Trial results for the Phase 1/2 study (NCT03123276) investigating pembrolizumab and gemcitabine chemotherapy in leiomyosarcoma and undifferentiated pleomorphic sarcoma were posted on ClinicalTrials.gov on 2026-02-13. The study explored dose-limiting toxicities and preliminary response rates across different gemcitabine dose cohorts, with up to 9 participants showing objective response and disease control in the highest dose expansion cohort.
Background
Soft tissue sarcomas (STS) are a group of rare mesenchymal neoplasms. Leiomyosarcoma (LMS) is a common STS, and undifferentiated pleomorphic sarcoma (UPS) is an aggressive sarcoma sub-type. Despite surgery and adjuvant treatment, more than half of patients with STS develop recurrent or metastatic disease. Previous studies have indicated that LMS has reasonable sensitivity to gemcitabine monotherapy, with objective response rates ranging from 8-19%.
Trial design
The study (NCT03123276) was a Phase 1/2 trial that enrolled 25 participants. It investigated the combination of pembrolizumab and gemcitabine chemotherapy in patients with sarcoma, specifically leiomyosarcoma and undifferentiated pleomorphic sarcoma. The trial evaluated different dose cohorts of gemcitabine: 800mg/m2, 1000mg/m2, and 1200mg/m2, including a Part B Dose Expansion Cohort at 1200mg/m2 gemcitabine.
Key results
The trial evaluated dose-limiting toxicities (DLTs) and preliminary response rates across the different treatment cohorts:
- For "Number of Patients With Dose Limiting Toxicities":
- Cohort 1 (800mg/m2 Gemcitabine) reported 0 Participants with DLTs.
- Cohort 2 (1000mg/m2 of Gemcitabine) reported 1 Participant with DLTs.
- Cohort 3 (1200mg/m2 Gemcitabine) reported 0 Participants with DLTs.
- For "Preliminary Evaluation of Response by Using RECIST v1.1. Number of Patients With Objective Response and Disease Control":
- Number of participants with objective response:
- Cohort 1 (800mg/m2 Gemcitabine) showed 0 Participants.
- Cohort 2 (1000mg/m2 Gemcitabine) showed 1 Participant.
- Cohort 3 (1200mg/m2 Gemcitabine) showed 2 Participants.
- Part B Dose Expansion Cohort (1200mg/m2 Gemcitabine) showed 2 Participants.
- Number of participants with objective response and disease control:
- Cohort 1 (800mg/m2 Gemcitabine) showed 3 Participants.
- Cohort 2 (1000mg/m2 Gemcitabine) showed 6 Participants.
- Cohort 3 (1200mg/m2 Gemcitabine) showed 1 Participant.
- Part B Dose Expansion Cohort (1200mg/m2 Gemcitabine) showed 9 Participants.
What this means
The results of this Phase 1/2 trial provide preliminary insights into the safety and efficacy of combining pembrolizumab with gemcitabine in patients with leiomyosarcoma and undifferentiated pleomorphic sarcoma. The low number of dose-limiting toxicities observed across the different gemcitabine dose cohorts suggests a manageable safety profile for the combination. The varying numbers of participants achieving objective response and disease control, particularly the higher numbers in the 1200mg/m2 gemcitabine cohorts, indicate potential activity for this regimen, warranting further investigation in larger studies.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03123276, titled "Pembrolizumab and Gemcitabine Chemotherapy in Leiomyosarcoma and Undifferentiated Pleomorphic Sarcoma," were posted on 2026-02-13 on clinicaltrials.gov.