432P - Tislelizumab (Tisle) combined with POFI (irinotecan, paclitaxel, oxaliplatin and 5-FU/levoleucovorin) as first-line treatment of advanced gastric/gastroesophageal junction adenocarcinoma (AGC): Update from a single-arm, open-label phase I/II trial (SYLT-0

Background

Tisle is an anti-PD-1 antibody. The combination of Tisle + XELOX/FP is a first-line treatment of AGC in China. Both irinotecan and paclitaxel have also shown antitumor activity in AGC. In this phase I/II study, we explore the safety, tolerability, and efficacy of Tisle + POFI as first-line treatment of HER-2 negative, pMMR AGC.

Methods

In a phase I dose finding study using a standard 3+3 design, subjects received four escalating dose levels (dl) of irinotecan/paclitaxel (mg/m²): 135/45 (dl #1), 150/45 (dl #2), 135/67.5 (dl #3), and 135/90 (dl #4) in combination with tisle 200 mg plus oxaliplatin 85 mg/m², levoleucovorin 200 mg/m², and 5-FU 2400 mg/m² for 46 hours every 2 weeks. Primary endpoints were safety, tolerability, and RP2D.

Results

Fifteen subjects with treatment naïve AGC were enrolled (3 each in dl #1, dl #2, and dl #3 and 6 in dl #4). The median age was 65 years (range 36-72); 80% were male. Two subjects (13.3%) were diagnosed with GE junction cancer, 9 (60%) had poorly differentiated disease, and 5 (33.3%) had liver metastasis. PD-L1 CPS scores were: 5 (n=5); 1 (n=1); and 0 (n=9). All subjects were evaluated for DLT. One DLT (grade 4 neutropenia) occurred within 28 days in dl #4. No maximum tolerated dose was reached; the RP2D was dl #4. As of 31th March 2024, confirmed objective response rate in 13 subjects with measurable disease was 100% (1 CR, 12 PR) per RECIST 1.1. Of the 2 subjects with non-measurable disease, one was a CR and the other was non-CR/non-PD. The median PFS was 9.9 (95% CI: 6.31, 15.28) months (versus 6.9 [5.7-7.2] months for ITT population for RATIONALE 305, ESMO 2023), the median DOR was 7.39 (95% CI: 4.12, 12.55) months, and the median OS was not reach (95% CI: 8.67 months, NR). All subjects (100%) had AEs. Ten (n=10, 66.67%) of the 15 subjects reported grade ≥3 AEs, including neutropenia (n=10; 66.67%), leukopenia (n=5; 33.33%), anemia (n=4; 26.67%).

Conclusions

Tisle+POFI was well tolerated and showed preliminary antitumor activity in AGC. A phase II study is ongoing.

Clinical trial identification

NCT05319639.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.