Immunotherapy with AlloStim for Metastatic Colorectal Cancer

(STIMVAX Trial)

Recruiting at5 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Mirror Biologics, Inc.

Must not be taking: Bevacizumab, Corticosteroids, Anticoagulants, others

Disqualifiers: MSI-H, Brain metastasis, Autoimmune, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests AlloStim, an immunotherapy using healthy donor immune cells, for patients with advanced colorectal cancer unresponsive to standard treatments. AlloStim helps train the patient's immune system to attack cancer cells by creating a temporary immune response.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take certain medications that interfere with platelet function or coagulation, like aspirin or warfarin, unless they can be stopped for a safe period before procedures. Also, you cannot use high doses of corticosteroids or have had recent bevacizumab treatment.

What data supports the effectiveness of the treatment AlloStim for metastatic colorectal cancer?

Research on cancer vaccines and immunotherapy for colorectal cancer shows potential benefits, with some studies indicating that immunotherapy can induce specific immune responses against cancer cells. Although the overall clinical response rates are low, there is evidence of immune activation, which suggests that treatments like AlloStim could have potential in enhancing antitumor immune responses. ^{1 2 3 4 5}

How does the treatment AlloStim differ from other treatments for metastatic colorectal cancer?

AlloStim is unique because it uses bioengineered immune cells from donors to stimulate the patient's immune system to attack cancer cells, unlike traditional treatments that often rely on chemotherapy or radiation. This approach is still experimental for colorectal cancer, as immunotherapy is not yet a standard treatment for this condition. ^{4 5 6 7 8}

Research Team

Eligibility Criteria

Adults aged 18-80 with metastatic colorectal cancer that has worsened after two previous chemotherapy treatments can join this trial. They must have an ECOG score of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory and able to carry out work. Participants need normal organ function and blood counts, not be pregnant or breastfeeding, agree to use contraception if capable of childbearing, and cannot have certain conditions like brain metastasis or severe heart disease.

Inclusion Criteria

I have had two chemotherapy treatments that did not work.

My cancer has spread to other parts of my body.

I am fully active or can carry out light work.

Exclusion Criteria

My cancer has spread to my brain or its coverings.

I am at high risk for bowel blockage due to my tumor.

I have had a bone marrow, stem cell, or organ transplant in the past.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AlloStim in three cycles with weekly administrations

16 weeks

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• AlloStim (Cell Therapy)

Trial Overview The study is testing AlloStim, an immunotherapy made from healthy donor blood cells. It's for patients whose cancer has spread even after treatment with common chemo regimens (FOLFOX/FOLFIRI) and possibly targeted drugs (anti-EGFR). This Phase IIB trial is open-label at multiple sites where everyone knows what treatment they're getting.

Participant Groups

Group I: AlloStim Experimental Treatment 1 Intervention

AlloStim is administered in three cycles: Cycle 1 Day 0: 0.5ml ID AlloStim® Day 7: 0.5ml ID AlloStim® Day 14: 0.5ml ID AlloStim® Day 21: 0.5ml ID AlloStim® Day 28: 0.5ml ID AlloStim® Cycle 2 Day 42: 0.5ml ID AlloStim® Day 49: 0.5ml ID AlloStim® Day 56: 0.5ml ID AlloStim® Day 63: 0.5ml ID AlloStim® Day 70: 0.5ml ID AlloStim® + 3ml IV AlloStim® Cycle 3 Day 84: 0.5ml ID AlloStim® Day 91: 0.5ml ID AlloStim® Day 98: 0.5ml ID AlloStim® Day 105: 0.5ml ID AlloStim® Day 112: 0.5ml ID AlloStim® + 3ml IV AlloStim®

Who Is Running the Clinical Trial?

Mirror Biologics, Inc.

Lead Sponsor

Trials

15

Recruited

360+

Immunovative Therapies, Ltd.

Lead Sponsor

Trials

14

Recruited

310+

Mirror Biologics, Inc.

Collaborator

Trials

3

Recruited

210+

Findings from Research

Anticancer vaccination shows promise as a novel therapeutic approach for colorectal carcinoma, with evidence suggesting that the immune system can be effectively targeted against cancer cells through specific immunotherapy strategies.

While no vaccination regimen is currently recommended outside of clinical trials, ongoing research aims to enhance the effectiveness of cancer vaccines by leveraging recent insights from preclinical tumor immunology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colorectal cancer vaccines: principles, results, and perspectives. Mocellin, S., Rossi, CR., Lise, M., et al.[2019]

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]

A systematic review and meta-analysis of 32 studies involving 527 patients with advanced colorectal cancer found that active specific immunotherapy resulted in a very low overall clinical response rate of only 0.9%.

While the clinical response was minimal, about 59% of patients exhibited humoral immune responses and 44% showed cellular immune responses, indicating that while the therapy may not significantly shrink tumors, it can still stimulate the immune system in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and immunologic responses to active specific cancer vaccines in human colorectal cancer. Nagorsen, D., Thiel, E.[2021]

Recent advancements in cancer immunotherapy have shown success with passive strategies like monoclonal antibodies and donor lymphocyte infusions, particularly in treating lymphoma and breast cancer.

Active stimulation of the immune system through vaccines and modified tumor cells has shown promise, with Phase III trials indicating that autologous tumor cell vaccines can improve disease-free survival in colorectal cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surrogate markers of response to cancer immunotherapy. Morse, MA., Clay, TM., Hobeika, AC., et al.[2019]

Immunotherapy for colorectal cancer has shown potential benefits in some clinical trials, but it is still considered an experimental treatment rather than a standard option.

The review discusses various immunotherapeutic strategies, such as cancer vaccines and adoptive cell therapy, highlighting their strengths and weaknesses, and aims to guide future research towards the approval and use of these therapies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colorectal cancer immunotherapy. Xiang, B., Snook, AE., Magee, MS., et al.[2022]

A novel vaccine combining irradiated human colon cancer cells and GM-CSF-producing cells was found to be safe and feasible in a phase 1 study involving nine patients with metastatic colorectal cancer.

Patients who had undergone curative metastasectomy showed promising outcomes, with six surviving longer than 36 months and four remaining disease-free, suggesting potential benefits of the vaccine in enhancing anti-tumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A safety and feasibility study of an allogeneic colon cancer cell vaccine administered with a granulocyte-macrophage colony stimulating factor-producing bystander cell line in patients with metastatic colorectal cancer. Zheng, L., Edil, BH., Soares, KC., et al.[2021]

A case study of a patient with metastatic microsatellite-stable (MSS) colorectal cancer showed an unexpected strong immune response characterized by a high frequency of tumor-reactive CD8+ T cells, despite the cancer's typical resistance to immunotherapy.

The study suggests that prior cytotoxic chemotherapy may have primed the immune system, leading to the emergence of immunogenic mutations in the metastatic tumor, indicating a potential strategy for combining cytotoxic treatments with immunotherapy in colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robust Antitumor Immunity in a Patient with Metastatic Colorectal Cancer Treated with Cytotoxic Regimens. Rajamanickam, V., Ballesteros-Merino, C., Samson, K., et al.[2022]

Supplementing mice with Lactobacillus rhamnosus GG (LGG) significantly increased CD8 T-cell responses in the gut, which is crucial for enhancing antitumor immune responses.

LGG administration led to a reduction in tumor burden in murine models of intestinal cancer, demonstrating its potential to improve the effectiveness of immunotherapy in colorectal cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus rhamnosus GG Orchestrates an Antitumor Immune Response. Owens, JA., Saeedi, BJ., Naudin, CR., et al.[2022]

References

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

Colorectal cancer vaccines: principles, results, and perspectives. [2019]

2. China pubmed.ncbi.nlm.nih.gov

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

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

Clinical and immunologic responses to active specific cancer vaccines in human colorectal cancer. [2021]

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

Surrogate markers of response to cancer immunotherapy. [2019]

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

Colorectal cancer immunotherapy. [2022]

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

A safety and feasibility study of an allogeneic colon cancer cell vaccine administered with a granulocyte-macrophage colony stimulating factor-producing bystander cell line in patients with metastatic colorectal cancer. [2021]

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

Robust Antitumor Immunity in a Patient with Metastatic Colorectal Cancer Treated with Cytotoxic Regimens. [2022]

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

Lactobacillus rhamnosus GG Orchestrates an Antitumor Immune Response. [2022]