Immunotherapy with AlloStim for Metastatic Colorectal Cancer

(STIMVAX Trial)

No longer recruiting at 6 trial locations

Overseen By Kim Demonte

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mirror Biologics, Inc.

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

Disqualifiers: MSI-H, Brain metastasis, Autoimmune, 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: 15

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new immunotherapy treatment called AlloStim for individuals with a specific type of metastatic colorectal cancer. The researchers aim to determine if AlloStim, derived from healthy donor cells, can benefit those whose cancer has not responded to two rounds of standard chemotherapy. This simple one-arm study means all participants receive the same treatment. Suitable candidates have metastatic colorectal cancer, have undergone two unsuccessful chemotherapy treatments, and do not exhibit high-frequency microsatellite instability (a genetic marker). As a Phase 2 trial, this research focuses on assessing 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 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.

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

Research has shown that AlloStim is generally well-tolerated. In earlier studies with patients who had advanced colorectal cancer, AlloStim was used safely. Most patients did not experience serious side effects. Common side effects included mild to moderate reactions at the injection site, such as redness or swelling, with only a few reports of serious side effects.

AlloStim is an "off-the-shelf" product, made from healthy donor blood without requiring genetic changes. This method proved safe in past trials. Since AlloStim is in a Phase 2 study, earlier trials demonstrated it was safe enough to continue testing.

Overall, the available safety information provides a positive outlook for using AlloStim to treat advanced colorectal cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

AlloStim is unique because it uses a novel immunotherapy approach to treat metastatic colorectal cancer. Unlike standard treatments, which typically involve chemotherapy or targeted therapies, AlloStim harnesses the body's immune system to attack cancer cells. Researchers are excited because it is administered both intradermally and intravenously, potentially enhancing the immune response more effectively than traditional methods. This dual delivery could offer a new way to combat cancer with fewer side effects, making it a promising option for patients.

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

Research has shown that AlloStim, the investigational treatment in this trial, might help the immune system fight cancer, similar to bone marrow transplants. It uses immune cells from healthy donors to strengthen the body's natural defenses against tumors. Studies have found that this method could be especially useful for patients with tumors that have a low number of mutations, which are often hard to treat with standard methods. Early results suggest that AlloStim can improve the immune response in these cases. While still under study, this approach aims to offer a new option for patients with advanced colorectal cancer. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• AlloStim

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

Citations

1. 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) ...

2. 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 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01741038

Study Details | NCT01741038 | AlloStim® In-Situ Vaccine ... This is a personalized anti-cancer vaccine protocol which includes an in-situ (in the body) cancer vaccine step which combines killing a single metastatic ...

4. 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) - ...

5. 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.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02380443?tab=table

AlloStim® Immunotherapy Dosing Alone or in Combination ... ... Safety of AlloStim® Immunotherapy Alone and in Combination With Cryoablation as Third Line Therapy for Metastatic Colorectal Cancer. Brief Summary *. This is ...

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

Trial | NCT02380443 ... Safety of AlloStim® Immunotherapy Alone and in Combination With Cryoablation as Third Line Therapy for Metastatic Colorectal Cancer. Snapshot. Phase. Phase 2.