Breakthrough Clinical Results
Avidicure announced it will present preclinical data at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. The data highlights AVC-S-101, a TROP2-targeting antibody, showing prolonged and significantly improved tumor control in animal models and immune system activation in non-small cell lung cancer (NSCLC) patient samples. AVC-S-101 is a first-in-class dual agonistic multifunctional antibody designed to harness the full power of the immune system. The company also announced its participation in the BIO International Convention.
Key Highlights
- Preclinical data on AVC-S-101, a TROP2-targeting antibody, will be presented at ASCO 2025.
- AVC-S-101 demonstrated prolonged and significantly improved tumor control in animal models.
- AVC-S-101 showed strong activation of the immune system in human NSCLC samples.
- Avidicure will also present at the BIO International Convention.
Emerging Mechanism of Action
Emerging Mechanisms of Action for Non-Small Cell Lung Cancer Treatment
Based on recent publications, several key mechanisms of action have emerged for the treatment of Non-Small Cell Lung Cancer (NSCLC):
Immune Checkpoint Inhibitors
- Immune checkpoint inhibitors play an important role in NSCLC management, with mechanisms involving anti-CTL4 and anti-PD1 antibodies
- These inhibitors are generally better tolerated and less toxic compared to conventional chemotherapy
- PD-1 and PD-1 ligand inhibitors such as nivolumab, pembrolizumab (MK3475), and MPDL3280 have demonstrated clinical efficacy in patients with advanced/metastatic NSCLC
PD-L1 Targeted Therapy
- FDA granted accelerated approval for pembrolizumab for treatment of metastatic NSCLC whose tumors express programmed death-ligand 1 (PD-L1)
- The PD-L1 immunohistochemistry 22C3 pharmDx is used as a companion diagnostic test for patient selection based on PD-L1 tumor expression
- Pembrolizumab showed 41% confirmed objective response rate in patients with tumors strongly positive for PD-L1
- Pembrolizumab plus chemotherapy showed efficacy in large-cell carcinoma (LCC) with 44.4% ORR and large-cell neuroendocrine carcinoma (LCNEC) with 70% ORR
Anti-Angiogenic Therapy
- Ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor receptor-2, is approved in combination with docetaxel for metastatic NSCLC with disease progression after platinum-based chemotherapy
Tyrosine Kinase Inhibitors
- Tyrosine kinase inhibitors (gefitinib, erlotinib, afatinib) are indicated for NSCLC adenocarcinoma positive for epidermal growth factor mutations
- Osimertinib is administered when T790M mutation is diagnosed after disease relapse
MET Inhibition
- Capmatinib targets and selectively binds to mesenchymal-epithelial transition (MET), including the mutant variant produced by exon 14 skipping
Recent Approvals for Early-Stage NSCLC
Recent approvals for early-stage NSCLC include: - Adjuvant osimertinib - Adjuvant atezolizumab - Adjuvant pembrolizumab - Neoadjuvant nivolumab combined with chemotherapy
These emerging mechanisms of action represent significant advances in the treatment landscape for NSCLC, offering more targeted and potentially effective therapeutic options for patients with various subtypes and stages of the disease.
Key Unmet Needs and Target Populations for Non-small Cell Lung Cancer Research
Unmet Needs
Treatment Resistance
- Patients inevitably develop resistance to ALK inhibitors leading to tumor relapse that commonly manifests as brain metastasis
- Several approaches aim to overcome resistance mechanisms in ALK-positive NSCLC including knowledge-based alternate use of different ALK inhibitors and combined therapies
- Lack of prolonged disease control in most NSCLC patients despite chemotherapy and molecular-targeted therapies
Biomarker Development
- Need for easy-to-use and robust clinical gene signatures for improved prognosis and treatment prediction
- Low RRM1 mRNA expression in both peripheral blood and tumor tissue is associated with better response to gemcitabine/carboplatin chemotherapy
- ERCC1 mRNA expression in tumor tissue may be a predictive and prognostic indicator in advanced NSCLC patients receiving gemcitabine/carboplatin chemotherapy
- Need for markers to determine which patients and tumor types are most likely to respond to new treatments
Targeted Therapies
- The role of PD-1 inhibitors in treating EGFR-mutant and ALK-rearranged lung cancer has yet to be determined
- Limited proportion of patients benefiting from receptor tyrosine kinase (RTK) targeting agents
- Difficulty in conducting randomized clinical trials for ALK-targeted therapies due to low frequency of ALK rearrangements (3-5% of NSCLC)
Novel Approaches
- Epigenetic modulation could be a potential therapeutic approach to prevent metastasis formation as prometastatic phenotype was reversed due to inhibition of DNA methyltransferase
- Traditional Chinese medicine (TCM) monomers show markedly inhibitory actions for NSCLC through M1/M2 macrophage modulation
Regional Disparities
- Lack of comprehensive data on lung cancer in India
Target Populations
Genetic Mutation Subgroups
- EGFR-mutant and ALK-rearranged populations
- ALK gene rearrangements are present in approximately 3.5% of lung carcinoma and 3.7% of lung adenocarcinoma patients
- Patients with ALK rearrangements do not respond to EGFR-specific tyrosine kinase inhibitors but benefit from ALK inhibitors
- Patients with KRAS mutations
- PD-L1 mutations
Rare Genetic Alterations
- PDGFRA gene amplification was detected in a sunitinib-sensitive adenosquamous NSCLC cell line and in a small fraction of squamous cell NSCLC primary tumor specimens
- Rare tumors showing PDGFC-mediated PDGFRA activation may be clinically responsive to pharmacologic PDGFRA or PDGFC inhibition
Disease Stage-Specific Groups
- Patients with early-stage disease, particularly stage IA or IB adenocarcinoma
- High-risk patients with stage I NSCLC who may benefit from adjuvant chemotherapy
Histological Subtypes
- Squamous cell carcinoma patients of all stages
Cell-Type Specific
- CD133-positive NSCLC cells (cancer stem cells)
- Tumor-associated macrophages (TAM) are abundant in numerous cancer types and may serve as potential therapeutic targets
Geographic Populations
- Indian population (where lung cancer is the fourth leading cause of cancer, 5.9% of cases, and third leading cause of cancer-related mortality)
Drug used in other indications
Based on the provided context, there is no information available about:
- A compound or drug called AVC-S-101
- Any clinical trials involving AVC-S-101
- Any indications for which AVC-S-101 is being trialed
- Any intervention models for AVC-S-101 trials
The context discusses various treatments for non-small cell lung cancer (NSCLC) and other conditions, but does not mention AVC-S-101 specifically.