Title
A Phase 1, Open-Label, Dose Escalation and Expansion Study of CUE-102 Monotherapy in HLA-A*0201 Positive Patients with WT1 Positive Recurrent/Metastatic Cancers

Description
This is a Phase 1, open-label, 2-part, multi-center study evaluating the safety, tolerability, PK, pharmacodynamics (PD), immunogenicity, and antitumor activity of CUE-102 intravenous (IV) monotherapy in HLA-A*0201 positive patients with WT1 positive recurrent/metastatic solid tumors who have failed conventional therapies.
CUE-102 is a novel fusion protein developed for the treatment of patients with WT1-positive malignancies by selective engagement and expansion of tumor antigen-specific T cells that should allow for increased potential for anti-cancer efficacy and reduced toxicity relative to non-targeted forms of immunotherapy that result in systemic activation of the immune system.

The goal of Part A is to characterize the safety, tolerability, and biological effects of CUE-102.

The goal of Part B is to expand the safety and immune activity data at the RP2D identified in Part A, and to evaluate antitumor activity at this dose.

Objective
Primary:
Part A:
-To evaluate dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) during the first cycle of treatment with CUE-102, and to establish a recommended phase 2 dose (RP2D)
Parts A & B: To evaluate the pharmacokinetics (PK) of CUE-102

Secondary:
-To evaluate safety and tolerability of CUE-102 using NCI CTCAE v5.0
-To evaluate safety and tolerability of CUE-102 as assessed by changes in laboratory values, ECGs, vital signs, and physical examinations
-To evaluate antitumor activity of CUE-102 in terms of objective response rate (ORR) as assessed by the Investigators using RECIST 1.1
-To evaluate additional measures of antitumor and clinical activity as assessed by the Investigators including:
-Duration of response (DOR) by RECIST 1.1
-Durable stable disease (DSD) by RECIST 1.1 (SD ? 6 weeks)
-Clinical benefit rate (CBR) by RECIST 1.1 (defined as complete response (CR) + partial response (PR) + DSD)
-Progression free survival (PFS) by RECIST 1.1
-Overall survival (OS)
-To evaluate the potential for immune response after treatment with CUE-102, including assessment of, but not limited to, number of WT1 tetramer-positive T cell lymphocytes or CTL markers of activation
-To evaluate the potential immunogenicity of CUE-102

Treatment Experimental: CUE-102 (1mg/kg) Dose Escalation
CUE-102 (1 mg/kg) Monotherapy IV infusion every 3 weeks for up to 2 years
Drug: CUE-102
CUE-102 is a novel fusion protein developed for the treatment of patients with WT1-positive malignancies.

Experimental: CUE-102 (2 mg/kg) Dose Escalation
CUE-102 (2 mg/kg) Monotherapy IV infusion every 3 weeks for up to 2 years
Drug: CUE-102

Experimental: CUE-102 (4 mg/kg) Dose Escalation
CUE-102 (4 mg/kg) Monotherapy IV infusion every 3 weeks for up to 2 years
Drug: CUE-102

Experimental: CUE-102 (8 mg/kg) Dose Escalation
CUE-102 (8 mg/kg) Monotherapy IV infusion every 3 weeks for up to 2 years
Drug: CUE-102

Experimental: CUE-102 Dose Expansion at Determined RP2D
Dose expansion of CUE-102 at determined RP2D Monotherapy IV infusion every 3 weeks for up to 2 years
Drug: CUE-102

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Colon and Rectum; Esophagus; Gastrointestinal cancers, other; Ovary; Pancreas; Stomach

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital