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

Colorectal Cancer Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05360680
• Other study ID #: CUE-102-01
• Status: Recruiting
• Phase: Phase 1
• Start date: June 14, 2022
• Est. completion date: December 2026

Study information

• Verified date: September 2023
• Source: Cue Biopharma
• Contact: Steven Margossian, M.D., Ph.D.
• Phone: 857-228-0636
• Email: smargossian[@]cuebio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: December 2026
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Gastric Cancer
• Neoplasm Metastasis
• Ovarian Cancer
• Pancreatic Cancer

Intervention

Drug:
• CUE-102
CUE-102 is a novel fusion protein developed for the treatment of patients with WT1-positive malignancies.

Locations

Country	Name	City	State
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	Gabrail Cancer Center	Canton	Ohio
United States	Cleveland Medical Center (University Hospitals)	Cleveland	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Carbone Cancer Center	Madison	Wisconsin
United States	Carol G. Simon Cancer Center - Morristown Medical Center	Morristown	New Jersey
United States	Stanford Advanced Medicine Cancer Center	Palo Alto	California
United States	Mayo Clinic	Phoenix	Arizona
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Cue Biopharma

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Maximum Tolerated Dose	Evaluate maximum tolerated dose (MTD) to establish a recommended Phase 2 dose (RP2D)	21 Days
Primary	Serum PK AUC for CUE-102	Area under the concentration-time curve (AUC) of CUE-102.	Up to 2 years
Primary	Serum PK Cmax for CUE-102	Maximum serum concentration (Cmax) of CUE-102.	Up to 2 years
Primary	Serum PK T1/2 for CUE-102	Terminal half-life (T1/2) of CUE-102.	Up to 2 years
Secondary	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
Secondary	Antitumor Response Rate with Treatment of CUE-102	To evaluate antitumor response rate of CUE-102 by RECIST 1.1	Up to 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall Survival with Treatment of CUE-102	To evaluate overall survival after treatment with CUE-102	From First CUE-102 to Date of Death
Secondary	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
Secondary	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