Isunakinra + Pembrolizumab for Colorectal Cancer

Recruiting at 1 trial location

Overseen By Hans Olivecrona, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Buzzard Pharmaceuticals

Must be taking: PD-1 inhibitors

Must not be taking: Systemic steroids

Disqualifiers: Pregnancy, Autoimmune diseases, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments to help people with a challenging type of colorectal cancer. It combines isunakinra, a new immunotherapy that blocks certain signals in the body, with an existing cancer drug, pembrolizumab. The goal is to determine if this pairing can be more effective for tumors that have resisted other treatments. Individuals with colorectal cancer that has spread or is not responding to standard treatments, and whose tumors have specific traits (such as kras mutations and high levels of DNA changes), might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires a minimum of 2 weeks without chemotherapy or radiation therapy and 4 weeks without immunotherapy before starting. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that isunakinra is generally safe and works well with other treatments. In previous studies, patients who took isunakinra with the drug nivolumab experienced manageable side effects. Similarly, pembrolizumab, included in this trial, has demonstrated an easy-to-handle safety profile. Common side effects include diarrhea, tiredness, and nausea, but these are usually not severe. As this trial is in an early stage, isunakinra has been reasonably safe so far, but more information is needed for confirmation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal cancer?

Researchers are excited about Isunakinra combined with Pembrolizumab for colorectal cancer because it introduces a new approach to treatment. Unlike traditional chemotherapy or existing immunotherapies that primarily target cancer cells directly, this combination harnesses the immune system in a novel way. Isunakinra works by targeting interleukin-1, a protein involved in inflammation and cancer progression, potentially enhancing the effectiveness of Pembrolizumab, an established immunotherapy. This dual-action strategy could provide a more powerful and precise attack on cancer cells, offering hope for better outcomes in colorectal cancer patients.

What evidence suggests that this treatment might be an effective treatment for colorectal cancer?

Research has shown that pembrolizumab, a drug that blocks PD-1, has helped about 33% of patients with a specific type of colorectal cancer. This is encouraging, but it may not work as well for tumors that are microsatellite stable (MSS) and have a high number of mutations (TMB-H). In this trial, researchers are testing isunakinra, a drug that blocks IL-1, in combination with pembrolizumab to see if it can improve outcomes. Isunakinra has been found safe and well-tolerated when used with a similar drug, nivolumab. The goal is for isunakinra to enhance the treatment's effectiveness against difficult-to-treat colorectal cancer. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with advanced or metastatic colorectal cancer that's microsatellite stable (MSS), has a high tumor mutational burden (TMB-H), and KRAS mutation. Participants must have tried all approved treatments already.

Inclusion Criteria

Patients must have measurable disease by radiographic criteria

Patients must meet specific washout periods from prior therapies

I can carry out all my self-care activities without assistance.

Exclusion Criteria

I do not have any major health issues that could affect my treatment.

Pregnant women or women presently breast-feeding their children

Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive isunakinra in combination with pembrolizumab for colorectal cancer

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Isunakinra

Trial Overview The study tests isunakinra, a new immunotherapy, alone and combined with Pembrolizumab, an existing immunotherapy. The goal is to see if adding isunakinra can make resistant tumors respond to treatment.

How Is the Trial Designed?

Group I: combination immunotherapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Buzzard Pharmaceuticals

Lead Sponsor

Trials

2

Recruited

40+

Published Research Related to This Trial

In the final analysis of the KEYNOTE-164 study, pembrolizumab demonstrated a 32.8% objective response rate in patients with advanced MSI-H/dMMR colorectal cancer who had received multiple prior treatments, indicating its efficacy in this difficult-to-treat population.

The treatment was associated with a median overall survival of 31.4 months for patients with more prior therapies and 47.0 months for those with fewer, while maintaining a manageable safety profile with no new safety concerns reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for previously treated, microsatellite instability-high/mismatch repair-deficient advanced colorectal cancer: final analysis of KEYNOTE-164. Le, DT., Diaz, LA., Kim, TW., et al.[2023]

Pembrolizumab significantly improved progression-free survival (PFS) in patients with unresectable or metastatic microsatellite instability-high (MSI-H) colorectal cancer, with a median PFS of 16.5 months compared to 8.2 months for standard chemotherapy, indicating its efficacy as a first-line treatment.

The FDA found no safety concerns during the approval process, and while both pembrolizumab and standard of care had similar adverse reactions, the duration of treatment with pembrolizumab was nearly double that of standard care, suggesting a potentially more favorable treatment profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the First-line Treatment of Patients with MSI-H/dMMR Advanced Unresectable or Metastatic Colorectal Carcinoma. Casak, SJ., Marcus, L., Fashoyin-Aje, L., et al.[2022]

In a study of 44 women with advanced or recurrent MMRd/MSI-H endometrial adenocarcinomas treated with pembrolizumab, obesity (BMI≥30) was linked to a higher disease control rate (85.2%) compared to those with a BMI<30 (59.8%).

Patients with obesity also experienced significantly longer progression-free survival (PFS) while overall survival (OS) rates remained similar regardless of BMI, suggesting that body weight may influence treatment outcomes with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity is associated with improved progression-free survival in Microsatellite-Instability-High endometrial cancer treated with pembrolizumab. Bernard, L., How, JA., Patel, S., et al.[2023]

In the KEYNOTE-177 study involving 307 patients with metastatic colorectal cancer, pembrolizumab significantly improved health-related quality of life (HRQOL) compared to chemotherapy, with a clinically meaningful difference in global health status scores.

Patients receiving pembrolizumab experienced a longer time to deterioration in quality of life measures, including physical and social functioning, indicating that pembrolizumab not only extends progression-free survival but also enhances overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Andre, T., Amonkar, M., Norquist, JM., et al.[2021]

The KEYNOTE-177 study demonstrated that pembrolizumab significantly improves progression-free survival compared to the current standard of care for patients with metastatic colorectal cancer that has DNA mismatch repair or microsatellite instability-high.

This finding suggests that pembrolizumab could be a more effective first-line treatment option for this specific type of colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 Inhibitor Bests Chemo for Colorectal Cancer. [2021]

Pembrolizumab has been approved as a first-line treatment for adults with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer, showing a significant improvement in progression-free survival (PFS) compared to standard of care, with a median PFS of 16.5 months versus 8.2 months.

The treatment was associated with manageable adverse events, including diarrhea and fatigue, and the European Medicines Agency deemed the benefit-risk balance positive, marking a significant advancement in targeted cancer therapy based on DNA repair deficiency biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The EMA assessment of pembrolizumab as monotherapy for the first-line treatment of adult patients with metastatic microsatellite instability-high or mismatch repair deficient colorectal cancer. Trullas, A., Delgado, J., Genazzani, A., et al.[2021]

In a study of 107 patients with advanced well-differentiated neuroendocrine tumors (NETs), pembrolizumab showed limited efficacy, with an objective response rate of only 3.7%, indicating that it may not be a highly effective treatment for this specific cancer type.

Despite the low response rate, pembrolizumab was associated with manageable safety, as 75.7% of patients experienced treatment-related adverse events, with only 21.5% classified as severe (grade 3-5).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Neuroendocrine Tumors: Results From the Phase II KEYNOTE-158 Study. Strosberg, J., Mizuno, N., Doi, T., et al.[2021]

In a phase II study involving 124 patients with metastatic MSI-H/dMMR colorectal cancer, pembrolizumab demonstrated an objective response rate of 33% in both treatment cohorts, indicating its efficacy in this difficult-to-treat population.

The treatment showed a manageable safety profile, with 16% of patients in cohort A and 13% in cohort B experiencing grade 3-4 adverse events, suggesting that pembrolizumab can be safely administered to patients with prior treatment failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: KEYNOTE-164. Le, DT., Kim, TW., Van Cutsem, E., et al.[2021]

In a phase I/II trial involving 55 patients with metastatic colorectal cancer, the combination of napabucasin and pembrolizumab showed promising antitumor activity, particularly in patients with microsatellite instability high (MSI-H) tumors, achieving an immune-related objective response rate (irORR) of 50%.

The treatment was generally well-tolerated, with no dose-limiting toxicities observed at the recommended phase 2 dose of napabucasin (480 mg), although the overall efficacy did not meet the primary endpoint, highlighting the need for further investigation into biomarkers that may influence treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Phase I/II Trial of Napabucasin and Pembrolizumab in Patients with Metastatic Colorectal Cancer (EPOC1503/SCOOP Trial). Kawazoe, A., Kuboki, Y., Shinozaki, E., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06634875

Study Details | NCT06634875 | Isunakinra Alone and in ... This study will enroll patients with colorectal cancer that is locally advanced or metastatic. The tumor must be microsatellite stable (MSS), ...

2. withpower.com withpower.com/trial/phase-2-colorectal-neoplasms-11-2024-9b768

Isunakinra + Pembrolizumab for Colorectal Cancer In a phase II study involving 124 patients with metastatic MSI-H/dMMR colorectal cancer, pembrolizumab demonstrated an objective response rate of 33% in both ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e14580

A phase I study of isunakinra, an IL-1 alfa/beta inhibitor, in ... Conclusions: Isunakinra is safe and well-tolerated in combination with standard dose nivolumab. Ongoing expansion cohorts and future studies ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39765187/

Efficacy of pembrolizumab in microsatellite-stable, tumor ... Conclusions: Pembrolizumab may be less effective than FTD/TPI in later-line treatment of MSS-TMB-H mCRC, potentially due to genomic similarities ...

5. scientificarchives.com scientificarchives.com/article/immunotherapy-in-mss-pmmr-metastatic-colorectal-cancer-insights-from-the-keynote

Immunotherapy in MSS/pMMR Metastatic Colorectal Cancer Overall, the combinations of chemotherapy with pembrolizumab alone were well-tolerated, with grade 3 or 4 adverse events (AEs) reported in 58% of patients in ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT06634875

Isunakinra Alone and in Combination With Pembrolizumab ... Outcome Measure, Measure Description, Time Frame ; Safety, The incidence, relatedness and severity of adverse events (includes safety laboratory abnormalities) ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31725351/

Phase II Open-Label Study of Pembrolizumab in ... - PubMed Pembrolizumab is effective with a manageable safety profile in patients with MSI-H/dMMR CRC.