Small illustration of ADC breakthroughs in 2024Introduction

An Antibody-Drug Conjugate (ADC) is a precision cancer therapy that harnesses the specificity of a monoclonal antibody to target cancer cells linking it to a potent cytotoxic drug via a chemical linker. This targeted design enables the antibody to selectively bind to cancer cells delivering the drug payload directly to the tumor site while sparing healthy tissues. The ADC’s mechanism of action involves internalization linker breakdown and release of the cytotoxic drug leading to cancer cell death. By minimizing systemic toxicity ADCs enhance efficacy and reduce side effects offering a breakthrough in cancer treatment. ADCs represent a rapidly evolving frontier in cancer therapeutics offering targeted delivery of cytotoxic agents directly to cancer cells while minimizing systemic toxicity.

Key Highlights from ASCO 2024

The 2024 American Society of Clinical Oncology (ASCO) meeting showcased significant advancements in ADC research highlighting both preclinical developments and clinical trial outcomes across various cancer types. This report encapsulates key findings from abstracts illustrating the diverse mechanisms targets and potential of ADCs in oncology. Below is a comprehensive summary of these studies followed by detailed tables categorizing ADCs in development and those undergoing clinical trials.

Summary of ADCs in Development

ADC Target Protein Type of Cancer
SV-BR-1-GM GM-CSF Metastatic Breast Cancer
Trop2 ADC Trop2 Triple-Negative Breast Cancer
BC3195 CDH3 Advanced Solid Malignancies
DS-3939a TA-MUC1 Advanced Solid Tumors
MRG003 EGFR EGFR-Positive Solid Tumors
SHR-A1811 HER2 HER2-Positive Breast Cancer with Brain Metastases
Sigvotatug vedotin IB6 Non-Small Cell Lung Cancer
ACR246 5T4 5T4-Positive Solid Tumors
ZV0203 HER2 HER2-Positive Tumors
9MW2821 Nectin-4 Advanced Solid Tumors
MRG004A Tissue Factor Advanced Solid Tumors
RC48-ADC HER2 High-Risk Non-Muscle Invasive Bladder Cancer
M9140 CEACAM5 Metastatic Colorectal Cancer
ESG401 TROP2 Metastatic Triple-Negative Breast Cancer
SHR-A1912 CD79b B-Cell Non-Hodgkin Lymphoma
CS5001 ROR1 Advanced Solid Tumors and Lymphomas
ABBV-706 SEZ6 Advanced Solid Tumors
AMT-116 CD44v9 Advanced Solid Tumors
ARX788 HER2 HER2-Positive Breast Cancer
MHB088C B7H3 B7H3-Positive Tumors
GQ1001 HER2 HER2-Positive Metastatic Breast Cancer
F0024 TROP2 Advanced Solid Tumors
Sequential ADC therapy TROP2 and HER2 Metastatic breast cancer
YB-800 NPTXR Gastro-Intestinal Cancers

Summary of ADCs in Clinical Trials

ADC Clinical Trial Phase Type of Cancer
SV-BR-1-GM Phase 2 Metastatic Breast Cancer
Trop2 ADC Preclinical Triple-Negative Breast Cancer
BC3195 Phase 1 Advanced Solid Malignancies
DS-3939a Phase 1/2 Advanced Solid Tumors
MRG003 Phase I/II EGFR-Positive Solid Tumors
SHR-A1811 Phase 2 HER2-Positive Breast Cancer with Brain Metastases
Sigvotatug Vedotin Phase 1 Non-Small Cell Lung Cancer
ACR246 Preclinical 5T4-Positive Solid Tumors
ZV0203 Phase 1 HER2-Positive Tumors
9MW2821 Phase 1/2a Advanced Solid Tumors
MRG004A Phase 1 Advanced Solid Tumors
RC48-ADC Early Phase High-Risk Non-Muscle Invasive Bladder Cancer
M9140 Phase 1 Metastatic Colorectal Cancer
ESG401 Phase 1b Metastatic Triple-Negative Breast Cancer
SHR-A1912 Phase 1 B-Cell Non-Hodgkin Lymphoma
CS5001 Phase 1a Advanced Solid Tumors and Lymphomas
ABBV-706 Phase 1 Advanced Solid Tumors
AMT-116 Phase 1 Advanced Solid Tumors
ARX788 Phase II/III HER2-Positive Breast Cancer
MHB088C Phase 1/2 B7H3-Positive Tumors
GQ1001 Phase 1b HER2-Positive Metastatic Breast Cancer
F0024 Phase 1 Advanced Solid Tumors

Details of Selected Studies

GM-CSF-ADC (SV-BR-1-GM) Shows Promise for ADC-Refractory Metastatic Breast Cancer

A study from Hoag Newport Beach and other institutions highlighted the potential of SV-BR-1-GM a GM-CSF secreting breast cancer cell line in patients with metastatic breast cancer (MBC) who have progressed on ADCs. The post-hoc analysis of a Phase 2 trial showed a median overall survival (OS) of 42 weeks and a disease control rate (DCR) of 40% among heavily pretreated patients. The absence of serious adverse events (AEs) and the favorable safety profile suggest SV-BR-1-GM as a viable treatment option. Read more: ASCO Abstract

Trop2 ADC in Combination with Checkpoint Inhibitors

Researchers from The Fourth Hospital of Hebei Medical University explored the role of human trophoblastic cell surface antigen 2 (Trop2) in breast cancer immune activity. Trop2 a transmembrane protein overexpressed in breast cancer tissues correlates with poor prognosis in triple-negative breast cancer (TNBC). Their study suggests the potential for Trop2 ADCs combined with immune checkpoint inhibitors to improve outcomes in different breast cancer subtypes. Abstract: ASCO Abstract

First-in-Human Study of CDH3 (BC3195) Targeting CDH3

A Phase I study from Guangdong Lung Cancer Institute (China) introduced BC3195 an ADC targeting Cadherin-3 (CDH3) in patients with advanced solid malignancies. Preliminary results demonstrated stable disease in 50% of evaluable patients and a manageable safety profile highlighting BC3195’s potential for treating cancers such as lung breast and ovarian. Read more: ASCO Abstract

Sequential ADC Therapy in Metastatic Breast Cancer

A retrospective study by Memorial Sloan Kettering Cancer Center examined the efficacy of sequential ADC therapy in MBC. Patients treated with sacituzumab govitecan followed by trastuzumab deruxtecan showed a median progression-free survival (PFS) of 3.5 months and 2.8 months respectively. These findings underscore the need for further studies to understand the potential cross-resistance between these ADCs. Read more: ASCO Abstract

ADCs Targeting TA-MUC1 (DS-3939a) in Advanced Solid Tumors

A multinational Phase 1/2 study evaluated DS-3939a an ADC targeting tumor-associated MUC1 (TA-MUC1) in advanced solid tumors. Early results indicate that DS-3939a has a favorable safety profile and shows preliminary signs of efficacy particularly in breast and pancreatic cancers. Read more: ASCO Abstract

PD-1 Inhibitor (HX008) and EGFR-Targeting ADC (MRG003) Combination for EGFR-Positive Tumors

A Phase I/II study in China assessed the combination of HX008 a PD-1 inhibitor and MRG003 an EGFR-targeting ADC in EGFR-positive solid tumors. The combination therapy showed an objective response rate (ORR) of 63% and a disease control rate (DCR) of 88.9% demonstrating significant antitumor activity and manageable adverse events (AEs). Read more: ASCO Abstract

HER2-ADC (SHR-A1811) in HER2-Positive Breast Cancer with Brain Metastases

A Phase 2 trial from Cancer Hospital of Zhengzhou University evaluated SHR-A1811 in HER2-positive breast cancer patients with brain metastases. The study reported an intracranial ORR of 84% and a manageable safety profile suggesting SHR-A1811 as a promising treatment for this challenging condition. Read more: ASCO Abstract

Integrin Beta-6 (IB6) Targeting ADC (Sigvotatug vedotin) for NSCLC

Phase 1 results for sigvotatug vedotin an ADC targeting integrin beta-6 (IB6) in non-small cell lung cancer (NSCLC). The study reported a confirmed objective response rate (cORR) of 19.5% and a median PFS of 3.5 months indicating the drug’s potential efficacy in heavily pretreated NSCLC patients. Read more: ASCO Abstract

Innovative 5T4-ADC (ACR246) Shows Preclinical Promise

Hangzhou Adcoris Biopharma reported preclinical results for ACR246 a novel 5T4-targeted ADC. The ADC demonstrated robust antitumor activity and a favorable safety profile in various 5T4-positive solid tumor models positioning ACR246 as a potential best-in-class therapeutic. Read more: ASCO Abstract

A Pertuzumab ADC (ZV0203) Targeting HER2-Positive Tumors

Hangzhou Adcoris Biopharma also presented early-phase results for ZV0203 a pertuzumab ADC targeting HER2-positive tumors. The Phase 1 study showed promising antitumor activity with an ORR of 71.4% and a manageable safety profile. Read more: ASCO Abstract

Meta-Analysis of ADCs in HER2-Low Breast Cancer

A systematic review and meta-analysis conducted by multiple institutions assessed the effectiveness of ADCs in HER2-low advanced/metastatic breast cancer. The analysis confirmed that ADCs significantly improve progression-free survival (PFS) and overall survival (OS) compared to standard treatments. Read more: ASCO Abstract

Nectin-4 Targeting ADC (9MW2821) in Advanced Solid Tumors

Fudan University Shanghai Cancer Center reported Phase 1/2a results for 9MW2821 a Nectin-4-targeting ADC. The study demonstrated an ORR of 35.3% and a DCR of 78.4% with notable efficacy in urothelial cervical and esophageal cancers. Read more: ASCO Abstract

Tissue Factor (TF)-ADC (MRG004A) for Solid Tumors

Memorial Sloan Kettering Cancer Center presented interim results for MRG004A a tissue factor-targeting ADC in advanced solid tumors. The ADC showed a promising ORR of 33.3% in pancreatic cancer patients and manageable safety supporting further investigation. Read more: ASCO Abstract

HER2-ADC (RC48-ADC) for High-Risk NMIBC

West China Hospital explored the use of RC48-ADC as adjuvant or rescue therapy in high-risk non-muscle invasive bladder cancer (NMIBC) with HER2 overexpression. Early results indicate better recurrence-free survival (RFS) compared to Bacillus Calmette-Guérin (BCG) therapy. Read more: ASCO Abstract

CEACAM5-ADC (M9140) for Metastatic Colorectal Cancer

The University of Texas MD Anderson Cancer Center reported Phase 1 results for M9140 an ADC targeting CEA cell adhesion molecule 5 (CEACAM5) in metastatic colorectal cancer (mCRC). The study found a median PFS of 6.7 months and an ORR of 10% highlighting its potential for heavily pretreated patients. Read more: ASCO Abstract

TROP2-ADC (ESG401) for Metastatic Triple-Negative Breast Cancer

Shanghai Escugen Biotechnology sponsored study presented Phase 1b results for ESG401 a novel antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 monoclonal antibody linked to the Topoisomerase I inhibitor SN-38 in first-line metastatic triple-negative breast cancer (mTNBC). The ADC showed an ORR of 78.6% and a DCR of 100% indicating strong antitumor activity. Read more: ASCO Abstract

CD79b-Targeting ADC (SHR-A1912) for B-Cell Non-Hodgkin Lymphoma

Shandong Cancer Hospital and Institute reported Phase 1 results for SHR-A1912 a CD79b-targeting ADC in B-cell non-Hodgkin lymphoma. The study demonstrated an ORR of 56.1% and a DCR of 73.2% with a manageable safety profile. Read more: ASCO Abstract

ROR1-Targeting ADC (CS5001) for Advanced Solid Tumors and Lymphomas

Scientia Clinical Research Limited introduced CS5001 a ROR1-targeting ADC in advanced solid tumors and lymphomas. Preliminary results from the Phase 1a study showed objective responses in Hodgkin lymphoma and pancreatic cancer indicating its potential efficacy. Read more: ASCO Abstract

SEZ6-Targeting ADC (ABBV-706) for Advanced Solid Tumors

A Phase 1 study by START Midwest and Memorial Sloan Kettering Cancer Center evaluated ABBV-706 a seizure related 6 homolog (SEZ6)-targeting ADC in advanced solid tumors. The study reported a confirmed ORR of 21% and a manageable safety profile supporting further development. Read more: ASCO Abstract

CD44v9-ADC (AMT-116) for CD44v9-Positive Tumors

ICON Cancer Centre presented Phase 1 results for AMT-116 a CD44v9-targeting ADC in advanced solid tumors. Early data indicated promising antitumor activity and a manageable safety profile. Read more: ASCO Abstract

HER2-ADC (ARX788) in HER2-Positive Breast Cancer

Fudan University Shanghai Cancer Center reported interim results from a Phase II/III trial of ARX788 in HER2-positive breast cancer. The ADC significantly prolonged PFS compared to lapatinib plus capecitabine demonstrating its potential as a new treatment option. Read more: ASCO Abstract

B7H3-ADC (MHB088C) for B7H3-Positive Tumors

Beijing Cancer Hospital and Shanghai Pulmonary Hospital presented Phase 1/2 results for MHB088C a B7H3 (CD276/ B7RP-2)-targeting ADC. The study showed an ORR of 41.7% and a manageable safety profile with notable efficacy in small cell lung cancer (SCLC). Read more: ASCO Abstract

HER2-ADC (GQ1001) Combined with Pyrotinib for Metastatic Breast Cancer

A Phase 1b study from Fudan University Shanghai Cancer Center investigated GQ1001 a HER2-targeted ADC combined with pyrotinib in HER2-positive metastatic breast cancer. The combination showed an ORR of 66.7%. Read more: ASCO Abstract

HER2-Directed ADC RC48 for Non-Muscle Invasive Bladder Cancer (HR-NMIBC)

This study highlighted the potential of RC48-ADC over BCG in high-risk non-muscle invasive bladder cancer with better recurrence-free survival and a favorable immune profile. The HER2-directed ADC RC48 has shown promising efficacy as an adjuvant therapy for patients with HR-NMIBC as indicated by improved recurrence-free survival (RFS). Read more: ASCO Abstract

HER3-Targeting ADC (YL202/BNT326) in NSCLC and Breast Cancer

YL202/BNT326 targeting HER3 demonstrated encouraging efficacy and safety in heavily pretreated non-small cell lung cancer (NSCLC) and breast cancer patients. Read more: ASCO Abstract

TROP2-Targeted ADC (MHB036C) in Advanced Solid Tumors

This TROP2-targeted ADC showed manageable safety and significant efficacy in non-small cell lung cancer (NSCLC) and HER2-negative breast cancer. Read more: ASCO Abstract

HER2-Directed ADC RC48 and Tislelizumab in MIBC

The combination of RC48-ADC (Disitamab vedotin) and tislelizumab a humanized monoclonal antibody directed against programmed death receptor-1 showed promising efficacy as a neoadjuvant treatment in HER2-positive muscle-invasive bladder cancer with manageable toxicities. Read more: ASCO Abstract

HER2-Directed ADC RC48 and Cadonilimab in Urothelial Carcinoma

The first study to evaluate RC48-ADC with cadonilimab a tetravalent PD-1/CTLA-4 bispecific antibody in urothelial carcinoma showed promising efficacy and a manageable safety profile in first-line treatment offering a potential new option for patients who cannot tolerate cisplatin-based chemotherapy. Read more: ASCO Abstract

Human NPTXR-Targeting ADC (YB-800) in Gastro-Intestinal Cancers

YB-800 targeting the human neuronal pentraxin receptor (NPTXR) showed potential as an ADC candidate for gastrointestinal cancers demonstrating specific tumor cell binding and internalization. Read more: ASCO Abstract

Anti-HER2 ADC (ARX788) in HER2+ Metastatic Breast Cancer Post-T-DXd

ARX788 showed antitumor activity in HER2+ metastatic breast cancer patients who progressed on trastuzumab deruxtecan (T-DXd) with a good safety profile. Read more: ASCO Abstract

HER2-Targeting ADC (BB-1701) in HER2+ and HER2-Low Metastatic Breast Cancer

BB-1701 an ADC targeting HER2 with an eribulin payload demonstrated promising efficacy and manageable safety in previously treated HER2+ and HER2-low metastatic breast cancer. Read more: ASCO Abstract