Dato-DXd + durvalumab (PCR) and event-free survival
(NCT06112379) a i van (EFS)

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11. Recognizing Disparities and the Need to Provide
Equitable Care to All Patients With Breast Cancer

+ Disparities and inequities exist across the entire cancer care continuum, disproportionately affecting
medically underserved populations encountering cultural, linguistic, economic, and other barriers to care"

* Contributing factors: social determinants of health, access to care, variable quality of care, differences in
treatment, implicit bias, and many other patient- and system-level factors

Female Breast Cancer Incidence
and Death Rates by Race/Ethnicity, US
150.

Some examples and facts:

+ Black women have lower rates of diagnosis of breast cancer than
White women, but are diagnosed at a younger age, at later stages,
with more aggressive forms like TNBC (=21%), and have the
highest death rate*

+ Racial and ethnic minorities are more likely to experience delays in
therapy, less likely to obtain adequate treatment, and significantly
underrepresented in clinical trials5®

3

Rao por 100,000,
8

=
4. Wong SL. J Oncol Pract. 2018:11:193-194. 2. HRSA Medically Underserved Areas and Populations. hips:/léhw.hesa,gowshortage-designation!muap.

2 Denti ei Concer Causes Conwol 201829611.018 4. Anorcan Conca Socio Brest Cancer Facts and Puta 019.2050, a
5. Foy KG et al NP Breast Cancer 2018.47, 6, Duma Net al J Oncol Prat 2018: 1401-010 PeerView.com

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12. Sacituzumab Govitecan: Outcomes by Race’

In the phase 3 ASCENT trial, 12% of patients self-reported their race as Black

Progression-Free Survival
ICR Anais SO ln=28) TPC (0

i se 22
a ModonPrs.mo (een) 2874) (1520)
HR 68% 6) 044 024080, P= 008
Fo
4
go
a
sc
o
OTA DT SOTO DMN MMO OD
Time, mo
No, at Ris

Em 129 9 66 53393 3332210
42111111 1000000

Safety in ITT population reporting Black race

E 5

08,%

Overall Survival
36 (n=28) TC (n= 38)
Res
ceño (6124)
HR S% CN Dee

Meson 08. mo 54.0)

©
so
so
2 TPC
0
OTE TTSOTEO WM BMI wR eS
Time, mo
Nat Riek
502m masnzamnennnws7ss43110
m UBH SRD UWHREHOT SES 4722240

‘The most common trealment-relaled adverse events (TRAEs; SG vs TPC) of any grade in this subgroup were neutropenia (64% vs 61%), diarrhea

(64% vs 13%), and fatigue (52% vs 39%)

and febrile neutropenia (8% vs 3%)

“The most common TRAES (SG vs TPC) of grade 3 in this subgroup were neutropenia (48% vs 42%), anemia (12% vs 6%), leukopenia (8% vs 16%),

— The safety profile of SG in this subgroup was consistent with that ofthe full trial population

1. Carey Leta SABCS 2021. Poster 5-16.07.

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13. Overcoming Disparities in Breast Cancer
Clinical Trial Participation!”

Clinical trial participants should reflect the 7
diversity of the general population, but Patient-led research found that 8 out of 10

racial/ethnic minorities are underrepresented Black people living with MBC would con:
in clinical trials: Black people represent only participating in clinical trials
4%-6% of patients in all cancer clinical trials

BECOME Research Project aims to better ACTIONS >>>
represent Black people in cancer research by
increasing access to clinical trials for MBC:

O
https //www.mbcalliance.org/projects/become O) &S

Methods: web-based survey of US adults en rones inet

living with MBC, following a literature review

and key informant interviews Only

Results presented at ASCO 2022 67% 64% 32%

Have difficulty Believe treat
fe

Full report: https://www.mbcalliance.org/wp- lie » ls
contentjuploads/BECOME-Final-Report-FULL pdf

9 SL. J Onco Prat. 2018:11:195-194. 2. n 3. al Cancer Causes Conte. 2018291511618
A ander portent cancer or) 2 sia ie andMgurea os st cancer ac nd But 20192020 pl
5. Foy KC et al NPY Breast Cancer 2018:4:7. 6. Duma N otal. J Oncol Pract. 2016; 141-010. 7. Walker Set al. ASCO 2022. Abstract 1014 PeerView.com

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14. Importance of Team-Based Collaboration
and Patient-Centered Care!

‘Advanced Practice
Providers

Patients +
Care
Partners

1. ps /cejoumals oniolbrary wey comidoi'10-33221c000-21249.

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15. Insights and Recommendations From
Holly, a Patient and Advocate, to Clinicians
and Other Patients

Please also access and review
resources available from our partner,
Living Beyond Breast Cancer

16. Let’s Consider a Case

Patient History and Presentation

Emily, a 43-year old Black woman
Diagnosed with TNBC (ER-, PR-, HER2-), metastatic disease with lung
and liver involvement

Previously treated with anthracycline-based chemotherapy, taxanes,
and pembrolizumab

At the time of diagnosis of metastatic disease she was on
pembrolizumab and capecitabine because at the time of surgery she
had residual disease

No brain metastases

Good performance status (ECOG 1)

Presents with worsening fatigue, dyspnea, and abdominal discomfort
Imaging reveals multiple new lung nodules and liver lesions
Socioeconomic considerations: unemployed, has no social support
system, lives alone, and has difficulty finding transportation to get
around

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Healthcare Provider Team Discussion

Y Identification of patients who may benefit
from TROP2-targeted therapy considering the
biomarker-agnostic role of these therapies
Factors influencing the selection and
sequencing of TROP2-targeting ADCs and
other available therapies, considering patient-
specific characteristics and disease status
Empowering patients in shared decision-
making: Emphasizing effective
communication and education to ensure
informed choices aligning with individual
patient preferences

+ Addressing socioeconomic considerations,
barriers, and disparities

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17. Making the Most of TROP2-Targeting ADCs

in the Treatment of HR+, HER2- MBC

18. Phase 3 TROPiCS-02: Expanding the Benefit
of Sacituzumab Govitecan to the HR+ Disease’

Metastatic or locally recurrent
inoperable HR+, HER2- (IHCO, IHC1+,
or IHC2+/ISH-) breast cancer that
progressed after“ Sacituzumab govitecan
+ Atleast one endocrine therapy, taxane, ee

and CDK4/6 inhibitor in any setting Seu “a
+ Atleast two, but no more than four, Me

lines of chemo for metastatic disease
+ Measurable disease by RECIST v1.1 Treatment of physician's choice‘

Randomization stratified by Gebe MOD
+ Vaceral metastases yes/no) Seen
+ Endocrine therapy in metastatic setting

26 mo (yes/no)
+ Prior lines of chemo (2 vs 3/4)
(N= 543)

Endpoints

+ Primary: PFS by
BICR

+ Secondary: OS,

ORR, DOR, CBR
by LIR, BICR,

PRO, safety
Exploratory: OS by
HER2 IHC status!

Treatment was continued until progression
or unacceptable toxicity

*NCTOS901399. Disease histology based on the ASCOICAP crtei. Singl-agent SOC treatment of physicians choice was specie before randomization
by tno imestoalor » HER low was defnod a IMC score of 1+ or a scor of 2+ win nogalvo ISH osu HERZ INGO was dined as ING sobr 00 en
1. Tolaney S et al. ASCO 2023. Abstract 1003. PeerView.com

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19. TROPiCS-02: PFS and OS With Sacituzumab Govitecan
in HR+, HER2- MBC12

+ 1L CDK4/6 inhibition was given to 31% patients in the SG group and 37% patients in the control group, and 67% in the SG
group and 62% in the control group in the 2L or later-line setting
+ Patients had received a median of three previous lines of chemotherapy

|

+

E A Seman

Bei: a

a À ame” es
o o A
ce ER
A | 5 3

>

| om] ae
e „ “Eee, quel
Ge |% 8 nn seras
ne E e crates
rare À à SSRIS SES SE
ge |} 2
|}: i
patie HE i nl
8° i me
mène
nn at rs

1. Tolanoy $ et al. ASCO 2023. Abstract 1003.2. Rugo HS et al. Lanca. 2023:402-1423-1433, PeerView.com

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20. TROPiCS-02: OS Subgroup Analysis!

Tacitazumab Govitecan Chemotherapy

Races
nite (n= 362) 12023168) 113003128)
Nor (0242) Saro MBH)
Visceral metastaco
Yaaazıım 146014161) 108100123)
Non=20) Bean) Zune)
Endocrine therapy for 6 mo o longer for MBC
Yes n= 489) 150082170) 117(104:195)
towers) Mora) 0049120
Previous chemotherapy regimens for MBC
20-20 155(13:1:187) 125004163)
35 (n=310) 1365 03186123)
Age
£85 yours (n= 403) 4027164) — 115(103:499)
265 yore ( = 140) 49020175) 1017612)
ECOS performance status
175142208) 154102)
] 3213152) — 10288118)
Previous COKA inhibitor duration
512 mo (n= 327) 152(131-169) 105(054124)
512 mo (n= 208) Wa) 1260011608)
TROPZ expression
score 00 (= 192) eG2ra81) 113000100) 0751054104)
H score 2100 = 270) 144 (127.104) — 112(99120) 0830062141
Overall (n= 543) 14a (130457) MAUERN) 030 (086.098)
ais ows os os 1 2 4 8 +
——_
Favor sactuzumab govtecan ‘Favors chemotherapy
+ n some regions lea regale dd not low cotton of ree or ele data. There were 69 patents ne sactuzumat govtecan group and 70 patents in re
‘chomotherapy group who dot have race or ny spec. and these patents wore not Hd nth race subgroup analyse a
1. Rugo HS et al Lancet. 2023,402:1429-1433. PeerView.com

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21. TROPiCS-02: Summary of Common Treatment-Related AEs
of Any Grade (210%) and by Worst Grade 23 (25%)!

san Chemotherap
TRAE) ‘All Grade, n (%) Grade 23,n (%) Al Grade, n (%) Grade 23.n (X)
Anemia? 91 (34) 176) €2(25) 86)
Leukopenia® 37 (14) 2319) 23(9) 136)
Hemalologe Lymphopenias 3112) 10@) 25(10) 8)
Thrombocytopenia! 176) 10) 41(17) sw
Febrile neutro 146 1465 114 114)
Diarra 152 (57 5 (9 22117 311
Nausea 148 (55) 30) 7761 7)
Gastrointestinal Vomiting 51 (19) 1) 30 (12) 40
Constipation 50(19) o 36 (15) o
Abdominal pain 34 (13 24 10 o
nn AST increased 1114) o 28111) 3m
ALT increased 1265 9 24 (10) se)
‘Alopecia 723 (46) o EC 0
Fatigue 101 (38) 50) 73 (29) 7
Other Asthenia 53 (20) 5€) 37 (15) 24
Decreased appetite 42(16) 10) 34 (14) 1(e1)
Neuropat! 249 34 3916) 60)

TRE te salty popuaion

Patan may topo more an on event pa rferd om. Adverse events were coded using MadDRA v25 0, an adverse event very was grados

par NCI CTCAE 180.» Combined prefered ts o "neutropenia" and nutephä count creased Combined paa arms of enema Ramon decreased," and “ed ood ol count

Gecreated«Continod prteod ters ol looperia” and We Blood cal count Seeaeed"» Combined preferred los ol "prphopenia and Iymphocyte count cecrease Combined

Deere tars of hrombocytoperia and plate count decias + Combined pres ls of Gat dfuancn. Typoesihoka. mc varas Teurapatıy peta

“paresthesia” and perpherl sersory newopathy sae
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Hugo HS et al. Lancet 2023: 402: 1429-2433

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22. PRIMED: Prevention of Sacituzumab Govitecan-Related
Neutropenia and Diarrhea in TNBC or HR+, HER2- MBC"

+ Prophylactic administration of G-CSF and loperamide
resulted in a clinically relevant reduction in the incidence
and severity of sacituzumab govitecan-related neutropenia
and diarrhea

+ This combination could help mitigate dose reductions and
treatment interruptions, as well as permanent
discontinuations due to these treatment-related AES

+ The study is ongoing, with global safety and efficacy
expected at the end of 2024

Primary Endpoints: Rates of Neutropenia and Diarrhea
During the First Two Cycles

Any Grade Grade Grade
Grade 2 3 4

Neutropenia, n(%) — 14(28) 4(8) 62) 2(4)

Diarrhea, n (%) 1784) 6(12) 24) 00)

1. Lombar-Cussae A et al ASCO 2024. Abstract 1101

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Rate of TRAES, %

AES %

‘Troatment-Rolated Rates of Neutropenia and Diarrhea
in ASCENT, TROPICSO2, and PRIMED (First Two Cycles)

G2 cs “ E G2 694
ou Neutropenia 8 lares
mor mm morue m rauen

‘AEs Leading to Dose Reductions, Treatment Interruptions, and Permanent
Discontinuations in ASCENT, TROPICSO2, and PRIMED (First Two Cycles)

660
Pr}
330 ai
20
40
5063
0

‘AES Loading to Es Loading to ‘AES Loading to
Dose Reducion Treatment neruptens Permanent Décorations
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23. SACI-IO HR+: Phase 2 Trial of Sacituzumab Govitecan
+ Pembrolizumab in HR+, HER2- MBC’

Treatment continued until progression

or unacceptable toxicity
Metastatic or locally advanced
unresectable breast cancer
HR+ (ER 21% or PR 21%), HER2- 10
(IHCO, 1+, or 2#/ISH-)
No restriction on PD-L1 status®
21 endocrine therapy for mBC
or progression on or within 12 mo
of adjuvant endocrine therapy
0-4 prior chemotherapy for mBC
No prior topoisomerase I-inhibitor ADC,
irinotecan, or PD-1/PD-L1 inhibitor
No known active brain metastases
or leptomeningeal disease

Sacituzumab govitecan (SG)
g IV D1, D8 of even
+
Pembrolizumab
200 mg IV D1 of every 21 days

Sacituzumab govitecan (SG)
10 mg/kg IV D1, DB of

N=110

jery 21 days

Endpoints
Primary
+ PFS (ITT)

Secondary

+ PFS (PD-L1+P

+ OS (ITT, PD-L1+)

+ ORR, DOR, TTOR, CBR
(TT, PD-L1+)

+ Safety

Exploratory
+ Correlative
+ HRQOL

‘Optional

EOT
biops;

NCTO4448886

‘Protocol amendment actvatod in 1/2022 to afow partcipants with any PO-L status lo ente Contra PD-L1 testing performed with PharmDx 2263 assay

POLL posiive, combined postive score (CPS) 21. Note Theres no approved CDx with 2203 for HRGIHER2- MBC.
1. Garrido Castro AC etal ASCO 2024. Abstract LBA100.

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24. SACI-IO HR+: Phase 2 Trial of Sacituzumab Govitecan
+ Pembrolizumab in HR+, HER2- MBC’

PFS os
=e FRS
Tmamam Am we En
Es y 2
E san OS, mo (85% 0) 1862 (ASS 1IO(IZSONA
> Medan ES no (SHC) MAAS 6228588) 10 mene poto
mosso at ast120) 2
08 Plegar test 37 o
06 as
Le pest
Eos 80
02 gas 02
volumes
o = o
STR STR A
Time From Randomization, mo Time From Randomization, mo
ast Rae Cntr) a sta. cand
pa PT | EA
ao mao

median

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1. Garido-Gastro AC et a. ASCO 2024. Abstract LBA1004.

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25. SACI-IO HR+: Phase 2 Trial of Sacituzumab Govitecan
+ Pembrolizumab in HR+, HER2- MBC’

PFS by PD-L1 IHC Status

PD-L1-Positive (CPS 21) PD-L1-Negative (CPS <1)
10 10
08 poz vs
peu
gos pos
Eos os
so»
emerizumad
02 Le 02 ss PR
5 2 o pembroicumab
o y y » y y y
Time From Randomization, mo Time From Randomization, mo
o Ra Canna a Ran lo Caron
ines eo) vo “o ow En] un m 20
= xo a 20 o Et sn se o
SCH Pembrolizamab SG 36 +Pembrolizumab SG
‘Treatment Arm He En Treatment Arm n= 33) (0 = 29)
BES evens, y 78 PFS events 7 20
Median PFS, mo(95% Cl) 11.05 (214NA) 6.68 (253.924) Median PFS, mo (95% Cl) 5.96(4.149.97) 507 (365-NA)
HR (95% Cl) (0.62 0201.36) HR (05% Ch) 1.08 (0591.50)
P (Log rank tos) 2 P (Log-rank test 24
1.Ganido.Castro AC ot al. ASCO 2024. Abstract LBA1O04, PeerView.com

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26. SACI-IO HR+: Phase 2 Trial of Sacituzumab Govitecan
+ Pembrolizumab in HR+, HER2- MBC’

OS by PD-L1 IHC Status Responses

PD-L1-Positive (CPS 21) PD-L1-Negative (CPS <1)
10

sc+

“ pembratzumao

Comes ANH) MAT 8903

os so 254

= u vs er
E > mets Wieser? ue asses

: ne son 32010 360
sce
a2 a2 = #
pembrokzuma PARA aa mar rn anna
o o » rout ay yen
o y 2 7 o y e y Run
Time From Randomization, mo Time From Randomization, mo RE fet set
aan cnn 1 am comin P Der ET ET

Tamm EC NE US
tne (0224 is zu we

‘OS events n° 4 8 OS events. n " 2 ati

Modan OS, mo (95%) 162 (16800) 12SO(MIIPMA) Macon OS,mo GK CU 1855(%404NN) 1000 17.960)

HR SK cD 06118209 HR Oxo 06802915)

Puros) 2 Puerro, Pi

1. Garde Castro AG ot al. ASCO 2024. Abstract LBA1O04, PeerView.com

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27. SACI-IO HR+: Phase 2 Trial of Sacituzumab Govitecan

+ Pembrolizumab in HR+, HER2- MBC’

Safety Summary

SG + Per

Izumab,n

(0= 82)
‘Any Woatmentolted AE (TRAE) 48 (023)
‘Any TEAE leading to dose discontinuation 369
‘Any reatment-emergent AE (TEAE) 51081)

ET 28(53 310695) 2342)
wes) 369 UE) 500
it Hood cl decroased 140209) 12033) 8054) 407
Lumonoeyte count decreases su sm) 36m 109)
Domes, man 868) Mm ET)
Nouses van 200 "Rm ses
Nopecia ET) - 20685) à
Fatigue 20085) 109 mu a
Anoreia cub) oo 9073) oo

The most common grade 23 TEAE ropa (68

Immune-Related TRAES
(Attributed to Pembrolizumab)

Hypothyroidism
Hypoabumnema

Alanine aminovansterase mereased
Akaine phosphatase increased
Aspartto aminctransoraso incas
‘eat Kidney Injury

Hepatitis vat

‘Adrenal insufcency

artigo

Bicod butin increased

Dyspnea

Pnoumonis

Pauus

362) 000)
268) oo
208) 119)
268) 1019)
19) 1419)
149) 109)
109) 109
109) oo
109) co
109) 00)
119) 0)
109) co)
109) oo

‘anemia (10%) (8%), lukope

1. Garido-Gastro AC et ol. ASCO 2024. Abstract LBA1004.

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28. TROPION-Breast01: Dato-DXd vs Chemotherapy in Pretreated
Inoperable or Metastatic HR+, HER2- Breast Cancer!

TROPION-Breast01: randomized, open-label phase 3 trial evaluating Dato-DXd vs investigator's choice of single-agent
chemotherapy (eribulin, capecitabine, vinorelbine, or gemcitabine) in patients with inoperable or metastatic HR+, HER2-low,
or -negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have previously progressed on or are not suitable for
endocrine therapy and have received at least one systemic therapy

Key eligibility criteria
HR+, HER2- inoperable
or metastatic breast cancer
with disease progression following
one or two lines of chemotherapy Stratification factors
(and progressed on and not + One vs two previous lines
suitable for endocrine therapy) of chemotherapy in the
+ Targeted agents (eg, inhibitors inoperable/metastatic setting
of mTOR, PD-1/PD-L1, CDK4/6, | | + Geographic location
PARP) and endocrine therapi (US/Canada/Europe vs RoW)
on their own do not count as prior | | » Previous CDK4/ inhibitor use

Dual primary
‘endpoints

+ PFS (BICR)
and OS

lines of chemotherapy Invostigator's choice
+ Atleast one measurable lesion

+ FFPE tumor sample (eribulin mesylate, vi
Adequate organ function capecitabine, or gem«

of chemother

+ Chemotherapywälbe acminstere a he loin doses. erbuin mesyato. 1.4 mpi on days aná of 21-day oyde ve Vision: vinrebiee, 26 main on ay Yana 8 ofa 21.cay
cyclo va NV Inn: copociabno, 1.0000 1,250 mom! PO BID on days 116 14 of 2i-cay eye; gone, 1.000 mg/m on days 1 and 8010 21-day ojo. fa
1 Bardia A et al Future Oncol, 2024:20:423-436, PeerView.com

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29. Primary Results From TROPION-Breast01:
PFS by BICR (Primary Endpoint)!

* Dato-DXd icc
08 —.
y ine Median PFS, mo (95% Cl) 6.9 (5.7-7.4) 4.9 (4.2-5.5)
A ar
3 06 HR = 0.63 (95% Cl, 0.52-0.75; P < .0001)
& 8 T
5 04 H
E as ! i
a2 H H
ar | h Er
| 7 y 3 ” 75
No. at Risk. Time From Randomization, mo
nude 20 PA “ s ‘
ke wT 208 s » 8 1

PFS by investigator assessment: median 6.9 vs 4.5 months; HR = 0.64 (95% Cl, 0.53-0.76)

1. Bardia A et al, ESMO 2023, Abstract LBA11,

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30. Primary Results From TROPION-Breast01:
Response Rate and Inte os!

Response Rate
=Partal response = Complete response

e ORR: 36.4 OS: Dual Primary Endpoint
6 35 cR:05 Ñ
2 OS data were not mature: median follow-up
g > 9.7 mo
3 25 ORR: 22.9
E E A trend favoring Dato-DXd was observed:
3 HR = 0.84 (95% Cl, 0.62-1.14)
15
2 10 The study is continuing to the next planned
Z analysis for OS
a 5
0 50% greater response rate with Dato-DXd
Dato-DXd (n= 365) ICC (n = 367) vs ICC
50% greater response rate with Dato-DXd vs ICC
À et al. ESMO 2023, Abstract LBA, PeerView.com

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31. Primary Results From TROPION-Breast01:
TRAEs in 215% of Patients!

System Organ Class Dato-DXd (n=360) | 1CC(n= 354)

Preferred Term, n (%) [Any Grade] Grade 23 [Any Grade] Grade 23

Blood and lymphatic system disorders

Anemia 4011) 4(1) 69 (20) 7 (2) + Most TRAEs were grade 1-2 and manageable
Rare 20 43 BB
ER + ABSIS
Dry eye 78 (22) 20) 27 (8) o — Oral mucositis/stomatitis: led to treatment
discontinuation in one patient in the Dato-DXd

Cssroimesina disorders Pe

pa
MET ICONO NETO NETO] discontinued treatment in the Dato-DXd group
Constipation 65 (18) 0 32 (9) 0 — Adjı ted drug-related ILD: rate was low;

mainly grade 1/2
General disorders.

Fatigue 85 (24) 6 (2) 64 (18) 7 (2)
‘Skin and subcutaneous disorders
Alopecia 13136) 0 72 (21) 0
Gjudicated drug-related ILD ETE) 20 y 2
1. Bardia A et a. ESMO 2023. Abstract LBA11. PeerView.com

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32. Additional Safety Analysis From TROPION-Breast01: AESIs!

Treatment-related Dato-DXd ff Treatment-related Dato-Dxd | Adjudicated drug-related Dato-DXd
oral mucositis/stomatitis, n (%) 360) ET o (n=360) PILOS, n(%) (n= 360)
Al grades? 200 (65.8) Ali grades? 144 (40.0) All grades 1283)
Grade 1 HH Cadet mero ade! 5 (14)
Grade 2 84 (23.3) Grade 2 4a
Grade 2 26 (7.2)
Grade 3 25(6.9) Grade 23" 3 (0.8)
Grade 3 3/08)
Leading to dose reduction 48 (13.3) Leading to dose reduction 103)
Leading to dose reduction andlor 42,83)
Leading to dose interruption 5(14) interruption Leading to dose interruption 308)
Leading to dose discontinuation 1 (0.3) Leading to dose discontinuation 1(0:3) Leading to dose discontinustion 5 (1.4)
+ Median time to onset: 22 days + Median time to onset: 65 days + Median time to onset: 84.5 days

+ Median time to resolution: 36.5 days + Median time to resolution: 67 days + Median time to resolution: 28 days

* Comprising the prelrrd tors of: aphthous uber, dysphagia, ossts, mouth lcerston, edynophagia, oral mucosa! bistering, ofl pain, oropharyngeal pain, phanyngealinlammaten,
‘and stomatits No grade 4/5 events.» Comprising the prelerre terme of Dephari, conjunctvte, comtal Csorder, comaal erosion, comal lesion, dy eye, lore gn body seneaton

eyes hertki, keratopathy, crmaton increase, Imhal stom cl daisency, meibomian gland Oysunclon, cela oxy, pholophoba, punctate hers, super Emi
Koratoconunciis,ucorato keratt, sion blued, vsual mpalmenl, and xrophihlm. *Compring the prelare tems af: ners ung ease and pnoumonts «Grado 3: n = 2

(08%) grado Sn = 1103). a

1. Jnaves Komal ot al ESMO Breast Cancer 2024. Abstract LBA2 PeerView.com

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33. Ongoing Trials Assessing TROP2-Targeting ADCs
in Advanced HR+, HER2- Breast Cancer

Indication

Primary

Treatment Endpoint

ASCENT-07
(NCT05840211)

TROFUSE-010
(NCT06312176)

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3 SG
3 Sacituzumab
tirumotecan

HR+, HER2-,
chemo-naive

HR+/, HER2-
unresectable locally
advanced or MBC.

SG vs TPC PFS by BICR

ST alone and in
combination with PFS
pembrolizumab vs TPC

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34. Let’s Consider Another Case

Patient History and Presentation
Anna, a 63-year-old woman with a + Receives therapy with fulvestrant

history of invasive carcinoma of
the breast, pT2N2, grade 3, ER+
(90%), PGR+ (50%), HER2-
received adjuvant chemotherapy
> radiation > adjuvant Al for 4
years before discontinuing
because of side effects

7 months later, develops right hip
pain > imaging revealed lytic
bone lesion

Staging scans revealed liver
metastases and bony metastases
involving spine/hipfribs

Biopsy of the liver: ER+, PgR+,
HER2-

Germline testing: BRCA1/2-

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+ CDK4/6i, and after a sustained
response (28-mo PFS), she
develops asymptomatic
progression in bone and 1.5-om
new liver lesions

CIDNA testing reveals an ESR1
mutation, no other alterations
Receives elacestrant, followed
later by exemestane and
everolimus, then capecitabin
Disease has progressed, and
further therapy is indicated

Liver biopsy and testing: disease
still ER+, HER2 is IHC 0

Healthcare Provider Team Discussion

Y Identification of patients with HR+, HER2-
MBC who may benefit from TROP2-targeted
ADC therapy

+ Factors influencing the selection and
sequencing of TROP2-targeting ADCs and
other available therapies

+ How would you advise the patient about what
to expect during treatment, including AEs?

+ What strategies could be used to prevent and
manage SG-related AEs?

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35. Educating Patients About AEs Associated
With Sacituzumab Govitecan

Inform patients: in he clinical als of SG, most common AES (Including laboratory abnormaliles) reported in 225% of patents included
Decreased appetite

+ Decreased creatinine clearance

+ Increased alkaline phosphatase

+ Decreased magnesium

+ Decreased potassium

+ Decreased sodium

+ Decreased leukocyte count
+ Decreased neutrophil count
+ Decreased hemoglobin

+ Diarrhea

+ Nausea

+ Decreased lymphocyte count

Advise your patients to contact their health

Neutropenia

Fever

Chis

Gough

Shortness

ofbreath

+ Burning or pain
when they urinate

+ Fatigue

+ Alopecia

+ Constipation

+ Increased glucose
+ Decreased albumin
+ Vomiting

Diarrhea

Patients should contact their
healthcare provider the fist time

they experience diarrhea during
treatment with sactuzumab govitecan
Black or bloody stools

‘Symptoms of dehydration, such

as lightheadedness, dizziness,
or faintness

Inability to take fulds by mouth
‘due to nausea or vomiing
Diarthea that is not under control
within 24 hours.

re provider right away if they experience any of th

Hypersensitivity and
Infusion-Related Reactions

they experience the following $

symptoms during their infusion

or within 24 hours afterward

+ Sweling of face, Nos, tongue,
or throat

+ Hives

+ Skin rash, Aching, or Aushing
of ther skin

+ Fever

+ Dificuty breathing or wheezing

+ Hypotension
Chil or shaking chils (igore)

following side effects

Nausea
and Vomiting

Nausea or vomiting
that is not controlled
wi the medicines.

prescribed for them

+ Encourage your patients to communicate with you and other healthcare providers to proactively manage potential AES
+ Develop an AE management plan to help support your patients

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36. Case Continues

Patient History and Presentation

Healthcare Provider Team Discussion

and fut Y How would you manage the neutropenia and
advise/educate the patient?

Treatment recommendation: sacituzumab govitecan
On C2D1 noted to have ANC = 800; afebrile

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37. Proposed Management of Selected Hematologic Toxicities
Associated With Sacituzumab Govitecan!

and Severity

Neutropenic Fever

Grade 3

Grade 4
Anomia
Grade 1
Grade 2

Grade 3

Grade 4

Presentation (CTCAE 5.0)

ANC LLN to >1.500 mm?
ANC 1,001-1,500 mm?

ANG 501-1,000 mm?

‘ANC <500 mm

ANG <1,000 mm? with a single

u

u

temperature >38.3° C or a
temperature of = 38.0° C
sustained for an hour

ife-threatening consequences

Hb <10 git
Hb 8.9.9 g/et

Hb <8 ofl

ife-hreatening consequences

-ommendation.

No dose modification
No dose modification
Consider growth factors (flgrastim after day 1 for 3-4 d and then pegfigrastim after day 8)
First event: i severe neutropenia delays treatment for >3 wk without recovery to grade 1

Discontinue treatment

First event: If sustained for over 7 d, 25% dose reduction and administer growth factors (figrastim

after day 1 for 3-4 d and then pegfigrastim after day 8)
‘Second event: 50% dose reduction

Third event: Discontinue treatment

oR

First event: if severe neutropenia delays treatment for >3 wk without recovery to grade 1:

Discontinue treatment

Fist event: If sustained for >7 days, 25% dose reduction and administer growth factors (figrastim

after day 1 for 3-4 9 and then pegfigrastim after day 6)
‘Second event: 50% dose reduction
Third event: Discontinue treatment

CConeider treatment discontinuation

No dose modification
No dose modification

Consider transfusion of PREC (i Hb <9 g/dL or if symptomatic)

I persistent, consider dose reductions
Consider transfusion of PREC

1.Schlam let a. Export Opin Bo! Ther. 2023:87.116-123, PeerView.com

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38. Case Continues

Patient History and Presentation

Healthcare Provider Team Discussion
Y How would you manage the grade 2 diarrhea
and advise/educate the patient?

ine testing: BRCA-

Treatment recommendation: sacituzumab govitecan
On C2D1 develops neutropenia > under control with management >
treatment continues

During next cycle of treatment patient develops grade 2 diarrhea

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39. Management of Sacituzumab Govitecan-Induced Diarrhea’

‘Onset during or shortly after infusion
+ Atropine 0.2 mg IV every 15 minutes for 2 doses, if required
+ Subsequent doses of atropine 0.2 mg IV for a total of 1 mg

+ Additional prophylaxis with atropine for future infusions

Discontinue loperamide
12 hours after last
diarrhea episode

+ Dietary management

Delayed Onset
+ Standard loperamide (4 mg + 2 mg

after each loose stool, up to 16 mg/day)
+ Dietary management

Diarrhea
Resolved?

If not resolved after 24 hours:

High-dose loperamide | |. Octreotide 100-150 mog
zu SCTID
every 2 hours)

+ Replace fluidslelectrolytes

Sars Dantes ‘Consider hospital admission

o a Begin intravenous fluids
progressing to

Octreotide 100-150 mog SC TID
grade 3/4 Consider antibiotic therapy as indicated

1. Spring LM et a. Oncologist 2021 26 827-734 PeerView.com

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40. SG Dose Modifications: Other AEs

Severe Non-Neutropenic Toxicity

Adverse Reactions Occurrence Dose Modification

Grade 4 nonhematologic toxicity of any duration, En
First from the original dose
Any grade 3-4 nausea, vomiting, or diarrhea due to treatment

that is not controlled with antiemetics and antidiarrheal agents,

OR Second
Other grade 3-4 nonhematologic toxicity persisting for >48 hours

despite optimal medical management,

OR

Grade 3-4 non-neutropenic hematologic or nonhematologic Third Discontinue treatment
toxicity at the time of a scheduled treatment that delays dosing

by 2 or 3 weeks to achieve recovery to grade <1

50% dose reduction
from the original dose

Grade 3-4 non-neutropenic hematologic or nonhematologic toxicity

which does not recover to grade <1 within 3 weeks First Discontinue treatment

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41. SG: Management of Other TRAEs'

+ Pre-infusion medication for patients receiving sacituzumab govitecan is recommended
WIN - Observe patients closely for infusion-related reactions during each sacituzumab govitecan infusion and for
MIES toast 30 minutes after completion of each infusion
+ Medication to treat such reactions, as well as emergency equipment, should be available for immediate
use

+ Premedicate with a two- or three-drug combination regimen (eg, dexamethasone with either a 5-HT;
receptor antagonist or an NK-1 receptor antagonist as well as other drugs as indicated) for prevention
of chemotherapy-induced nausea and vomiting (CINV)
DETTES . withhold sacituzumab govitecan doses for grade 3 nausea or grade 3/4 vomiting at the time of scheduled

Vomiting inistration and resume with additional supportive measures when resolved to grade <1

+ Additional antiemetics and other supportive measures may also be employed as clinically indicated; all

patients should be given take-home medications with clear instructions for prevention and treatment of
hausea and vomiting

1. ps va accessdata da gorérugsaféa_docsiabel2020/761 1163000 pat PeerView.com

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42. Counseling Patients About Alopecia on Sacituzumab

Govitecan

+ Hair loss is common with SG
+ Some tips that may help patients:

If you are considering a wig, buying it before treatment begins can help you
match it to the color and style of your hair

Check to see if your insurance company will cover the cost for a wig (cranial
prosthesis)

Wear a hair net at night or sleep on a satin pillowcase to keep hair from
coming out in clumps

Protect your scalp from the sun by using sunscreen, and wear a hat or scarf
outside

The effectiveness and safety of cooling caps is still being researched in clinical
trials, but it is an option that can be discussed and considered

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43. Let’s Hear From Holly, a Patient and
Advocate, About Her Experiences

Receiving Treatment With a
TROP2-Targeting ADC

44. Case Continues

Patient History and Presentation

Healthcare Provider Team Discussion

+ How would you manage these toxicities and
advise/educate the patient?

ine testing: BRCA-

What if the patient receives treatment with Dato-DXd and develops ILD?
What if the patient develops ocular surface toxicity?
What if the patient develops oral mucositis?

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45. ILD/Pneumonitis

Respiratory, Thoracic, and Mediastinal Disorder:

Ai
Term

Grade 1 Grade 2 Grade 3 Grade 4 Grade 5

f-threatening respiratory
compromise; urgent
intervention indicated Det)

‘Asymptomatic; clinical or ‘Symptomatic; medical Severe symptoms;
Pneumonitis diagnostic observations only; — intervention indicated; limiting self-care ADL;
intervention not indicated limiting instrumental ADL. ‘oxygen indicated

(eg, tracheotomy or intubation)

+ Have you been coughing recently? Is it a dry cough?
+ Have you had any shortness of breath, especially during or after physical activity?

+ Have you experienced any new breathing or respiratory problems?
+ Ifyou already have respiratory problems, have they gotten worse?
! + Have you had a fever?

+ Have you been feeling tired?

+ Have you lost weight?

+A disorder characterized by inflammation focally o ditusey affecting the lung parenchyma PeerView.com

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46. ILD/Pneumonitis Management Guidelines!

Step 1: Monitor

Step 3: Manage

Suspected LO/pneumonitis Aula ut ILDIpneumanHis if a patient dovelops

radiographie changes potentially consistent with

ILO/pnoumoniis or develops an acute onsat of new or

‘worsening pulmonary or other elated sins/sympioms,
Such as dyspnea, cough or fever

Hold Data-DXA for any ILD/pneumonitis events, regardless of grade

[Grade
+ Monitor symptoms and closely flow up in 2-7 days lor onset of inial symptoms and SpOs
+ Consider folow-up imaging in 1-2 weeks (or as clinically indicated)
+ Consider staring system steroids
+ Ho Dato-OX< unt uly resolved then

= Hfresoived in 528 days trom onset cate, maintain cose

= iftesotved in >28 days trom onset dato, reduce dose one level

“ifthe grade 1 LD/psoumoniis event does nat resol

‘thin 94 days from the lst infusion, permanent escontinu

Hold Dato-DXa

Step 2: Confirm
[Evaluations should include
"Het resolution computed tomography Puimonary funtion tests
| Puimanelogist eonsutaton (infecsous + Puso animotry (Sp0:)
<és0as0 consultaton as ciniealy nested) + Aner blood gases if clnicaly indicated
Blood eure and complete load count, and. + One blood sample collection for PK analysis
‘thor blood tests as needed as soon as IL Dipneumonis is suspected,
- Bronchoscopy and bronchoalveolar lavage, # feasible,
cinialy indicated and tease

the Dato-DX4

[Grade 2
+ Pormananty discontinuo Dat-0xa
| Monitor symptoms closely, and reimage as circa indicated
+ Promptly sta treatment with systemic torts
worsening or no improvement l observed in <5 days, then
= Consider increasing the dose o trois
= Reconsicer workup for akernatve tologís (atu to Stop 2)
Escalate care as cbicaly indicated

A ILDIpneumonitis events, regardless of severity or seriousness, must be followed
"until resolution, Including after discontinuation of Dato-DX4

Example lung scan from a patient with adjudicated ILDIpneumonitis

y discontinuo Dato-Dxa
Hosptazaton requires
+ Prompt inate high-dose systeme steroids
Reimage as ica indicated
I no improvement win 3-5 day, then
= Reconsider workup for akematve etologis (otum to Stop 2)
Consider otherimmunosuppressants andlor treat per kcal practice

ter four cycles of Dato-Dxa

æ

1. Heist RS et al. Cancor Trent Rev. 2024:125:102720.

z
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47. Oral Mucositis/Stomatitis Management Guidelines!

+ Oral mucositis/stomatitis has been Step 1: Prophylaxis Step 2: Confirm
observed in clinical trials of Dato-DXd Initiate daily OCP prior to administration Example image of stomatitis after one week
‘ ire to Da done a Bato OX dose delay aná estiment
+ Mechanism is undetermined, but + Gert aan ar msi dal ina wing
TROP2 is known to be expressed on | Za meno, ues Rennes pave bese ease
aa {Daly un la ars comi mouth Gur tmos
mucosal surfaces, including na a
epithelium of esophagus, tonsil Pine izan oa ad conan daly

crypts, and salivary gland, suggesting | .Eiscsin en vo moots cf tral hygiene, heaton,
cion tears mus and nen BOP

a possible on-target off-tumor
mechanism of toxicity

+ In the Dato-DXd clinical trial program, Step 3: Manage
oral mucositis/stomatitis is an AESI Supportive Care ‘Optimize prophylacde and supporivo medications for any ral
defined by selected preferred terms, | na ten atten nostro ‘muscositltemalts ern, regards of grade
including stomatitis and mouth prov pan marapanent Dato OXd dose recommendations

eos odeur remate ender» Grade: Manin,

ulceration, of which stomatitis is the — |'écentoncerci sony cos vahga | Grade 2 Corera des Clay or eduction cnica inated
most commonly reported; other RE e cage metales ha na yt an cts, lay eso
selected preferred terme Include Bonn sic codant nne “wales Da > are cc receto
mouth ulceration, pharyngeal o —lHpmephjuclonappotve medcaton hve and ben opin, toy
inflammation, and oropharyngeal pain IS

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48. Ocular Surface Events Management Guidelines!

Step 1: Prophylaxis Step 3: Manage

‘Advise patients to
+ Use artificial tears (four times daily for prevention and up to
eight times daly if cinically needed)
+ Avoid use of contact lenses |
+ Consider obtaining ophthalmologic assessment
+ No change in Dato-Dxd dose

Ensure patient is adhering to prophylactic guidelines,
regardless of grade

Step 2: Confirm
Grade 2

Ophthalmologic assessment to ensure an accurate + Obtain an ophthalmologic assessment
diagnosis, event grading, appropriate treatment, + Delay dose until event has been resolved to grade <1,
and event resolution should be considered and then maintain dose

Corneal Toxicity Severity Grading Seale Grade 3
Normal: Clear comea, no epithelia defects + Obtain an ophthalmologic assessment
Grade 1: nonconfluent superficial keratitis + Delay dose unti event has been resolved to grade <1,
Grade 2: nonconfluent superficial keratitis, a corea defect, and then reduce dose by one level
er 3-ine or more loss in best corrected distance visual acuity
Grade 3: corneal ulcer or stromal opacity, or best corrected Grade 4
distance visual acuity $20/200 + Obtain ophthalmologic assessment
Grade 4: corneal perforation + Discontinue Dato-DXd

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49. Conclusions & Key Takeaways