Introduction
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 |
Read Our Blog: Evaluating Antibody-Drug Conjugate (ADC) Potency Through Robust Assays.
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
Assays for Antibody-Drug Conjugate (ADC) Drug Discovery and Development
MarinBio offers a wide range of cell-based and in vitro assays for antibody-drug conjugate (ADC) drug discovery and development. These assays can also be applied to peptide-drug conjugate (PDC), oligonucleotide-drug conjugate, and RNA-drug conjugate drug discovery and development.
In Vitro Cytotoxicity Assays
- Cell viability assays: Measure the number of viable cells.
- Cell apoptosis assays: Detect apoptotic cells.
- Cell cycle analysis: Examine cell cycle stages.
Internalization Assays
- Flow cytometry: Monitors internalization of ADCs into target cells using fluorescent tags.
Binding and Functional Assays
These assays examine the ADC’s ability to bind targets and elicit desired responses:
- Enzyme-linked immunosorbent assay (ELISA): Measures antigen binding and ADC concentration.
- Flow cytometry: Validates antigen expression on target cells and evaluates ADC binding.
- ADCC and ADCP assays: Assess Fc effector activity of ADCs.
Pharmacokinetic (PK) Assays
- Ligand binding assays (LBA): Quantify total antibody and ADC concentrations in biological samples.
- Enzyme-linked immunosorbent assay (ELISA): Quantifies total ADC, free antibody, and drug levels in serum or plasma.
Stability Assays
- Cell-based assays: Quantify the stability of ADCs.
Pharmacodynamics (PD) Assays
- Biomarker analysis: Identifies changes in biological markers in response to ADC treatment (e.g., ELISA or cell-based assays).
- Flow cytometry: Monitors receptor expression changes on target cells.
Immunogenicity Assays
- Anti-drug antibody (ADA) assays: Detect antibodies against the ADC, which could affect efficacy and safety.
- Neutralizing antibody (NAb) assays: Determine whether the detected ADA can neutralize the ADC’s activity.
Potency Assays
- Cell-based potency assays: Measure ADC-mediated cytotoxicity to ensure the drug’s biological activity is within specifications.
Targeted Protein Degradation Assays
These assays characterize ADC payloads that function as targeted protein degraders or proteolysis-targeting chimeras (PROTACs). Click here to see the targeted protein degradation assays offered by MarinBio.
Immunogenic Cell Death (ICD) Assays
ADCs are known to trigger immunogenic cell death (ICD), resulting in the release of damage-associated molecular patterns (DAMPs) and attracting immune cells to the tumor site. Assays used in ICD are also available.
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