On September 6, 2025, at the MOASC and ANCO Immuno-Oncology Symposium, Dr. Alexis LeVee, MD, from UCLA’s Division of Hematology/Oncology, shared exciting 2025 breast cancer immunotherapy trial updates. The session covered approved treatments, early-stage and metastatic strategies, new combinations, emerging drugs, and biomarkers. Therefore, these insights are vital for oncologists adapting to evolving care in triple-negative breast cancer (TNBC) and beyond.
Approved Immunotherapy Treatments
Breast cancer immunotherapy trial updates refine standards. Pembrolizumab is approved for early TNBC based on KEYNOTE-522. This trial showed better pathologic complete response (pCR) rates, event-free survival (EFS), and overall survival (OS) with added immunotherapy.
In KEYNOTE-522, pembrolizumab plus chemo gave a 64.8% pCR versus 51.2% with placebo (delta 13.6%, P=0.00055). Later analyses confirmed improved OS and lower recurrence risks. As a result, the regimen’s toxicity pushes for de-escalation efforts.
Neoadjuvant Trials: Reducing Therapy Intensity
A key focus in 2025 breast cancer immunotherapy trial updates is lowering treatment intensity. The Phase II neoPACT trial used an anthracycline-free approach with carboplatin, docetaxel, and pembrolizumab. It achieved a 58% pCR rate, matching KEYNOTE-522 but with fewer cardiac and cancer risks.
The NeoSTAR trial combined sacituzumab govitecan (SG) with pembrolizumab. It reported a 32% pCR alone and 50% with added non-anthracycline chemo.
In the iSPY2.2 trial, datopotamab deruxtecan (Dato-DXd) plus durvalumab yielded a 65% pCR in HER2- Immune+ cases. This rose to 77% with extra chemo and IO.
The BELLINI trial explored chemo-free options for high-TILs (≥50%) TNBC patients. Dual ICIs—nivolumab + ipilimumab—gave 33% pCR, while nivolumab + relatlimab reached 47%. This suggests some patients may skip chemo. Moreover, more trials are needed to confirm this.
Ongoing Phase III studies, like SCARLET and TROPION-Breast04, will validate these approaches.
Adjuvant Setting: Improving Post-Surgery Care
For patients with pCR, can adjuvant immunotherapy be reduced? Neoadjuvant-only trials like neoPACT showed over 95% EFS in pCR cases. Benefits were greater with neoadjuvant versus adjuvant ICI. Furthermore, trials such as OptimICE-pCR and OPT-PEMBRO are testing shorter pembrolizumab use.
For residual disease, escalation is key. Ongoing Phase III 2025 breast cancer immunotherapy trial updates include:
- SG + pembrolizumab (ASCENT-05) or SG alone (SASCIA)
- Dato-DXd +/- durvalumab (TROPION-Breast03)
- Sacituzumab tirumotecan + pembrolizumab (TROFUSE-12)
- T-DM1 + atezolizumab (ASTEFANIA)
These aim to boost cure rates using ADCs with ICIs.
Metastatic TNBC: New Combinations and Data
In advanced cases, ASCENT-04 positioned SG + pembrolizumab as a potential new standard for PD-L1+ mTNBC. Median PFS hit 11.2 months versus 7.8 months with chemo + pembrolizumab (HR 0.65, P<0.001), a 35% risk drop.
Side effects matched known profiles, with no extra immune issues.
New strategies include ICI + ADCs (e.g., TROPION-Breast05), ICI + targeted drugs like PARP inhibitors, and emerging treatments such as anti-LAG-3, TIGIT inhibitors, bispecific antibodies, cellular therapies (TILs, CAR-T), and vaccines.
The Phase II ivonescimab trial in 1L mTNBC showed a 52.7% ORR and 9.7-month PFS, beating KEYNOTE-355 results regardless of PD-L1 status. Additionally, a Phase III trial is ongoing.
Biomarkers for Personalized Care
Biomarkers like MammaPrint, TILs, and ImPrint signatures guide patient selection. Higher TILs linked to better pCR in KEYNOTE-173, neoPACT, and BELLINI. ImPrint aided response predictions in iSPY2.2, enabling tailored de-escalation.
