Results from a Phase 2 trial (NCT04849364) investigating genomically directed therapy for patients with residual triple-negative breast cancer (TNBC) were posted on ClinicalTrials.gov on 2025-05-31. The study included pembrolizumab as an intervention and reported a 100% 2-year Disease Free Survival (DFS) in the ctDNA-positive, genomically directed PI3K pathway arm (Arm 1c), compared to 0% in the ctDNA-positive standard of care arm (Arm 2).
Background
The trial, titled "Circulating Tumor DNA Enriched, Genomically Directed Post-neoadjuvant Trial for Patients With Residual Triple Negative Breast Cancer," investigated treatment strategies for patients with residual triple-negative breast cancer (TNBC) following pre-operative therapy. It aimed to stratify patients based on plasma circulating tumor DNA (ctDNA) positivity and genomic markers to guide treatment decisions.
Trial design
The study (NCT04849364) was a Phase 2 trial that enrolled 52 participants with Breast Cancer and Triple Negative Breast Cancer. It was designed as a 3-arm study, stratifying patients with residual TNBC disease after pre-operative therapy into one of three arms based on plasma ctDNA positivity and genomic marker(s). The interventions investigated included capecitabine, talazoparib, pembrolizumab, and inavolisib. The trial's overall status is listed as TERMINATED.
Key results
The trial reported several key measurements related to disease-free survival (DFS) and distant disease-free survival (DDFS) across the three study arms:
- For Disease Free Survival (DFS) at 2 Years:
- Arm 1c: ctDNA Positive Genomically Directed - PI3K Pathway showed 100 Percentage of participants.
- Arm 2: ctDNA Positive - Standard of Care showed 0 Percentage of participants.
- Arm 3: ctDNA Negative - Physician's Choice showed 40.2 Percentage of participants.
- For 1-year Disease Free Survival (DFS):
- Arm 1c: ctDNA Positive Genomically Directed - PI3K Pathway showed 100 Percentage of participants.
- Arm 2: ctDNA Positive - Standard of Care showed 0 Percentage of participants.
- Arm 3: ctDNA Negative - Physician's Choice showed 79.8 Percentage of participants.
- For Overall Disease Free Survival (DFS):
- Arm 1c: ctDNA Positive Genomically Directed - PI3K Pathway had a median of 27.7 Months.
- Arm 2: ctDNA Positive - Standard of Care had a median of 8.1 Months.
- Arm 3: ctDNA Negative - Physician's Choice had a median of 23.1 Months.
- For Overall Distant Disease Free Survival (DDFS):
- Arm 1c: ctDNA Positive Genomically Directed - PI3K Pathway had a median of 27.7 Months.
- Arm 2: ctDNA Positive - Standard of Care had a median of 8.1 Months.
- Arm 3: ctDNA Negative - Physician's Choice had a median of 23.1 Months.
What this means
The results from this Phase 2 trial suggest a significant difference in outcomes for patients with residual triple-negative breast cancer based on ctDNA status and treatment approach. The observation of 100% 2-year DFS and 1-year DFS in the ctDNA-positive, genomically directed PI3K pathway arm (Arm 1c) compared to 0% in the ctDNA-positive standard of care arm (Arm 2) highlights the potential benefit of a genomically guided approach in this specific patient subgroup. These findings indicate that personalized treatment strategies based on molecular markers and ctDNA status could substantially improve disease-free survival in patients with residual TNBC, particularly for those with ctDNA positivity.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04849364, titled "Circulating Tumor DNA Enriched, Genomically Directed Post-neoadjuvant Trial for Patients With Residual Triple Negative Breast Cancer," were posted on 2025-05-31 on clinicaltrials.gov.