Table 2 Immunoregulatory anti-cancer bispecific and multi-specific antibodies

From: Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities

Basic information

Representative trial

Agent

Manufacturer

Components

Highest developmental phase

Phase

Cancer type

Therapeutic combination

Study

Identifier

Status

Component 1

Component 2

Component 3

T Cell Engagers

  

CD3 × TAA

Blinatumomab (AMG-103, MEDI538)

Amgen

anti-CD3

anti-CD19

 

FDA approved

II

B-precursor ALL

–

BLAST

NCT01207388

Completed

Teclistamab (JNJ-64007957)

Janssen, Genmab

anti-CD3

anti-BCMA

 

FDA approved, EMA approved

I

MM

–

MajesTEC-1

NCT03145181

Recruiting

Mosunetuzumab (RG7828, RO7030816)

Genentech, Roche

anti-CD3

anti-CD20

 

FDA approved, EMA approved

I/II

FL, NHL, CLL

anti-PD-L1 (Atezolizumab)

 

NCT02500407

Recruiting

APVO436

Aptevo Therapeutics

anti-CD3

anti-CD123 (IL-3Rα)

 

I

I

AML, MDS

–

 

NCT03647800

Recruiting

GB261

Genor Biopharma

anti-CD3

anti-CD20

 

I/II

I/II

CLL, B-Cell NHL

–

 

NCT04923048

Recruiting

Epcoritamab (GEN3013)

AbbVie, Genmab

anti-CD3

anti-CD20

 

III

III

DLBCL

chemotherapy

EPCORE DLBCL-1

NCT04628494

Recruiting

Glofitamab (RG6026, RO 7082859)

Roche, Genentech, Chugai Pharmaceutical

anti-CD3

anti-CD20

 

III

III

DLBCL

anti-CD20 (Obinutuzumab), anti-IL-6 (Tocilizumab), chemotherapy

 

NCT04408638

Recruiting

Plamotamab (XmAb13676)

Xencor, Janssen, Novartis

anti-CD3

anti-CD20

 

II

II

DLBCL

anti-CD19 (Tafasitamab)

 

NCT05328102

Recruiting

Odronextamab (REGN-1979)

Regeneron

anti-CD3

anti-CD20

 

II

II

B-Cell NHL

–

ELM-2

NCT03888105

Recruiting

Runimotamab (RG6194, RO-7227780)

Genentech

anti-CD3

anti-HER2

 

I

I

Solid Tumors

anti-HER2 (Trastuzumab), anti-IL-6 (Tocilizumab)

 

NCT03448042

Recruiting

AMX 818

Amunix, Sanofi

anti-CD3

anti-HER2

 

I

I

HER2-Expressing Cancers

anti-PD-1 (Pembrolizumab)

 

NCT05356741

Recruiting

ISB-1342 (GBR 1342)

Glenmark Pharmaceuticals

anti-CD3

anti-CD38

 

I

I

MM

–

 

NCT03309111

Recruiting

Vixtimotamab (AMV-564)

Affimed Therapeutics

anti-CD3

anti-CD33 (Siglec-3)

 

I

I

AML

anti-PD-1 (Pembrolizumab)

 

NCT03144245

Completed

Cevostamab (BFCR-4350A, RG 6160, RO-7187797)

Genentech

anti-CD3

anti-FcRH5

 

I

I

MM

anti-IL-6 (Tocilizumab), anti-CD38 (Daratumumab), chemotherapy

CAMMA 1

NCT04910568

Recruiting

Elranatamab (PF-06863135)

Pfizer

anti-CD3

anti-BCMA

 

III

III

MM

chemotherapy

MagnetisMM-7

NCT05317416

Recruiting

Pavurutamab (AMG701)

Amgen

anti-CD3

anti-BCMA

 

I

I

MM

–

ProxiMMity-1

NCT04998747

Not yet recruiting

CM336

Keymed Biosciences

anti-CD3

anti-BCMA

 

I/II

I/II

MM

–

 

NCT05299424

Not yet recruiting

TNB-383B (ABBV-383)

TeneoBio, AbbVie, Amgen

anti-CD3

anti-BCMA

 

I

I

MM

–

 

NCT03933735

Recruiting

Ubamatamab (REGN4018)

Regeneron

anti-CD3

anti-MUC16

 

I/II

I/II

Ovarian Cancer

anti-PD-1 (Cemiplimab)

 

NCT03564340

Recruiting

AMG199

Amgen

anti-CD3

anti-MUC17

 

I

I

MUC17-positive Solid Tumors

–

 

NCT04117958

Recruiting

Tarlatamab (AMG757)

Amgen

anti-CD3

anti-DLL3

 

II

II

SCLC

–

DeLLphi-301

NCT05060016

Recruiting

BI 764532

Boehringer Ingelheim

anti-CD3

anti-DLL3

 

I

I

SCLC, Neuroendocrine Tumors

–

 

NCT04429087

Recruiting

Cibisatamab (RG7802, RO6958688)

Roche

anti-CD3

anti-CEA

 

I/II

I/II

NSCLC

anti-PD-1 (Atezolizumab), anti-IL-6 (Tocilizumab)

Morpheus Lung

NCT03337698

Recruiting

Acapatamab (AMG 160)

Amgen

anti-CD3

anti-PSMA

 

I/II

I/II

PC

anti-PD-1 (AMG404)

 

NCT04631601

Active, not recruiting

AMG 340 (TNB-585)

Amgen

anti-CD3

anti-PSMA

 

I

I

PC

–

 

NCT04740034

Recruiting

CCW702

Calibr, AbbVie

anti-CD3

anti-PSMA

 

I

I

PC

–

 

NCT04077021

Recruiting

AMG 509

Amgen, BeiGene, Xencor

anti-CD3

anti-STEAP1

 

I

I

PC

anti-PD-1 (Pembrolizumab), chemotherapy

 

NCT04221542

Recruiting

ERY974

Chugai Pharmaceutical

anti-CD3

anti-Glypican 3 (GPC3)

 

I

I

HCC

anti-PD-1 (Atezolizumab), anti-IL-6 (Tocilizumab), anti-VEGF (Bevacizumab)

 

NCT05022927

Recruiting

CM350

KeyMed Biosciences

anti-CD3

anti-Glypican 3 (GPC3)

 

I/II

I/II

Solid Tumors

–

 

NCT05263960

Recruiting

Talquetamab (JNJ-64407564)

Janssen, Gemnmab

anti-CD3

anti-GPRC5D

 

II

II

MM

–

 

NCT04634552

Recruiting

AMG 427

Amgen, BeiGene

anti-CD3

anti-FLT3

 

I

I

AML

–

 

NCT03541369

Recruiting

NVG-111

NovalGen

anti-CD3

anti-ROR1

 

I/II

I/II

CLL, Lymphoma

–

 

NCT04763083

Recruiting

IBI-389

Innovent Biologics

anti-CD3

anti-Claudin 18.2

 

I

I

Solid Tumors

anti-PD-1 (Sintilimab)

 

NCT05164458

Not yet recruiting

  

CD3 × TAA × co-stimulatory molecule

SAR442257

Sanofi

anti-CD3

anti-CD38

CD28 agonist

I

I

MM, NHL

–

 

NCT04401020

Recruiting

  

CD3 × TAA × PK/PD improvement element

HPN424

Harpoon Therapeutics

anti-CD3

anti-PSMA

human serum albumin

I/II

I/II

PC

–

 

NCT03577028

Recruiting

HPN536

Harpoon Therapeutics

anti-CD3

anti-mesothelin

human serum albumin

I/II

I/II

Solid Tumors With Mesothelin Expression

–

 

NCT03872206

Recruiting

HPN328

Harpoon Therapeutics

anti-CD3

anti-DLL3

human serum albumin

I/II

I/II

SCLC

–

 

NCT04471727

Recruiting

TAK-186 (MVC-101)

Takeda, Maverick Therapeutics

anti-CD3

anti-EGFR

human serum albumin

I/II

I/II

HNSCC, SCLC, CRC

–

 

NCT04844073

Recruiting

  

CD3 × HLA-intracellular oncoprotein

RG6007 (RO7283420)

Roche

anti-CD3

HLA-A2-WT1

 

I

I

AML

anti-IL-6 (Tocilizumab), TKI (Dasatinib), chemotherapy

 

NCT04580121

Recruiting

  

CD3 x affinity-enhanced TCR (ImmTAC)

Tebentafusp (IMCgp100)

Immunocore

anti-CD3

gp100 TCR

 

FDA approved

      

IMC-C103C (RG6290)

Immunocore, Roche

anti-CD3

MAGE-A4 TCR

 

I/II

I/II

Solid Tumors

anti-PD-1 (Atezolizumab)

IMC-C103C-101

NCT03973333

Recruiting

IMC-F106C

Immunocore

anti-CD3

PRAME TCR

 

I/II

I/II

Solid Tumors

anti-PD-(L)1

 

NCT04262466

Recruiting

  

Vγ9Vδ2 TCR × TAA

LAVA-051

Lava Therapeutics

anti-Vγ9Vδ2 TCR

anti-CD1d

 

I/II

I/II

CLL, MM, AML

–

 

NCT04887259

Recruiting

NK Cell Engagers

AFM13

Affimed Therapeutics

anti-CD16a/FcγRIIIA

anti-CD30

 

II

II

T Cell Lymphoma, Mycosis Fungoides

–

REDIRECT

NCT04101331

Active, not recruiting

AFM24

Affimed Therapeutics

anti-CD16a/FcγRIIIA

anti-EGFR

 

I/II

I/II

Solid Tumors

–

 

NCT04259450

Recruiting

General immunoregulatory anti-cancer bsAb/msAb

Group I (stimulating co-stimulatory molecules)

  

Co-stimulatory molecule x TAA/Tumor microenvironment protein

BT7480

Bicycle Therapeutics

4-1BB agonist

anti-Nectin-4

 

I/II

I/II

Solid Tumors

anti-PD-1 (Nivolumab)

BT7480-100

NCT05163041

Recruiting

Cinrebafusp alfa (PRS-343)

Pieris Pharmaceuticals

4-1BB agonist

anti-HER2

 

II

II

HER2-positive GC

HER2 TKI (Tucatinib), anti-VEGFR2 (Ramucirumab), chemotherapy

 

NCT05190445

Recruiting

CB307

Crescendo Biologics

4-1BB agonist

anti-PSMA

human serum albumin

I

I

Solid Tumors

–

POTENTIA

NCT04839991

Recruiting

RG6076 (RO7227166)

Roche

4-1BBL

anti-CD19

 

I

I

NHL

CD3 x CD20 BiTE (Glofitamab), anti-CD20 (Obinutuzumab), anti-IL-6 (Tocilizumab)

 

NCT04077723

Recruiting

RG7827 (RO7122290)

Roche

4-1BBL

anti-FAP

 

I/II

I/II

CRC

CD3 x CEA BiTE (Cibisatamab), anti-CD20 (Obinutuzumab)

 

NCT04826003

Recruiting

RG6189 (RO7300490)

Roche

CD40 agonist

anti-FAP

 

I

I

Solid Tumors

anti-PD-1 (Atezolizumab)

 

NCT04857138

Recruiting

MP0317

Molecular Partners

CD40 agonist

anti-FAP

 

I

I

Solid Tumors

–

 

NCT05098405

Recruiting

REGN5678

Regeneron

CD28 agonist

anti-PSMA

 

I/II

I/II

PC

anti-PD-1 (Cemiplimab)

 

NCT03972657

Recruiting

REGN5668

Regeneron

CD28 agonist

anti-MUC16

 

I/II

I/II

Ovarian Cancer

anti-PD-1 (Cemiplimab), CD3 x MUC16 BiTE (Ubamatamab)

 

NCT04590326

Recruiting

REGN7075

Regeneron

CD28 agonist

anti-EGFR

 

I/II

I/II

Solid Tumors

anti-PD-1 (Cemiplimab)

COMBINE-EGFR-1

NCT04626635

Recruiting

  

Co-stimulatory molecule x Co-stimulatory molecule

GEN1042

Genmab, BioNTech

4-1BB agonist

CD40 agonist

 

I/II

I/II

Solid Tumors

anti-PD-1 (Pembrolizumab), chemotherapy

 

NCT04083599

Recruiting

Group II (blocking inhibitory molecules)

  

Inhibitory checkpoint x TAA

Fidasimtamab (IBI-315)

Hanmi Pharmaceutical, Innovent Biologics

anti-PD-1

anti-HER2

 

I

I

Solid Tumors

–

 

NCT04162327

Recruiting

SSGJ-705

Sunshine Guojian Pharmaceutical

anti-PD-1

anti-HER2

 

I

I

Solid Tumors

–

 

NCT05145179

Not yet recruiting

  

Inhibitory checkpoint x Inhibitory checkpoint

SHR-2002

Jiangsu Hengrui

anti-TIGIT

anti-CD112R

 

I

I

Solid Tumors

anti-PD-1 (Camrelizumab), anti-PD-L1 (SHR-1316), PD-L1xTFG-βRII bsAb (SHR-1701)

 

NCT05198817

Enrolling by invitation

AGEN1777

Agenus, Bristol-Myers Squibb

anti-TIGIT

Undisclosed (T/NK cell inhibitory receptor)

 

I

I

Solid Tumors

anti-PD-1

 

NCT05025085

Recruiting

Vudalimab (XmAb717)

Xencor

anti-PD-1

anti-CTLA-4

 

II

I

Solid Tumors

–

DUET-2

NCT03517488

Active, not recruiting

Lorigerlimab (MGD019)

MacroGenics

anti-PD-1

anti-CTLA-4

 

II

II

Cervical Cancer

–

TRACTION

NCT05475171

Not yet recruiting

Cadonilimab (AK104)

Akeso Biopharma

anti-PD-1

anti-CTLA-4

 

III

I/II

GC, GEJC

chemotherapy

 

NCT03852251

Recruiting

Erfonrilimab (KN046)

Alphamab

anti-PD-L1

anti-CTLA-4

 

III

III

NSCLC

–

 

NCT04474119

Active, not recruiting

RG6139 (RO7247669)

Roche

anti-PD-1

anti-LAG-3

 

II

II

ESCC

–

 

NCT04785820

Recruiting

Tebotelimab (MGD013)

MacroGenics, Zai Lab

anti-PD-1

anti-LAG-3

 

II/III

II/III

GC, GEJC

anti-HER2 (Margetuximab), chemotherapy

MAHOGANY

NCT04082364

Active, not recruiting

ABL501

ABL Bio

anti-PD-L1

anti-LAG-3

 

I

I

Solid Tumors

–

 

NCT05101109

Recruiting

FS118

F-star Therapeutics

anti-PD-L1

anti-LAG-3

 

I/II

I/II

Solid Tumors

–

 

NCT03440437

Recruiting

IBI-323

Innovent Biologics

anti-PD-L1

anti-LAG-3

 

I

I

Solid Tumors

–

 

NCT04916119

Recruiting

NGM707

NGM Biopharmaceuticals

anti-LILRB1

anti-LILRB2

 

I/II

I/II

Solid Tumors

anti-PD-1 (Pembrolizumab)

 

NCT04913337

Recruiting

  

Inhibitory checkpoint x Other inhibitory molecule

HX009

Waterstone Hanxbio

anti-PD-1

anti-CD47

 

II

II

Solid Tumors

–

 

NCT04886271

Active, not recruiting

Simridarlimab (IBI-322)

Innovent Biologics

anti-PD-L1

anti-CD47

 

II

II

NSCLC

TKI (Lenvatinib), chemotherapy

 

NCT05296278

Not yet recruiting

LBL-015

Nanjing Leads Biolabs

anti-PD-1

TGF-βRII

 

I/II

I/II

Solid Tumors

–

 

NCT05107011

Recruiting

Retlirafusp alfa (SHR-1701)

Jiangsu Hengrui

anti-PD-L1

TGF-βRII

 

III

III

NSCLC

anti-VEGF (Bevacizumab), chemotherapy

 

NCT05132413

Not yet recruiting

BJ-005

BJ Bioscience

anti-PD-L1

TGF-βRII

 

I

I

Solid Tumors, Lymphoma

–

 

NCT05115292

Recruiting

TST005

Transcenta Holding

anti-PD-L1

TGF-βRII

 

I

I

Solid Tumors

–

 

NCT04958434

Recruiting

  

Other inhibitory molecule x TAA

BCA101

Bicara Therapeutics

TGF-β-trap

anti-EGFR

 

I/II

I/II

Solid Tumors

anti-PD-1 (Pembrolizumab)

 

NCT04429542

Recruiting

  

Inhibitory checkpoint x Anti-angiogenesis

Ivonescimab (AK112)

Akeso Biopharma

anti-PD-1

anti-VEGF

 

III

III

NSCLC

–

 

NCT05184712

Recruiting

Group III (targeting of co-stimulatory and inhibitory molecules)

  

Inhibitory checkpoint x Co-stimulatory molecule

Izuralimab (XmAb104)

Xencor

anti-PD-1

ICOS agonist

 

I

I

Solid Tumors

anti-CTLA-4 (Ipilimumab)

DUET-3

NCT03752398

Recruiting

CDX-527

Celldex Therapeutics

anti-PD-1

CD27 agonist

 

I

I

Solid Tumors

–

 

NCT04440943

Recruiting

PRS-344 (S095012)

Pieris Pharmaceuticals, Servier

anti-PD-L1

4-1BB agonist

 

I/II

I/II

Solid Tumors

–

 

NCT05159388

Recruiting

LBL-024

Nanjing Leads Biolabs

anti-PD-L1

4-1BB agonist

 

I/II

I/II

Solid Tumors

–

 

NCT05170958

Recruiting

FS222

F-star Therapeutics

anti-PD-L1

4-1BB agonist

 

I

I

Solid Tumors

–

 

NCT04740424

Recruiting

MCLA-145

Merus, Incyte Corporation

anti-PD-L1

4-1BB agonist

 

I

I

Solid Tumors, B-cell Lymphoma

–

 

NCT03922204

Recruiting

ABL503 (TJ-L14B)

ABL Bio, I-MAB Biopharma

anti-PD-L1

4-1BB agonist

 

I

I

Solid Tumors

–

 

NCT04762641

Recruiting

DSP107

KAHR Medical

SIRPα

4-1BBL

 

I/II

I/II

Solid Tumors

anti-PD-1 (Atezolizumab)

 

NCT04440735

Recruiting

  

Inhibitory checkpoint x Stimulatory cytokine (immunocytokine)

AMG 256

Amgen

anti-PD-1

IL-21 mutein

 

I

I

Solid Tumors

–

 

NCT04362748

Recruiting

RG6279 (RO7284755)

Roche

anti-PD-1

IL-2v

 

I

I

Solid Tumors

–

 

NCT04303858

Recruiting

SAR445710 (KD033)

Kadmon Holdings, Sanofi

anti-PD-L1

IL-15

IL-15RA

I

I

Solid Tumors

–

 

NCT04242147

Recruiting

GI-101

GI Innovation, Simcere Pharmaceutical

CD80 (CTLA-4 trap)

IL-2v

 

I/II

I/II

Solid Tumors

anti-PD-1 (Pembrolizumab), TKI (Lenvatinib), Radiation

 

NCT04977453

Recruiting

  1. The data are up to December 2022. For each agent, only one representative clinical trial is listed. All ongoing clinical trials for each agent are listed in Supplementary Table 4. The therapeutic combination described in the representative trial is a simplified summary. For each drug, the cases of all kinds of combinations of the drug and other agents in one or several cohorts in a multi-cohort study, or the combination of the drug and other agents in a mono-cohort study are not separately described
  2. FDA Food and Drug Administration, ALL acute lymphoblastic leukemia, MM multiple myeloma, FL follicular lymphoma, NHL non-Hodgkin lymphoma, CLL chronic lymphocytic leukemia, MDS myelodysplastic syndrome, DLBCL diffuse large B cell lymphoma, SCLC small-cell lung cancer, NSCLC non-small cell lung cancer, PC prostate cancer, HCC hepatocellular carcinoma, AML acute myeloid leukemia, HNSCC head and neck squamous cell carcinoma, CRC colorectal cancer, TKI tyrosine kinase inhibitors, GC gastric cancer, BiTE bispecific T-cell engager, GEJC gastroesophageal junction cancer, ESCC esophageal squamous-cell carcinoma
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