First-in-human/phase I trial of PE0116 (4-1bb Ig G4 McAb) as single agent in patients with solid tumors progressed after lines of therapies in China.

Abstract

2640 Background: The 4-1BB co-stimulatory protein is an important modulator of the adaptive T Cell immune responses, and potentially a vital target for immunotherapies in oncology. HE0116 is a humanized agonist antibody to 4-1BB that promotes proliferation and activation of T cells. The FIH/phase Ia/Ib study was conducted to establish a maximum tolerated dose, identify dose-limiting toxicities (DLTs) and to assess safety, tolerability, and pharmacokinetics of HE0116 as single agent in patients with solid tumors who have progressed on standard of care (SoC) and experimental therapies. Methods: Patients (pts) with histologically confirmed solid tumors who progressed after prior SoC and experimental therapies were enrolled. A Fibonacci 3+3 design was employed for the phase 1a dose escalation of 9 dose levels. HE0116 was administered intravenously once in first 28-day cycle for PK analysis and DLT assessment. Pts continued HE0116 treatment every 3 weeks until experiencing an intolerable toxicity, disease progression or withdrawing consent. Results: As of January 25, 2022, 19 pts were enrolled in the dose-escalation phase). All pts had progressed on multiple lines of therapies, including but not limited to, chemotherapy, hormonal therapy, or/and immunotherapy. As defined in study protocol, pts received HE0116 intravenously at least once at six dose levels: 0.03 mg/kg (n = 1), 0.1 mg/kg (n = 3), 0.3 mg/kg (n = 3), 1 mg/kg (n = 4), 2 mg/kg (n = 3), and 3 mg/kg (n = 5). One DLT of Grade (g) 4 platelets decrease was reported at 3 mg/kg, thus 3 new pts were added at this dose. The grade1 and grade2 HE0116 related adverse events (AEs) per CTCAE v5 that occurred ( < 10% frequency) were ALT and AST increase, platelet decrease, WBC decrease, anemia, hypokalemia, hyponatremia, hypoalbuminemia, hypothyroidism, or bone pain. Three SAE were reported: 1 g2 ascites, 1 g4 dyspnea, 1 g2 fever. To date there was one iPR at 1 mg/kg for a pt with advanced ovarian cancer with liver met after 6 cycles of treatment, and 4 iSD (1 in 2 mg/kg, 3 in 3 mg/kg) were recorded. Conclusions: HE0116 administrated intravenously every 3 weeks is well tolerated with minimal toxicities. Preliminary data are very encouraging as single agent HE0116 showed durable responses with 1 iPR, 4 iSD in several difficult to treat late-stage cancer pts. Dose escalation is ongoing as per study protocol. Phase II in select patient populations, and clinical investigation of the combination of HE0116 with CTLA-4 or PD-1 are warranted. Clinical trial information: CTR20201794.