— Three-fold increase in PFS with rolditamig deuderuxtecan versus chemotherapy
October 24, 2026 • 4 min read
Patients with recurrent or metastatic HER2-low breast cancer had dramatic improvement in progression-free survival (PFS) when treated with a novel antibody-drug conjugate (ADC) targeting HER2, a large randomized trial showed.
Median PFS tripled from 5.5 months with chemotherapy to 16.4 months with rolditamig deuderuxtecan (TQB2102). A preliminary analysis of overall survival (OS), a secondary endpoint, showed more than a 50% reduction in the hazard ratio with the bispecific antibody in both the majority subgroup with hormone receptor (HR)-positive/HER2-low breast cancer and in overall HER2-low population. In prespecified exploratory analyses, even larger improvements in PFS and OS were seen in patients with HR-negative/HER2-low breast cancer.
Treatment-related adverse events (TRAEs) occurred in a similar proportion of patients treated with rolditamig deuderuxtecan or chemotherapy, reported Shusen Wang, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, at the European Society for Medical Oncologyopens in a new tab or window (ESMO) congress in Madrid.
"Rolditamig deuderuxtecan demonstrated a statistically significant and clinically meaningful improvement in PFS and a clear trend toward OS benefit versus chemotherapy in patients with HER2-low recurrent or metastatic breast cancer," said Wang. "PFS benefits were observed across all prespecified subgroups. The objective response rate in the HER2-low population was 68.8% with rolditamig deuderuxtecan and 31% with chemotherapy. The overall safety profile was manageable and generally consistent with previous experience with TQB2102, with a low incidence of ILD [interstitial lung disease]."
"The results of the APEX-Breast01 trial support TQB2102, a first-in-class HER2 biparatopic ADC, as a promising treatment option for patients with HER2-low breast cancer who have not previously received chemotherapy in the metastatic setting," he added.
APEX-Breast01 demonstrated a "substantial, impressive" improvement in PFS, which will help usher rolditamig deuderuxtecan into an already-crowded treatment landscape, joining multiple ADCs in late-stage clinical development, said ESMO invited discussant Barbara Pistilli, MD, of Gustave Roussy Cancer Center in Villejuif, France. TQB2102 differs from trastuzumab deruxtecan (T-DXd, Enhertu), the first approved HER2-targeting ADC, primarily in the antibody, which is biparatopic, targeting two non-overlapping epitopes of HER2opens in a new tab or window.
Speaking beyond the current study to the crowded ADC field in general, Pistilli asked, "Do these pharmacological differences translate into clinically meaningful advantages? We don't know, because we don't have a study with head-to-head ADC comparison in this setting," adding that "pivotal trials should generate evidence for regulatory approval by comparing a new ADC with the current standard of care."
"If we want to establish whether pharmacological innovation translates into clinical benefit [we need to] identify biomarkers that guide optimal patient-ADC matching," she added. "In the near future, we need early-phase trials that integrate multidimensional biomarkers, including quantitative assessment of the target, and adaptive trial design for a more biologically informed patient-ADC matching."
Pistilli emphasized that "we need late-phase trials in which multidimensional biomarkers should be used, not only to pick the right ADC for the patient, but the optimal ADC sequencing strategy. This is particularly important because, as we have just seen, ADCs with the same target and the same payload are increasingly available."
Rolditamig deuderuxtecan's biparatopic targeting of HER2 enhances receptor crosslinking and internalization, suggesting a greater potential for affecting HER2-low malignancies, said Wang. The agent led to promising efficacy in phase I trialsopens in a new tab or window, including an objective response rate of 58%.
Clinical evaluation continued in the phase III APEX-Breast01 trial (conducted only in China) involving patients with HER2-low metastatic breast cancer, defined as immunohistochemistry (IHC) 1 or IHC2+/in-situ hybridization-negative, and no prior chemotherapy in the metastatic setting. Investigators randomized 543 patients to single-agent TQB2102 or investigator's choice of chemotherapy.
The study population included 461 patients with HR-positive breast cancer and 82 with HR-negative breast cancer. The primary endpoint was PFS by independent review in the HR-positive subgroup. More than 60% of the patients had three or more metastatic sites, and they had received a median of two prior lines of systemic therapy.
The trial had a prespecified interim analysis after 216 (75%) of PFS events. The analysis showed a 71% reduction in the PFS hazard in favor of TQB2102 (95% CI 0.22-0.39, P<0.0001). The 6-month PFS was 81.4% with the ADC and 45.9% in the control group. Investigator-assessed PFS was consistent with the independent review, showing a 69% reduction in the PFS hazard.
After a median survival follow-up of 8.6 months, the preliminary OS analysis of the HR-positive subgroup showed that 7% of the TQB2102 group had died versus 13.3% of the control group, representing a 53% reduction in the hazard (95% CI 0.26-0.87). The OS event rate in the HR-negative subgroup also favored TQB2102 (6.3% vs 13.1%, HR 0.44, 95% CI 0.25-0.79).
Analysis of objective response rate, clinical benefit rate, and duration of response also showed large advantages favoring TQB2102.
Grade ≥3 TRAEs occurred more often with TQB2102 (69.1% vs 42.4%), but the rate of discontinuation because of TRAEs was 1.5% in each group. The most common TRAEs in both groups were hematologic in nature.
TQB2102 has yet to be approved anywhere in the world. The FDA granted breakthrough therapy designationopens in a new tab or window for the ADC in 2025 for HER2-positive colorectal cancer.