Isunakinra Alone and in Combination With Pembrolizumab in Patients With Colorectal Cancer (MSS)

NCT06634875 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BUZ02CD101
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This study will enroll patients with colorectal cancer that is locally advanced or metastatic. The tumor must be microsatellite stable (MSS), have a tumor mutational burden that is high (TMB-H) and be kras mutated. Patients must have been treated with available approved treatments already. In this study the investigators are testing a new type of immunotherapy, the potent IL-1 inhibitor isunakinra to be added to already approved immunotherapy (PD-1/PD-L1 inhibitor) in an attempt to get this treatment to work in this treatment resistant type of tumor.

Conditions

Colorectal Cancer Metastatic

Keywords

colorectal cancer; microsatellite stable; MSS; kras mutated; TMB-H; metastatic

Outcome Measures

Primary Outcomes (2)

• Safety

  The incidence, relatedness and severity of adverse events (includes safety laboratory abnormalities) per CTCAE v. 5

  6 months

• PFS

  Progression Free Survival per iRECIST

  6 months

Study Arms (1)

combination immunotherapy

EXPERIMENTAL

Drug: isunakinra

Interventions

isunakinra DRUG

Isunakinra is a potent IL1R1 inhibitor

Also known as: EBI-005

combination immunotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Subjects must have:
• Histologically or cytologically confirmed adenocarcinoma of the colon or the rectum
• Tumor is determined to be RAS-mutated (KRAS, NRAS or HRAS) and microsatellite stable/proficient in mismatch repair, as assessed by immunohistochemistry (IHC) and/or polymerase chain reaction (PCR)/next generation sequencing (NGS) in a Clinical Laboratory Improvement Act (CLIA) environment and with a tumor mutational burden (TMB) of 10 MB or more.
• \. The study patients are required to have measurable disease by radiographic criteria (RECIST 1.1 and iRECIST).
• \. Prior therapy: Patients must have completed or had disease progression on at least one prior line of disease-appropriate therapy for metastatic disease (with or without PD-1 inhibitors), with no available therapy likely to convey clinical benefit, or not be candidates for therapy of proven efficacy for their disease.
• \. There should be a minimum of 4 weeks from any prior chemotherapy (except for the nitrosoureas and mitomycin C, requiring a minimum of 6 weeks), immunotherapy and/or radiation. Patients with prostate cancer on hormone deprivation therapy may continue that therapy while on study.
• \. Patients must have recovered (grade 1 or baseline) from any clinically significant toxicity associated with prior therapy (for example, alopecia is not clinically significant).
• \. ECOG performance status ≤ 1 7. Patients must have normal organ and hematologic function as defined below:
• Serum creatinine ≤ 1.5 x upper limit of normal OR creatinine clearance and a 24-h urine collection of ≥ 60 mL/min.
• ALT and AST ≤ 3x the upper limits of normal.
• Total bilirubin ≤ 1.5 x upper limit of normal OR in patients with Gilbert's syndrome, a total bilirubin ≤ 3.0.
• Hematological eligibility parameters (within 16 days of starting therapy):
• Granulocyte count ≥ 1,500/mm3
• Platelet count ≥ 75.000/mm3 8. Patients must have baseline pulse oximetry \> 90% on room air at rest.

You may not qualify if:

• Subjects must have:
• ⦁ Histologically or cytologically confirmed adenocarcinoma of the colon or the rectum
• Tumor is determined to be RAS-mutated (KRAS, NRAS or HRAS) and microsatellite stable/proficient in mismatch repair, as assessed by immunohistochemistry (IHC) and/or polymerase chain reaction (PCR)/next generation sequencing (NGS) in a Clinical Laboratory Improvement Act (CLIA) environment and with a tumor mutational burden (TMB) of 10 MB or more.
• The study patients are required to have measurable disease by radiographic criteria (RECIST 1.1 and iRECIST).
• Prior therapy: Patients must have completed or had disease progression on at least one prior line of disease-appropriate therapy for metastatic disease (with or without PD-1 inhibitors), with no available therapy likely to convey clinical benefit, or not be candidates for therapy of proven efficacy for their disease.
• There should be a minimum of 2 weeks wash out period from chemotherapy and/or radiation therapy, and 4 weeks wash out period for immunotherapy.
• Patients must have recovered (grade 1 or baseline) from any clinically significant toxicity associated with prior therapy (for example, alopecia is not clinically significant).
• ECOG performance status ≤ 1
• Patients must have normal organ and hematologic function as defined below:
• Serum creatinine ≤ 1.5 x upper limit of normal OR creatinine clearance and a 24-h urine collection of ≥ 60 mL/min.
• ALT and AST ≤ 3x the upper limits of normal.
• Total bilirubin ≤ 1.5 x upper limit of normal OR in patients with Gilbert's syndrome, a total bilirubin ≤ 3.0.
• Hematological eligibility parameters (within 16 days of starting therapy):
• Granulocyte count ≥ 1,500/mm3
• Platelet count ≥ 75.000/mm3

Sponsors & Collaborators

• Buzzard Pharmaceuticals: lead

Study Sites (2)

USC/Norris Cancer Center

Los Angeles, California, 90089, United States

RECRUITING

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92658, United States

RECRUITING

Related Publications (3)

• Kovalchin J, King B, Masci A, Hopkins E, Fry J, Hou J, Li C, Tenneson K, Weber S, Wolfe G, Collins K, Furfine ES. Preclinical Development of EBI-005: An IL-1 Receptor-1 Inhibitor for the Topical Ocular Treatment of Ocular Surface Inflammatory Diseases. Eye Contact Lens. 2018 May;44(3):170-181. doi: 10.1097/ICL.0000000000000414.

  PMID: 28727604 BACKGROUND

• Hou J, Townson SA, Kovalchin JT, Masci A, Kiner O, Shu Y, King BM, Schirmer E, Golden K, Thomas C, Garcia KC, Zarbis-Papastoitsis G, Furfine ES, Barnes TM. Design of a superior cytokine antagonist for topical ophthalmic use. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3913-8. doi: 10.1073/pnas.1217996110. Epub 2013 Feb 19.

  PMID: 23431173 BACKGROUND

• Spella M, Ntaliarda G, Skiadas G, Lamort AS, Vreka M, Marazioti A, Lilis I, Bouloukou E, Giotopoulou GA, Pepe MAA, Weiss SAI, Petrera A, Hauck SM, Koch I, Lindner M, Hatz RA, Behr J, Arendt KAM, Giopanou I, Brunn D, Savai R, Jenne DE, de Chateau M, Yull FE, Blackwell TS, Stathopoulos GT. Non-Oncogene Addiction of KRAS-Mutant Cancers to IL-1beta via Versican and Mononuclear IKKbeta. Cancers (Basel). 2023 Mar 20;15(6):1866. doi: 10.3390/cancers15061866.

  PMID: 36980752 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

EBI-005

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Maarten de Chateau, MD PhD

CONTACT

+46 763 103031; info@buzzardpharma.com

Hans Olivecrona, MD PhD

CONTACT

info@buzzardpharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2024
• First Posted: October 10, 2024
• Study Start: January 30, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 31, 2026

Record last verified: 2025-03

Locations

US (2)