Editor’s Note: On May 8, local time, at the ESMO Breast Cancer Congress 2026 (ESMO BC 2026), Professor Jian Zhang from Fudan University Shanghai Cancer Center delivered a rapid oral presentation of efficacy and safety results from the Phase II expansion cohort evaluating the PD-L1×VEGF-A bispecific antibody Pumitamig in combination with the TROP2 antibody-drug conjugate (ADC) BNT325 (sacituzumab drozuntecan) as first-line treatment for advanced or metastatic triple-negative breast cancer (a/mTNBC) (NCT05438329).The study demonstrated high objective response rates and durable tumor responses in an unselected a/mTNBC population without biomarker screening, while maintaining a manageable safety profile, suggesting the potential for a new first-line treatment option in advanced TNBC.
Novel TROP2 ADC Strategies Continue to Advance Frontline TNBC Treatment
In recent years, next-generation TROP2 ADCs have achieved major breakthroughs in first-line treatment. Phase III clinical trials have already demonstrated that TROP2 ADCs combined with immune checkpoint inhibitors (ICIs) outperform traditional chemotherapy, providing new therapeutic options and combination strategies for patients with a/mTNBC.
BNT325 is an investigational TROP2 ADC carrying a novel topoisomerase I inhibitor payload designed to induce DNA damage, immunogenic tumor cell death, and bystander killing effects. Early clinical studies have already demonstrated activity in a/mTNBC.
Pumitamig, meanwhile, is a bispecific antibody simultaneously targeting PD-L1 and VEGF-A. Phase II data previously showed encouraging efficacy when combined with paclitaxel in patients with a/mTNBC.
Preclinical and early clinical evidence suggests that VEGF-A inhibition may improve ADC penetration within the tumor microenvironment (TME) and enhance sensitivity to PD-L1 blockade. Therefore, combining BNT325 with Pumitamig may produce synergistic effects by simultaneously activating antitumor immune responses and modulating the tumor microenvironment to improve ADC distribution and delivery.
Study Design
At this year’s congress, Professor Jian Zhang presented efficacy and safety data from the Phase II portion of a multicenter, open-label Phase I/II study evaluating Pumitamig plus BNT325 as first-line therapy for a/mTNBC.
Eligible patients had:
- Histologically confirmed unresectable advanced or metastatic TNBC
- No prior systemic therapy for advanced disease
- ECOG performance status 0–1
- At least one measurable lesion per RECIST v1.1
Importantly:
- No screening for TROP2 or PD-L1 expression was required
- Patients with asymptomatic brain metastases were eligible
Treatment consisted of:
- Pumitamig 30 mg/kg intravenously every 3 weeks
- BNT325 3.5 mg/kg intravenously every 3 weeks
Primary Endpoints
- Investigator-assessed objective response rate (ORR) per RECIST v1.1
- Safety
Key Secondary Endpoints
- Disease control rate (DCR)
- Duration of response (DoR)
- Progression-free survival (PFS)
Baseline Characteristics
As of the February 28, 2026 data cutoff:
- 30 patients had been enrolled
- Median follow-up was 7.7 months
- 66.7% of patients remained on treatment
- Median treatment duration was 6.9 months (range: 0.7–10.8 months)
Baseline demographic and disease characteristics reflected a real-world frontline a/mTNBC population. A small proportion of patients had previously received:
- Immunotherapy (6.7%)
- Targeted therapy (10.0%)
Efficacy Results
The study demonstrated highly encouraging antitumor activity:
- Confirmed ORR: 76.7%
- Unconfirmed ORR: 83.3%
- DCR: 96.7%
Importantly, all evaluable patients experienced target lesion shrinkage, with the median best percentage change showing overall tumor reduction.
Among responding patients:
- 95.2% of responses remained ongoing at 6 months
At the time of analysis:
- Median duration of response (DoR) had not yet been reached
- Median progression-free survival (PFS) had not yet been reached
Follow-up is ongoing.
Safety Profile
Overall, the combination demonstrated a manageable safety profile.
Key Safety Findings
- Grade 3–4 treatment-related adverse events (TRAEs): 43.3%
- Serious treatment-emergent adverse events (TEAEs): 23.3%
- TEAEs leading to treatment discontinuation: 3.3% (1 patient)
Adverse Events of Special Interest (AESIs)
The most common AESI was stomatitis, although most cases were grade 1–2:
- Grade 3 stomatitis: 16.7%
Other AESIs included:
- Conjunctivitis
- Dry eye
These ocular adverse events were all grade 1–2.
Notably:
- Infusion-related reactions (IRRs): 10.0%
- Interstitial lung disease/noninfectious pneumonitis: 3.3%
All IRR and ILD/pneumonitis events were grade 1–2.
Other Common TRAEs (>15%)
Included:
- Nausea
- Fatigue
- Elevated ALT/AST
- Anemia
- Leukopenia
Most were grade 1–2 in severity.
No unexpected safety signals were observed, and there was no overall trend toward treatment discontinuation due to toxicity.
Conclusion
This Phase II study demonstrated that first-line treatment with Pumitamig plus BNT325 achieved strong antitumor activity in patients with advanced or metastatic TNBC.
Key findings included:
- ORR of 76.7%
- DCR of 96.7%
- Tumor shrinkage in all evaluable patients
- Durable responses lasting beyond 6 months in more than 95% of responders
The regimen also demonstrated a manageable safety profile, with stomatitis being the most common toxicity, predominantly grade 1–2, and only one patient discontinuing treatment because of a TRAE.
In his presentation, Professor Jian Zhang emphasized that these results further validate the synergistic strategy of combining a PD-L1/VEGF-A bispecific antibody with a TROP2 ADC.
He concluded that the approach warrants further confirmation in Phase III clinical trials and has the potential to become a superior first-line treatment option for patients with advanced or metastatic TNBC.
Professor Jian Zhang
