Innovent's IBI354 HER2 ADC posts high response rate in first-line breast cancer trial

Overview

Updated 1 hour ago

Innovent presented Phase 2 results at the European Society for Medical Oncology (ESMO) congress showing its experimental HER2-targeting antibody-drug conjugate (ADC), IBI354, produced a 95% confirmed response rate in first-line HER2-positive metastatic breast cancer. All 20 patients responded to IBI354 plus pertuzumab, and none developed interstitial lung disease (ILD), the lung inflammation that is a known risk with the current standard drug.

The results set up a race against trastuzumab deruxtecan (Enhertu), which established the first-line benchmark in the DESTINY-Breast09 trial. Innovent has already started a Phase 3 study, HeriCare-Breast01, comparing IBI354 with or without pertuzumab against the current standard of care, and it is planning additional Phase 3 trials in adjuvant and neoadjuvant breast cancer.

Why it matters

If IBI354 matches Enhertu's efficacy with less interstitial lung disease risk, first-line HER2-positive breast cancer treatment could shift toward a next-generation ADC with a better safety profile.

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Key Indicators

95%

Confirmed objective response rate (cORR)

In 20 first-line HER2-positive metastatic breast cancer patients receiving IBI354 plus pertuzumab, as of July 1, 2026.

Patients enrolled in Phase 2 first-line cohort

All received IBI354 at 9 mg/kg every three weeks plus pertuzumab.

72.4%

Objective response rate in earlier heavily pretreated cohort

Phase 1/2 data as of March 2025 in 29 breast cancer patients at the 9 mg/kg dose, presented at ASCO 2025.

1.2%

Interstitial lung disease rate in Phase 1/2 (all grade 1)

From 368 solid tumor patients in the global Phase 1 study; the first-line Phase 2 cohort reported no ILD.

20%

Patients with Grade 3 or higher treatment-related adverse events

Common events were nausea, vomiting, and anemia. No dose reductions, one discontinuation, no deaths.

Voices

Curated perspectives — historical figures and your fellow readers.

Ever wondered what historical figures would say about today's headlines?

People Involved

Xiaohua Zeng

Professor, Chongqing University Cancer Hospital; presenter of IBI354 Phase 2 first-line data

Lead investigator presenting Poster 1776P at ESMO 2026

Hui Zhou

Chief R&D Officer (Oncology Pipeline), Innovent Biologics

Oversees IBI354 Phase 3 development including HeriCare-Breast01 and HeriCare-Ovarian01

Organizations Involved

Innovent Biologics

Biopharmaceutical company (HKEX: 01801)

Developer of IBI354; running two Phase 3 trials across breast and ovarian cancer

China-based biopharmaceutical company developing IBI354 on its proprietary SoloTx ADC platform.

European Society for Medical Oncology (ESMO)

Professional medical society

Host of the 2026 congress where IBI354 data was presented

Europe's leading oncology society, whose annual congress is a primary venue for presenting cancer trial data.

Timeline

March 2025 October 2026

6 events Latest: Today

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October 2026
Innovent issues press release on Phase 2 results
Today Announcement

Company highlights efficacy and safety data, positioning IBI354 as potentially best-in-class and progressing toward first-line registration.
Today
IBI354 Phase 2 data presented at ESMO Congress (Poster 1776P)
Conference

95% confirmed response rate and 100% disease control rate reported; no interstitial lung disease observed.
Yesterday
July 2026
Phase 2 first-line data locked at 20 patients
Clinical Data

Median follow-up 9.6 months; one progression event and no deaths in the IBI354 plus pertuzumab cohort.
July 1st, 2026
February 2026
First patient dosed in HeriCare-Breast01 Phase 3 trial
Clinical Trial

Pivotal study compares IBI354 with or without pertuzumab against paclitaxel plus trastuzumab and pertuzumab in first-line HER2-positive breast cancer.
February 12th, 2026
June 2025
Phase 1/2 data presented at ASCO 2025
Conference

IBI354's safety and efficacy across solid tumors presented at the American Society of Clinical Oncology annual meeting.
June 2025
March 2025
Phase 1/2 data cut-off shows 72.4% ORR in pretreated breast cancer
Clinical Data

In 29 heavily pretreated breast cancer patients at 9 mg/kg, confirmed response rate reached 72.4% with median PFS of 14.1 months.
March 24th, 2025

Scenarios

IBI354 wins first-line approval after HeriCare-Breast01 readout

Likely Resolves by End of 2030

Discussed by: Innovent management; oncology analysts tracking the ADC class

HeriCare-Breast01 is already enrolling. If the Phase 3 confirms a progression-free survival benefit over the standard of care and maintains the low ILD rate seen in earlier studies, IBI354 could reach regulators at the end of the decade. Innovent is also planning Phase 3 trials in adjuvant and neoadjuvant breast cancer, which would broaden the indication set.

HeriCare-Breast01 misses its primary endpoint

Unlikely Resolves by End of 2029

Discussed by: Clinical trial watchers; analysts comparing IBI354 to trastuzumab deruxtecan

The Phase 3 tests IBI354 against paclitaxel plus trastuzumab and pertuzumab, the current first-line regimen. If it fails to show progression-free survival benefit, the program would stall and first-line registration would be out of reach. The ovarian cancer trial, HeriCare-Ovarian01, would remain a separate path to approval.

IBI354 approved but interstitial lung disease rate rises in Phase 3

Possible Resolves by End of 2029

Discussed by: Observers of ADC safety data comparing IBI354 with Enhertu's known ILD profile

The 20-patient Phase 2 reported zero ILD events, and the broader Phase 1/2 showed a 1.2% rate, all grade 1. A larger, less selected Phase 3 population could reveal more lung toxicity. If the rate climbs toward the range regulators have accepted for trastuzumab deruxtecan, the safety case that differentiates IBI354 would narrow.

Historical Context

2 moments from history that rhyme with this story — and how they unfolded.

2019-2025

Trastuzumab deruxtecan (Enhertu) redefines first-line HER2-positive breast cancer

Daiichi Sankyo and AstraZeneca's trastuzumab deruxtecan, an HER2-targeting ADC, was approved in 2019 for previously treated HER2-positive metastatic breast cancer. The DESTINY-Breast09 trial later established it as a first-line standard, setting a high efficacy benchmark for the class.

Then

Enhertu became the backbone of HER2-positive breast cancer treatment, with regulatory submissions for first-line use expected.

Now

Its interstitial lung disease risk, a known toxicity of the drug, opened the door for competitors offering comparable efficacy with a cleaner safety profile.

Why this matters now

IBI354 is positioned directly against Enhertu's first-line benchmark, with the Phase 2 safety data as its point of differentiation.

2013

Ado-trastuzumab emtansine (Kadcyla) pioneers the HER2 ADC class

Roche's ado-trastuzumab emtansine, or Kadcyla, was approved for HER2-positive metastatic breast cancer in 2013. It was the first antibody-drug conjugate to succeed in this setting, linking trastuzumab to a cytotoxic payload.

Then

Kadcyla extended the HER2 treatment paradigm beyond antibody and small-molecule therapies.

Now

It proved the ADC concept but showed limits in efficacy, which newer conjugates with higher drug-to-antibody ratios and better linker design aimed to overcome.

Why this matters now

IBI354 follows this generational arc, using a drug-to-antibody ratio of 8 and a hydrophilic linker to improve potency while limiting toxicity.