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In previously treated ES-SCLC patients, especially in those previously treated with 1 prior line, iza-bren showed cORR of 75.0% with mOS of 15.0 months
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- egfr her3 adc izalontamab brengitecan phase i trial result
SystImmune's Bristol Myers Squibb-partnered EGFR x HER3 ADC izalontamab brengitecan shows early efficacy signal in Treatment-Resistant SCLC
SystImmune, through its parent company Sichuan Biokin Pharmaceutical (Sichuan Baili) has collaborated with Bristol Myers Squibb on the development and commercialization of iza-bren (BL-B01D1), a bispecific ADC that targets both EGFR and HER3. iza-bren is a first-in-class ADC composed of an EGFR x HER3 bispecific antibody conjugated to a novel topo-I inhibitor payload (Ed-04) via a stable tetrapeptide-based cleavable linker. The company is investigating this phase III programme. At ASCO 2025, data from Phase I trial (NCT05194982) presented (included data as of December 5, 2024, with a total of 58 SCLC patients’ enrollment).
|
Category |
Total (N = 58) |
2.5 mg/kg D1D8 Q3W | ||
|
Total (N = 52) |
1 Prior Line (N = 22) |
2L+ Prior Lines (N = 30) | ||
|
Median (range) LoT |
2 (1–7) |
2 (1–7) |
1 (1–1) |
3 (2–7) |
|
BOR, n | ||||
|
- PR |
32 |
31 |
17 |
14 |
|
- Confirmed PR |
26 |
25 |
16 |
9 |
|
- SD |
5 |
4 |
1 |
3 |
|
- PD |
5 |
5 |
1 |
4 |
|
- NE |
16 |
12 |
3 |
9 |
|
ORR, % (95% CI) |
55.2 (41.5, 68.3) |
59.6 (45.1, 73.0) |
77.3 (54.6, 92.2) |
46.7 (28.3, 65.7) |
|
cORR, % (95% CI) |
44.8 (31.7, 58.5) |
48.1 (34.0, 62.4) |
72.7 (49.8, 89.3) |
34.5 (17.9, 54.3) |
|
DCR, % (95% CI) |
81.0 (68.6, 90.1) |
80.8 (67.5, 90.4) |
90.9 (70.8, 98.9) |
75.9 (54.1, 87.7) |
|
Median DOR, months (95% CI) |
4.6 (4.2, 6.0) |
4.9 (4.2, 6.2) |
4.9 (3.7, 6.7) |
4.6 (2.0, 7.4) |
|
Median PFS, months (95% CI) |
4.5 (3.5, 6.1) |
4.7 (3.5, 6.1) |
6.2 (3.7, 10.6) |
3.9 (2.0, 4.4) |
|
Median OS, mo (95% CI) |
12.0 (9.1, 13.2) |
12.2 (9.1, 13.2) |
15.0 (8.7, NR) |
10.3 (7.9, 12.4) |
|
Patients received at least one study drug use included in analysis | ||||
The most common hematologic treatment-related adverse events (TRAEs) (all grades) were anemia (84.5%), leukopenia (74.1%), thrombocytopenia (72.4%), and neutropenia (70.7%). Common non-hematologic TRAEs included asthenia (41.4%), hypoalbuminemia (39.7%), stomatitis (34.5%), nausea (31.0%), and vomiting (31.0%). Grade ≥3 TRAEs, mainly hematologic, were manageable with standard supportive care, with a 12.1% discontinuation rate. Two infection-related deaths occurred. No interstitial lung disease (ILD) or new safety signals were observed.
KOL insights
“Recent data have bolstered our confidence in iza-bren's safety profile while highlighting its encouraging efficacy across tumors that have been difficult to treat. Iza-bren emerges as a promising therapeutic option, potentially fulfilling the unmet need of patients with few treatment alternatives. Our commitment to advancing this therapy through a series of comprehensive clinical trials remains steadfast, as we explore its potential both as a standalone treatment and in combination with other agents to improve cancer patient outcomes globally. ” – Expert Opinion
Conclusion
SCLC is a disease with limited therapeutic advancements if compared to NSCLC. SCLC accounts for approximately 15% of all new lung cancer cases in the US. The current pipeline of SCLC is robust with many companies investigating new therapies and expanding existing labels. Several companies investigating their ADCs are Daiichi Sankyo/Merck (Ifinatamab deruxtecan), MediLink [YL201 (B7H3 ADC)], Zai Lab [ZL-1310 (DLL3 ADC)], Duality Biologics/BioNTech [BNT324/DB-1311 (B7H3 ADC)], Gilead Sciences [TRODELVY (TROP-2 ADC)], AbbVie [ABBV-706 (SEZ6 ADC)], and others for the treatment of SCLC. In addition to ADCs, several other classes are being studied for the treatment of SCLC, such as T-cell engagers (TCE) [e.g. MK-6070/DS3280 (DLL3 tri-specific TCE; Daiichi Sankyo/Merck)], bispecific antibodies [e.g. BNT327 (PD-L1 x VEGF-A; BioNTech), radiopharmaceuticals [e.g. ABD-147 (Abdera Therapeutics), SSO110 (Ariceum Therapeutics)], etc.
The high confirmed response rate of 75% in patients with limited prior treatment underscores its potential as a novel therapeutic option for SCLC. A Phase III study of iza-bren in SCLC patients (with 1 prior line of PBC and anti-PD(L)-1 combination treatment) is ongoing in China (NCT06500026).
Executive Summary
iza-bren demonstrated promising efficacy and a manageable safety profile in previously treated SCLC patients (1 Prior Line), including those with prior PBC, anti-PD(L)-1, or irinotecan treatment, with a cORR of 75.0%, mPFS of 6.9 months, and mOS of 15.0 months. iza-bren showed encouraging efficacy in SCLC patients regardless of platinum-resistance or platinum-sensitive relapse.