≥2L HER2 positive GC

High Affinity CD47
Binding Domains of SIRPαA Phase 2 Study of Evorpacept (ALX148) in Combination with Pembrolizumab in Patientswith Advanced Head and Neck Squamous Cell Carcinoma (HNSCC); ASPEN-03

Partial Response (PR)
Stable Disease (SD)
Progressive Disease (PD)

PR

PR

PR

Optimized, picomolarbinding affinity

Deceased Patients

PR

SD

PR

Patient

Fc domain mutated toeliminate Fcγ receptor
binding and minimize
associated toxicity

Inactive
Fc Domain

Patients on Treatment

PR

PR

PR

PR

Kevin Harrington1, Bhumsuk Keam2, Jean-Pascal Machiels3, Sjoukje Oosting4, Brett GM Hughes5, Jong Chul Park6, Haiying Liu7, Tim Welliver7, Christine Ju7, Feng Jin7, Alison Forgie7, Jaume Pons7, Sophia S Randolph7, Athanasios C Tsiatis7, Ezra Cohen8
Partial Response (PR)SD

Stable Disease (SD)SD

Progressive Disease (PD)SD

Patient on Treatment

1The Royal Marsden Hospital / The Institute of Cancer Research, London, United Kingdom; 2Seoul National University Hospital, Seoul, Korea; 3Cliniques Universitaires Saint-Luc, Brussels, Belgium; 4University of Groningen, University Medical Center Groningen, Netherlands;
5Royal Brisbane and Women’s Hospital, and University of Queensland, Brisbane, Australia; 6Massachusetts General Hospital Cancer Center, Boston, United States; 7ALX Oncology Inc., South San Francisco, United States; 8University of California San Diego, San Diego, United States
PD0Study Methods
CD47

Evorpacept and Pembrolizumab Have Complementary
Mechanismsof Action
High Affinity CD47

• Evorpacept is a high affinity CD47-blocking fusion protein• Pembrolizumab as a single agent is a standard treatment option for patients withFc domain
topreviously untreated recurrentor mutatedmetastatic(R/M) HNSCC with PD-L1-positiveeliminate Fcγ receptor2
Inactive.
(combinedpositivescore
[CPS]
≥1)
tumorsbinding and minimize
Fc Domain
associated toxicity• The combination of evorpacept with pembrolizumab has the potential to augment

CD47

T cell≥2L HER2 positive GCT cell

PRPRPR

Evorpacept binds to CD47
expressed by cancer cells
to block the CD47-SIRPα
myeloid checkpoint
leading to activation ofdendritic cells andenhanced phagocytosis

2

Activated dendritic cells
cross-present tumor
antigens to cytotoxic
T cellsSDPD

103ritic cell

ritic cell20

CD47 TO (%)

CD47 TO (%)

0200

050

ALX + Tras + Chemo
Gatric ALX(10)N=3Patientson Treatment
Deceased Patients

ALX + Tras + Chemo
Gatric ALX(15) N=10

ALX + Pembro + Chemo
HNSCC ALX(10) N=3•
Measurable
disease(RECISTv1.1).
CD4120Pembrolizumab
200mg
Pembrolizumab
200mg•
Adequate
renal, liver and bone marrow function.
10020Time (day)CD47 TO (%)

20than 6 months prior to enrollment.

40

100

150

40

Randomized Portion*

60

50100Q3W(N≈59)

60

100Time (day)

150150200

ALX + Pembro + Chemo
HNSCC ALX(15) N=2

recurrent HNSCC who have not received
prior systemic
Q3W
304050 mg
60
Pembrolizumab
200
therapyfor
theiradvanceddisease.
Study Weeks(N≈118)
Q3W• Prior systemic therapy for treatment of locoregionally(N≈118)advanced disease is permitted if it was completed more

80

050

Partial Response (PR)Time (day)Stable Disease (SD)

Pembrolizumab 200 mg

80

Key Inclusion Criteria

100

0100

20

Evorpacept 45 mg/kg +Pembrolizumab 200 mg

Randomized
CD4
2:1

120

40060

Q3W(N≈118)

Pembrolizumab binds toPD-1, relieving PD-1/PD-L1mediated inhibition ofPartial Response (PR)
activated T cells
leading
Randomized
Portion*Stable Disease (SD)to enhanced T cell
Progressive Disease (PD)
Evorpacept
45mg/kg+
Patient on Treatment
cytotoxic activity• Patients with PD-L1 positive
metastatic/unresectable,
Pembrolizumab
200mg
against cancercells
Evorpacept
45 mg/kg +RBC

1206050200

Q3W(N≈59)

806040• Age ≥18 years.
• ECOG performance status ≤1.

200050120

CD4100Co-Primary Endpoints
8060100

Time (day)

150200Q3W(N≈59)• Overall survival
Evorpacept• Safety 45 mg/kg +Pembrolizumab 200 mg

Q3W
Exploratory endpoints will characterize pharmacodynamic(N≈118)properties.

Randomized Portion*Sample Size Determination

Pembrolizumab 200 mg

Q3W• Statistical assumptions for the sample size determination:(N≈59)• 1-sided α = 2.5% and 80% power for 12-month OS rate.
• Rule out 12-month OS rate of 51%3, assuming a 12-month OS
rate of 63.7% for the Evorpacept + Pembrolizumab arm.

• Testing strategy: Fixed sequence procedure will be used for

Eligibility Criteria

Randomized2:1Cancer cellContact email: Evorpacept
info@alxoncology.com
Pembrolizumab
Trial Registration: ClinicalTrials.gov
identifier, NCT04675294
SIRPαPresented at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting;
November
8-12,
2022.
Abstract
#678.
PD-1

PR

SD

Recurrent or
Metastatic HNSCC

3PR

SD

0

Tumor
antigen

PRStudy Weeks

40* The study includes Progressivea safetyDiseaselead-infor Evorpacept+ Pembrolizumab (N≥6) prior to initiation of randomized portion.
(PD)

PRPR800PR

Patient11

ritic cellTumor
antigenT cell• ≥18 Years Old• ECOG 0-1
CD47
We would like to thank all the participating patients, their families and site research staff.
•PD-L1CPS≥1PD-L1
This trial is being conducted in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

TCR

100

PD-1

TCR

30

RBCYears Old• ≥18• ECOG 0-1• PD-L1 CPS ≥1120SD• Fc domain enables antibody-like PK.
• Molecular weight half the size of typical antibody.

23 PD-L1

SIRPα20Recurrent or
Metastatic HNSCC

Pembrolizumab210Cancer cell

Tumorantigen

1
Dendritic cell

Evorpacept

Optimized, picomolarbinding affinity

Cancer cell

Cancer cell

Cancer cellHigh Affinity CD47
Binding Domains of SIRPα

Cancer cell
Acknowledgments

0Figure 2. The Combination of Evorpacept and Pembrolizumab Can
Bridge the Innate and Adaptive Immune Responses

Figure 1. Evorpacept Selectively and PotentlyBinds CD47 to Block Interaction with SIRPαInactive
Fc Domain

Randomized Portion*

Patient on Treatment

PDof evorpacept in combination with pembrolizumabin previously untreated patients with metastatic or
unresectable, recurrent PD-L1 positive HNSCC.

Fc domain mutated toeliminate Fcγ receptor
binding and minimize
associated toxicity

Progressive Disease (PD)SD

CD47 TO (%)• The ASPEN-03 study will assess the efficacy and safety

Stable Disease (SD)SD
Figure 3. ASPEN-03
Trial Design

Dendritic cellshown preliminary activity and acceptable tolerability innd
patients with previously untreated and ≥2 line advanced
HNSCC in the Phase 1 ASPEN-01 study1.

SD

both adaptive and innate anti-tumor immune responses (Figure 2).

Dendritic cell

• The combination of evorpacept + pembrolizumab has

60

Patientand pembrolizumab has demonstrated
anti-tumor
efficacy
through
activationofOptimized, picomolar
tumor-infiltrating lymphocytes.
binding affinity

with an inactive Fc region (Figure 1) designed to enhance
standard anticancer therapeutics without exacerbating
their toxicities.

80

50

Study Endpoints

100• Geography,CPS, HPV (p16) status, tobacco habits andPembrolizumab
602Dendritic cell

• Pembrolizumab inhibits PD-1/PD-L1 signaling, which is a T cell immune checkpoint,

Study Weeks

40SIRPα
open-label, randomized Phase
2 global study of
ECOG will be used as minimization factors across
4040HER2 positive GC alone inevorpacept + pembrolizumab≥2Lor pembrolizumab
botharms.
PD-120• 12-month 20overall survival rate
Partial Response (PR)
Stable Disease (SD)00patients with metastatic or unresectable recurrent,PRPD-L1Progressive
Disease(PD)050100150200
050
100150200•
Patients
intheevorpacept+
pembrolizumab
treatment
PR• Objective response rate
Patients on Treatment
positive (CPS≥1) HNSCC who have not yet beenTCR
treatedTime (day)Time (day)DeceasedPatients evorpacept 45 mg/kg IV Q3W.
T cellPRarm will
receiveTumor
ALX + Tras + Chemo
ALX + Tras + Chemo
ALX + Pembro + Chemo
ALX + Pembro + Chemo
for their advanced disease.
antigen
PR
Gatric ALX(10) N=3
Gatric ALX(15) N=10
HNSCC ALX(10) N=3
HNSCC ALX(15) N=2
T cellSD•
All patients will receive pembrolizumab 200 mg IV
T cellKey
SecondaryEndpoints• ASPEN-03 will randomize approximately
177 patients toPR
Q3W (for a maximum of 35 cycles).
PR
receive evorpacept + pembrolizumab or pembrolizumab
PR•
Duration of response
alone using a 2:1 allocation
after an initial safety lead-in.
PRPR• Progression-free survival
Partial Response (PR)Binding Domains of SIRPα

myeloid immune cells, inhibiting their function. CD47 isupregulated by tumors to evade immune responses andits expression is associated with poor prognosis.

120RBC30

Dendritic cell

• CD47 is a marker of self that interacts with SIRPα on3 PD-L1

Dendritic cellroles in anticancer immunity.

Evorpacept• ASPEN-03 (Figure3) is an ongoing, non-comparative,

CD47 TO (%)• The innate and adaptive immune responses play key

Cancer cell

Tumorantigen

120

CD47 TO (%)

Background

Cancer cell

Cancer cell10

the testing of co-primary endpoints.

Key Exclusion Criteria• HNSCC amenable to local therapy.
• Progressive disease within 6 months of completion ofsystemic therapy for the treatment of locoregionallyadvanced HNSCC.

• Nasopharyngeal carcinoma (NPC).
• Prior treatment with any anti-CD47 or anti-SIRPα agent.
• Prior treatment with an anti-PD-1 or anti-PD-L1, oranti-PD-L2 agent or with an agent directed to anotherstimulatory or co-inhibitory T cell receptor (e.g., CTLA-4,CD137, OX40).

References
1. Lakhani NJ, Chow LQM, Gainor JF, LoRusso P, Lee KW, Chung HC, Lee J, Bang YJ,
Hodi FS, Kim WS, Santana-Davila R, Fanning P, Squifflet P, Jin F, Kuo TC, Wan HI,Pons J, Randolph SS, Messersmith WA. Evorpacept alone and in combination
with pembrolizumab or trastuzumab in patients with advanced solid tumours(ASPEN-01): a first-in-human, open-label, multicentre, phase 1 dose-escalationand dose-expansion study. Lancet Oncol. 2021 Dec;22(12):1740-1751.
2. Burtness B, Rischin D, Greil R, et al. Pembrolizumab Alone or With Chemotherapy
for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in
KEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined
Positive Score. J Clin Oncol. 2022 Jul 20;40(21):2321-2332.
3. Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab Alone or WithChemotherapy Versus Cetuximab With Chemotherapy for Recurrent or
Metastatic Squamous Cell Carcinoma Of The Head And Neck (Keynote-048):
A Randomised, Open-Label, Phase 3 Study. The Lancet. 2019 Nov 23; 394(10212): 1915-1928.