Aakash Desai, Associate Director of Phase 1 and Precision Oncology Program at UAB O’Neal Comprehensive Cancer Center, shared on LinkedIn:
“Lung cancer at ESMO26: the first phase 3 readout of a bispecific antibody-drug conjugate after third-generation EGFR TKI failure
On Oct 26 (LBA71, Proffered Paper session, Madrid), results from the randomized Phase 3 PANKU-Lung01 trial (NCT06382116) were presented and simultaneously published in The Lancet. The trial tested izalontamab brengitecan (iza-bren), an EGFR×HER3 bispecific ADC with a topoisomerase I inhibitor payload, against platinum-pemetrexed chemotherapy.
Who was enrolled
- 422 patients (iza-bren 216, chemotherapy 206), randomized 1:1; sponsored in mainland China by Sichuan Biokin
- EGFR-mutant (exon 19 deletion or L858R) non-squamous advanced NSCLC that progressed on a third-generation EGFR TKI
- Iza-bren 2.5 mg/kg IV on days 1 and 8 of a 3-week cycle vs pemetrexed plus cisplatin or carboplatin every 3 weeks
- Primary endpoint: PFS by blinded independent central review (BICR); OS a secondary endpoint
- Prespecified interim analysis (data cutoff July 15, 2026), serving as the final PFS analysis and an interim OS analysis
What was reported
- Median PFS 11.1 vs 5.7 months (HR 0.40, 95% CI 0.31–0.51; p<0.0001), median PFS follow-up 14.6 months
- Confirmed ORR by BICR 60.2% vs 34.5%; median duration of response 10.4 vs 5.7 months
- OS immature, with a favorable trend (HR 0.66, 95% CI 0.47–0.91, per the abstract report)
- Grade ≥3 treatment-related AEs were predominantly hematologic; 1.9% discontinued iza-bren for TRAEs
- Adjudicated ILD in 2 patients (0.9%): one grade 3, one grade 1. No new safety signals reported
Investigator Prof. Li Zhang (Sun Yat-sen University Cancer Center) said in the release:
‘These results could mark an important shift in how we approach acquired resistance in this disease.’
The abstract authors conclude the data support iza-bren as a new standard of care for this population in China; a global trial is ongoing (NCT07100080). Outside China, iza-bren is co-developed by SystImmune and Bristol Myers Squibb and holds FDA Breakthrough Therapy Designation in previously treated EGFR-mutated NSCLC.
A question for my thoracic oncology colleagues: with SAFFRON, OptiTROP-Lung04, HERON-Lung01 and now PANKU-Lung01 all reporting after osimertinib, how are you thinking about sequencing biomarker-directed therapy and ADCs in this space? EGFR gets complicated again! (In a good way!)
Sources: ESMO 2026 Abstract LBA71 (Oct 26, 2026); SystImmune/Bristol Myers Squibb press release, Oct 26, 2026; Oncoletter congress report of the abstract.”
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