A phase 2 pilot trial at Johns Hopkins' Sidney Kimmel Comprehensive Cancer Center is enrolling patients with stage II/III triple-negative breast cancer to assess whether early PET imaging and biomarker changes after one cycle of paclitaxel/carboplatin/pembrolizumab can guide individualized neoadjuvant sequencing and rescue strategies.
Investigators at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins have initiated a phase 2 pilot trial (NCT06245889) examining the utility of early metabolic imaging to inform response-adapted neoadjuvant therapy in stage II and III triple-negative breast cancer (TNBC). The trial is currently recruiting and aims to characterize PET dynamics and circulating biomarkers following a single cycle of chemoimmunotherapy as potential predictors of pathologic response.
All enrolled participants receive four cycles of paclitaxel, carboplatin, and pembrolizumab as initial neoadjuvant therapy. FDG-PET is performed at baseline and after cycle one, with breast MRI obtained upon completion of the full induction regimen. This early imaging window is intended to capture metabolic response signals before clinical or radiologic response becomes apparent on conventional imaging.
Response-adapted escalation is built into the protocol design. Participants achieving complete clinical response proceed directly to surgery, while those with residual disease undergo neoadjuvant rescue with four cycles of doxorubicin and cyclophosphamide prior to resection. For patients with pathologic residual disease at surgery, adjuvant intensification—potentially incorporating doxorubicin/cyclophosphamide/pembrolizumab, capecitabine, or olaparib—is determined at the treating oncologist's discretion.
The trial's primary focus on early PET and biomarker dynamics addresses a critical unmet need in TNBC management: identifying non-responders early enough to pivot therapy before surgical delay or disease progression. The pilot design limits definitive conclusions about efficacy endpoints, and the optimal PET response threshold for guiding rescue decisions remains to be established.
Key points
- Phase 2 pilot trial at Johns Hopkins enrolling stage II/III TNBC patients to evaluate early PET and biomarker dynamics after one cycle of paclitaxel/carboplatin/pembrolizumab
- FDG-PET performed at baseline and post-cycle one; breast MRI obtained after completion of four induction cycles
- Response-adapted design: complete clinical responders proceed to surgery; residual disease triggers doxorubicin/cyclophosphamide rescue prior to resection
- Adjuvant options for post-surgical residual disease include pembrolizumab-containing regimens, capecitabine, or olaparib at oncologist discretion
- Trial status: actively recruiting (NCT06245889); pilot design limits generalizability of efficacy conclusions
Why it matters
Early metabolic response assessment via FDG-PET could enable timely de-escalation or rescue in TNBC, a subtype with limited targeted options and significant heterogeneity in neoadjuvant response. Defining reliable early imaging and biomarker thresholds may ultimately reduce unnecessary toxicity for responders and prevent surgical delay for non-responders.