Triple-negative breast cancer (TNBC) is an aggressive subtype accounting for 10–15% of all breast cancers. Often affecting younger women (<40–50), African Americans, Hispanics, or those with BRCA1 mutations, the disease is defined by cells lacking estrogen receptors, progesterone receptors and low HER2 protein, making it unresponsive to hormonal or HER2-targeted therapies. TNBC is also associated with a high risk of central nervous system (CNS) metastases. Brain metastases (BMs) in TNBC are common, devastating, and often associated with poor prognosis, with a median overall survival (OS) ranging from 6 to 12 months. Studies show that up to 40% of patients diagnosed with TNBC develop brain metastases.[1]
Effective systemic treatment options for TNBC with active brain metastases have been lacking, in part due to challenges in drug delivery across the blood-brain barrier (BBB) and the exclusion of patients with active BMs from pivotal clinical trials. While advances such as antibody-drug conjugates (ADCs)* and immune checkpoint inhibitors (ICIs) have dramatically changed the landscape for certain breast cancer subtypes, their efficacy in TNBC with brain involvement remains poorly defined. However, while patients diagnosed with breast cancer, including TNBC, may live longer due to better therapies and treatment options, the development of brain metastases generally limits their survival. [2]
Adebrelimab (SHR-1316; AiRuiLi®; 艾瑞利; Jiangsu Hengrui Pharmaceuticals/Shanghai Shengdi Pharmaceutical), approved in 2023 by China’s National Medical Products Administration (NMPA), formerly the China Food and Drug Administration (CFDA) for treating extensive-stage small-cell lung cancer (ES-SCLC) in combination with chemotherapy, is a next-generation, high-affinity, humanized IgG4 anti–PD-L1 antibody that has demonstrated survival benefits and a manageable safety profile in extensive-stage small cell lung cancer (SCLC) and is now being investigated for additional malignancies, including TNBC.[3]
The combination of ICIs with anti-angiogenic agents (such as bevacizumab; Avastin®; Genentech/Roche) and platinum-based chemotherapy (cisplatin/carboplatin) has shown promise in other solid tumors with CNS involvement. Building on these findings, the phase 2 ABC (BCBM-001) study (NCT04303988)** evaluated the efficacy and safety of adebrelimab, bevacizumab, and platinum chemotherapy (cisplatin or carboplatin) in patients with TNBC and active brain metastases.
Study design
Between July 2020 and October 2024, the single-arm, investigator-initiated phase 2 ABC study enrolled 35 patients with pathologically confirmed TNBC and measurable, active brain metastases at the Fudan University Shanghai Cancer Center. Eligible participating patients were between 18 and 70 years old, had an ECOG performance status of 0–2, and were unsuitable for curative surgery or radiation therapy. Key exclusions included prior exposure to bevacizumab or anti–PD-1/PD-L1 therapies, except for platinum agents in platinum-sensitive cases.
Patients received intravenous adebrelimab (20 mg/kg), bevacizumab (7.5 mg/kg), and cisplatin (75 mg/m², n=30) or carboplatin (AUC=5, n=5) every 3 weeks. Treatment continued until disease progression, unacceptable toxicity, withdrawal, or study completion.
The primary endpoint was the CNS objective response rate (CNS-ORR) per RANO-BM criteria.*** [4] Secondary endpoints included CNS clinical benefit rate (CNS-CBR), progression-free survival (PFS), CNS-PFS, OS, site of first progression, and safety. Tumor molecular subtyping and PD-L1 expression were examined as exploratory biomarkers.
Study Results
Patient Characteristics
- All 35 enrolled patients were female, with a median age of 50 years (range 36–64).
- Median prior lines of therapy for metastatic disease: 2 (range 0–4).
- 14.3% had prior CNS-directed radiation; 42.9% had baseline neurologic symptoms.
Efficacy
- CNS-ORR: 77.1% (27/35; 95% CI: 59.9–89.6%), with 5 complete responses (CRs) and 22 partial responses (PRs).
- CNS-CBR: 80.0% (28/35; 95% CI: 63.1–91.6%).
- Median overall PFS: 8.3 months (95% CI: 5.8–11.5).
- Median CNS-PFS: 10.3 months (95% CI: 7.4–14.3).
- Median OS: 21.1 months (95% CI: 13.2–not reached).
- Among 28 patients who progressed, progression was intracranial-only in 32.1%, extracranial-only in 35.7%, and both in 32.1%.
- Neurologic symptom relief was achieved in over half of symptomatic patients.
- Subgroup analyses suggested improved outcomes in patients with PD-L1 CPS ≥1 (median CNS-PFS 14.3 months) and in those with the immunomodulatory TNBC subtype.
Safety
- All patients experienced at least one treatment-related adverse event (TRAE).
- Most common AEs (any grade): anemia (80.0%), hypomagnesemia (74.3%), neutropenia (71.4%), and asthenia (62.9%).
- Grade ≥3 TRAEs occurred in 65.7% of patients, most commonly thrombocytopenia (11.4%), neutropenia, peripheral sensory neuropathy, and hypertension (8.6% each).
- Serious adverse events occurred in 14.3% of patients, with no treatment-related deaths.
- Chemotherapy dose modifications were common, but dose reductions did not appear to compromise efficacy.
High intracranial response
This is the first prospective study to demonstrate that the triplet combination of adebrelimab, bevacizumab, and platinum chemotherapy yields high intracranial response rates and prolonged CNS-PFS in patients with TNBC and active brain metastases. The confirmed CNS-ORR of 77.1% compares favorably with previous reports for other regimens, including doublet therapies and antibody-drug conjugates in HER2-positive or TNBC populations with brain metastases.
The median CNS-PFS of 10.3 months and median OS of 21.1 months are markedly longer than historical benchmarks for this population. Notably, patients with PD-L1 CPS ≥1 and the immunomodulatory subtype showed trends toward even better outcomes, suggesting potential predictive biomarkers for response.
The safety profile was manageable, with hematologic toxicities predominating and no unexpected adverse events or treatment-related deaths. The incidence of grade ≥3 TRAEs is comparable to those reported in prior pivotal trials of immunotherapy and chemotherapy in metastatic TNBC.
Mechanistic Rationale and Broader Implications
Adebrelimab’s design as an IgG4 anti–PD-L1 antibody with Fc modifications minimizes unwanted immune cell depletion and enhances specificity for the PD-1/PD-L1 axis. Its high affinity (Kd ~0.27 × 10-10 nmol/L) and unique epitope targeting may contribute to its efficacy in the CNS microenvironment. The combination with bevacizumab (an anti-VEGF agent) may further improve T-cell infiltration and overcome the immunosuppressive tumor vasculature, while platinum agents remain a backbone for TNBC therapy due to their cytotoxic and radiosensitizing properties.
Emerging data support the synergy of ICIs with antiangiogenic therapy and chemotherapy, potentially improving immune cell access to brain metastases and sustaining antitumor responses. This triplet approach is among the first to demonstrate robust activity in TNBC with active BMs, a group for whom effective systemic options have been extremely limited.
The combination of adebrelimab, bevacizumab, and platinum chemotherapy is the first regimen to demonstrate robust intracranial antitumor activity and prolonged CNS-PFS in patients with triple-negative breast cancer and active brain metastases, with a manageable safety profile. These findings warrant further investigation in randomized controlled trials to establish the therapeutic benefit of this regimen and to identify biomarkers predictive of response.
Study Limitations
While the early results are highly promising for a patient population with limited treatment options, the authors noted that the study uses a single-arm design, has a relatively small sample size, and lacks formal quality-of-life or neurocognitive assessments. Additionally, subgroup analyses are exploratory and require validation in larger cohorts. Hence, the authors argue that further, ongoing, randomized clinical trials are essential to confirm the benefit of the combination of adebrelimab, bevacizumab, and platinum chemotherapy. This, the authors say, will clarify the risk–benefit profile before wider adoption of the treatment strategy.
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Note: * Sacituzumab Govitecan (Trodelvy®; Gilead Sciences), a TROP-2 targeting ADC, is approved for the treatment of advanced, previously treated TNBC, significantly improving survival compared to standard chemotherapy. Another antibody-drug conjugate, datopotamab deruxtecan (Datroway®; Daiichi Sankyo and AstraZeneca), approved in January 2025 for metastatic hormone receptor (HR)-positive, HER2-negative breast cancer, shows significant promise in improving survival in metastatic TNBC. However, data on its specific efficacy against active brain metastases are primarily emerging from studies in lung cancer (NSCLC), suggesting potential intracranial activity.
** The study was supported by the National Natural Science Foundation of China, Shanghai Science and Technology Innovation Action Plan, and Jiangsu Hengrui Pharmaceuticals. Adebrelimab was provided free of charge for this study.
*** Since 2015, the RANO-BM criteria (Response Assessment in Neuro-Oncology working group for Brain Metastases) have become a standard schema for evaluating brain metastases treatment response, providing uniform definitions and methodology, particularly practical in prospective clinical trials of systemic therapy. [3]
Clinical trials
A Phase II Study of Triple-negative Breast Cancer Brain Metastases. – ClinicalTrials.gov ID NCT04303988
Adebrelimab Combined With Dalpiciclib and Standard Endocrine Therapy for HR+/HER2 – Advanced Breast Cancer – ClinicalTrials.gov ID NCT06149130
Study of SHR-A1921 Combined Adebrelimab in HR-positive, HER2-negative Advanced Breast Cancer – ClinicalTrials.gov ID NCT06470672
SHR-A2102 Combined With Adebrelimab as Neoadjuvant Therapy for Early Triple-Negative Breast Cancer – ClinicalTrials.gov ID NCT06819319
Study of ADCs Combined With Adebrelimab in HER2-negative Advanced Breast Cancer – ClinicalTrials.gov ID NCT06433609
SHR-A1811 Alone or in Combination With Adebrelimab as Neoadjuvant Treatment in HR Positive/HER2 Low Breast Cancer – ClinicalTrials.gov ID NCT06340230
Highlights of prescribing information
Bevacizumab (Avastin®; Genentech/Roche)[Prescribing Information]
Sacituzumab Govitecan (Trodelvy®; Gilead Sciences)[Prescribing Information]
Datopotamab deruxtecan (Datroway®; Daiichi Sankyo and AstraZeneca)[Prescribing Information]
Reference
[1] Bansal R, Van Swearingen AED, Anders CK. Triple Negative Breast Cancer and Brain Metastases. Clin Breast Cancer. 2023 Dec;23(8):825-831. doi: 10.1016/j.clbc.2023.07.008. Epub 2023 Aug 4. PMID: 37586926.
[2] Kuksis M, Gao Y, Tran W, Hoey C, Kiss A, Komorowski AS, Dhaliwal AJ, Sahgal A, Das S, Chan KK, Jerzak KJ. The incidence of brain metastases among patients with metastatic breast cancer: a systematic review and meta-analysis. Neuro Oncol. 2021 Jun 1;23(6):894-904. doi: 10.1093/neuonc/noaa285. PMID: 33367836; PMCID: PMC8168821.
[3] Li T, Zhou T, Wang B, Tao Z, Zhao M, Wang L, Jin J, Zhao Y, Gong C, Cao J, Miao H, Peng W, Wang J, Jin M, Hu X, Zhang J. Phase II Clinical Study of Adebrelimab and Bevacizumab Combined With Cisplatin/Carboplatin in Patients With Triple-Negative Breast Cancer With Brain Metastases (ABC Study). J Clin Oncol. 2026 Mar 4:JCO2502021. doi: 10.1200/JCO-25-02021. Epub ahead of print. PMID: 41779972.
[4] Kashtanova T, Ramakrishna N. Challenges of Applying the RANO-BM Criteria for Characterization of Brain Metastases Treatment Response. Curr Oncol. 2026 Jan 28;33(2):77. doi: 10.3390/curroncol33020077. PMID: 41744841; PMCID: PMC12938896.
Feature image © 2018 – 2026 Fotolia/Adobe. Used with permission.
DOI: 10.14229/onco.2026.04.08.002
