A Phase 2 Study of Evorpacept (ALX148) in Combination with Pembrolizumab and Chemotherapy
in Patients with Advanced Head and Neck Squamous Cell Carcinoma (HNSCC); ASPEN-04≥2L HER2 positive GC

High Affinity CD47
Binding Domains of SIRPαPartial Response (PR)
Stable Disease (SD)
Progressive Disease (PD)

PRPR

Patients on Treatment

PR

Optimized,
picomolarbinding affinity

Deceased Patients

PRSD
PR

Patient

Fc domain Christine Ju8, Feng Jin8, Alison Forgie8, Jaume Pons8, Sophia S Randolph8, Athanasios C Tsiatis8, Kevin Harrington9
Ezra Cohen1, Jean-Pascal Machiels2, Sjoukje Oosting3, Bhumsuk Keam4, Beatriz Cirauqui5, Annette M Lim6, Keun-Wook Lee7, Haiying Liu8, Tim Welliver8,mutated toPR

PReliminate Fcγ
PRInactive
1University of California San Diego, San Diego, United States; 2Cliniques Universitaires Saint-Luc, Brussels, Belgium; 3University of Groningen, University
Groningen,
Catala d’Oncologia Badalona, Barcelona, Spain;
binding Netherlands; 4Seoul National University Hospital, Seoul, Korea; 5InstitutPR
Fc DomainMedical Centerreceptor
Partial Response (PR)and minimize
SD
Stable Disease (SD) London, United Kingdom
6Peter MacCallum Cancer Centre, Melbourne, Australia; 7Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; 8ALX
Oncology
Inc.,
SouthSanFrancisco,UnitedStates;
9TheRoyal
Marsden
Hospital/ The Institute of Cancer Research,
associatedSD
Progressive Disease (PD)
toxicity
Patient on Treatment
SDPD

Study Methods
Evorpacept, Pembrolizumab, and Chemotherapy Have
Complementary
Mechanisms of Action
High Affinity CD47
• Pembrolizumab, a T cell checkpoint inhibitor, represents a standard treatment

option for patients with previously
Optimized, untreated recurrent/metastatic (R/M) HNSCC,
both as a monotherapy picomolar
andincombination
withplatinum+5FU.
Throughincreasedbinding affinity
activation of the immune system, the combination of evorpacept + pembrolizumab
Fc domain+ platinum/5FU might havegreater anti-tumor activity in R/M HNSCC than standard
mutated to 2
therapeutic approacheseliminate(FigureFcγ2) .
Inactiveover cetuximab + platinum/5FU.

T cellTCRT cell2enables
antibody-like PK.

1• Molecular weighthalf the size oftypical antibody.

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

Recurrent or
Metastatic HNSCC• ≥18 Years Old• ECOG 0-1• PD-L1-Unselected

2

Activated dendritic cells
cross-present tumor
antigens (including tumorPR
antigens released in SD
response to treatment PRwith chemotherapy) to PR
PR
cytotoxic T cells
PRPatient• Fc domain

SIRPα

3 PD-L1

Pembrolizumab

3• All PD-1
patients will receive pembrolizumab 200 mg IV Q3W

2040

Dendritic cell• Progression-free survival• Overall survival• Safety

Randomized Portion*

Exploratory endpoints will characterize pharmacodynamicproperties.

Sample Size Determination

Q3W(N≈108)• Statistical assumptions for the sample size determination:• 1-sided α = 2.5% and 80% power for 12-month OS rate.
• Rule out a 12-month OS rate of 53%2, assuming a 12-month

Q3W(N≈54)

OS rate of 66.3% for the Evorpacept + Pembrolizumab +Chemotherapy arm.
60

80

Eligibility Criteria

50• Prior systemic therapy for the treatment of locoregionallyadvanced disease is permitted if it was completed more than
6 60
months prior to enrollment.

Pembrolizumab 200 mg +Study Weeks
Chemotherapy• Measurable disease (RECIST v1.1).
Q3W(N≈54)

6080• ECOG performance status ≤1.
60
40• Testing strategy: Fixed sequence procedure will be used

Key Exclusion Criteria• HNSCC suitable for local therapy.

40

References

200–-20• Progressive disease within 6 months of completion of -40
systemic therapy for the treatment of locoregionallyadvanced HNSCC.

40
200-20-40-60

48

72-80

050

100

150200250

Time from Initiation of Treatment (days)

300

Partial Response (PR)
Stable Disease (SD)
Progressive Disease (PD)
Patient on Treatment

ALX148 10 mg/kg + Pembrolizumab (N=12)
ALX148 10 mg/kg + Trastuzumab (N=10)
ALX148 10 mg/kg + Trastuzumab/Pembrolizumab + Chemo (N=6)
ALX148 15 mg/kg + Trastuzumab + Chemo (N=10)24-60

Complete Response (CR)100
agent or with an agent directed to anotherstimulatory or
50
co-inhibitory T cell receptor (e.g., CTLA-4, CD137, OX40).

0-40

2. Burtness B, Rischin D, Greil R, et al. Pembrolizumab Alone or With Chemotherapy
for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma inKEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined
Positive Score. J Clin Oncol. 2022 Jul 20;40(21):2321-2332.

• Prior treatment with an anti-PD-1 or anti-PD-L1, or anti-PD-L2

1-20

400
1. Lee
KW, ChungH, Kim50
TM, etCPS
al. 498 Evorpacept (ALX148), a CD47 myeloid
checkpoint inhibitor, in patients with head and neck squamous cell carcinoma
Complete
Response(HNSCC) and with gastric/gastroesophageal
cancer(GC); ASPEN-01. Journal for
ResponseImmunoTherapy of Cancer 2021;9:doi: Partial
10.1136/jitc-2021-SITC2021.498.

500

50

Progressive Disease• Nasopharyngeal carcinoma (NPC).

1020for the testing of co-primary endpoints.

• Prior treatment with any anti-CD47 or anti-SIRP
αagent.
1000• Adequate liver, renal, and bone marrow function.
• Age ≥18 years.

4060

Partial Response (PR)
Stable Disease (SD)
Progressive Disease (PD)
Patients on Treatment
Deceased Patients

Patient on Treatment30• Duration of response

Pembrolizumab 200 mg +Chemotherapy

who have not received prior systemic therapy for their
Partial Response (PR)
Q3W
Stable Disease (SD) advanced disease.
(N≈108)Progressive Disease (PD)SD
Randomized
PD
2:1

60

Randomized
2:1

Chemotherapy

Study Endpoints
Study Weeks

Key Secondary Endpoints

Evorpacept 45 mg/kg +Pembrolizumab 200 mg +Chemotherapy

Key Inclusion CriteriaSD

10

Study Weeks

50

Pembrolizumab
binds toPR
PD-1, relieving
PD-1/PD-L1- Portion*
PR Randomized
mediated inhibition ofactivated T cells leading
Evorpacept
45 mg/kg +to enhanced
T cellcytotoxic
activity against
Pembrolizumab
200 mg +• Patients with metastatic or unresectable, recurrent HNSCC
the cancer cellSD040* The study includes a safety lead-in for Evorpacept + Pembrolizumab +Chemotherapy (N≥6) prior to initiation of randomized portion.

PRPR

We would like to thank all the participating patients and their families as well as site research staff.
This trial is being conducted in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Cancer cell
Cancer cellContactCancer
email: cell
info@alxoncology.com
Tumorantigen
Trial Registration: ClinicalTrials.gov identifier, NCT04675333
CD47
Presented at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting; November 8-12, 2022. Abstract #676.
Evorpacept

Tumorantigen

T cell≥2L HER2 positive GC

Acknowledgments

1PD-1

230

• ≥18 Years Old• ECOG 0-1• PD-L1-Unselected

Pembrolizumab

SIRPα2060

Deceased Patients

Patient on Treatment

1050• Objective response rate

evorpacept
45
mg/kg
IVQ3W.
Pembrolizumab
Patients on Treatment% Change in Baseline
Measurable LesionsFigure 1. Evorpacept Selectively and Potently
Binds CD47 to Block Interaction with SIRPα

Stable Disease (SD)
Progressive Disease (PD)SD

Recurrent or
Metastatic HNSCC

3 PD-L1

1Dendritic cell

Evorpacept

Partial Response (PR)ALX148 Concentration (µg/mL)of evorpacept in combination with pembrolizumab andchemotherapy in previously untreated patients with
PD-L1-unselected R/M HNSCC.

Cancer cell

Tumorantigen

Dendritic cell

CD47

• The ASPEN-04 study will assess the efficacy and safety

InactiveFc Domain

Cancer cell

Cancer cell

Dendritic cell+ platinum/5FU has been evaluated in the Phase 1
ASPEN-01 study in previously untreated, PD-L11
unselected recurrent/metastatic (R/M) HNSCC patients ,demonstrating initial clinical activity and tolerability.

Fc domain
mutated toeliminate Fcγ
receptor binding
and minimize
associatedtoxicity040• 12-month overall survival rate

• Patients in the evorpacept treatment arm will receive

PDFigure 2. Evorpacept, Pembrolizumab, and Chemotherapy Combine
to Activate Both the Innate and Adaptive Immune Responses• The combination of evorpacept + pembrolizumab

3 PD-L1

will be used as minimization factors across both arms.

Progressive Disease (PD)2
Figure 3. ASPEN-04 Trial Design

30

Co-Primary Endpoints• Geography, CPS, HPV (p16) status, tobacco habits and ECOG

SD% Change in Baseline
Measurable Lesions

with an inactive Fc region (Figure 1) designed to enhance
standard anticancer therapeutics and not exacerbate
their toxicities.

Cancer cell

Dendritic cell

receptor bindingand minimize• This combination approach
could be especially beneficial to R/M HNSCC patientsassociatedwith low PD-L1 expression,
where anti-PD-(L)1 therapy does not provide benefit
toxicity
Fc Domain• Evorpacept is a high affinity CD47-blocking fusion protein

220(for a maximum of 35 cycles), 5FU (1000 mg/m2/day
PRcontinuous infusion Days 1, 2, 3, 4 Q3W x 6 cycles) andPR• ASPEN-04 will randomize approximately 162 patients
toTCR
TumoreitherT cell
carboplatin (AUC 5 mg/ml/min as a 60 min infusionPR
receive evorpacept + pembrolizumab+ chemotherapy orantigen
2PRas a 60 minDay1Q3Wx6cycles)
orcisplatin(100mg/mT cellT cellPRpembrolizumab+ chemotherapy
using a 2:1 allocation. Partial Response (PR)infusion
Day1Q3Wx6cycles).
SD
Stable Disease (SD)Patientimmune cells and can be upregulated by cancer cells
to evade immune responses.

Optimized,picomolarbinding affinity

1

Binding Domains of SIRPα• CD47, a marker of self, interacts with SIRPα on myeloid

High Affinity CD47
Binding Domains of SIRPα

open-label, randomized Phase
CD47 2 global study of evorpacept≥2L HER2
positive
GCcarboplatin+ pembrolizumab + chemotherapy(5FU+ eitheror cisplatin) or pembrolizumab + chemotherapy in PRpatients
Evorpacept
PRwith PD-L1-unselected metastatic
SIRPα or unresectable
PR
recurrent HNSCC who have
PR not yet been treated fortheir advanced disease. SD
Dendritic cell

antigens and subsequent activation of both the innate
and adaptive immune systems. Myeloid checkpoint
inhibitors have been shown to help potentiate innate
immune cell activity including antigen presentation
after neoantigen release induced by chemotherapy.

Tumorantigen• ASPEN-04 (Figure 3) is an ongoing, non-comparative,lineons• Anticancer immunity relies on the release of tumor

Cancer cell

Cancer cell

10% Change in Baseline
Measurable Lesions

Background096120

144168