Cancer Vaccine + GM-CSF/Pembrolizumab for Advanced Stage Adenocarcinoma

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Tianhong Li

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune diseases, Splenectomy, Pregnancy, others

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

Compensation: Varies

Number of Visits: 17

77 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer vaccine, Labvax 3(22)-23, to determine its safety and effectiveness in helping the immune system combat adenocarcinoma that has metastasized. The trial also examines the vaccine in combination with GM-CSF (Sargramostim), which boosts the immune system, and pembrolizumab, which may enhance the body's ability to attack cancer cells. It seeks participants with adenocarcinoma who have not responded to other treatments, particularly those with lung cancer testing positive for a protein called labyrinthin. Participants should have undergone previous cancer treatments and still have the condition, but must be stable enough for new treatments. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative approach.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you must have completed any prior chemotherapy, immunotherapy, or targeted therapy at least 3 weeks before starting the study treatment, and you cannot be on systemic steroid therapy greater than 10 mg of prednisone daily within 7 days prior to the first dose of trial treatment.

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

Research shows that the cancer vaccine Labvax 3(22)-23, when combined with GM-CSF (a protein that boosts white blood cells), is generally well tolerated. Earlier studies found that patients with hard-to-treat adenocarcinomas managed the vaccine without major problems.

GM-CSF, known for strengthening the immune system, has a long history of safe use. It has been part of various treatments for over 20 years, demonstrating a good safety record.

Pembrolizumab, which also enhances the immune system, has been widely studied and received FDA approval for several conditions. It continues to show positive results in improving survival rates for different cancers, maintaining a good safety record.

Overall, previous research has shown these treatments to be well-tolerated, suggesting they are safe options for patients considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about LabVax 3(22)-23 because it represents a novel approach to treating advanced stage adenocarcinoma by combining cancer vaccination with immune system boosters. Unlike standard treatments like chemotherapy or radiation, which directly attack cancer cells but can also harm healthy cells, LabVax 3(22)-23 aims to stimulate the body's own immune system to fight the cancer more effectively. The treatment includes a new cancer vaccine delivered intradermally and an immune stimulant, GM-CSF, administered subcutaneously, potentially enhancing the immune response. Moreover, in combination with pembrolizumab, an established immune checkpoint inhibitor, this treatment could offer a more targeted and less toxic alternative to conventional therapies.

What evidence suggests that this trial's treatments could be effective for advanced stage adenocarcinoma?

Research shows that Labvax 3(22)-23, a cancer vaccine, may help treat adenocarcinoma by targeting a protein called labyrinthin on tumor cells. In past studies, patients with adenocarcinoma demonstrated that the vaccine can trigger strong immune responses. In this trial, participants in the Phase 1 treatment arm will receive Labvax 3(22)-23 alongside Sargramostim, also known as GM-CSF, which boosts the immune system. Participants in the Phase 2 treatment arm will receive Labvax 3(22)-23, Sargramostim, and Pembrolizumab. Pembrolizumab, a drug that helps the immune system attack cancer, has improved survival rates in various advanced cancers, making it a good option alongside other treatments. Together, these treatments aim to strengthen the body's ability to fight cancer cells, potentially leading to better outcomes for patients with advanced adenocarcinoma. ^{1 2 3 5 6}

Who Is on the Research Team?

Tianhong Li

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

Adults with advanced or recurrent adenocarcinoma, who have measurable disease and a positive immune response to common antigens. They must be in good physical condition (ECOG 0-1), not pregnant, agree to contraception, and have no untreated brain metastases or severe autoimmune diseases. Prior treatments should be completed at least 2-3 weeks before the vaccine.

Inclusion Criteria

I have been treated with anti-PD-1 or anti-PD-L1 therapy for lung cancer.

I've had cancer treatment but either didn't respond or couldn't tolerate it, and I've mostly recovered from side effects.

I don't have untreated brain metastases and if treated, I've been stable and off steroids for a week.

Exclusion Criteria

I haven't had cancer treatment in the last 2 weeks or have recovered from its side effects.

I haven't had cancer treatment with monoclonal antibodies in the last 3 weeks or have recovered from their side effects.

Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive LabVax 3(22)-23 and GM-CSF on weeks 1, 2, 4, 8, and 12

16 weeks

5 visits (in-person)

Phase 2 Treatment

Participants receive pembrolizumab every 3 weeks for up to 12 cycles, and LabVax 3(22)-23 and GM-CSF on weeks 7, 8, 10, 14, and 18

34 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Chart review

What Are the Treatments Tested in This Trial?

Interventions

• Labvax 3(22)-23
• Sargramostim

Trial Overview The trial is testing Labvax 3(22)-23 cancer vaccine with GM-CSF alone or combined with pembrolizumab for advanced adenocarcinoma. The vaccine targets labyrinthin on tumor cells to stimulate an immune response, potentially enhanced by GM-CSF and pembrolizumab.

How Is the Trial Designed?

Group I: Phase 2 Treatment (sargramostim, LabVax 3(22)-23, pembrolizumab) Experimental Treatment 3 Interventions

Pembrolizumab will be given intravenously every 3 weeks for up to 12 cycles on Day 1 of Weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, and 34. Participants will be given LabVax 3(22)-23 (intradermally) and adjuvant GM-CSF (subcutaneously) on weeks 7, 8, 10, 14, and 18.

Group II: Phase 1 Treatment (sargramostim, LabVax 3(22)-23) Experimental Treatment 2 Interventions

Patients receive sargramostim SC and LabVax 3(22)-23 ID on weeks 1, 2, 4, 8, and 12 in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Tianhong Li

Lead Sponsor

Trials

2

Recruited

80+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

LabyRx Immunologic Therapeutics

Collaborator

Trials

1

Recruited

80+

Published Research Related to This Trial

The KRM-20 cancer vaccine, which targets 12 different tumor-associated antigens, was found to be safe in a study of 17 patients with castration-resistant prostate cancer, with no serious adverse reactions reported.

The 20 mg dose of KRM-20 showed the best immune response, leading to increased cytotoxic T lymphocyte activity and fewer immune suppressive cells, making it a promising candidate for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of a cancer vaccine consisting of 20 mixed peptides in patients with castration-resistant prostate cancer: dose-related immune boosting and suppression. Noguchi, M., Arai, G., Matsumoto, K., et al.[2015]

The HER-2/neu E75-peptide vaccine, combined with GM-CSF, is safe and effectively stimulates E75-specific CD8(+) T cell immunity in breast cancer patients, with a booster enhancing this response.

Immunity from the initial vaccination wanes over time, but a booster given around 6 months after the primary series significantly increases E75-specific immunity, especially in patients who initially lacked elevated residual immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of booster inoculations to sustain the clinical effect of an adjuvant breast cancer vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Holmes, JP., Clifton, GT., Patil, R., et al.[2014]

The SA-GM-CSF modified tumor cell vaccine enhances dendritic cell activation and increases tumor-specific CD8+ T-cells, but these T-cells often express PD-1, which contributes to immune resistance.

Combining PD-1/PD-L1 blockade with the GM-CSF vaccine significantly boosts the population of active T-cells and enhances the immune response, leading to effective tumor rejection in prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 blockade enhances the efficacy of SA-GM-CSF surface-modified tumor vaccine in prostate cancer. Shi, X., Zhang, X., Li, J., et al.[2018]

The combination of personalized peptide vaccination (PPV) and estramustine phosphate (EMP) was found to be safe for patients with castration-resistant prostate cancer (CRPC), with no serious treatment-related adverse events reported and only mild skin reactions observed.

The treatment successfully boosted immune responses in a significant portion of patients, with 67% showing enhanced cytotoxic T lymphocyte responses, and a median survival time of 23.8 months, suggesting promising antitumor activity that warrants further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of personalized peptide vaccination using 14 kinds of vaccine in combination with low-dose estramustine in HLA-A24-positive patients with castration-resistant prostate cancer. Noguchi, M., Uemura, H., Naito, S., et al.[2013]

The novel PD-1 B-cell peptide vaccine (PD1-Vaxx) demonstrated superior efficacy compared to standard anti-PD-1 monoclonal antibodies in preclinical mouse models of colon carcinoma, suggesting it may be a promising alternative for cancer treatment.

Combining PD1-Vaxx with a HER-2 peptide vaccine resulted in enhanced tumor growth inhibition, and both vaccines showed a favorable safety profile with no observed toxicity or autoimmunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse model. Kaumaya, PTP., Guo, L., Overholser, J., et al.[2021]

The combination of personalized peptide vaccination and low-dose glucocorticoids was well tolerated in 11 patients with advanced hormone refractory prostate cancer, showing no severe adverse effects.

The treatment led to significant immunological responses, with increased IgG responses in 8 out of 10 patients receiving dexamethasone, and a notable decline in PSA levels in 6 out of 10 patients, suggesting potential clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone did not suppress immune boosting by personalized peptide vaccination for advanced prostate cancer patients. Naito, M., Itoh, K., Komatsu, N., et al.[2013]

The combination of AMG 820 and pembrolizumab was found to have an acceptable safety profile, with 99.1% of patients experiencing adverse events, primarily grade ≥3, but only a small number of patients (3%) showed a partial response to treatment.

Despite some pharmacodynamic effects observed, such as increased PD-L1 expression and changes in immune cell populations, the combination did not demonstrate sufficient antitumor activity to warrant further investigation in the selected patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors. Razak, AR., Cleary, JM., Moreno, V., et al.[2021]

In a study of 10 patients with advanced melanoma, individualized peptide vaccinations combined with GM-CSF showed promising results, with a median progression-free survival of 6 months after a mean of 6.5 vaccination cycles.

The treatment was well tolerated, with most patients experiencing only mild side effects, and 5 out of 10 patients remained relapse-free for over a year, indicating potential efficacy and safety for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized synthetic peptide vaccines with GM-CSF in locally advanced melanoma patients. Atzpodien, J., Fluck, M., Reitz, M.[2012]

In a phase 1 study involving 9 participants with ovarian cancer, a peptide-based vaccine was found to be safe, with all reported side effects being mild (grade 1 to 2), including injection site reactions and fatigue.

The vaccine elicited T-cell responses in 89% of participants after stimulation, indicating immunogenicity, but the responses were of low potency, suggesting that future studies may need to combine this vaccine with additional immunomodulatory treatments to enhance T-cell activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multipeptide vaccine is safe and elicits T-cell responses in participants with advanced stage ovarian cancer. Chianese-Bullock, KA., Irvin, WP., Petroni, GR., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05101356

NCT05101356 | A Cancer Vaccine (Labvax 3(22)-23) and ... This phase 1/2 trial tests the safety and effectiveness of a cancer vaccine called Labvax 3(22)-23 and GM-CSF alone or in combination with pembrolizumab in ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e14660

A first-in-human phase I trial of a novel peptide vaccine ... LabVax 3(22)-23 and GM-CSF were well tolerated in these heavily pre-treated patients with Lab-expressing, refractory adenocarcinomas.

3. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A722

632 A phase 1/2 open label study of LabVax 3(22)-23 and ... We hypothesize that vaccination against LAB can elicit strong immune responses against the LAB-expressing adenocarcinomas in cancer patients.

4. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/labyrinthin-peptide-vaccine-labvax-322-23

Clinical Trials Using Labyrinthin Peptide Vaccine LabVax 3 ... Review the clinical trials studying labyrinthin peptide vaccine labvax 3(22)-23 on this list and use the filters to refine the results by age and location.

5. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A45

40 Novel biomarker assays for detecting labyrinthin ... LabVax 3(22)-23 is a novel anti-tumor vaccine that contains four synthetic labyrinthin-based peptides designed to elicit both B-cell and T-cell ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT05101356

A Cancer Vaccine (Labvax 3(22)-23) and GM-CSF Alone ... LB215 - Safety and preliminary effects of LabVax 3(22)-23 and GM-CSF, with ... (22)-23 and adjuvant GM-CSF in patients with advanced stage adenocarcinomas.