A Phase 1 in Patients With HLA-A*0201+ and WT1+ Recurrent/Metastatic Cancers

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

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Ovarian Cancer
• Intervention / Treatment: Drug: CUE-102

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Palo Alto, California, United States, 94304
      • Stanford Advanced Medicine Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins University
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Carol G. Simon Cancer Center - Morristown Medical Center
  • New York
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
    • Cleveland, Ohio, United States, 44106
      • Cleveland Medical Center (University Hospitals)
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Tacoma, Washington, United States, 98405
      • NorthWest Medical Specialties, PLLC
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ability to provide informed consent and documentation of informed consent prior to initiation of any study-related tests or procedures that are not part of standard of care for the patient's disease.
2. Age ≥18 years old
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Life expectancy ≥12 weeks
5. Measurable disease as per RECIST 1.1 and documented by CT and/or MRI.
6. All tumors must have histologically or cytologically confirmed cancer diagnosis

7. Patients must have any of the following cancers to be eligible:

   A. Colorectal cancer

   1. Histologically or cytologically documented adenocarcinoma of colon or rectum at the time of initial presentation
   2. Metastatic or locally advanced/unresectable disease
   3. Documented disease progression after the last administration of standard therapies or intolerance to at least 2 prior systemic treatment regimens (CUE-102 will be 3rd line therapy or greater).

   B. Gastric cancer (including gastroesophageal junction)

   1. Histologically or cytologically documented gastric cancer at the time of initial presentation
   2. Metastatic or locally advanced/unresectable disease
   3. Documented disease progression after last administration of standard therapies or intolerance to standard therapies. (CUE-102 will be 2nd line therapy or greater).

   C. Pancreatic cancer

   1. Histologically or cytologically documented pancreatic adenocarcinoma at the time of initial presentation
   2. Patients with metastatic or locally advanced/unresectable disease.
   3. Prior systemic treatment must include either a fluoropyrimidine-based or gemcitabine-based regimen in either the (neo)adjuvant or relapsed setting. (CUE-102 will be 2nd line therapy or greater).

   D. Ovarian cancer

   1. Histologically or cytologically documented ovarian cancer at the time of initial presentation
   2. Metastatic or locally advanced/unresectable disease, with documented disease progression after last administration of standard therapies or intolerance to standard therapies.
   3. Prior systemic treatment must include a platinum-based regimen. (CUE-102 will be 2nd line therapy or greater).
   4. For patients determined to have platinum-sensitive disease, treatment with a second platinum-based combination regimen +/- bevacizumab should be considered prior to treatment with CUE-102 (CUE-102 will be 3rd line therapy or greater).
8. Patient must have HLA-A*0201 genotype as determined by genomic testing.
9. Patient must have histologically and/or cytologically proven tumor(s) that is WT1 positive.
10. Acceptable laboratory parameters.
11. Female patients of childbearing potential must agree to use acceptable contraceptive measures from the time of main study consent through 90 days after discontinuation of study drug administration.
12. Non-vasectomized male patients with partners of childbearing potential must use barrier contraception from the time of main study consent through 90 days after discontinuation of study drug.
13. Patients who have previously received an immune CPI (e.g., anti-programmed cell death ligand 1 (anti PD-L1), anti-programmed cell death 1 (anti-PD-1), anti-cytotoxic T lymphocyte-associated antigen 4 [CTLA-4]) prior to enrollment must have toxicities related to the CPI resolved to CTCAE ≤ Grade 1 or baseline (level prior to the CPI) to be eligible for enrollment. Patients who have experienced CPI-related endocrinopathies (e.g., diabetes, adrenal insufficiency) may participate if endocrinopathies are controlled (CTCAE ≤ Grade 1) with endocrinology support and appropriate repletion. Note: Patients who experienced previous hypothyroidism toxicity on a CPI are eligible to enter study regardless of CTCAE grade resolution as long as the patient is well controlled on thyroid replacement hormone.

Exclusion Criteria:

1. Female patients who are pregnant or plan to become pregnant during the course of the trial
2. Female patients who are breastfeeding

3. Patients with symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic, and not have any of the following at the time of enrollment:

   1. Need for concurrent treatment for the CNS disease (e.g., surgery, radiation, corticosteroids >10 mg prednisone/day or equivalent)
   2. Progression of CNS metastases on CT or MRI for at least 28 days after last day of prior therapy for the CNS metastases
   3. Concurrent leptomeningeal disease or cord compression.
4. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is permitted.
5. History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation
6. Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 14 days (or 28 days, for antibody drugs), before the first dose of CUE-102.
7. Treatment with radiation therapy within 14 days before the first dose of CUE-102
8. Treatment with corticosteroids (> 10 mg per day prednisone or equivalent) or other immune suppressive drugs within 14 days before the first dose of CUE-102. Steroids for topical, ophthalmic, inhaled, or nasal administration are permitted. Physiological replacement with up to a maximum dose of 5 mg equivalence of prednisone per day is permitted.
9. History of clinically significant cardiovascular disease
10. Clinically significant pulmonary compromise (e.g., requirement for supplemental oxygen)
11. Clinically significant gastrointestinal (GI) disorders

12. Patients who experienced the following immune CPI-related AEs are ineligible even if the AE resolved to ≤ Grade 1 or baseline:

    1. ≥ Grade 3 ocular AE
    2. Changes in liver function tests that met the criteria for Hy's Law (> 3× ULN of either ALT/AST with concurrent > 2× ULN of total bilirubin (total and direct) and without alternate etiology)
    3. ≥ Grade 3 neurologic toxicity
    4. ≥ Grade 3 colitis
    5. ≥ Grade 3 renal toxicity
13. Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days before the first dose of CUE-102.
14. No known history of infection or positive test for HIV, Hepatitis B or Hepatitis C, testing prior to enrollment is not required unless mandated by local authority
15. Second primary invasive malignancy that has not been in remission for > 2 years.
16. History of trauma or major surgery within 28 days before the first dose of CUE-102
17. Any serious underlying medical or psychiatric condition that would impair the ability of the patient to receive or tolerate the planned treatment at the investigational site
18. Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient contained in the drug formulation for CUE-102
19. Vaccination with any live virus vaccine within 28 days before the first dose of CUE-102. Inactivated annual influenza vaccination is allowed.
20. Dementia or altered mental status that would preclude understanding and rendering of informed consent
21. Active or history of significant alcohol or other substance abuse within 1 year before the first dose of CUE-102

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / 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; CUE-102 is a novel fusion protein developed for the treatment of patients with WT1-positive malignancies.
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; CUE-102 is a novel fusion protein developed for the treatment of patients with WT1-positive malignancies.
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; CUE-102 is a novel fusion protein developed for the treatment of patients with WT1-positive malignancies.
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; CUE-102 is a novel fusion protein developed for the treatment of patients with WT1-positive malignancies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity	Evaluate dose-limiting toxicities (DLTs) during the first cycle of treatment with CUE-102, and to establish a recommended Phase 2 dose (RP2D)	21 Days
Maximum Tolerated Dose	Evaluate maximum tolerated dose (MTD) to establish a recommended Phase 2 dose (RP2D)	21 Days
Serum PK AUC for CUE-102	Area under the concentration-time curve (AUC) of CUE-102.	Up to 2 years
Serum PK Cmax for CUE-102	Maximum serum concentration (Cmax) of CUE-102.	Up to 2 years
Serum PK T1/2 for CUE-102	Terminal half-life (T1/2) of CUE-102.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of CUE-102 Assessed by NCI CTCAE v5.0	To evaluate safety and tolerability of CUE-102 using NCI CTCAE v5.0.	Up to 2 years
Antitumor Response Rate with Treatment of CUE-102	To evaluate antitumor response rate of CUE-102 by RECIST 1.1	Up to 2 years
Antitumor Duration of Response with Treatment of CUE-102	To evaluate antitumor duration of response of CUE-102 by RECIST 1.1	Up to 2 years
Antitumor Clinical Benefit Rate with Treatment of CUE-102	To evaluate antitumor clinical benefit rate of CUE-102 by RECIST 1.1	Up to 2 years
Progression-Free Survival with Treatment of CUE-102	To evaluate antitumor progression-free survival of CUE-102 by RECIST 1.1	Up to 2 years
Overall Survival with Treatment of CUE-102	To evaluate overall survival after treatment with CUE-102	From First CUE-102 to Date of Death
Immune Response Assessed by WW1 Tetramer-Positive T cell Lymphocytes	To evaluate the potential for immune response after treatment with CUE-102 using assessment of number of WT1 tetramer-positive T cell lymphocytes.	Up to 2 years
Immune Response Assessed by CTL Markers of Activation	To evaluate the potential for immune response after treatment with CUE-102 using assessment of cytotoxic T lymphocyte (CTL) markers of activation	Up to 2 years

Collaborators and Investigators

• Sponsor: Cue Biopharma
• Investigators: Study Chair: Matteo Levisetti, MD, Cue Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2022
• Primary Completion (Actual): March 12, 2025
• Study Completion (Actual): March 12, 2025

Study Registration Dates

• First Submitted: April 19, 2022
• First Submitted That Met QC Criteria: April 29, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Wilms' tumor 1; HLA A*0201
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Rectal Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Pancreatic Diseases; Colonic Diseases; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Urologic Neoplasms; Kidney Neoplasms; Neoplastic Syndromes, Hereditary; Neoplasms, Complex and Mixed; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Stomach Neoplasms; Colorectal Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms; Wilms Tumor
• Other Study ID Numbers: CUE-102-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No