ALX148, a CD47 Blocker, in Combination with Rituximab in Patients with Relapsed/Refractory (R/R)
Non-Hodgkin Lymphoma
Tae Min Kim1, Nehal Lakhani2, Justin Gainor3, Manali Kamdar4, Philip Fanning5, Pierre Squifflet6, Feng Jin5, Hong Wan5, Jaume Pons5, Sophia S Randolph5, and Won Seog Kim7.
1

Seoul National University Hospital, Seoul, Republic of Korea; 2START Midwest, Grand Rapids, MI, USA; 3Massachusetts General Hospital Cancer Center, Boston, MA, USA; 4University of Colorado Cancer Center, Aurora, CO, USA; 5ALX Oncology, Burlingame, CA, USA; 6International Drug Development Institute,
Brussels, Belgium; 7Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background

Treatment Related Adverse Events

Endpoints and Assessments• CD47-SIRPα signaling is a myeloid checkpoint mechanism that signals
the macrophage to ignore the cell on which CD47 is expressed.1• Tumors upregulate CD47 to evade the immune response, and highexpression of CD47 mRNA in DLBCL is reported to correlate with a worseOS, while CD47 blockade in addition to rituximab augments rituximabmediated phagocytosis.2,3• ALX148 is an engineered fusion protein comprised of a high affinity CD47
blocker linked to an inactive human immunoglobulin Fc region (Figure 1).
It blocks the CD47-SIRPα interaction enhancing anti-tumor immunity.3• AT148001 is a first-in-human Phase 1 study, evaluating ALX148
administered as a single agent (Part 1) and in combination withestablished anticancer antibodies (Part 2) including in combination
with rituximab in patients with relapsed or refractory non Hodgkin
lymphoma (NHL).

Figure 1. ALX148 Potently and Selectively Binds CD47 to BlockSIRPα Interaction• Fc domain enables
antibody-like PK.
• Molecular weight half thesize of typical antibody.

• Primary endpoint: First cycle ALX148 dose limiting toxicity (DLT) in
combination with rituximab.
• Additional assessments include:• Characterization of adverse events using NCI CTCAE v 4.03.
• Investigator-assessed objective response every 8 weeks using Lugano Working
Group 2014 response criteria in NHL.
• Pharmacokinetic parameters of ALX148, and CD47 target occupancy.

• Here we report preliminary results from the fully enrolled ALX148 plus
rituximab NHL combination cohort as of April 1, 2020.

Results

Figure 4. ALX148 + Rituximab Clinical Activity in Patients with
Non-Hodgkin Lymphoma (N=33)

Numbers in box represent the number of subjects for each responder category.

Table 7. PK Model Predicted ALX148 Steady-state PK Parameters

Table 4. ALX148 + Rituximab (N=33)
Adverse Event

Total n (%)≥Grade 3 n (%)

Rash

6 (18%)–

Fatigue

3 (9%)–

Nausea2 (6%)–

Neutrophil Count Decreased

2 (6%)

2 (6%)

Anemia2 (6%)

1 (3%)• ALX148 in combination with rituximab has been administered to
33 patients with advanced non-Hodgkin lymphoma (Table 2).

Figure 3. Exposure-Safety Relationships• Across the exposure range evaluated (10 mg/kg QW - 15 mg/kg QW),
increased ALX148 exposure was observed in subjects with a best
response of CR and PR compared to subjects with a best responseof SD and PD.

• Enrollment into both the ALX148 10 mg/kg QW and ALX148 15 mg/kg
QW combination cohorts is complete.
• The majority of patients enrolled were male (70%), Asian (82%) and had
an ECOG PS score of 1 (70%).

ALX148 Clinical Pharmacokinetics andPharmacodynamics

Table 2. Baseline Characteristics
ALX148 10 mg/kg
QW + Rituximab(N=22)

ALX148 15 mg/kg
QW + Rituximab(N=11)

5

3

Marginal Zone

2

1

DLBCL

11

6

Mantle Cell4

1

66 (32-80)

64 (53-78)

M

17

6

F

5

5

Response

Asian

18

9

White

4

2

• Clinical activity of ALX148 in combination with rituximab in responseevaluable patients is summarized below and in Table 5.

0

7

2

1

15

8

Figure 5. Duration of Treatment in Patients with NHL (ALX148
10 mg/kg QW)Primary Disease, nFigure 2. ALX148 Bridges Innate and Adaptive Immunity2

Figure 10. PK Model Predicted ALX148 ConcentrationTime Profiles

Notes: Data cut off April 1, 2020. Events occurring in ≥2 patients.

Patient Baseline Characteristics

Follicular

Figure 7. Exposure-Response Relationships

Figure 8. ALX148 Concentration-Time Profiles Following First IV
Infusion at Cycle 1 Day 1 as Single Agent or in Combination
with Rituximab

Years (range)

Race, nECOG PS, n

Methods

Table 3. Patient Drug Exposure and Disposition
ALX148 + Rituximab

AT148001 Study Design• Part 1 (single agent): No MTD reached, maximum administered dose
30 mg/kg QOW4.
• Part 2 (combination): ALX148 (administered 10 mg/kg or 15 mg/kg QW)
combined with standard regimens of rituximab (administered 375 mg/m2
QW x 4 followed by once monthly x 8).

Table 1. ALX148 Combination Relapsed/refractory NHL
Tumor Cohorts

ALX148 10 mg/kg(N=22)

ALX148 15 mg/kg(N=11)

00

Discontinuation Due to TRAE

1^0

Discontinuation Due to PD

124

Discontinuation Due to Death

2*0

Discontinuation Due to Other

1

1

Ongoing Treatment

66

Dose Reductions, n

Numbers in box represent the number of subjects for each AE category.

Notes: ^Discontinuation due to rituximab infusion reaction; *Death due to disease progression.

Combination Safety
Confirmation

Combination Dose
Expansion

ALX148 (10 mg/kg QW) +rituximab

ALX148 (10 mg/kg QW) +rituximab

ALX148 (15 mg/kg QW) +rituximab

Study Population
Key Inclusion Criteria• Patients age ≥18 years with B cell non-Hodgkin lymphoma for which no
curative therapy is available, or that are relapsed or refractory to standard
approved therapies.
• Adequate organ function and hemoglobin ≥8 g/dL; absolute neutrophil
count ≥1,000/mm3, and platelets ≥50,000/mm3.
• No prior treatment with any anti-CD47 or anti-SIRPα agent.

• No patient required a dose reduction, and the most common reason for
discontinuation was disease progression.

Safety• ALX148 in combination with rituximab was well tolerated, and mosttreatment related adverse events (TRAEs) were of low grade andfrequency.
• Twenty-six (78.8%) patients experienced any adverse event. Fifteen(45.5%) patients experienced any TRAE.
• The most common TRAE of ALX148 in combination with rituximab was
Grade 1-2 rash (18%). TRAEs ≥Grade 3 severity were of low frequency(Table 4).
• No ALX148 dose limiting toxicities were reported, the maximum
administered dose was 15 mg/kg QW.
• No treatment related serious adverse events were reported.
• There were 2 deaths on study, both due to disease progression.

• No significant exposure-cytopenia relationship was observed across the
ALX148 exposure range evaluated (10 mg/kg QW - 15 mg/kg QW).

• 3 CR (Mantle Cell, Follicular, Marginal Zone)• 6 PR (2 DLBCL, 2 Mantle Cell, 2 Follicular)• 6 SD (2 DLBCL, 1 Mantle Cell, 2 Follicular, 1 Marginal Zone)

Table 6. ALX148 PK Parameters Following IV Infusion at Cycle 1
Day 1 as as Single Agent or in Combination with Rituximab• ALX148 15 mg/kg + rituximab (N=11)• 2 CR (2 Follicular)• 4 PR (1 Marginal Zone, 2 DLBCL, 1 Mantle Cell)• 1 SD (Follicular)

Population
ALX148 DoseNHL
(10 mg/kg ALL)

N

ORR
(95% CI)MedianDOR(95% CI)MedianPFS(95% CI)Median OS(95% CI)

40.9%(23.3; 61.3)

NC

7.4(1.9; 13.2)

NC

11.3
(10.2; 15.2)

15

33.3%
(15.2; 58.3)

5.6(1.8; NC)

2.5
(1.0; 7.4)

8.9
(2.5 ; NC)

10.4(9.5; 15.2)

NHL (10 mg/kg
indolent)

7

57.1%(25.1; 84.2)

NC

NC

NC

11.3
(7.8; 20.4)

NHL(15 mg/kg ALL)

11

54.6%
(28.0; 78.7)

NC

NC

NC

5.1
(4.0; 5.6)

NHL (15 mg/kg
aggressive)

7

42.9%
(15.8; 75.0)NC

1.9(1.1; NC)NC

4.7
(4.0; 5.4)

NHL (15 mg/kg
indolent)

475%(30.1; 95.4)

NC

NC

NC

5.9
(3.5; 7.4)

NHL (10 mg/kg
aggressive)

Figure 6. Duration of Treatment in Patients with NHL (ALX148
15 mg/kg QW)*MedianFollow-Up(95% CI)

22

Notes: Data Cutoff April 1, 2020; Aggressive: Relapse/refractory Diffuse Large B Cell Lymphoma and Mantle
Cell Lymphoma; Indolent: Follicular Lymphoma and Marginal Zone Lymphoma; ORR objective response rate(complete + partial response rate); mDOR median duration of response (months); mPFS median progression
free survival (months); mFollow-up median follow-up (months); NC could not be calculated.

Cmax (µg/mL)

T1/2 (Day)13,500706

30

30 mg/kg QoW

13,500964

31

60 mg/kg Q4W

13,6001,48031Conclusions• ALX148 in combination with standard regimens of rituximab is welltolerated with a favorable hematologic safety profile and no
maximum tolerated dose reached. The maximum administereddose is 15 mg/kg QW (molar equivalent to 30 mg/kg QW of an
antibody) with no exposure dependent anemia, thrombocytopenia
or neutropenia observed across the exposure range evaluated.

• ALX148 10 mg/kg + rituximab (N=22)

Table 5. ALX148 + Rituximab Combination Clinical Activity in ResponseEvaluable Patients

AUC (µg*Day/mL)

15 mg/kg QWIntended for combination with anti-cancer therapeutics,
ALX148 maximizes the innate and adaptive immune
response to cancer while avoiding the dose-limiting
hematologic toxicities associated with other CD47-targeted
approaches in the clinic.

Median Age
Sex, nDosing Regimen

Parameters

ALX148Single Agent(30 mg/kg QoW)
N=12

ALX148with Rituximab(10 mg/kg QW)
N=10

ALX148with Rituximab(15 mg/kg QW)
N=4Cmax (µg/mL)

701 ± 169175 ± 36.2

243 ± 40.8

AUCinf (µg*h/mL)

101,000 ± 31,900

13,300 ± 2,300

25,100 ± 5,970

CL (mL/h/kg)

0.326 ± 0. 108

0.771 ± 0.126

0.622 ± 0.146

Vss (mL/kg)

80.9 ± 19.9

86.0 ± 19.9

91.8 ± 15.5

• ALX148 demonstrates linear PK at 10 mg/kg and 15 mg/kg QW
with near complete peripheral CD47 target occupancy in
combination with rituximab at both dose levels. Population PK
models predict linear PK up to 60 mg/kg once monthly.
• ALX148 demonstrates emerging anti-cancer activity with durable
responses in combination with rituximab in patients withrelapsed/refractory NHL whose tumors have progressed on prior
CD20 targeted therapies that compares favorably to historiccontrols.
• Preliminary data suggests ALX148 is well tolerated and thathigher exposure of ALX148 is observed in responders vs nonresponders.
Patients in all cohorts continue to be followed (NCT03013218).

Mean +/- SD, standard derivation

Figure 9. Near Complete CD47 Target Occupancy by ALX148

References
1. Weiskopf, K., Eur J Cancer. 2017 May;76:100-109.
2. Bouwstra, R. et al., Cancer Immuno Research. 2019 Oct;7(10):1663-1671.
3. Kauder, S.E. et al., PLoS ONE. 2018 August;13(8): e0201832.
4. Lakhani N. et al, #P335, SITC 2018.
5. Chow et al., #3056, ASCO 2020.

Acknowledgments*One patient with clinical progression Study Day 8 as best response not shown.

• We would like to thank all of the participating patients and their families aswell as site research staff.
• Presented at the European Hematology Association (EHA) Annual
Meeting, June 12, 2020. Abstract #EP1247.
• Contact email: info@alxoncology.com