Abstract 1924P
Background
Recent pre-clinical data have suggested that the antitumor activity of trabectedin is not only related to their effects on tumor cells, but also on its ability to affect the tumor microenvironment (TME), in particular tumor associated macrophages and their pro-tumoral functions. We report results of the phase II part of the first study evaluating trabectedin in combination with metronomic chemotherapy on the TME of patients (pts) with advanced sarcomas.
Methods
TARMIC is an open-label multicenter phase I/II study of trabectedin in combination with low-dose cyclophosphamide in pts with advanced STS. The RP2D was of 0.5 mg/m2. Primary endpoint was 6-month non progression rate. Secondary endpoints included efficacy and evaluation of impact on TME through mandatary tumor biopsies at baseline and after one cycle of treatment.
Results
30 patients (17 males, 13 females) have been included. Median age was 67 years (23 – 80). The two most frequent histologies were undifferentiated pleiomorphic liposarcoma (n=9) and leiomyosarcoma (n=7). The median number of previous lines of treatment was 2 (range 1-5). The most frequent adverse events were: grade 1/2 fatigue (86.7%), nausea (66.7%) and anemia (66.7%). 24 pts were eligible and assessable for efficacy. Best objective response as per RECIST based on central review was: partial response for 2 (8.3%), stable disease for 9 (37.5%) and progressive disease for 13 pts (54.2%) respectively. 3 pts (12.5% IC95% [2.7%; 32.4%]) were progression-free at 6 months indicating that the first endpoint was not reached. Median progression-free survival and overall survival were 1.9 months (95% CI: [1.7; 4.4]) and 12.0 months (95% CI: [5.8; -]), respectively. RNA sequencing of paired biopsies indicated that patients with activation immune response and Th17 differentiation had a better outcome. Increase in CD8 T cell density was significantly associated with improved PFS. No impact of trabectedin on macrophage infiltration was observed.
Conclusions
We report the first clinical study investigating the immunological activity of trabectedin in patients with advanced STS. Modulation of TME under trabectedin appear to be correlated with outcome.
Clinical trial identification
NCT02805725.
Editorial acknowledgement
Legal entity responsible for the study
Institut Bergonie.
Funding
PharmaMar.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1820P - Cardiovascular effects of androgen receptor signalling inhibitors in the treatment of advanced and metastatic prostate cancer: A systematic review and meta-analysis of randomised controlled trials
Presenter: Omar El-Taji
Session: Poster session 15
1821P - High serum FSH/T ratio as a marker for the development of cardiovascular disease in ADT recipients
Presenter: Jehonathan Pinthus
Session: Poster session 15
1822P - PSMA-alpha targeted radionuclide therapy (TRT) with or without prior PSMA-beta TRT
Presenter: Michael Sun
Session: Poster session 15
1823P - The impact of baseline PSMA PET/CT vs. CT on outcomes of Radium-223 therapy in mCRPC patients
Presenter: Dianne Bosch
Session: Poster session 15
1824P - Treatment patterns among novel hormonal therapy-experienced patients with metastatic castration-resistant prostate cancer
Presenter: Vivek Narayan
Session: Poster session 15
1825P - Molecular features of circulating tumour cells (CTCs) associate with response to 177Lu-PSMA-617 plus pembrolizumab for metastatic castration resistant prostate cancer (mCRPC)
Presenter: David Goode
Session: Poster session 15
1826P - Lutetium-177-PSMA in pre- and post-taxane mCRPC setting: Results from a phase II clinical trial
Presenter: Emilio Giunta
Session: Poster session 15
1827P - Real-world (RW) overall survival (OS) with enzalutamide (ENZ) and abiraterone acetate (ABI) in patients (pts) with chemotherapy (cx)-naïve metastatic castration-resistant prostate cancer (mCRPC)
Presenter: Daniel George
Session: Poster session 15
1828P - ARX517: A next generation anti-PSMA antibody drug conjugate (ADC) demonstrates notable stability and pharmacokinetic (PK) profile in the ARX517 phase I clinical trial (APEX-01)
Presenter: Scott Tagawa
Session: Poster session 15
1829P - Exposure-safety analyses of talazoparib in combination of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) in TALAPRO-2 trial
Presenter: Arun Azad
Session: Poster session 15