PD1 inhibition in soft-tissue sarcomas with tertiary lymphoid structures: A multicenter phase II trial.

11507 Background: PD1 inhibition has shown limited activity in all comers clinical trials including patients with advanced soft-tissue sarcomas (STS). In the PEMBROSARC study, objective response rate, progression-free (PFS) and overall survival (OS) were respectively 2.1%, 1.4 and 7.1 months respectively (Toulmonde et al. Jama Oncol 2017). We have recently shown that the presence of tertiary lymphoid structures (TLS) may represent a biomarker to select patients who are more likely to benefit from immunotherapy (PetitPrez et al., Nature 2020). We report here the first clinical trial investigating the efficacy of PD1 inhibition in TLS-positive STS. Methods: PEMBROSARC is an open-label multicenter phase II study of pembrolizumab in combination with low-dose cyclophosphamide in pts with STS selected based on the presence of TLS. TLS status has been assessed centrally has previously described (PetitPrez et al., Nature 2020). Eligible patients received pembrolizumab 200mg IV q21 days and cyclophosphamide 50 mg BID 1week on, 1 week off. All patients had confirmed progressive disease at inclusion based on central review of two imaging performed at less than 6 months interval. The primary efficacy endpoint was 6-month non-progression (as per RECIST evaluation criteria v1.1). Based on the following hypotheses: 15% 6-month non-progression rate (H0), 40% acceptable 6-month non-progression rate (H1), 5% type I error rate, 90% power, a total of 29 assessable patients were necessary and 8 patients or more had to be progression-free at 6 months to reach the first endpoint. Results: 240 patients were screened for TLS status between September 2018 and January 2020 in 7 centers of the French Sarcoma Group. Among them, 48 were found to be TLS+ as per central review and 35 were included in the study. The three most frequent histological subtypes were: well-differentiated/dedifferentiated liposarcoma (n = 13); UPS (n = 6), and leiomyosarcoma (n = 4). 30 patients were eligible for efficacy. Of those, as per central imaging review, 13 patients (43.3%) had tumor shrinkage resulting in partial response in 8 patients (26.7%) and stable disease in 5 cases (16.7%). 10 patients had progressive disease. Twelve patients were progression-free at 6 months (40.0% 95%CI = [22.7 – 59.4]).Median PFS and OS were 4.1 months (95%CI, 1.4-9.6) and 14.5 months (95%CI, 8.5- 18.3 months), respectively. Conclusions: With an objective response and a 6-month non-progression rates of 26.7% and 40% respectively versus 2.1% and 4.2% in all comers, the PEMBROSARC study confirms that selection based on TLS status is an efficient approach to tailor immunotherapy in STS patients. Clinical trial information: NCT02406781.