AlloStim + Anti-PD-L1 for Colorectal Cancer

(COMUNITY Trial)

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mirror Biologics, Inc.

Must not be taking: Corticosteroids

Disqualifiers: MSI-H, Bowel obstruction, Brain metastasis, COPD, 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: 168

50 Participants Needed

Trial Summary

What is the purpose of this trial?

Experimental immunotherapy in chemotherapy-refractory and immunotherapy-refractory metastatic colorectal cancer patients that have progressed, or are intolerant to, Longsurf (TAS-102) +/- Avastin (bevacizumab) or Stivarga (regorafenib) or Fruzaqla (fruquintinib) combining experimental AlloStim with an anti-programmed death ligand 1 (PD-L1) checkpoint inhibitor drug.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that chronic use of high-dose corticosteroids is not allowed, so you may need to adjust if you're on such medication.

What data supports the effectiveness of the treatment AlloStim + Anti-PD-L1 for colorectal cancer?

Research shows that combining immune checkpoint inhibitors like anti-PD-1 with therapies that target specific tumor mutations can enhance the immune system's ability to fight cancer. In colorectal cancer, using personalized neoantigen-based immunotherapy alongside checkpoint inhibitors has shown promise in inducing strong anti-tumor responses. ^{1 2 3 4 5}

Is the AlloStim + Anti-PD-L1 treatment generally safe for humans?

The safety data for similar immunotherapies, like GVAX, show they are generally safe, with common side effects being mild, such as injection site reactions and flu-like symptoms. However, treatments involving PD-1 inhibitors can sometimes lead to serious side effects like colitis (inflammation of the colon). ^{1 6 7 8 9}

What makes the AlloStim + Anti-PD-L1 treatment unique for colorectal cancer?

The AlloStim + Anti-PD-L1 treatment is unique because it combines bioengineered immune cells with a checkpoint inhibitor to enhance the body's immune response against colorectal cancer. This approach aims to boost the effectiveness of the immune system in recognizing and attacking cancer cells, offering a novel strategy compared to traditional treatments. ^{1 2 10 11 12}

Eligibility Criteria

This trial is for patients with metastatic colorectal cancer that has not responded to chemotherapy or other immunotherapies and have progressed after, or cannot tolerate, treatments like Longsurf (TAS-102) with or without Avastin (bevacizumab), or Stivarga (regorafenib).

Inclusion Criteria

Patients with childbearing potential must have a negative ß-HCG test and agree to use a highly effective contraceptive method during the course of the study

My blood counts meet the required levels for treatment.

I am not pregnant or breastfeeding.

Exclusion Criteria

My cancer has spread to my brain or the lining around my brain.

I plan to use high-dose steroids for more than 2 weeks during the study.

My cancer has high microsatellite instability or mismatch repair deficiency.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - AlloStim® Priming

Participants receive AlloStim® administered weekly in two 21-day cycles with intradermal doses followed by an intravenous dose

6 weeks

Weekly visits for intradermal and intravenous doses

Treatment - Combination Therapy

Combination of AlloStim® IV boosters and anti-PD-L1 checkpoint therapy with avelumab

5 weeks

Bi-weekly visits for avelumab administration

Expansion Phase

An additional cycle of combined AlloStim® and avelumab for stable patients

5 weeks

Visits for combined therapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 weeks

Final restaging CT scan on Day 168

Treatment Details

Interventions

• AlloStim
• Anti-PD-L1

Trial Overview The study is testing a new combination of experimental AlloStim immunotherapy with an anti-PD-L1 drug, which blocks a pathway cancers use to hide from the immune system. The goal is to see if this combo can help patients whose cancer hasn't responded to standard treatments.

Who Is Running the Clinical Trial?

Mirror Biologics, Inc.

Lead Sponsor

Trials

15

Recruited

360+

Findings from Research

Three specific neoepitopes (P31, P50, and P52) were identified as immunogenic in non-MSI-H colorectal cancer, capable of inducing tumor-specific cytotoxic T cell responses in both healthy donors and cancer patients.

The combination of adoptive T cell therapy using these neoepitopes with anti-PD-1 immune checkpoint inhibitors showed promising results in inhibiting tumor growth, suggesting a potential personalized treatment strategy for patients with non-MSI-H colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening and identification of HLA-A2-restricted neoepitopes for immunotherapy of non-microsatellite instability-high colorectal cancer. Shi, R., Li, Y., Ran, L., et al.[2022]

In a study of 108 patients with advanced colorectal cancer and high MSI expression, the combination of PD-1 customization and autoimmune T-cell therapy resulted in a treatment efficiency of 90.74%, significantly higher than the 61.11% efficiency observed in the control group.

The study also found that after treatment, the levels of immune markers like CD107a, perforin, and GranB cells increased in both groups, but the study group showed a more pronounced expression of PD-1, particularly in patients with more advanced cancer stages (grade III-IV).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study of PD-1 Customization and Autoimmune T Cells for Advanced Colorectal Cancer with High MSI Expression. Li, N., Zhang, X., Zhang, Y., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

Screening and identification of HLA-A2-restricted neoepitopes for immunotherapy of non-microsatellite instability-high colorectal cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Study of PD-1 Customization and Autoimmune T Cells for Advanced Colorectal Cancer with High MSI Expression. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Tumor-Infiltrating Lymphocyte Therapy and Neoantigens. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

'Final common pathway' of human cancer immunotherapy: targeting random somatic mutations. [2022]

6. England pubmed.ncbi.nlm.nih.gov

GM-CSF gene-modifed cancer cell immunotherapies: of mice and men. [2007]

7. England pubmed.ncbi.nlm.nih.gov

Prophylactic TNF blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Distribution of mucosal PD-1 expressing T cells in patients with colitis of different etiologies. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Immune Marker Spatial Distribution and Clinical Outcome after PD-1 Blockade in Mismatch Repair-deficient, Advanced Colorectal Carcinomas. [2023]

11. Germany pubmed.ncbi.nlm.nih.gov

PD-L1-specific T cells. [2021]

12. Germany pubmed.ncbi.nlm.nih.gov

Relationship between T cell receptor clonotype and PD-1 expression of tumor-infiltrating lymphocytes in colorectal cancer. [2021]