Iza-bren Plus Tagrisso May Offer a New Option for Advanced Lung Cancer

A combination of Iza-bren (izalontamab brengitecan; BL-B01D1) and Tagrisso showed beneficial results as an initial treatment for people with advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR mutations. The treatment was generally well tolerated and helped shrink tumors, according to results from a phase 2 study shared at the 2025 World Conference on Lung Cancer.

Notably, when Iza-bren was given at a dose of 2.5 milligrams per kilogram (mg/kg) on days one and eight of an every-three-weeks cycle and combined with Tagrisso (40 patients), it led to an objective response rate of 100% and a confirmed objective response rate of 95%. At a median follow-up of 12.5 months, the 12-month progression-free survival rate was 92%. At a median follow-up of 12.8 months, the 12-month overall survival rate was 95%. The median duration of response and median progression-free survival had not yet been reached at the time of analysis, which had a data cutoff date of June 30, 2025.

When the first-in-class bispecific antibody-drug conjugate was given at doses combined with Tagrisso, the first-line regimen was found to be tolerable with a manageable side effect profile. The most common treatment-related side effects were hematologic, and a low incidence of side effects led to treatment discontinuation.

“These results are remarkable and suggest that this combination could offer a potentially transformative first-line treatment option for EGFR-mutant NSCLC,” Dr. Fei Zhou, presenting author from Shanghai East Hospital, stated in a news release spotlighting the data. “Importantly, the regimen was also manageable from a safety perspective.”

What Is the Design of the Phase 2 Study Examining Iza-bren Plus Tagrisso in NSCLC?

The phase 2 trial enrolled treatment-naive patients with locally advanced or metastatic NSCLC harboring EGFR-sensitizing mutations. Patients had an ECOG performance status of zero or one and measurable disease by RECIST criteria.

Patients received Iza-bren at doses of 2.2 mg/kg (41 patients), 2.5 mg/kg (40 patients), and 2.75 mg/kg (42 patients) on days one and eight of every three-week cycles and 4 mg/kg (18 patients) and 4.5 mg/kg (13 patients) on day one of every three-week cycles in combination with 80 mg of Tagrisso given once daily. The primary end points were objective response rate and to identify the recommended phase 2 dose of Iza-bren. Secondary end points included progression-free survival, disease control rate, duration of response, and safety. Exploratory end points comprised pharmacokinetics, neutralizing antibody, drug-drug interactions, overall survival, and biomarker analysis.

A total of 154 patients received the regimen spanning doses. At the time of data cutoff, 111 patients were still receiving treatment and 43 had discontinued. The most common reasons for discontinuation were progressive disease (14 patients), followed by side effects (7 patients) and death (2 patients). All patients were included in the safety and efficacy analysis sets. The median patient age was 60 years, and just under half were male (43.5%). More than half were never smokers (60.4%), and most had an ECOG performance status of 1 (80.5%). The median number of metastatic organs was three, and 27.3% of patients had baseline brain metastases. Moreover, 57.8% and 42.2% of patients had EGFR exon 19 deletion mutations or EGFR L858R mutations, respectively.

What Was the Preliminary Efficacy of Iza-bren Plus Tagrisso?

In the total population, the regimen induced an objective response rate of 84.4%; the confirmed objective response rate was 80.5%. At a median follow-up of 12.7 months and 15 months for progression-free survival and overall survival, respectively, the 12-month rates were 86.5% and 95.9%.

In those who received Iza-bren at a dose of 2.2 mg/kg on days 1 and 8 of every 3-week cycles, the objective response rate was 78% and the confirmed objective response rate was 73.2%. In those who received the antibody-drug conjugate at a dose of 2.75 mg/kg on days one and eight of every three-week cycles, the objective response rate was 78.6% and the confirmed objective response rate was 76.2%. In those given Iza-bren at 4 mg/kg on day one of every three-week cycles, the objective response rate and confirmed objective response rate were both 77.8%. In the group of patients who received Iza-bren at a dose of 4.5 mg/kg on day one of every three-week cycles, the objective response rate was 84.6% and the confirmed objective response rate was 76.9%.

Of the patients who received Iza-bren at doses given on the day one and eight schedule (123 patients), 95.9% experienced tumor shrinkage; the median shrinkage percentage was –53.8%. All patients who received Iza-bren at a dose of 2.5 mg/kg on this schedule experienced tumor shrinkage; the median shrinkage percentage was –56.7%.

What Was the Safety Profile of Iza-bren Plus Tagrisso?

The majority of side effects were hematologic, with high incidences of anemia (91.9%), neutropenia (91.1%), leukopenia (91.1%), and thrombocytopenia (75.6%). Non-hematologic side effects included nausea, stomatitis, decreased appetite, vomiting, diarrhea, asthenia, elevated aspartate aminotransferase and alanine aminotransferase levels, hypokalemia, hypoalbuminemia, weight loss, rash, and alopecia.

Grade 3 or higher side effects were manageable with supportive measures, including dose reductions and growth factor support. The discontinuation rate of Iza-bren due to side effects was 13%, and no new safety signals were identified. Zhou noted that there were 2 cases of interstitial lung disease reported; one case was grade 2 and the other was grade 3.

What Are the Next Steps for Iza-bren?

A phase 3 clinical trial is further evaluating Iza-bren at 2.5 mg/kg on days one and eight of every three-week cycles in combination with Tagrisso as a first-line treatment for patients with EGFR-mutated NSCLC. This trial is currently being conducted in China and is designed to confirm the efficacy and safety of the combination in a larger, randomized population.

References

1. “Phase II study of iza-bren (BL-B01D1) in combination with osimertinib in patients with EGFR-mutated locally advanced or metastatic non–small cell lung cancer,” by Dr. Fei Zhou, et al. by. Presented at: IASLC 2025 World Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain. Press Briefing. Abstract 2114.
2. Iza-bren in combination with osimertinib shows 100% response rate in EGFR-mutated NSCLC, phase II study finds,” by WCLC. News Release. September 6, 2025. https://wclc.iaslc.org/

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