Breakthrough Clinical Results

SystImmune, Inc. announced that data from clinical trials evaluating izalontamab brengitecan (iza-bren), an EGFRxHER3 bispecific antibody-drug conjugate (ADC), will be presented at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting. The data will include results from patients with advanced Small Cell Lung Cancer (SCLC) and Non-Small Cell Lung Cancer (NSCLC) with driver genomic alterations outside of classic EGFR mutations. Iza-bren is being jointly developed by SystImmune and Bristol Myers Squibb. The presented data will highlight the drug's safety profile and efficacy in difficult-to-treat tumors, showcasing its potential as a standalone treatment or in combination with other agents.

Incidence and Prevalence

Latest Estimates of Small Cell Lung Cancer Incidence and Prevalence Globally

According to the latest information from PubMed, Small Cell Lung Cancer (SCLC) represents a significant portion of all lung cancer cases worldwide. The global incidence of SCLC ranges between 13-25% of all lung cancer cases:

• SCLC accounts for approximately 15% of all lung cancers
• Some sources indicate SCLC constitutes 15-20% of lung cancer cases
• Other research suggests SCLC comprises 15% to 25% of all lung cancers
• More conservative estimates place SCLC at approximately 13% of lung cancers
• Historical data from 1993 showed that approximately 25% of all lung cancer cases were due to SCLC

In the United States specifically, there are approximately 30,000 new cases of SCLC diagnosed each year.

The survival rate for SCLC remains extremely poor, with: - The 5-year survival rate remaining below 7% - SCLC causing the demise of >90% of affected individuals within 5 years

Regional variations in SCLC prevalence have been noted: - In India, one study found that SCLC represented 14.7% of lung cancer cases - A registry-based survey reported that nine cases were SCLC, whereas the expected frequency was 18% - In Hebei Province, China, there have been significant increases in the proportion of both population- and hospital-based SCLC cases in recent years

• This increase is particularly notable in males and in patients aged over 55 years
• The proportion of SCLC is higher in males than females based on both population and hospital-based cases

These statistics highlight the significant global burden of SCLC and its particularly poor prognosis compared to other lung cancer types.

Recent Studies

Recent Studies for Small Cell Lung Cancer

EGFR/mTOR Pathway Inhibition Study

• Intervention: Combination of erlotinib and RAD001

• Key findings:

• Expression rates: EGFR (37%), p-AKT (24%), p-ERK (13%), p-mTOR (55%), and p-p70s6K (91%) in tumor specimens

• Synergistic effects of the combination therapy on cell viability, proliferation, and autophagy

Chemotherapy-Induced Myelosuppression Study

• Study included 204 SCLC patients

• Key efficacy outcomes:

• Mild myelosuppression significantly associated with objective response rate (OR, 2.78; 95% CI, 1.30 to 6.14; P=0.010)

• Both mild (OR, 4.61; 95% CI, 1.35 to 18.27; P=0.020) and severe (OR, 7.22; 95% CI, 1.30 to 72.44; P=0.046) myelosuppression positively associated with disease control rate

BDNF-TrkB Signaling Study

• Study included 58 SCLC patients
• Intervention: Evaluation of pan-Trk inhibitor GNF-5837

• Key findings:

• TrkB staining score was 3.60±0.15 in SCLC specimens

• BDNF score was 2.76±0.14

• High levels of both TrkB and BDNF expression significantly associated with poor overall survival (hazard ratio=1.821, P=0.036)

• BDNF activated AKT and ERK signaling pathways and promoted migration of TrkB-overexpressing SCLC cells

• These effects were attenuated by GNF-5837

Gene Expression Profiling Study

• Study analyzed 38 surgically resected lung neuroendocrine tumors and 11 SCLC cell lines

• Key efficacy outcomes:

• High-grade neuroendocrine tumors classified into two groups independent of SCLC and LCNEC

• One group showed significantly better clinical outcome (83% vs 12% five-year survival; p=0.0094)

Primary Xenograft Model Study

• Used endobronchial tumor specimens from chemo-naive patients
• Specimens were serially propagated in immunodeficient mice

• Key findings:

• A group of tumor-specific genes expressed in primary SCLC and xenografts was lost during transition to tissue culture

PARPi/Anti-PD-1 Combination Study

• Retrospective study analyzing efficacy and safety in advanced solid tumors
• Included data from 40 patients
• Intervention: Combination of PARP inhibitors (PARPi) and anti-PD-1 immune checkpoint inhibitors

• Key efficacy outcomes:

• Overall objective response rate (ORR): 27.5% (95% CI, 13.0-42.0%)

• Overall disease control rate (DCR): 85.0% (95% CI, 73.4-96.6%)

• For SCLC patients: ORR 28.6%, DCR 71.4%

• SCLC median progression-free survival: 3.7 months

• SCLC median overall survival: 5.4 months

• BRCA1/2 mutation positively correlated with ORR (P=0.008)

• Key safety outcomes:

• 37.5% patients had ≥grade 3 adverse events

Drug used in other indications

Based on the provided context, there is no information available about izalontamab brengitecan being trialed for Small Cell Lung Cancer or any other indications. The context does not contain any mention of izalontamab brengitecan in clinical trials or otherwise.

The context instead mentions several other treatments being investigated for Small Cell Lung Cancer, including:

• Tarlatamab (a DLL3-directed CD3 T-cell engager)
• Atezolizumab and durvalumab (PD-L1 inhibitors)
• Vorolanib with nivolumab
• Sunitinib
• Bevacizumab combined with dual immunotherapy
• Other PD-1/PD-L1 inhibitors such as pembrolizumab, nivolumab, and avelumab
• Rovalpituzumab tesirine (Rova-T)
• BMS-986012 (monotherapy and in combination with nivolumab)
• Thalidomide
• Quavonlimab with pembrolizumab
• Ganitumab

Similarly, there is no information in the provided context about intervention models for any trials involving izalontamab brengitecan.