What side effects are associated with this type of intervention?

Common treatments for Small Cell Lung Cancer (SCLC), such as pembrolizumab (an anti-PD-1 monoclonal antibody), often lead to immune-related side effects. These can include pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Severe (grade 3 or higher) adverse effects are less frequent but can occur. Chemotherapy, another common treatment, typically causes side effects like nausea, vomiting, hair loss, fatigue, and increased risk of infections due to bone marrow suppression. Combining immunotherapy with chemotherapy can increase the risk of these side effects, necessitating careful monitoring and management.

What prior FDA approvals exist?

Pembrolizumab, an anti-PD-1 monoclonal antibody, is being studied for its efficacy in treating Small Cell Lung Cancer (SCLC). Similar FDA-approved treatments for SCLC include atezolizumab, a PD-L1 inhibitor, which has been approved in combination with carboplatin and etoposide for the first-line treatment of extensive-stage SCLC. Another notable treatment is nivolumab, an anti-PD-1 antibody, which has shown promise in combination with ipilimumab, an anti-CTLA-4 antibody, for the treatment of SCLC. These approvals highlight the growing role of immune checkpoint inhibitors in the management of SCLC.

What other types of research exist?

Promising novel alternatives to Pembrolizumab for Small Cell Lung Cancer patients include Nivolumab (another anti-PD-1 monoclonal antibody) and Atezolizumab (an anti-PD-L1 monoclonal antibody). Both have shown significant clinical activity and manageable toxicities in advanced NSCLC, which may translate to benefits in SCLC. Additionally, investigational agents in combination with Pembrolizumab are being evaluated for safety and efficacy, which could offer new therapeutic options.

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PD-1/PD-L1 Inhibitor

Pembrolizumab Combinations for Small Cell Lung Cancer

Phase 1 & 2

Waitlist Available

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

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

Must have

Has submitted an archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated

Has progressed on or after treatment with an anti-programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb) administered as part of first-line platinum-based systemic therapy for ES-SCLC

Must not have

Has progressive disease as initial response to first-line systemic chemotherapy in combination with PD-1/L1 inhibitor for ES-SCLC

Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 60 months

Awards & highlights

Summary

This trial will study the safety and efficacy of pembrolizumab in combination with investigational agents in people with anti-PD-1/PD-L1 refractory ES-SCLC who need second-line treatment. The trial will have two parts: a safety lead-in to determine safety and tolerability for experimental combinations of investigational agents without an established recommended phase 2 dose (RP2D), and an efficacy evaluation.

Who is the study for?

This trial is for adults with Stage IV small cell lung cancer who need second-line therapy after not responding to first treatments including PD-1/PD-L1 inhibitors. They must have a life expectancy over 3 months, measurable disease, and be willing to use contraception. Exclusions include recent major surgery or radiation, active infections, other cancers within 3 years, severe allergies to study drugs, and certain heart or blood vessel problems.Check my eligibility

What is being tested?

The study tests pembrolizumab combined with investigational agents (quavonlimab/lenvatinib/MK-4830/favezelimab) in two parts: initial safety assessment followed by efficacy evaluation for those with extensive-stage small cell lung cancer resistant to standard treatments. No hypothesis testing; focuses on determining safe dosages and observing effectiveness.See study design

What are the potential side effects?

Potential side effects may include immune-related reactions affecting organs, infusion-related symptoms like fever or chills, fatigue, changes in blood pressure or heart rhythm issues due to lenvatinib's cardiovascular risks. Specific side effects will depend on the combination of drugs each participant receives.

Eligibility Criteria

Inclusion Criteria

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

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I have provided a sample of my tumor that has not been treated with radiation.

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My small cell lung cancer worsened after treatment with a PD-1/PD-L1 inhibitor.

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My cancer can be measured by scans.

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My small cell lung cancer diagnosis is confirmed and I need second-line therapy.

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My small cell lung cancer is at stage IV.

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I have had one treatment for small cell lung cancer.

Exclusion Criteria

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

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My small cell lung cancer worsened after initial chemotherapy and immunotherapy.

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My scans show my tumor is affecting major blood vessels or has hollow areas.

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I am currently being treated for an infection.

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I have another cancer that is getting worse or was treated in the last 3 years.

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I was taken off a PD-1/L1 inhibitor due to side effects.

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I've had lung radiation of more than 30 Gray in the last 6 months.

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I have fluid buildup in my abdomen, chest, or around my heart.

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I have or had lung inflammation that needed steroids.

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I have been diagnosed with HIV.

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I have received an organ or tissue transplant from another person.

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I have a history of or currently have a neurological disorder related to cancer.

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I haven't had serious heart problems or major blood clot events in the last year.

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I had radiotherapy less than 2 weeks before starting the study treatment.

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I have a condition that affects how my body absorbs medication taken by mouth.

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I have a severe fistula.

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I have a history of inflammatory bowel disease.

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I have been treated with specific immune or targeted cancer therapies before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 60 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 60 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 60 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)

Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

Number of Participants Who Experience at Least One Adverse Event (AE)

+1 more

Secondary outcome measures

Duration of Response (DOR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)

Progression-free Survival (PFS) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)

Trial Design

4Treatment groups

Experimental Treatment

Group I: Coformulation Pembrolizumab/Quavonlimab + MK-4830Experimental Treatment2 Interventions

Participants receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS MK-4830 800 mg. Pembrolizumab/quavonlimab will be administered by intravenous (IV) infusion once every 6 weeks (Q6W) for up to 18 infusions (up to approximately 2 years) or until progressive disease or discontinuation. MK-4830 will be administered by IV infusion once every 3 weeks (Q3W) for up to 36 infusions (up to approximately 2 years) or until progressive disease or discontinuation.

Group II: Coformulation Pembrolizumab/Quavonlimab + LenvatinibExperimental Treatment2 Interventions

Participants receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered by intravenous (IV) infusion once every 6 weeks (Q6W) for up to 18 infusions (up to approximately 2 years) or until progressive disease or discontinuation. Lenvatinib will be administered orally once-daily (QD) until progressive disease or discontinuation.

Group III: Coformulation Pembrolizumab/QuavonlimabExperimental Treatment1 Intervention

Participants receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg) administered by intravenous (IV) infusion once every 6 weeks (Q6W) for up to 18 infusions (up to approximately 2 years) or until progressive disease or discontinuation.

Group IV: Coformulation Favezelimab/PembrolizumabExperimental Treatment1 Intervention

Participants receive favezelimab/pembrolizumab (coformulation of favezelimab 800 mg and pembrolizumab 200 mg) administered by intravenous (IV) infusion once every 3 weeks (Q3W) for up to 36 infusions (up to approximately 2 years) or until progressive disease or discontinuation.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

lenvatinib

2018

Completed Phase 2

~270

0 / 23Eligibility 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 and immunotherapy. Chemotherapy agents like etoposide and platinum compounds (cisplatin or carboplatin) work by causing DNA damage in cancer cells, leading to their death. Immunotherapy, such as pembrolizumab (an anti-PD-1 monoclonal antibody), blocks the PD-1 pathway, preventing cancer cells from evading the immune system. This allows the immune system to better recognize and attack the cancer cells. These mechanisms are crucial for SCLC patients due to the aggressive nature of the disease, making it essential to use treatments that can effectively target and destroy cancer cells.

Propelling Immunotherapy Combinations Into the Clinic.