Novel ADC Achieves Impressive PFS Advantage In HER2-Low Metastatic Breast Cancer

The investigational antibody-drug conjugate TQB2102 extended median progression-free survival to 16.4 months, compared with 5.5 months with chemotherapy, in a phase III trial of recurrent or metastatic HER2-low breast cancer. The APEX-Breast01 results, reported at the European Society for Medical Oncology congress, suggest a substantial benefit in delaying disease progression, but overall-survival findings are still preliminary and the drug is not approved anywhere.

APEX-Breast01 randomized 543 patients in China to receive either TQB2102, also called rolditamig deuderuxtecan, or investigator-selected chemotherapy. Participants had HER2-low disease—defined as immunohistochemistry (IHC) 1+ or IHC 2+ with a negative in-situ hybridization result—and had not received chemotherapy for metastatic disease. The primary endpoint was progression-free survival, assessed by independent review, in the hormone receptor-positive subgroup.

At a prespecified interim analysis, researchers reported a 71% reduction in the hazard of progression or death with TQB2102 in the primary analysis, with a 95% confidence interval of 0.22 to 0.39 and P<0.0001. Six-month progression-free survival was 81.4% in the ADC group and 45.9% in the chemotherapy group. Investigator-assessed progression-free survival was consistent with the independent review, with a reported 69% reduction in the hazard.

The objective response rate in the overall HER2-low population was 68.8% with TQB2102 and 31% with chemotherapy. After a median 8.6 months of survival follow-up, an interim overall-survival analysis favored the ADC in both the hormone receptor-positive subgroup and the full population, but the source report characterizes the survival evidence as preliminary. The trial included 461 hormone receptor-positive and 82 hormone receptor-negative patients.

A Longer Delay in Disease Progression

The reported difference in median progression-free survival could matter to patients whose cancer has returned or spread and who have not yet received chemotherapy for metastatic disease. In this trial, the result indicates a longer period before documented progression or death for patients assigned to TQB2102 than for those assigned to chemotherapy. It does not establish that the ADC improves survival or is better than other ADCs, and the reported median figures do not predict an individual patient’s outcome.

Safety needs to be weighed alongside efficacy. Although the investigators described treatment-related adverse events as occurring in a similar proportion overall, grade 3 or higher treatment-related events were more frequent with TQB2102: 69.1%, compared with 42.4% in the chemotherapy group. Discontinuation due to treatment-related events was 1.5% in each group. These results make the severity and management of side effects an important part of interpreting the apparent benefit.

The findings add another candidate to a field where several HER2-targeting ADCs are being developed. Whether TQB2102 offers a clinical advantage over existing or emerging drugs cannot be determined from this trial, which compared it with chemotherapy rather than another ADC.

How TQB2102 Differs From Other ADCs

TQB2102 is described as a HER2 biparatopic ADC: its antibody binds two non-overlapping sites on HER2. Presenter Shusen Wang of Sun Yat-sen University Cancer Center said this design may increase receptor crosslinking and internalization. That is a proposed explanation for the drug’s activity, not proof that the design itself caused the difference in outcomes.

The trial enrolled patients with HER2-low disease, a category defined by low levels of HER2 expression rather than the higher expression associated with HER2-positive breast cancer. More than 60% of participants had at least three metastatic sites, and patients had received a median of two prior lines of systemic therapy. The phase III study followed promising phase I results, but it was conducted only in China.

ESMO discussant Barbara Pistilli of Gustave Roussy Cancer Center noted that the comparison does not answer whether TQB2102 is superior to trastuzumab deruxtecan or another ADC. TQB2102 has not been approved anywhere in the world, according to the source report.

“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.”

— Shusen Wang, MD, Sun Yat-sen University Cancer Center

Survival and Comparative Benefit Remain Open

The overall-survival analysis is preliminary, based on a median follow-up of 8.6 months. In the hormone receptor-positive subgroup, deaths had occurred in 7% of the TQB2102 group and 13.3% of the chemotherapy group; the reported hazard ratio was 0.47, with a 95% confidence interval of 0.26 to 0.87. For the hormone receptor-negative subgroup, the reported death rates were 6.3% and 13.1%, respectively, with a hazard ratio of 0.44. These interim results require longer follow-up before the effect on survival can be judged reliably.

The source material does not provide full details on the duration of response, complete safety-event breakdowns, or the final analysis plan and timing. It also does not establish how results from a China-only trial will translate to other populations or health systems. No head-to-head comparison with another ADC was conducted, so the relative performance of TQB2102 against those treatments remains unknown.

Wang described a low incidence of interstitial lung disease and a manageable safety profile, but the supplied report does not give a specific rate for that condition. The FDA status mentioned in the source is incomplete; the confirmed information provided is that TQB2102 has not been approved anywhere.

Longer Follow-Up and Regulatory Evidence

Further follow-up is needed to clarify whether the progression-free survival advantage translates into a durable overall-survival benefit and to better characterize adverse events. The report does not specify when the next analysis will be released or provide a regulatory submission timetable.

Any future evaluation will also need to address how TQB2102 compares with the current standard of care and other ADCs. Pistilli said trials should generate evidence against the current standard and use biomarkers to guide treatment selection and sequencing. Until those comparisons and longer-term results are available, the APEX-Breast01 findings support continued study of TQB2102 but do not establish its place in treatment or its approval status.

Key Questions

What did the APEX-Breast01 trial find?

Median progression-free survival was 16.4 months with TQB2102 and 5.5 months with chemotherapy among patients with recurrent or metastatic HER2-low breast cancer. The trial also reported a higher objective response rate with the ADC.

Does TQB2102 improve overall survival?

The interim overall-survival analysis favored TQB2102, but follow-up was a median of 8.6 months and the findings are preliminary. The available results do not establish a confirmed overall-survival benefit.

Is TQB2102 approved?

No. The source report says TQB2102 has not been approved anywhere. The trial results alone do not establish approval or availability.

How did the side effects compare?

Grade 3 or higher treatment-related adverse events were reported in 69.1% of patients receiving TQB2102 and 42.4% receiving chemotherapy. Treatment-related adverse events led to discontinuation in 1.5% of each group.

Was TQB2102 compared with another HER2-targeting ADC?

No. APEX-Breast01 compared TQB2102 with investigator-selected chemotherapy. It did not directly compare TQB2102 with trastuzumab deruxtecan or another ADC, so their relative effectiveness is unknown.

Source: rss