Advancing Immunotherapy: Revolutionizing Cervical Cancer Treatment

Co-Chairs Prof. Domenica Lorusso, MD, PhD, and Bradley J. Monk, MD, FACS, FACOG discuss metastatic cervical cancer in this CME/MOC activity titled “Advancing Immunotherapy: Revolutionizing Cervical Cancer Treatment.” For the full presentation, downloadable Practice Aids, and complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3xcw2CM. CME/MOC credit will be available until August 25, 2025.

1. Advancing Immunotherapy
Revolutionizing Cervical Cancer Treatment

Bradley J. Monk, MD, FACS, FACOG

Vice President and Member Board of Directors GOG-Foundation
Director GOG-Partners

Florida Cancer Specialists and Research Institute

Medical Director Late-Phase Clinical Research

West Palm Beach, Florida

Prof. Domenica Lorusso, MD, PhD
Director of Gynaecological Oncology Medical Unit at Humanitas Hospital
San Pio X, Milan

Full Professor of Obstetrics and Gynaecology

Humanitas University

Rozzano, Italy

Go online to access full CME/MOC information, including faculty disclosures.

Copyright © 2000-2023, PeerView

2. Our Goals for Today

Augment your knowledge of the evidence supporting modem
immunotherapy approaches for patients with cervical cancer

Share tips on integrating these approaches into personalized care
plans for patients with localized or advanced cervical cancer to
optimize their treatment outcomes

Equip you with skills to confidently create proactive and collaborative
strategies to mitigate and manage adverse events

Copyright © 2000-:

3. Proportions and Incidence of Locally Advanced
Cervical Cancer: A Global Systematic Literature Review!

Proportion of Locally Advanced Stages Among All Cervical Cancer Cases

1. Monk BJ et al. Int J Gynecol Cancer. 2022:32 1831-1539. PeerView.com

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4. Immune Dynamics of Cervical Cancer‘

Cytokine, chemokine
release results in
activation of adaptive
immune system

E
/

E6- and E7-induced
somatic mutations
increase PD-L1 and
eytokine expression

PD-L1
tres
1-10

Neoantigen release
activates innate
immune system

1. Yang Wet a. J Obstet Gynaecol Res. 2013:43:1602-1612. 2 Formenti SCet al J Nat! Cancer Inst 2013.105:256-265. 3. Weichselbaum RR et al Nat Rev Cin

(Oncol 2017;14:365-379. 4. Salama etal. Cancer. 2016;122:1659-1671.5. Tuyman-Santet al Nature. 2015;520:373-377 PeerView.com
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5. Six Practice-Changing Phase 3 Trials in Cervical Cancer!*?

2009 2014 2021-2023 2024

GOG 3047/Keynote-A18

GOG 204 GOG 240 GOG 3057/innovaTV 301 4 >
Pt as Adding paclitaxel | | Adding bevacizumab || | Replacing chemotherapy — RE
lo radeon’ to cisplatin to chemotherapy with tisotumab vedotin chemöihera

in 48/P/R CC? in ABIPIR CC% in 2-L and 3-L CC? ey

and radiation?

Keynote-826
Adding pembrolizumab to
chemotherapy in 48/P/R CC

(sms)

1. Rose PG tal N Ere J Med. 1999340: 1144-1163.2. Monk BJ etal. J Cin Oncol 2009:27 4649-4685, 3, Tewari KS eal N Engh J Med 2014370734 743.
4 Tewan KS etal. Lancet 2017-390 1864-1663, 5 Colombo Net al. N Engl) Med 2021:385:1856:1867. 6. Merk Bet lJ Cin Oncol 2023:41:55055511 :
7. Vergoe letal N Eng J Med. 2024:391:44-55. 8, Lousso Det el Lancet. 2024:403:1341-1350. 9, Tewar KS, Monk BJ. N Eng Med 2226544655. Peer View.com

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6. Four Immune Checkpoint Inhibitors in
Five Phase 3 Trials in Cervical Cancer

EME anes EOS ST)

1L / KEYNOTE-82612

Pembrolizumab 1964 humanized + CCRT / KEYNOTE-A18*
Cemiplimab PD-1 1964 humanized 2L / EMPOWER-Cervical-14
Durvalumab PD-L1 1961 humanized + CORT/CALLAS
Atezolizumab PD-L1 IgG1 humanized 1L/ BEATco®

1.C00mbo N etal. N Eng J Med, 20213851856 1867.2. Mek Bet. J Cin Oncol 2023:41:56053611 3 LoussoD tal Lance! 24408941950. ya

4. Tewari KS et al. N Engl J Med, 2022:386 544-555. 5. Monk BJ et al. Lancet Oncol. 2023/24:1334-1348. 6. Oaknin A et al. Lancet. 2024:403:31-43, PeerView.com

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7. Key Milestones From Phase 3 Trials of
Immune Checkpoint Inhibitors in Cervical Cancer

Pembrolizumab*

Accelerated FDA approval as monotherapy in the 2L (June 2018; KEYNOTE-158)?
— Full FDA approval as monotherapy in the 2L (October 2021)?

Full approval in combination with chemotherapy + bevacizumab in the 1L (FDA: October 2021; EMA:
April 2022: KEYNOTE-826)?

Full FDA approval when added to CCRT for 2014 FIGO stage III-VA (January 2024; KEYNOTE-A18)*

Cemiplimab

+ EMA, PMDA approval of monotherapy in 2L (November 2022)58

1. Keytuda(perbrolizumeb) Presctbing Inormabon. ps wa acces ct fda govdugsatéa_ docsfebel/2024/125514s S50 pat.
2 sw 4d. govicrugste sources nfrmaton-approved-crugs/ca-approves-pembrolzumab-advanced-cenicalcancer-<dease-progression-duing orar
remaiherapy. 3 ps aw da govidrugsesources-foraton-approved-drug/ida-approves-pembrolzumab-combinaion-rst-ine-teatmerk-eveabcancer.
4. ips Zr fa govidrugsesources-nformelon approved drugs/éa-approves-pembrolzumab chemarod ctherapy-ig0-2014-siagesi-vacenvca-cancer
$5 mps investor regeneron comes el asasInews el as cela itayor-cemiplmab-approved-european commission fr. PeerView.
ayo, eerView.com

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8. Incremental Improvements in Survival (OS)
in 1L Cervical Cancer With Combinations and Biomarkers

Chemotherapy backbone (platinum + taxane)

GOG 204 established the Adeinalbevackumab
global standard with a : hi
Median OS of 12.9 mos! Adding pembrolizumab
GOG 240 added
bevacizumab in eligible KEYNOTE-826 added

no LS a : Bembrol aural in see,

0, median OS of 17.5 mos: positive ( 21%) CC,

ORR = 29% resulting in a median OS of
ORR = 48% 28.6 mos?

ORR = 69%

41. Monk BU etal J Cha Oncol 2009274619655. 2 Tewari KS etal Lancet 2017.350-1654-1663. a
3. Monk BJ etal. J Cn Oncol. 202341:5505-5511. PeerView.com

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9. Phase 3 KEYNOTE-826:
1L Pembrolizumab + Chemotherapy + Bevacizumab''?

Pembrolizumab 200 mg IV Q3W

Key Eligibility Criteria» Mi N for up to 35 cycles

+
+ Persistent, recurrent, or a IV a3
3 th aclitaxel + cisplatin or carboplatin IV Q3W

metastatic cervical Stratification Le = up to 6 c: 5

cancer not amenable to + Metastatic disease at +

curative treatment diagnosis (yes vs no) bevacizumabis'moka
+ No prior systemic + PD-LICPS

chemotherapy (prior (<1 vs 1 to <10 vs 210)

redoßereny and + Planned bevacizumab

'emoradiotherapy use (yes vs no) +
cerco) paclitaxel + cisplatin or carboplatin

for up to 6 cycles
+ ECOG PSO ort N
bevacizumab 1

+ Dual primary endpoints®: OS and PFS per RECIST v1.1 by investigator ‘October 2021
+ Secondary endpoints: ORR, DOR, 12-mo PFS, and safety FDA approval was granted to pembrolizumab plus chemotherapy|

N a with or without bevacizumab for metastatic cervical cancer in
Exploratory endpont PROS asees sed por BroQul EG:SD'SLVAS: patients whose tumors express PD-L1 (CPS 21)?*

“Coch tested sequentially in patents wth a PD-LT combined positive score of 21, in the ITT population, and in patents wth a PL combined postive score of 210.
1. Colombe Nel al N Engl Med 2021:195 1886-1887, 2. Monk EJ et al J Clin Oneal 202341:5505:511. 3. pa man fa govierugarescutees-nformation-
sppraved-drugeea-approves-pembrolzumab-combnatonfrstne-teatmentcervical-cancer. 4 Keytruds(penrlzumab) Preserbing formation. a

Its win acoessda (da gowdrugsatiéa_docslabe’/2024/1255 14515501 pal PeerView.com

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10. KEYNOTE-826: Protocol-Specified Final PFS'2*

All-Comer Population PD-L1 CPS 21 Population
MN Events% HR (95% CI) mM Events, % HR (95% Cl)
Pembro arm 795808 633 Pembrosm 170273 626
061 (050-074) acto Ts 800 58 (047-071)

Placebo am 248209 803
nm |

447 2°
#1 ws

so
so so
70 10
co
40 à 2 40
20 Pembro » Pembro
20 20
10 Ge 10 Placebo
o o
0 3 6 0 12 18 18 21 24 27 20 39 26 39.42 45 48 D 36 9 121640 21.2427 d0 39 de 39 4245 48
Time, mo Time, mo
dom Neta Eng ued 201 05 1856 1087 2 Monk lea. Ein Onc 21550 5611 PeerView.com

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11. KEYNOTE-826: Protocol-Specified Final OS"?

All-Comer Population PD-L1 CPS 21 Population

nN Events % _HR (95% Ci) FIN Events % HR (95% Ci
Pembroam 17880 578 Pemboam 158273 560
Paceboam 228209 738 06052077) Placeboam 201275 731 09004074

100
so
so
70

100
so

12m0
755
632

240
5
394

80
7

60

60
® Median (95% €) ® Median (85% Cl)
g 0 26410 (213325) 50 288 mo 221.380)
8, women) 8 165me (145200)
Pembro Pembro

30 30

ss Placebo = Placebo

10 10

o o

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 0 3 6 9 12 15 18 24 24 27 30 33 36 39 42 45 48
Time, mo Time, mo

QOL was also not negatively affected with the combination of pembrolizumab plus chemotherapy
Data culo date: October 3, 2022. jew;
1. MorkBJ eta. J Cha Oncol 2023:41:5505-551 1.2. Monk BJ et al. Lancet Oncol 2023/24:392-402. PeerView.com

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12. KEYNOTE-826: Protocol-Specified
Final ORR and DOR, All Analysis Populations’?

" PD-L1 CPS 21 = All-Comer = PD-L1 CPS 210
» ss e 2 Al os
ao] Wera ae) (07715) al erszen
5 509 8 ss 5
= CE EJ 487-572) En
En | “= ] za
7 de ce Luz eel
É [| É .
* pene + nme er Pero Ch er rene + Cm Der Pet Chane Be °° pente + cinme ser Peabo creme bev
zw uw =”
$ Median, mo ange): Ez Median, mo (range): a" Median, mo (range:
a 192 (13210 400%) o 180134104094) » 283 (13+ 1040.9")
H ” 104 (15+ to 40.7) Ê » 104 (1,5% 10 40.7) Bo 101 @1+ 10 38.3)
2: ie 8:
sz £6 Es Pembro + chemo bev
Fa Pembro + chomet bev m © Pembro +chomos bev À ©
a3 I» ji» Placebo +
sn Pmbes chmoter EN Pixceboe chmosber À %; chemo bev
en Time, mo as Time, mo ha wet Time, mo
ESweegesupecrtrss RERwEEEessasy tess WHESSESRSaeyys sss
1. Colombo N et al. N Engl J Med.2021:11:385:1856-1867. 2. Monk BV et al. J Cin Oncal.2023:41:5505:5511. PeerView.com

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13. KEYNOTE-826: Summary of Bevacizumab Use’

Reasons for Bevaclzumab Exclusion Et ae

617 patenta wa) | were)
= 7

Not approved for use in country 200%) 43.4%)

No local standard of care 720 | 17(147%)

a Lack of experience with use for cervical cancer 1(09%) 3(26%)

cowed bevecizumab Medical reasons (76%)

[patent ets tor ]

Gastrointestinal perforation or fistula Ba) 153%)

Hemorhage 664%) 6(62%)

Pare + He New or worsened hypertension sem | 207%)

an ical conditions. 40 (357%) 98 (31.0%)

Not specified 405%) 7 (6.0%)

2 The reatment regimen in both arms included chemo. Data cof date: October 3, 2022.
1. Teen KS eta. JAMA Oncol 2024;10:185-192,

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14. KEYNOTE-826: PFS by Bevacizumab Use,
All-Comer Population?

With Bevacizumab (N = 389) Without Bevacizumab (N = 228)
MN Events % HR (95% CI) MN Events, % HR (95% CI)
Pembroam 1161198 587 Pemboam 0112 714

Piaceboam 14993 772 097045070) Placeboam seme esa 09905009)

100 100 ss
1216
ES so ES
© so
70 no
co so
= Modian @5% CD = Median (95% CI)
gs 152m0(105233) yf 50 - 63mo (61-83)
a 102mo(83:122) E 62mo(44-63)
40 “0
Pembro
20 20
20 20 Pembro
Placebo
10 10
ü o Placebo
D 3 6 9 1215 18 24 24 27 30 39 36 39 42 45 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45
Time, mo Time, mo
+ Response assessed per RECIST v1.1 by ivesigator ven Daa cil date: October 3 2022 A
1. Tewan KSet al JAMA Oncol 2024.10.185-192 PeerView.com

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15. Phase 3 BEATcc:
1L Atezolizumab + Chemotherapy + Bevacizumab'
+ Open-label, multicenter, randomized, phase 3 trial in an all-comer population

Atezolizumab 1200 mg + Dual pr

ary
bevacizumab 15 mg/kg +
paclitaxel + cis/carboplatins endpoints
+ Metastatic, persistent, or recurrent cervical cancer all lV Q3W + Investigator-assessed
not amenable to curative therapy - PFS (RECIST 1.1)
dore Rage oncle toi + os
52 No pin oysters anticancer thorny for RMS À Patents with CR after 26 cytes coud stop
+ Inpatients with pelvie disease, no bladder or rectal chemotherapy and continue biological Key secondary

‘mucosa involvement
+ Available archival or fresh tumor sample for
PD-L1 expression

therapy alone endpoints
Crossover from standard arm at progression . ORR (RECIST v1.1)

not permitted + DOR (RECIST v1.1)

Stratification factors = ee : Lu
+ Prior concurrent chemoradiation (yes vs no) all + Salaty
+ Histology (squamous cell carcinoma vs adenocarcinoma?
including adenosquamous carcinoma)
+ Chemotherapy backbone (cisplatin vs carboplatin)
+ Pact 17 mg ey it an 50 myn EG AUS). Cap 20% he cer pui Dessen

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16. Dual Primary Endpoints of BEATcc: PFS and OS!

10
æ 09 pes Aero + Bev+T_Ber+ ct
B % Even Men och
Eu Stated HRY) 062028070; P< 0M
3% Mesa mo GG) 1971123166) 104(07:117)
2 04 RE
Eos Alezo + bev Statistically significant 38%
a reduction in risk of
3 i progression or death
0 6 8 © Me À Dur Tr
ate ime, mo
pores nm ns 2
10
os ‘Aero + evs CT _ger+ cr
=o omg wo Ci
É Sites HR GK CD 028 (022080: P= D040"
2 oe SI Medan,mo (98% Cl) 221(253-353) 228 203-280)
Bos Statistically significant 32%
E 3 | ezo + bev | reduction in risk of death
% 02 i
8 0 |
a |
o 6 2 © a 8 2 4 à
Meme om mw mM gk
+ Data cut-off: July 17, 2023 (median follow-up: 32.9 months; 95% Cl, 31.2-34.6 months). * Interim OS was statistically significant, crossing the boundary
P= 028 N
1.Oakrin A et al. Lancet. 2024405:31-43. PeerView.com

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17. Secondary Endpoints of BEATcc: ORR and DOR"

10 Atezo + Bev +CT Bev+ CT.
ORR: 72 68 pee (n= 173) (n= 147
(95% Cl, 66-78) en Events, n (%) 109 (63) 120 (62)
a HR 95% CI) 060 (046-078)
so Median, mo (95% Gi) 196 (106-213) 86 (80-106)
Eos
zos
& = ezo + Bev + CT
03
Su
01
- o
Tente BRO o 6 2 m % © % 2 « 4
mars Time, mo
Ama m
saver oom © » » 7 8 + 4
+ Data cto JU 17, 2023 (macianfolow.up: 329 mans; 96% CI, 31.246 ments '
Von oa 202403313 d PeerView.com

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18. Key Differences and Similarities Between
KEYNOTE-826 and BEATcc?

Y” BEATcc was an ENGOT-led trial with
participation of GOG
Foundation/Partners

v BEATcc was an investigator-initiated
trial

v BEATcc required bevacizumab

Y” KEYNOTE-826 included a placebo

y” KEYNOTE-826 reported on PD-L1
status

> Similar eligibility between BEATcc and KEYNOTE-826

Gross trial comparisons are not possible, PeerView.com

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19. Evolution of Treatment of Stage 4B,
Persistent, Recurrent Cervical Cancer (1L)

The Past The Present

GOG 204 (cisplatin + paclitaxel) + KEYNOTE-826 (addition of
+ JCOG 0505 (noninferiority of pembrolizumab)
carboplatin and 3 hour paclitaxel) « BEATcc (addition of atezolizumab)

+ GOG 240 (addition of
bevacizumab)

> Every patient in the first-line setting should, if they are
checkpoint-naïve, be offered immune therapy

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20. Introduction to Catherine’s Case: A 66-Year-Old Patient
With High-Risk, Locally Advanced Cervical Cancer

Patient Case

A 66-year-old woman presented with

postmenopausal bleeding; + What are the first steps in evaluating
her last pap test was >10 years ago this patient for treatment selection?
Physical examination revealed | + How should the care team approach
a large cervical mass, PD-L1 expression to guide therapeutic
and subsequent imaging showed decisions?

tumor invasion of the bladder

Clinical workup confirmed invasive
squamous cell carcinoma (stage IVA) Let’s look at data supporting a
treatment selection that would be an

option for Catherine...

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21. Phase 3 KEYNOTE-A18: 1L Pembrolizumab + CRT
for High-Risk, Locally Advanced Cervical Cancer!

= Cisplatin 40 mg/m? QW
Er 5 + EBRT
Stratification followed by brachytherapy

Pembrolizumab

Key Eligibility Criteria 400 mg Q6W for

5 à + Planned EBRT type (IMRT + MAR
FIGO 2014 stage III-IVA é
(either node-positive or + Stage at screening (stage
node-negative disease) 182-118 vs II-IVA)
+ RECIST 1.1 measurable + Planned total Cisplatin 40 ma)
or nonmeasurable disease radiotherapy dose un
. (<70 Gy vs 270 Gy ibaa
‘Treatment naive 20)

+ Primary endpoints: PFS (per RECIST v1.1) by investigator or histopathologic confirmation and OS
+ Secondary endpoints: 24-mo PFS, ORR, patient-reported outcomes, and safety

4. Lorusso D et al. Lancet 2024:403:1341-1350, PeerView.com

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22. Phase 3 KEYNOTE-A18:
Baseline Characteristics’?

Pembro Arm Placebo Arm. Pembro Arm Placebo Arm:

(N= 529) (N=531) (N= 529) (N=531)
Age, median, y (range) 49(22:87) (2278) Stage at screening (FIGO 2014 criteria), n (%)
18218 25444 227427)
Race, n (%P LAVA 24(556) 204 67.3)
White 254 (48) 284407)
Bea ee GT) Lymphnode involvement, n Je
wi = un eye Positive pelvic only 326(61.6) ACT)
cree An ae Posiive para-aortic only 1428 10(19)
ee hen us Posiive pelvic and para-aortic 105(198) 1041196)
Native Hawaian or Other Pac stander 2 (0.4) 1002) NO postive palo or Bora san use) 83(175)
[PD-L1 CPS, n
3 he 20(63) | Planned type of EBRT, n (%)
5 48638 | IMRTovmAr 469(88.7) — 470(885)
Missing 5/09) Non-IMRT and non-VMAT CITO)
ECOG PS 1, n (%) HO 062) 104052 Plamed etal RT dose Ban ea) een
‘Squamous cell carcinoma, n (6) 433(813) 451649 =706y 482(91.1) 485013)
Data culo ate: January , 2023, In each treatment arm, 2 patients (04%) had missing information for race. < Per proocal, a postive mph node's defined as
21,5 em shortest dimension by MRL or CT. ñ
1. Lorusso D etl. Lancet 2024:403:1341-1350 PeerView.com

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23. KEYNOTE-A18: Clinically Meaningful PFS Benefit Was
Shown With Pembrolizumab + CRT vs CRT Alone’?

100 N
| 24-mo rate (95% Cl)
2 | 67.8 (61.8-73.0)
80 À 57.3(51.2-62.9)
70 i Pembro
60
= so | | HR = 0.70 (95% Cl, 0.55-0.89) H Placebo
2 P=.0020 H
a 4 i
30 Patients With Median, mo |
Est 4 Buch |
20 | Pembroarm 217 WR (NR-NR) H
10 | Placebo arm 22 NRINR-NR) |
Median (ange) fotow-up, mo: 17.9 (09:31) i
o
o 3 5 I 2 6 © a a m 30
Time, mo
No, at Risk
Pembro 529 a2 400 331 22 22 71 10 2% 3 o
Placebo 531 463 379306 263 208 189 88 20 0 o
+ Dota cto date: January 9, 2023. "
1.Lorusso D etal Lancet 2024:403:1341-1360. PeerView.com

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24. KEYNOTE-A18: OS With Pembrolizumab + CRT
vs CRT Alone’

100

24-mo rate (95% CI)

70
x ‘| HR = 0.73 (95% Cl, 0.49-1.07)
a)
© 40 Patients With Median, mo
Event, % (95% cl)
Pembro 83 NR (NR-NR)
201 placebo ma NR (NR-NR)

Median (range) folow-up, mo: 17.9 (09-31)

Pembro arm
Placebo arm

87.2 (824-90.8)
80.8 (74.8-85.5)

March 2024 Press Release
Primary endpoint was met with a
statistically significant and clinically
meaningful improvement in OS with
the addition of pembrolizumab
versus concurrent CRT alone?

o 3 6 9 2 8 8 A A A 3 38
No at Risk Time, mo

Pembro — 29 496. 456 405 351 294 223 151 67 10 1 0
Placebo 931 498 449 402 339 278 214 139 62 12 0 0

* Atthis analysis, 103 of the 240 deaths expected at the final analysis hed occurred. Data cutof date: January 9, 2023.
1. Lorusso D etal Lancet 2024:403:1341-1350, 2. ips www businesswre.comhews/Mome/202403 1585580 1/enVerck0sE2980995-KEYTRUDANC2MAE-

pembrolzumab Plus-Chemoradiaherapy-CRT-Significanty-Improved-OverallSunival-0S Versus-CRT-Alone-Í Patents With-Newy-Diagnosed-High-Risk-

Locally Advanced-Cenvical

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25. KEYNOTE-A18/GOG 3047: Efficacy in Patients With
FIGO 2014 Stage III-IVA Cervical Cancer!

+ In an exploratory subgroup analysis for the 462 patients (44%) with
FIGO 2014 Stage IB2-IIB disease, the PFS HR estimate was
0.91 (95% Cl, 0.63-1.31)

+ OS data were not mature at the time of PFS analysis, with 10% deaths
in the overall population

PFS by investigator

Patients with event, (2) 61 (21) 94 (31)
Median, mo (95% Cl) NR (NR-NR) NR (18.8.NR)
12-mo PFS rate (95% CI) 81 (75-85) 70 (64-76)

HR (95% CD) 0.59 (043-082)

Kaplan-Meier Curve for PFS in KEYNOTE-A18
(Patients With FIGO 2014 Stage IIIHVA Cervical Cancer)

Pare + CRT

PFS, %
oeeeesearad

January 2024: FDA approval was granted to pembrolizumab with

chemoradiotherapy for FIGO 2014 stage III-IVA cervical cancer2%

1. Monk BJ etal. Gynecol Oncol. 2024:188:81-82 2 htps war fé
_chemeracotherapy-figo-2014-stagei-iva-cervca-cancer. 3.
Intps:ww.eccessdatafée.gowerugsatida_docslabe/2024/12551451 950 pat.

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.gowrugsiresources information 2ppr0
Keyruda (pemeralizumab) Prescribing Information

ved drugs ida-approves-pembrolizumab-
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26. KEYNOTE-A18 Safety: TRAE Incidence 220% in Either Arm!

Grade

12 34
Pembro arm Ii il

Placebo arm fll D

Incidence, %

ES

WBC Count “Neutrophil Count” Vomiting _ Leukopenia
Decreased "Decreased,

Platelet Count
Decreased

The safety profile for pembrolizumab + chemoradiotherapy was manageable and as expecte«
with no negative impact on patient-reported outcomes with the addition of pembrolizumab

4. Lorusso D eta. Lancet 2024:403:1341-1350. Peer

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27. irAEs From Immune Checkpoint Inhibitors
Can Affect Any Organ System!

a
Ear

Dermatologic Gastrointestinal Endocrine Pulmonary
Rash, pruritus Diarrhea, nausea, Hypothyroidism Pneumonitis
vomiting
Consider Treating Wi
Topical steroids, Steroids, antiemetics, Synthroid Steroids
topical antihistamines antidiarrheals

1. Marins Feta. Nat Rev Glin Oncol. 2019,16:563-560. PeerView.com

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28. Immune-Related Adverse Events
Can Occur at Any Time

Variable Timing of irAEs*

Patient Communication
Is Essential

Pneumonitis

+ Discuss potential onset,
duration, and symptoms
of irAES

Toxicity, grade

+ Patients may be more
likely to adhere to treatment
when they have a full
picture of irAEs

Duration of Treatment, wk

1. Marins F etal Nat Rev Gin Oncol. 2019:16:563-580. PeerView.com

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29. The Controversy of Anti-PD-1 vs Anti-PD-L1

+ Clinically relevant across multiple solid tumors, not just cervical cancer
+ Definitive randomized comparisons lacking

+ Cross trial comparisons inappropriate, but inferential hypotheses can inform
clinical decision-making

+ Adding immunotherapy to CCRT
— Negative in the phase 3 CALLA trial assessing durvalumab
— Positive in the phase 3 KEYNOTE-A18 trial assessing pembrolizumab
- Differing eligibility but also different agents

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30. Adding Immune Checkpoint Inhibitors CCRT in LACC

Durvalumab in CALLA? Pembrolizumab in KEYNOTE-A18?

10 ; ; 100
1200 PFS rate CDA atom BSH;
E o
08 Tom 5731812029
g Eo Pemoro
5 08 a |
2 q © | HR= 0.70 (95% CI, 0.55-0.88) Fin Placebo
2 Placebo+cRT $ 5p y
È É P=.0020 H
304 “o i
3 ES Patents Wits Medan mo |
Event % (95% Cl
& 02 | ay a 8 | roo SANO |
‘owt B 10) Pecevo 3 NR(NRANR) i
4 j à * | Median tow uo. mo (age) 1780331) i
0 3 6 9 1215 18 À 24 2% 0 à 0 3 6 9 2 15 8 À A A %
Time, mo Time, mo
Not Rsk Not Risk
385,369 so 290 210 215 103 M0 4 1 1 0 mn 400 si 282222711008
305 360 SO 262 257 203 149 100 49 14 2 0 EE E 2 0 0
1. Monk BJ et al. Lancet One. 202324 1334-1348. 2. Loruso D et al. Lance. 2024:403:1341-1350. PeerView.com

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31. Key Differences and Similarities Between
CALLA and KEYNOTE-A18?

+ CALLA enrolled lower risk patients

— Approximately 10% positive para-aortic nodes vs. 22% in KEYNOTE-A18
+ Similar progression or death events for primary analysis

— Approximately 227 events in CALLA vs 237 events in KEYNOTE-A18
+ Similar maturity

— Median follow-up of 18.5 months in CALLA vs 17.9 months in KEYNOTE-A18

CALLA studied an anti-PD-L1 Ab (durvalumab) and
KEYNOTE-A18 an an D-1 Ab (pembrolizumab)

Gross il comparisons are not possible, PeerView.com

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32. The Controversy of Anti-PD-1 vs Anti-PD-L113

+ Results of KEYNOTE-826 (bevacizumab cohort) and BEATce (lacked placebo and biomarker subsets) regardless of PD-L1
‘expression

+ 37% of participants in KEYNOTE-826 did not receive bevacizumab at investigator's discretion
- Reduced grade >1 fistula rate to 2.5% in KEYNOTE-826 compared to 11% in GOG 240

KEYNOTE-826 (Bev Cohort! BEATcc

N 389 410

Persistent = 8% =5%

Stage 4B untreated = 20% = 22%

Recurrent =72% =73%

Hazard Ratios

Survival J | i 3

(median months and HR; 95% cl) 37.8 vs. 22.5; 0.61 (0.47-0.80) 32.1 vs. 22.8; 0.68 (0.52-0.88)

dt

Progression or death S E

(median months and HR; 95% Cl) 15.2 vs.10.2; 0.57 (0.45-0.73) 13.7 vs 10.4; 0.62 (0.49-0.78)
1. OakninA et a, Lancet. 2024:403:31-43. 2. Colombo N et al. N Engl J Med. 2021:385-1956-1867. 3. Monk BJ e al. J Clin Oncol. 2023:41:55055611, PeerView.com

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33. Back to Catherine’s Case: Practical Treatment Considerations for
High-Risk, Locally Advanced Cervical Cancer

Patient Case

A 66-year oman presented with
postmenopausal bleeding; her last pap test
was >10 years ago

Physical examination revealed a large
ical mass, and sul
d tumor invasi

quent imaging
he bladder

Clinical workup confirmed invasiv:
cell carcinoma (stage IVA)

amous

Expression revealed
PD-L1 CPS =1

The patient initiated 1L cisplatin/EBRT
followed by brachytherapy +
pembrolizumab

For Discussion

+ Does PD-L1 score matter in treatment
selection for this patient?

+ How can providers effectively discuss the
unique safety considerations to take into
account with checkpoint inhibitor therapy in
this setting?

+ How would these conversations differ for a
patient in the recurrent or metastatic setting?

In the absence of a contraindication, every patient
with cervical cancer at a substantial risk of
recurrence should receive immunotherapy as
soon as possible

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