A Phase 1 Study of ALX148: CD47 Blockade in Combination with AntiCancer Antibodies to Bridge Innate and Adaptive Immune Responses
for Advanced Malignancy (#P335)

Nehal Lakhani,1 Patricia LoRusso,2 Laura Q Chow,3 Yung-Jue Bang,4 Justin Gainor,5 Jeeyun
Lee,6 Hyun Chung,7 Keun-Wook Lee,8 Stephen Hodi,9 Philip Fanning,10 Yonggang Zhao,10Feng Jin,10 Hong Wan,10 Jaume Pons,10 Sophia Randolph,10 Wells Messersmith11
1START Midwest, Grand Rapids, MI; 2Yale Cancer Center, New Haven, CT; 3Seattle Cancer Care Alliance,Seattle, WA; 4Seoul National University Hospital, Seoul, Korea; 5Massachusetts General Hospital Cancer
Center, Boston, CA; 6Samsung Medical Center, Seoul, Korea; 7Yonsei Cancer Center, Yonsei University
College of Medicine, Seoul, Korea; 8Seoul National University Bundang Hospital, Seongnam, Korea; 9Dana
Farber Cancer Center, Boston, MA; 10ALX Oncology, Burlingame, CA, USA, and Dublin, Ireland;
11University of Colorado Cancer Center, Aurora, CO.

1

SITC 2018

Disclosures

2• ALX Oncology• InhibRx• Amgen• Incyte• Arqule• Macrogenics• Ascentage• Loxo• Apexian• Livzon Mabpharm• Asana Biosciences• Merck• Formation Biologics• Northern Biologics• Beigene• Pfizer• Constellation Pharma• Regeneron• CytomX• Symphogen• Daiichi Sankyo• TaiRx• Forty Seven, IncSITC 2018

ALX148: A Unique High Affinity SIRPα Fusion Protein• CD47, a marker of self, is upregulated by tumors to evade the immune system• CD47-SIRPα signaling represents a myeloid checkpoint mechanism in cancer• CD47 engages SIRPα and signals the macrophage to ignore the cell on which it is expressed

ALX148 is a Myeloid Checkpoint InhibitorHigh Affinity
CD47 Binding Domains of SIRPαInactive
Fc Domain3

Molecular weight halfof typical antibody
but with antibody-like PK

Kauder, SE. et al. PLoS ONE. 2018 August;13(8): e0201832

1. ALX148 blocks CD47 andenhances macrophage
phagocytosis
2. ALX148 increases the ratio ofinflammatory M1 tumor
associated macrophages(TAMs) to suppressive M2 TAMs
3. ALX148 activates dendritic
cells and enhances crosspriming of T cells

SITC 2018AT148001 Phase 1 Study Design and Combination Demography
Data Cutoff 12Oct2018

Part 1 ALX148 Single Agent – enrollment complete+Pembrolizumab*
n=39+Trastuzumabn=1859 (32-79)

57 (45-71)

F

207M

17110

1171

26

11+Pembrolizumab
n=39+Trastuzumab
n=18Lung

24-

Part 2 ALX148 Combinations – enrollment ongoing

HNSCC

9-

•

ALX148 (10 mg/kg IV QW), pembrolizumab (200 mg IV Q3W),
trastuzumab (8 mg/kg IV followed by 6 mg/kg Q3W)

Gastric/GEJ-

11•

Primary: Safety DLT; Secondary: Response, PK/PD

Breast-2

Colorectal

2-Esophageal-

2

Ovarian2

1

Pancreatic-

1

Peritoneal

1-

Appendiceal

1-

Urothelial-1•

Primary: Safety DLT; Secondary: Response, PK/PD

CohortDose
mg/kg

10.3

QW

21.0

QW33.0

QW4510.0
30.0

QW
QOW

Median Age, yr (range)

ScheduleSex, nECOG PS, n

No MTD reached

Primary Tumor

Dose
Advanced solid tumors (each combo)
Escalation
NSCLC (pembrolizumab); progressed on prior CPI/TPS<50%Dose
HNSCC (pembrolizumab); progressed on prior platinum
Expansion
Gastric/GEJ (trastuzumab); progressed on prior fluoropyrimidine
4*Partial demography for 2 pembrolizumab patients in database.

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ALX148 Generally Well Tolerated in Combination withStandard Regimens of Pembrolizumab and Trastuzumab
Treatment Related Adverse
Events in ≥ 2 Patients
ALX148 + Pembrolizumab (N=39)
Adverse Event

Total n(%)

ALT increased

4 (10)

AST increased

3 (8)Anaemia

2 (5)Fatigue

2 (5)Infusion reaction

2 (5)Myalgia2 (5)Pruritus

2 (5)Alkaline phosphatase
incr

2 (5)

Rash

2 (5)

ALX148+Pembrolizumab (N=39)

Fatigue
5

Total n(%)
3 (16)

ALX148 Exposure/Patient Disposition

GradeAdverse Event

ALX148 +Pembrolizumab(N=39)

ALX148 +Trastuzumab(N=18)

Dose interruptions
due to TRAEs, n42

1

Dose reductions, n2--

1-

Platelet count decr

1

Discontinuation due toTRAE, n1-1#

Hyponatremia

1-

1Discontinuation due toPD, n138Lymphocyte count decr

1-

1

ALX148+Trastuzumab (N=18)

Global Deterioration ofHealth Status, n1-

Grade

Ongoing Treatment, n24

1034Total

AIHA/pancytopenia

-

1*

1

ALT increased

1-

1Anaemia

1#-

Febrile neutropenia

1#

Adverse Event
34TotalThrombocytopenia

1-

1

Neutrophil count decr

1^-

1

WBC count decr1^-1

ALX148+Trastuzumab (N=18)
Adverse Event

Data Cutoff 12Oct2018

Treatment Related Adverse Events ≥Grade 3 in any Patient#^ All reported as one event in patient*Dose Limiting Toxicity

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Preliminary Anti-Cancer Activity Seen Across all ALX148 Combinations andTumor Histologies in Expansion Cohorts
Data Cutoff 25Oct2018

Response SummaryBaseline

Day 4564 yo pt with NSCLC-adenocarcinoma• NSCLC ALX148 + pembrolizumab: 16 evaluable(TPS 10%,CMET/TP53)
patients (progressed on prior CPI and/or TPS<50%)
ALX148 + pembrolizumab
as of data cutoff. Patients experienced a best
• 6 prior therapies; nivolumab refractory;
response of 1PR (↓51%), 5SD (one SD >24 weeks)
CMET inhibitor refractorywith 5 patients continuing on trial.
• Day 45 partial response (↓48%),• HNSCC ALX148 + pembrolizumab: 6 evaluabledisappearance of chest wall lesion;
patients (progressed on prior platinum therapy) as of• Day 100 confirmed PR (↓51%)
data cutoff. Patients experienced a best response of• The patient continues on treatment
1PR (↓47%), 2SD with 3 patients continuing on trial.

71 yo pt with Her2+ gastric canceradenocarcinoma
ALX148 + trastuzumab

Baseline

6SITC 2018

Day 58• Prior therapy: cisplatin/5FU;
oxaliplatin/capecitabine/trastuzumab;
paclitaxel/ramucirumab• Day 58 partial response ↓52%;• The patient continues on treatment• Her2+ Gastric/GEJ ALX148 + trastuzumab:
5 evaluable patients (progressed on priorfluoropyrimidine-containing regimen) as of data
cutoff. Patients experienced a best response of1PR (↓52%), 1SD (↓48% + new CNS lesion) withboth continuing on trial.
70% evaluable continuing patients had only one
response assessment at point of data cutoff.

AT148001: Conclusions
Intended for combination, ALX148 is designed to avoid the dose-limiting toxicities associated withother CD47-targeted approaches in the clinic, while maximizing the efficacy of antibody-based therapies• No MTD was reached with ALX148 in combination. The maximum administered dose of ALX148 is 10 mg/kg QW incombination with standard regimens of pembrolizumab and trastuzumab.
• ALX148 contains an inactive Fc region that eliminates dose-dependent hematologic toxicity.
• ALX148 has antibody-like PK and maintains complete CD47 target occupancy over the dosing interval at ≥ 3 mg/kg QW.
(#P340)• ALX148 demonstrates preliminary anti-cancer response in combination with pembrolizumab and trastuzumab in patients
resistant and refractory to prior checkpoint inhibitors or trastuzumab.

Enrollment into combination expansion cohorts is ongoing (NCT03013218)

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We would like to thank all of the participating patients and their families as well as site research staff.
SITC 2018