What is the mechanism of action of this treatment?

The most common treatments for Small Cell Lung Cancer (SCLC) include chemotherapy, radiation therapy, and immunotherapy. Chemotherapy, often using etoposide combined with platinum-based drugs like carboplatin or cisplatin, works by damaging the DNA of cancer cells, leading to cell death. Radiation therapy uses high-energy rays to kill cancer cells or shrink tumors. Immunotherapy, such as the Personalized Neoantigen Vaccine and Durvalumab (a PD-L1 inhibitor), stimulates the immune system to recognize and attack cancer cells. The Personalized Neoantigen Vaccine introduces tumor-specific antigens to the immune system, enhancing its ability to target cancer cells. Durvalumab blocks the PD-L1 protein on cancer cells, preventing them from evading immune detection. These immunotherapy approaches are particularly important for SCLC patients as they offer a targeted method to boost the body's natural defenses against cancer, potentially leading to better outcomes and fewer side effects compared to traditional treatments.

What side effects are associated with this type of intervention?

Common treatments for Small Cell Lung Cancer (SCLC), such as immune checkpoint inhibitors and chemotherapy, have notable side effects. Immune checkpoint inhibitors like Durvalumab can cause immune-related adverse events, including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Chemotherapy can lead to nausea, vomiting, hair loss, fatigue, and increased infection risk due to bone marrow suppression. Combining these treatments may increase the risk of severe adverse events, including higher rates of treatment discontinuation and death.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of Small Cell Lung Cancer (SCLC). Notably, nivolumab (a PD-1 inhibitor) and ipilimumab (a CTLA-4 inhibitor) have been used in combination for extensive-stage SCLC. Additionally, atezolizumab (a PD-L1 inhibitor) has been approved in combination with carboplatin and etoposide for first-line treatment of extensive-stage SCLC. These treatments are similar to the combination of durvalumab (a PD-L1 inhibitor) and a personalized neoantigen vaccine currently being studied, which aims to stimulate the immune system to target cancer cells more effectively.

What other types of research exist?

Promising novel alternatives for Small Cell Lung Cancer (SCLC) patients in 2024 include: 1) Atezolizumab (another PD-L1 inhibitor) combined with chemotherapy, which has shown efficacy in first-line treatment of metastatic non-squamous NSCLC and may be applicable to SCLC. 2) Combination of Nivolumab (PD-1 inhibitor) and Ipilimumab (CTLA-4 inhibitor), which has demonstrated benefits in other cancers and is being explored in SCLC. 3) Lurbinectedin, a novel chemotherapy agent approved for SCLC, which has shown promising results in clinical trials. 4) Emerging therapies targeting tumor microenvironment or specific genetic mutations in SCLC, which are currently under investigation in clinical trials.

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PD-L1 Inhibitor

Neoantigen Vaccine + Durvalumab for Small Cell Lung Cancer

Phase 2

Recruiting

Led By Jeffrey Ward, M.D., Ph.D.

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

At least one lesion must be able to be biopsied at the time of enrollment

Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients

Must not have

Contraindication to intramuscular injections and/or blood draws

Prior treatment with a PD-1 or PD-L1 inhibitor (including durvalumab)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through completion of treatment (estimated to be 2 years)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a custom-made vaccine combined with an immune-boosting drug called durvalumab. It aims to help patients with advanced small cell lung cancer, a severe type of lung cancer that has spread widely. The vaccine targets unique markers on cancer cells, while durvalumab helps the immune system fight these cells more effectively.

Who is the study for?

Adults with extensive stage small cell lung cancer (ES-SCLC) suitable for platinum-based chemo and durvalumab as a first treatment. They must have good organ function, be willing to use birth control, weigh over 30 kg, and have a life expectancy of at least 12 weeks. Exclusions include those with certain medical conditions or treatments that could interfere with the trial.

What is being tested?

The trial is testing if adding a personalized neoantigen vaccine to the drug durvalumab improves survival without disease progression in ES-SCLC patients. Participants will receive regular blood draws and injections using the TDS-IM v2.0 Device alongside their standard treatment.

What are the potential side effects?

Potential side effects may include typical reactions from vaccines such as soreness at injection site, fatigue, flu-like symptoms; Durvalumab can cause immune-related issues like inflammation in organs, infusion reactions similar to allergic responses, and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a tumor that can be biopsied.

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I am post-menopausal or not pregnant if pre-menopausal.

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I weigh more than 30 kilograms.

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I am fully active and can carry on all my pre-disease activities without restriction.

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I am 18 years old or older.

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My lung cancer is confirmed to be extensive stage small cell.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I cannot have shots or blood taken from my veins due to medical reasons.

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I have been treated with a PD-1 or PD-L1 inhibitor before.

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I do not have any current infections.

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I have had cancer spread to the lining of my brain and spinal cord.

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I have or had an autoimmune or inflammatory disorder.

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I have fewer than 2 suitable spots for injection and electroporation.

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I have had brain metastases.

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I haven't taken immunosuppressive drugs in the last 14 days.

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I haven't had major surgery in the last 28 days.

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I haven't had extensive radiation to my bone marrow or wide field radiation in the last 4 weeks.

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I do not have any uncontrolled illnesses.

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I have had cancer before, but it fits the exceptions.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through completion of treatment (estimated to be 2 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through completion of treatment (estimated to be 2 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and through completion of treatment (estimated to be 2 years) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Feasibility of combining durvalumab with a neoantigen vaccine as measured by the number of participants that had a vaccine produced for them

Safety and tolerability of the combination of durvalumab and a neoantigen vaccine as measured by number of participants experiencing adverse events

Secondary study objectives

Duration of response (DOR)

Overall survival (OS)

Progression-free survival (PFS)

+1 more

Side effects data

From 2022 Phase 2 trial • 80 Patients • NCT03015129

65%

Fatigue

63%

Abdominal pain

55%

Diarrhea

43%

Pain

40%

Weight loss

35%

Hypertension

30%

Anorexia

30%

Constipation

28%

Nausea

28%

Pruritus

25%

Vomiting

20%

Dyspnea

20%

Urinary tract infection

18%

Rash maculo-papular

15%

Cough

15%

Abdominal Pain

15%

Back pain

15%

Increased Urinary Frequency

15%

Weight gain

13%

Arthralgia

10%

Dizziness

10%

Anxiety

10%

Bladder infection

10%

Nasal congestion

10%

Vaginal discharge

Colitis

Dry mouth

Dry skin

Fever

Anal pain

Edema limbs

Flatulence

Headache

Hot flashes

Myalgia

Small intestinal obstruction

Thromboembolic event

Urinary frequency

Urinary tract pain

Confusion

Renal and urinary disorders - Other, specify

Adrenal insufficiency

Anemia

Ascites

Gastroesophageal reflux disease

Hypomagnesemia

Lymphedema

Memory impairment

Mucositis oral

Pneumonitis

Rash acneiform

Sinus bradycardia

Upper respiratory infection

Urinary urgency

Vaginal hemorrhage

Alanine aminotransferase increased

Aspartate aminotransferase increased

Alkaline phosphatase increased

Colonic perforation

Dysarthria

Blood bilirubin increased

CPK increased

Creatinine increased

Myositis

Rectal hemorrhage

Hypothyroidism

Left ventricular systolic dysfunction

Lethargy

Muscle weakness left-sided

Myocarditis

Rectal pain

Weight Loss

Fall

Generalized muscle weakness

Hyperglycemia

Hyperkalemia

Pain in extremity

Peripheral sensory neuropathy

Pleural effusion

Skin infection

100%

80%

60%

40%

20%

Study treatment Arm

Durvalubmab

Durvalubmab + Tremelimumab

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Neoantigen DNA vaccine+durvalumabExperimental Treatment4 Interventions

* Patients will receive durvalumab (1500mg Q3W) in combination with standard of care carboplatin and etoposide for a total of 4 cycles given every 3 weeks * Beginning 4 weeks following Cycle 4 of carboplatin/etoposide/durvalumab, patients on will then receive 6 cycles of durvalumab 1500 mg with the polyepitope neoantigen DNA vaccine, both administered once every 4 weeks * Patients may then receive durvalumab every 4 weeks until disease progression or drug toxicity * Should a delay in vaccine preparation occur, patients will begin durvalumab and the vaccine will be added with the subsequent cycle.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Peripheral blood draws

2017

Completed Phase 1

~20

Durvalumab

2017

Completed Phase 2

~3750

Neoantigen DNA vaccine

2018

Completed Phase 1

~20

0 / 18Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Small Cell Lung Cancer (SCLC) include chemotherapy, radiation therapy, and immunotherapy. Chemotherapy, often using etoposide combined with platinum-based drugs like carboplatin or cisplatin, works by damaging the DNA of cancer cells, leading to cell death. Radiation therapy uses high-energy rays to kill cancer cells or shrink tumors. Immunotherapy, such as the Personalized Neoantigen Vaccine and Durvalumab (a PD-L1 inhibitor), stimulates the immune system to recognize and attack cancer cells. The Personalized Neoantigen Vaccine introduces tumor-specific antigens to the immune system, enhancing its ability to target cancer cells. Durvalumab blocks the PD-L1 protein on cancer cells, preventing them from evading immune detection. These immunotherapy approaches are particularly important for SCLC patients as they offer a targeted method to boost the body's natural defenses against cancer, potentially leading to better outcomes and fewer side effects compared to traditional treatments.

The Evolving Continuum of Diagnosis in the Modern Age of Non-Small Cell Lung Cancer.Immune evasion and current immunotherapy strategies in mycosis fungoides (MF) and Sézary syndrome (SS).Combining immunotherapy and radiation therapy for small cell lung cancer and thymic tumors.