Personalized Immunotherapy for Advanced Cancers

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ezra Cohen

Must not be taking: Immunosuppressants, Steroids, Anti-cancer, others

Disqualifiers: HIV, Untreated brain metastases, Autoimmune, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat advanced cancers using personalized immunotherapy. Researchers aim to determine if a custom-made vaccine can safely combat cancer when other treatments are unavailable. The trial tests different combinations of this vaccine and pembrolizumab (also known as KEYTRUDA), which aids the immune system in attacking cancer cells. Suitable participants have incurable cancer that is not a blood cancer and have not had success with other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as other anti-cancer therapies, immunotherapies, and immunosuppressive treatments, for a specific period before starting the study. If you are on these medications, you may need to stop them for 2 to 4 weeks before the trial begins.

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

Research has shown that pembrolizumab, one of the treatments in this trial, has FDA approval for several cancers, including melanoma and lung cancer, indicating its general safety for humans. Studies have found that pembrolizumab can extend survival and is considered safe for various cancers in real-world use.

Regarding the personalized vaccine, early findings suggest it is safe to produce and administer to patients. Initial studies show that patients tolerate these vaccines well, without major safety concerns.

When used together, pembrolizumab and personalized vaccines are generally well-tolerated, as other studies indicate, with most people not experiencing serious side effects.

This trial is in an early phase, focusing on safety and how people's bodies respond to the treatments. While other studies suggest these treatments are safe, this trial will help confirm how well people tolerate them when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these personalized immunotherapy treatments for advanced cancers because they offer a tailored approach that differs from traditional methods. Unlike standard treatments that often use a one-size-fits-all strategy, these therapies involve personalized vaccines designed specifically for each patient's unique tumor profile. By combining this with pembrolizumab, an anti-PD-1 antibody that enhances the immune system's ability to fight cancer, the treatment aims to improve effectiveness and reduce side effects compared to conventional chemotherapy. This personalized approach could potentially lead to better patient outcomes and a more precise attack on cancer cells.

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

Research shows that pembrolizumab, a treatment in this trial, can extend the lives of people with advanced cancers, such as melanoma. One study found it reduced the risk of death by about 28% compared to treatments using a placebo instead of chemotherapy. Personalized vaccines, another treatment option in this trial, also show promise. In one trial, a personalized cancer vaccine left 87.5% of patients cancer-free after 36 months. This trial will explore the combination of pembrolizumab with a personalized vaccine, which might enhance the immune system's ability to fight cancer by targeting specific cancer cells, offering hope for patients with advanced cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Erza Cohen, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for adults with advanced, incurable solid tumors who have measurable disease or high risk of mortality. They must have a tumor site accessible for biopsy, good organ function, and agree to use contraception. Excluded are those with certain immune conditions, recent immunotherapy or major surgery, active hepatitis or HIV infection, untreated brain metastases, pregnancy/breastfeeding women.

Inclusion Criteria

My condition worsened or I couldn't tolerate previous beneficial treatments.

My cancer can't be measured by scans and I have a high risk of dying within 5 years.

My cancer is not lymphoma and cannot be cured with surgery.

Exclusion Criteria

I have been treated with PD1/PDL1 inhibitors within the last 4 weeks.

I have been treated with anti-PD1 or anti-CTLA4 drugs during the vaccine preparation period.

Received an investigational agent within 28 days prior to the first dose of study drug

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a personalized vaccine in combination with an anti-PD1 antibody, pembrolizumab, to increase anti-cancer immunity

6 weeks

Multiple visits for administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of immune response and adverse events

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Personalized Vaccine

Trial Overview The study tests the safety and effectiveness of a personalized vaccine combined with Pembrolizumab in treating advanced cancers. The vaccine is tailored to each patient's tumor makeup and aims to boost the body's immune response against cancer cells.

How Is the Trial Designed?

Group I: vaccine and anti-PD-1 Experimental Treatment 2 Interventions

personalized vaccine and anti-PD-1 administered concurrently at the start of study therapy

Group II: vaccine Experimental Treatment 1 Intervention

personalized vaccine therapy

Group III: anti-PD1 before vaccine Experimental Treatment 2 Interventions

anti-PD-1 antibody for 6 weeks followed by personalized vaccine therapy

Group IV: anti-PD1 and vaccine Experimental Treatment 2 Interventions

anti-PD-1 antibody followed by personalized vaccine therapy

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Ezra Cohen

Lead Sponsor

Trials

5

Recruited

70+

Published Research Related to This Trial

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

The combination of the immune checkpoint inhibitor atezolizumab and the tumor vaccine sipuleucel-T was found to be safe and well tolerated in 37 subjects with metastatic castration-resistant prostate cancer, with no severe toxicities reported.

While the objective response rate was low at 4.3%, the treatment did show some immune response benefits, including increased T-cell receptor diversity and immune responses to specific antigens, suggesting potential for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib study of patients with metastatic castrate-resistant prostate cancer treated with different sequencing regimens of atezolizumab and sipuleucel-T. Dorff, T., Hirasawa, Y., Acoba, J., et al.[2022]

In the phase Ib KEYNOTE-001 study, pembrolizumab monotherapy showed durable antitumor activity in advanced non-small-cell lung cancer (NSCLC), with a median overall survival (OS) of 22.3 months for treatment-naive patients and 10.5 months for previously treated patients, and 5-year OS rates of 23.2% and 15.5%, respectively.

Patients with a PD-L1 tumor proportion score of 50% or greater had even better outcomes, with 5-year OS rates of 29.6% for treatment-naive and 25.0% for previously treated patients, while the treatment maintained a favorable safety profile with minimal late-onset adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Overall Survival for Patients With Advanced Non‒Small-Cell Lung Cancer Treated With Pembrolizumab: Results From the Phase I KEYNOTE-001 Study. Garon, EB., Hellmann, MD., Rizvi, NA., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Citations

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NCT03380871 | A Personal Cancer Vaccine (NEO-PV-01) ... The purpose of this study is to find out if treatment with NEO-PV-01 in combination with pembrolizumab and chemotherapy (pembrolizumab/chemotherapy) is safe ...

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KEYNOTE Trial Data Presented at ESMO 2025 Congress ... The pembrolizumab regimen reduced the risk of death by about 28% (HR = 0.72 [95% CI, 0.56-0.93]; p = .0103) compared to the chemotherapy-placebo ...

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Efficacy of Pembrolizumab in Advanced Melanoma Pembrolizumab has been shown to increase survival in patients with metastatic melanoma. Considering the numerous oncoming studies, we decided to conduct a ...

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Cancer vaccine shows promise for patients with stage III ... All nine patients treated at Dana-Farber Cancer Institute in a phase 1 trial of a personalized cancer vaccine for patients with stage III or ...

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Personalized Immunotherapy in Adults With Advanced ... The purpose of this study is to determine if it is possible to make and administer safely a 'personalized' vaccine to treat patients that have been diagnosed ...

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Ten-Year Data for Merck's KEYTRUDA® (pembrolizumab ... At 10 years, more than one-third (34.0%) of patients with advanced melanoma were alive after treatment with KEYTRUDA, compared to 23.6% of patients treated ...

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NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.

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Clinical utility of pembrolizumab in the management of ... KEYNOTE-590 is designed to evaluate efficacy and safety of pembrolizumab vs placebo plus cisplatin and 5-FU chemotherapy as first-line treatment in participants ...

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Real-world outcomes after pembrolizumab treatment for ... Pembrolizumab is safe and effective for advanced and recurrent cervical cancer in a real-world population. For those with good performance, further study is ...

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Advanced Nonsquamous NSCLC Combination Therapy Cancer did not progress in 40% of patients receiving KEYTRUDA with chemotherapy compared to 19% of patients receiving chemotherapy alone. You also might be ...