AlloStim + Anti-PD-L1 for Colorectal Cancer

(COMUNITY Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with advanced colorectal cancer unresponsive to standard treatments. The focus is on an experimental immunotherapy called AlloStim, combined with a drug called Anti-PD-L1, which helps the immune system attack cancer cells. The researchers aim to determine if this approach is more effective than previous treatments. Suitable candidates have metastatic colorectal cancer and have not benefited from at least two lines of chemotherapy. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that AlloStim, a type of immune cell therapy from a donor, triggers an immune response similar to that in bone marrow transplants rather than directly killing tumors. Although data on AlloStim remains limited, no strong evidence of serious safety concerns has emerged so far.

Studies have found that anti-PD-L1 therapies, which help the immune system recognize and attack cancer cells, often cause side effects. In one study, about 85% of patients experienced side effects, ranging from mild to severe, but most tolerated the treatment well.

Overall, while both treatments can cause side effects, they are generally considered manageable. Participants should discuss any concerns with their healthcare providers to better understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for colorectal cancer?

Researchers are excited about the combination of AlloStim and Anti-PD-L1 for colorectal cancer because it takes a novel approach to targeting the immune system. Unlike traditional treatments like chemotherapy and radiation, which directly attack cancer cells, this combination focuses on boosting the body's immune response to fight the cancer. AlloStim is an innovative therapy that stimulates immune cells, while Anti-PD-L1 blocks a protein that often helps cancer cells hide from the immune system. This dual strategy has the potential to enhance the body's natural ability to combat cancer, offering new hope for patients with colorectal cancer.

What evidence suggests that AlloStim and Anti-PD-L1 could be effective for colorectal cancer?

This trial will evaluate the combination of AlloStim and anti-PD-L1 therapy for colorectal cancer. Research has shown that AlloStim helps the body's immune system learn to attack and destroy cancer cells, which can stop them from growing and spreading. Patients with advanced colorectal cancer have experienced positive results with AlloStim, especially when other treatments have failed.

Studies have found that anti-PD-L1 therapy can assist some colorectal cancer patients by blocking a pathway that tumors use to evade the immune system. While not everyone benefits, some studies report that 20% to 50% of patients see improvements with this treatment.

Combining AlloStim with anti-PD-L1 therapy in this trial might enhance the immune system's ability to fight cancer cells, offering hope for those who haven't had success with other treatments. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

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

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

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

History of severe hypersensitivity to monoclonal antibody drugs

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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+

Published Research Related to This Trial

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]

Citations

1.

cdek.pharmacy.purdue.edu

cdek.pharmacy.purdue.edu/trial/NCT02380443/

Trial | NCT02380443

Official Title. In-Situ Cancer Vaccine: Phase IIA, Open-Label Study to Assess the Safety of AlloStim® Immunotherapy Alone and in Combination With Cryoablation ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04444622

Immunotherapy for Third Line Metastatic Colorectal Cancer

Rather, the novel AlloStim mechanism is designed to modify and train the host immune system to kill tumors and prevent tumor growth and spread. Uniquely, the ...

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.TPS318

A phase 2, multicenter, open-label study of AlloStim ...

A phase 2, multicenter, open-label study of AlloStim combined with anti-PD-L1 immunotherapy as 4L therapy in patients with MSS/pMMR metastatic colorectal ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01741038

Study Details | NCT01741038 | AlloStim® In-Situ Vaccine ...

This is a Phase II/III, randomized, open-label, multicenter, controlled, two arm study designed to determine the efficacy in terms of OS and the safety of the ...

5.

trial.medpath.com

trial.medpath.com/clinical-trial/b6139e8463c02551/nct02380443-in-situ-cancer-vaccine-allostim-cryoablation-metastatic-colorectal-cancer

AlloStim® Immunotherapy Dosing Alone or in Combination ...

The current drugs used to treat colorectal cancer provide important treatment options for patients, their limitations including drug resistance, poor efficacy ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00861965

Bioengineered Allogeneic Immune Cells (AlloStim) Not ...

AlloStim is being tested to determine if it might elicit the same anti-tumor mechanism that occurs in allogeneic bone marrow/stem cell transplant (BMT) ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.TPS317

A phase 2, multicenter, open-label study of AlloStim in-situ ...

Novel approaches that boost the immune response in low TMB tumors may benefit mCRC patients. AlloStim is an allogeneic, non-genetically ...

8.

adisinsight.springer.com

adisinsight.springer.com/drugs/800032575

T cell vaccine AlloStim - Immunovative Therapies - AdisInsight

Intentionally mis-matched, allogeneic Th1 memory Cells (AlloStim) conjugated With CD3/CD28-coated microbeads; Mis-matched immune cell therapy (AlloStim) - ...

9.

mycancergenome.org

mycancergenome.org/content/clinical_trials/NCT04444622/

Clinical Trial: NCT04444622

Unlike autologous immune cell therapies, like CAR-T cells or TIL cells, AlloStim is allogeneic and is not intended to directly kill tumors.