KOLs Discussing PANKU-Breast02
PANKU-Breast02 Key Slides & Visuals
Presentation slides shared by KOLs at the #ASCO26 oral abstract session (LBA1003, presented by Jiong Wu, MD, PhD). Click any image to expand; expand the OCR toggle to read the full slide text.
Top PANKU-Breast02 Tweets
新規ADCのIza-Bren(anti-HER3/EGFR TOPO1)がトリプルネガティブ2-3rd lineで中国のPhase3で、かなりいい成績。 結局ペイロードはTOPO1阻害なわけだけど… ADCも単一ターゲットからマルチターゲットの時代になるのか。 #ASCO26
Impressive results from a phase 3 trial of Iza-Bren (anti-HER3/EGFR TOPO1 ADC) vs chemo in pretreated mTNBC, with improvement in PFS and OS. High rate of hematologic toxicities, including 5% febrile neutropenia. Phase 3 ongoing to confirm these results in a global population.
PANKU-Breast02: Izalontamab Brengitecan Redefines Outcomes in Pretreated mTNBC PANKU-Breast02 demonstrates significant dual PFS/OS benefit, with a 40% reduction in mortality risk and a median OS gain of 3.4 months versus chemotherapy @OncoAlert #ASCO26 #BreastCancer #bcsm
#ASCO26 PANKU-Breast02 The concept of a bispecific topo-I ADC targeting EGFR×HER3 in TNBC is interesting in itself The fact that iza-bren showed clear activity against chemotherapy in this population is a promising signal that the ADC field in TNBC may move beyond Trop-2.
However, it might be hard to say manageable because of high hematologic toxicities. #ASCO26
#ASCO26 to watch — LBA1003 iza-bren Izalontamab brengitecan: bispecific EGFR×HER3 ADC + TopoI payload (Ed-04) vs TPC in pretreated, post-taxane mTNBC. China trial (BL-B01D1-307). Met both PFS and OS. Discussion points:
PANKU-Breast02 #ASCO26 Impressive data of iza-bren! Phase III trial of the EGFR×HER3 bispecific ADC izalontamab brengitecan (iza-bren) vs physician’s choice chemotherapy in previously treated advanced/metastatic TNBC. 🔹 Met both dual primary endpoints at interim analysis.
- Phase 3 "first" for a bispecific ADC in TNBC — does dual targeting beat single-target ADCs? - Magnitude of PFS / OS benefit and biomarker selection - Generalizability of a China-only trial to global TNBC populations
Overview
PANKU-Breast02 (NCT06382142 / BL-B01D1-307) is a multicenter, randomized, open-label Phase 3 study at 81 centers in China evaluating izalontamab brengitecan (iza-bren) versus physician's choice of chemotherapy in patients with unresectable locally advanced or metastatic triple-negative breast cancer that progressed after 1–2 prior lines of systemic therapy, including a taxane. Iza-bren is a potentially first-in-class EGFR×HER3 bispecific antibody-drug conjugate carrying a topoisomerase-I inhibitor payload (Ed-04; DAR 8). The interim analysis was presented at #ASCO26 (Abstract LBA1003) by Dr. Jiong Wu (Fudan University Shanghai Cancer Center) and met both dual primary endpoints — PFS and OS. PANKU-Breast02 is sponsored in China by Sichuan Biokin Pharmaceutical Co., Ltd. (Baili-Bio); outside China, iza-bren is co-developed by SystImmune and Bristol Myers Squibb. Iza-bren is investigational (not FDA approved).
Study Design
Phase 3, multicenter (81 China centers), randomized 1:1, open-label. Iza-bren 2.5 mg/kg IV on days 1 & 8 Q3W vs physician's choice chemotherapy. Dual primary endpoints: PFS (BICR) and OS. ~412–418 patients (207 iza-bren / 205–211 chemo).
Population
Adults with unresectable locally advanced or metastatic TNBC, progressed after 1–2 prior systemic lines (incl. prior taxane), ECOG 0–1, measurable disease per RECIST v1.1. ~70% had received one prior line; ~25% had prior anti-PD(L)1. Pre-specified subgroups by HER2 status (IHC0 vs IHC1+/2+ ISH-).
Intervention
Experimental: Iza-bren (EGFR×HER3 bispecific ADC, topo-I payload), 2.5 mg/kg D1/D8 Q3W. Control: Physician's choice of eribulin, capecitabine, gemcitabine, or vinorelbine.
Endpoints
Dual primary: PFS (BICR) and OS. Secondary: ORR (BICR), PFS (investigator), DCR, DoR, safety, PK, immunogenicity. Stratified by prior lines, prior anti-PD(L)1, and HER2 expression.
Results — Interim Analysis (#ASCO26, LBA1003)
Progression-Free Survival (Dual Primary Endpoint — MET)
By blinded independent central review (BICR), iza-bren produced a statistically significant and clinically meaningful PFS improvement versus physician's choice chemotherapy: median PFS 8.5 vs 3.1 months (HR 0.29; 95% CI 0.22–0.38; p<0.0001) — a 71% reduction in the risk of progression or death. The benefit was consistent across prespecified subgroups, including the two HER2-defined populations: HER2 IHC0 median PFS 8.3 vs 2.6 months (HR 0.28; 95% CI 0.20–0.41) and HER2-low (IHC1+/2+ ISH-) median PFS 9.7 vs 4.1 months (HR 0.32; 95% CI 0.22–0.46).
Median PFS 8.5 vs 3.1 mo · HR 0.29 (0.22–0.38) · p<0.0001 · HER2 IHC0 8.3 vs 2.6 mo · HER2-low 9.7 vs 4.1 moSources: ASCO 2026 LBA1003 (Jiong Wu) · MedPage Today · SystImmune / BMS press release (Jun 2, 2026) · Drugs.com MedNewsOverall Survival (Dual Primary Endpoint — MET)
With a median follow-up of 11.0 months, iza-bren showed a statistically significant overall-survival benefit at the prespecified interim analysis: median OS 15.9 vs 12.5 months (HR 0.60; 95% CI 0.42–0.85; p=0.0019) — a ~40% reduction in the risk of death and a 3.4-month median gain. OS events: 56/207 (27.1%) with iza-bren vs 77/205 (37.6%) with chemotherapy; 12-month OS 68.7% vs 53.5%.
Median OS 15.9 vs 12.5 mo · HR 0.60 (0.42–0.85) · p=0.0019 · Δ3.4 moSources: ASCO 2026 LBA1003 OS slide (BICR/ITT) · SystImmune / BMS press release · Drugs.com MedNewsResponse & Duration of Response
Iza-bren roughly doubled the confirmed objective response rate: cORR 51.7% vs 20.5% by BICR (odds ratio 4.3; 95% CI 2.8–6.7). Responses were also more durable — median duration of response 8.3 vs 4.0 months favoring iza-bren.
cORR 51.7% vs 20.5% · OR 4.3 (2.8–6.7) · median DoR 8.3 vs 4.0 moSources: ASCO 2026 LBA1003 (Jiong Wu) · MedPage Today · SystImmune / BMS press release · Drugs.com MedNewsSafety & Tolerability
The adverse-event profile was consistent with the earlier Phase 1 study, with no new safety signals — but at a higher overall rate than chemotherapy. Grade ≥3 treatment-emergent adverse events occurred in 88.9% (iza-bren) vs 62.9% (chemotherapy), and serious adverse events in 44% vs 19%. The most common Grade ≥3 events were hematologic toxicities, managed with standard supportive care; @PTarantinoMD noted a ~5% febrile-neutropenia rate. Interstitial lung disease was low and all low-grade (3 patients, 1.4%; one Grade 1, two Grade 2). AE-related discontinuation was rare (1.9% vs 0.5%). KOLs (incl. @kazuki_nozawa) cautioned that “manageable” should be weighed against the hematologic-toxicity burden.
Grade ≥3 TEAE 88.9% vs 62.9% · serious AE 44% vs 19% · mainly hematologic · FN ~5% (Tarantino) · ILD 1.4% · AE discontinuation 1.9%Sources: ASCO 2026 LBA1003 safety data · MedPage Today · Drugs.com MedNews · KOL commentary (#ASCO26: @PTarantinoMD, @kazuki_nozawa)Clinical Implications
PANKU-Breast02 is the first Phase 3 of a bispecific ADC to report positive dual PFS and OS in TNBC, moving the treatment window earlier (2L) than prior Trop-2 ADC trials such as ASCENT. KOLs framed the EGFR×HER3 dual-targeting concept as a promising signal that the ADC field in TNBC may move beyond single-target Trop-2 agents. Invited discussant Valentina Guarneri (University of Padova) noted the OS benefit was captured despite substantial crossover — 63.4% of the chemotherapy arm received subsequent anti-cancer therapy (42% of them a subsequent ADC) versus 38.6% in the iza-bren arm — and questioned whether physician's-choice chemotherapy was the right comparator given that other ADCs have already beaten chemotherapy in similar patients. Open questions also remain around hematologic toxicity and whether a China-only population generalizes globally; a global confirmatory Phase 3 is ongoing. Iza-bren remains investigational.
First bispecific-ADC Phase 3 with dual PFS/OS wins in 2L TNBC · OS held despite crossover · comparator & global generalizability debated · confirmation pendingSources: ASCO 2026 LBA1003 invited discussant (Valentina Guarneri) · MedPage Today · Targeted Oncology · KOL commentary (#ASCO26)