Phase 1b/2 study of GX-I7 plus pembrolizumab in patients with refractory or recurrent (R/R) metastatic triple-negative breast cancer (mTNBC): The KEYNOTE-899 Study.

1081 Background: GX-I7 (efineptakin alfa) is a hybrid Fc-fused long-acting recombinant human IL-7 which plays an essential role in the development and homeostasis of T-cells. GX-I7 can potentially enhance the anti-tumor effect of pembrolizumab via induction of T-cell activity. Here, we report results of phase 1b/2 study of GX-I7 plus pembrolizumab in patients with R/R mTNBC. Methods: Eligible patients had R/R mTNBC that failed up to 3rd lines of chemotherapy in the metastatic setting. Phase 1b patients received GX-I7 in 5 dose levels ranging from 360 µg/kg to 1,440 µg/kg every 9 (Q9W) or 12 (Q12W) weeks plus pembrolizumab 200 mg Q3W (n=51). Phase 2 is an expansion cohort where 33 patients were treated with the recommended phase 2 dose (RP2D). The primary objective was to determine the RP2D for phase 1b and to assess the objective response rate (ORR) for phase 2. Results: The study included 84 patients (phase 1b, n=51; phase 2, n=33) and 53.6% (45/84) of patients have received 2nd to 3rd lines of previous therapy. In phase 1b, one dose-limiting toxicity (DLT; grade 3 skin rash) was reported in the 1,440 µg/kg cohort and GX-I7 1,200 µg/kg Q9W was selected as RP2D. The ORRs were 15.7% [95% confidence interval (CI): 7.0 – 28.6] for phase 1b (n=51) and 21.2% [95% CI: 9.0 – 38.9] for phase 2 (n=33). Median PFS was 2.4 months (95% CI: 2.1 – 2.7) at the median follow-up of 10.4 months for all patients combined (n=84). GX-I7 induced up to 3.6-fold (range 1.2 – 8.1) increase in absolute lymphocyte counts (including CD4+ and CD8+ T cell) in all dose levels. The most common treatment-related adverse events (AEs) of any grade were injection site reaction (50.0%), ALT increased (39.3%), pyrexia (38.1%) and rash (35.7%). The additional correlative study data will be presented. Conclusions: GX-I7 in combination with pembrolizumab demonstrated a manageable safety profile with promising anti-tumor activity in patients with R/R metastatic TNBC. Clinical trial information: NCT03752723. [Table: see text]