Table 3 Clinical trials of drugs targeting the CD47-SIRPα signaling pathway to regulate macrophages

CC‑90002

NCT02641002^a

I

28

\

R/R AML and MDS

\

SAE: 82%;

TRAE: 32–46%

³²⁰

Magrolimab

NCT02953782

Ib/II

78

With Cetuximab

Advanced Solid Malignancy and CRC

PFS: KRASwt CRC: 3.6 months

KRASm CRC: 1.9 months

OS: KRASwt CRC: 9.5 months

KRASm CRC: 7.6 months;

SAE^b: 25–60%

TRAE: 5%

³²¹

NCT03558139

I

34

With Avelumab

Checkpoint-Inhibitor-Naive Ovarian Cancer Patients

PFS: 2.0 months

OS: 10.2 months

SAE: 0–66.67%

³²²

Lemzoparlimab (TJC4)

NCT04202003

I/IIa

105

\

R/R AML and MDS

1 patient in primary refractory AML achieved the morphologic leukemia-free state

TRAE: 40%

³²³

Ligufalimab (AK117)

NCT04349969

I

15

With or without Cadonilimab (AK104)

Advanced or Metastatic Solid Tumors or Lymphomas

\

TRAE: 10.5% (5 cases)

³²⁴

NCT04728334

I

49

\

Advanced Solid Tumors or Lymphomas

\

\

³²⁵

BI-765063

NCT04653142

I

17

With BI-754091

Advanced Solid Tumors

\

SAE: 41%;

TRAE: 53%

³²⁶

NCT03990233

I

50

\

Advanced Solid Tumors

In HCC: PR: 0.02%

TRAE: mild to moderate

³²⁷

Anzurstobart (CC-95251)

NCT03783403

I

17

With Rituximab

R/R Non-Hodgkin Lymphoma

ORR: 41%;

TRAE: 29%

³²⁸

BI 770371

NCT05327946

I

36

With or without Ezabenlimab

Advanced Solid Tumors

\

\

³²⁹

CD47/

PD-L1

IBI322

NCT04328831

NCT04912466

Ia/Ib

58

\

Advanced Malignant Tumors

PR: 20%

SD: 35%

74.1%

³³⁰

NCT04795128^b

I

24

\

Anti-PD-(L)1 Treatment-Resistant Classic Hodgkin lymphoma

ORR: 47.8%;

DCR: 91.3%

91.7%

³³¹

HX009

NCT04097769

I

21

\

Advanced Malignancies

PR: 14.2%;

SD: 28.6%

SAE: 4.7%;

TRAE: 47.6%

³³²

CD47/CD20

IMM0306

NCT05805943

I

48

\

R/R CD20-positive B-cell Non-Hodgkin’s Lymphoma

PFS: 10.58 months;

SAE: 16.7%

Grade ≥3 TRAE: 68.8%

³³³

NCT05771883

I

8

With Lenalidomide

R/R CD20-positive B-cell Non-Hodgkin’s Lymphoma

ORR: 71.4%;

DCR: 85.7%

SAE: 12.5% (1/8

Grade ≥3 TRAE: 75.0%

³³⁴

CD47/

CD19

TG-1801

NCT03804996

I

30

With or without Ublituximab

R/R B-cell Lymphoma

Monotherapy: PR: 21.4%

Combination: ORR: 44%; PR: 37.5%

Monotherapy: TRAE: 30.0%

Combination:

TRAE: 31%

³³⁵

NI-1701

NCT04806035^a

Ib

21

With or without Ublituximab

B-cell Lymphoma or Chronic Lymphocytic Leukemia

\

\

²⁹⁶

CD47

/HER2

IMM2902

NCT05805956^a

I/II

105

\

HER2-expressing Advanced Solid Tumors

\

\

³³⁶

NCT05076591^a

I

135

\

HER2-expressing Advanced Solid Tumors

\

\

³³⁷

CD47/

4-IBB

DSP107

NCT04440735

I

23

\

Advanced Solid Tumors

SD: 50%

Grade 1-2 TRAE: 70%

³³⁸

SIRPα-Fc-CD40L

SL-172154

NCT04406623^a

I

27

\

Platinum-Resistant Ovarian Cancer

SD: 22%

Grade ≥3 TRAE: 14%

³³⁹

NCT04502888^a

I

5

\

Squamous Cell Carcinoma of the Head and Neck or Skin

\

\

³⁴⁰

NCT05483933^a

Ib

86

With Mirvetuximab or PLD

Ovarian Cancers

\

\

³⁴¹

SIRPα-Fc lgG1

IMMO1

ChiCTR

1900024904

I

14

\

R/R Lymphoma

SD: 7.1%

SAE: 7.1%

³⁴²

ALX148

NCT03013218

I/II

41

With or without chemotherapy or immunotherapy

Advanced Head and Neck Squamous Cell Carcinoma (HNSCC) or HER2-positive GC

HNSCC: ORR: 38.5%

GC: ORR: 72.2%

HNSCC: 15.4%

GC: 44.4%

³⁰⁷

TTI-621

NCT04996004

I/II

23

With or without Doxorubicin

Unresectable or Metastatic High-grade Leiomyosarcoma

PR: 25.0%

SD: 55%

Monotherapy: Grade ≥3 TRAE: 9.0%

Combination:

Grade ≥3 TRAE: 30.0%

³⁴³

SIRPα-FclgG4

TTI-622

NCT05261490

I/II

10

With Pegylated Liposomal Doxorubicin

Platinum-Resistant Ovarian Cancer

SD: 50%

SAE: 10%

³⁴⁴

NCT03530683

I

42

\

Advanced Hematologic Malignancies (Lymphoma, Leukemia and Multiple Myeloma)

ORR: 33.3%

TRAE: 47%

^345,346