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

Recruiting in Palo Alto (17 mi)

Overseen by Tianhong Li

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Tianhong Li

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune diseases, Splenectomy, Pregnancy, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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 treating adenocarcinoma that has spread to other places in the body (advanced stage). Labvax 3(22)-23 is designed to target a specific antigen (labyrinthin), which is a protein found on the surface of adenocarcinoma tumor cells. Labyrinthin is a protein that is not expressed on normal cells in the skin, lungs, salivary glands, pancreas, nor other tissues. In adenocarcinoma, the tumor cells produce too much labyrinthin causing them to express this protein on the surface of the tumor cells. One way to control the growth of these tumor cells is to teach the immune system to generate an immune response against the labyrinthin protein by vaccination against labyrinthin. GM-CSF, or sargramostim, is a protein that acts as a white blood cell growth factor. It has also been shown to stimulate immune system. Thus, administration of GM-CSF may help to boost the immune system response when given together with the vaccine. This study may improve the general knowledge about Labvax 3(22)-23 and how the body may generate an immune response to kill adenocarcinoma tumor cells. In the second phase of the study, participants will also receive pembrolizumab, which may improve anti-cancer activity when given with Labvax 3(22)-23 and GM-CSF.

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.

What data supports the effectiveness of the treatment Labvax 3(22)-23, Labyrinthin Peptide Vaccine, Sargramostim, Leukine, GM-CSF Leukine, rGM-CSF, rHu GM-CSF for advanced stage adenocarcinoma?

Research on similar treatments, like peptide vaccines combined with GM-CSF, shows they can be safe and stimulate immune responses in cancer patients, such as those with melanoma and breast cancer. These studies suggest that combining vaccines with GM-CSF can help the body’s immune system better recognize and fight cancer cells. ^{1 2 3 4 5}

Is the Cancer Vaccine + GM-CSF/Pembrolizumab treatment generally safe for humans?

The treatment involving GM-CSF (granulocyte-macrophage colony-stimulating factor) has been tested in various cancer vaccine studies and is generally well tolerated. Common mild side effects include injection site reactions, fatigue, and headache, with no severe adverse effects reported in the studies. ^{2 3 4 5 6}

What makes the Labvax 3(22)-23 treatment unique for advanced stage adenocarcinoma?

The Labvax 3(22)-23 treatment is unique because it combines a cancer vaccine with GM-CSF (a protein that stimulates immune cells) and pembrolizumab (an immune checkpoint inhibitor) to enhance the body's immune response against cancer cells, potentially overcoming immune resistance seen in other treatments. ^{2 3 7 8 9}

Research Team

Tianhong Li

Principal Investigator

University of California, Davis

Eligibility Criteria

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)

Trial Timeline

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

Treatment Details

Interventions

• Labvax 3(22)-23 (Cancer Vaccine)
• Sargramostim (White Blood Cell Growth Factor)

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.

Participant Groups

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+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

LabyRx Immunologic Therapeutics

Collaborator

Trials

1

Recruited

80+

Findings from Research

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 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]

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]

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 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]

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]

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 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]

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]

References

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

Dexamethasone did not suppress immune boosting by personalized peptide vaccination for advanced prostate cancer patients. [2013]

2. United States 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. [2013]

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

Individualized synthetic peptide vaccines with GM-CSF in locally advanced melanoma patients. [2012]

4. United States 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. [2014]

5. Germany 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. [2015]

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

A multipeptide vaccine is safe and elicits T-cell responses in participants with advanced stage ovarian cancer. [2020]

7. Ireland pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 blockade enhances the efficacy of SA-GM-CSF surface-modified tumor vaccine in prostate cancer. [2018]

8. England 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. [2021]

9. United States 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. [2021]