1532 A phase 1/2 study of safety, tolerability, and pharmacokinetics of SNS-101, a pH-sensitive anti-VISTA mAb, as monotherapy and in combination with cemiplimab in patients with advanced solid tumors

• Published in: Journal for immunotherapy of cancer 2023-11, Vol.11 (Suppl 2), p.A1755-A1755
• Main Authors: Sen, Shiraj, Call, Justin, Papadopoulos, Kyriakos, Smith, FD, Horst, Edward H van der
• Format: Article
• Language: English
• Subjects: Antibodies; Cytokines; Drug dosages; Immunotherapy; Late-Breaking Abstracts; Pharmacokinetics; Tumors
• ISSN: 2051-1426
• DOI: 10.1136/jitc-2023-SITC2023.1532

BackgroundVISTA (V-domain Ig suppressor of T-cell activation) is a significant emerging immuno-oncology target. Despite the therapeutic potential of VISTA inhibition demonstrated in preclinical studies,1 clinical development of anti-VISTA antibodies has been challenging due to dose-limiting on-target cytokine release at sub-therapeutic doses and target mediated drug disposition (TMDD).2 SNS-101 is a fully human IgG1 monoclonal antibody designed to selectively disrupt the VISTA:PSGL-1 immune checkpoint in the acidic tumor microenvironment. Preclinical data demonstrate the potential of SNS-101 to exhibit favorable safety and tolerability profiles and promote anti-tumor activity as monotherapy or in combination with PD-1 blockade.3–5 MethodsThis is a first-in-human, open-label, multi-center, dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics and efficacy of SNS-101 as monotherapy or in combination with cemiplimab in patients with advanced solid tumors (NCT05864144). The study is being conducted in 3 parts: Part A: Phase 1 (P1) Monotherapy Dose Escalation (SNS-101 alone); Part B: P1 Combination Dose Escalation (SNS-101 + cemiplimab); Part C: Phase 2 (P2) Expansion Cohorts (SNS-101 ± cemiplimab). Patients will receive SNS-101 ± cemiplimab as intravenous infusion(s) every 3 weeks and may continue until confirmed progressive disease or unacceptable toxicity. Dose escalation follows the Bayesian Optimal Interval Design until the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) is determined. Primary objectives include safety, tolerability and RP2D/MTD (P1), and evaluation of anti-tumor activity (P2). Safety and tolerability assessments include monitoring of dose limiting toxicities (DLTs) and adverse events (AEs), PK, anti-drug antibodies and inflammatory cytokine release. Tumor imaging and T-cell immunophenotyping are being utilized to monitor responses.ResultsAs of August 31, 2023, 7 patients were enrolled in Part A across three dosing cohorts (0.3 mg/kg, 1 mg/kg and 3 mg/kg). No DLTs or CRS events were noted. Nine AEs (8/9 Grade 1–2) have been reported in 5 patients. One Grade 5 AE related to disease progression and not to the treatment was observed. One AE, dermatitis acneiform, is considered treatment-related. Infusions have not required premedications. PK results show high concordance with preclinical modeling data, demonstrating dose-proportional exposure, linear elimination kinetics