What is the mechanism of action of this treatment?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) often involve immune checkpoint inhibitors such as Pembrolizumab. Pembrolizumab works by inhibiting the PD-1 receptor, a protein on T cells that normally helps keep these cells from attacking other cells in the body, including cancer cells. By blocking PD-1, Pembrolizumab enhances the immune system's ability to detect and destroy cancer cells. This mechanism is significant for NSCLC patients as it offers a targeted approach to boost the body's natural defenses against cancer, potentially leading to better treatment outcomes and prolonged survival.

What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) using immune checkpoint inhibitors like pembrolizumab can cause side effects such as pneumonitis, fatigue, and severe immune-related adverse effects. When combined with chemotherapy, additional side effects include neutropenia, febrile neutropenia, and hypertension. Other similar treatments like atezolizumab and cemiplimab also show side effects including pneumonia, chronic obstructive pulmonary disease, and sepsis. Generally, severe treatment-related adverse effects are lower with immunotherapy compared to chemotherapy alone.

What prior FDA approvals exist?

Pembrolizumab, an anti-PD-1 therapy, has been FDA approved for the treatment of advanced NSCLC with high PD-L1 expression (≥50%) without EGFR or ALK mutations. Other similar FDA-approved treatments include nivolumab, another PD-1 inhibitor, and atezolizumab, a PD-L1 inhibitor. These drugs have shown efficacy in improving overall survival and progression-free survival in various subgroups of NSCLC patients. Additionally, combinations of these immunotherapies with chemotherapy have also received FDA approval for broader patient populations.

What other types of research exist?

Promising alternatives to pembrolizumab for NSCLC patients include nivolumab (another PD-1 inhibitor), atezolizumab (a PD-L1 inhibitor), and combination therapies such as ramucirumab plus pembrolizumab. Additionally, investigational treatments like cabozantinib with or without atezolizumab are showing potential in ongoing trials.

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Anti-metabolites

MK-3475 + Gemcitabine for Lung Cancer

Phase 1 & 2

Waitlist Available

Led By Rachel Sanborn, MD

Research Sponsored by Providence Health & Services

Eligibility Criteria Checklist

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

Must have

Women or men with advanced, histologically proven NSCLC

Patients must have received at least one but no more than three prior systemic therapies for advanced disease

Must not have

Prior therapy with any anti-PD-1, anti-PD-L1, or anti-CTLA4 antibody

Prior therapy with gemcitabine

Timeline

Screening 3 weeks

Treatment Varies

Follow Up every 12 weeks (up to 2 years)

Awards & highlights

No Placebo-Only Group

Summary

This trial is for patients with advanced non-small cell lung cancer who have already received treatment. It tests a new drug, MK-3475, combined with a standard chemotherapy drug, gemcitabine. MK-3475 helps the immune system fight cancer, while gemcitabine kills cancer cells. The study aims to find the safest dose of MK-3475 when used with gemcitabine. Gemcitabine is a well-established chemotherapy drug that has shown significant activity against non-small-cell lung cancer (NSCLC) over the past two decades.

Who is the study for?

This trial is for men and women with advanced NSCLC who have had 1-3 prior treatments but not with anti-PD-1, anti-PD-L1, or gemcitabine. Participants must be in good health otherwise, have a life expectancy of at least 3 months, and cannot be pregnant. They should not have active autoimmune diseases (except stable hypothyroidism or vitiligo), other cancers except controlled skin carcinoma, or serious medical conditions.

What is being tested?

The study tests the safety of adding MK-3475 to standard gemcitabine treatment in advanced NSCLC patients. It aims to find the best dose for this combination therapy. Patients will receive MK-3475 alongside their regular chemotherapy regimen to see how well they work together.

What are the potential side effects?

Possible side effects include those common to immunotherapy like fatigue, skin reactions, inflammation-related symptoms affecting various organs including lungs (pneumonitis), as well as typical chemotherapy side effects such as nausea and low blood counts leading to increased infection risk.

Eligibility Criteria

Inclusion Criteria

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

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I have advanced non-small cell lung cancer confirmed by a biopsy.

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I have had 1 to 3 treatments for my advanced disease.

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I am capable of becoming pregnant and have a negative pregnancy test.

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My blood tests for organ and marrow function are normal.

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I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

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

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I have been treated with drugs targeting PD-1, PD-L1, or CTLA4.

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I have been treated with gemcitabine before.

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I have an autoimmune disease, but it's either vitiligo or stable hypothyroidism.

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I have no active cancer except for treated skin cancer.

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I am HIV positive or have Hepatitis B or C.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ every 12 weeks (up to 2 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~every 12 weeks (up to 2 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and every 12 weeks (up to 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

Frequency of Toxicities (determine any changes in signs or symptoms that may represent drug toxicity)

Secondary study objectives

Disease Response

Overall Survival

Progression Free Survival

Side effects data

From 2022 Phase 1 & 2 trial • 35 Patients • NCT03003468

40%

FATIGUE

37%

INFUSION RELATED REACTION

37%

NAUSEA

23%

ANOREXIA

23%

DIARRHEA

23%

BACK PAIN

23%

ABDOMINAL PAIN

20%

ARTHRALGIA

20%

NON-CARDIAC CHEST PAIN

20%

COUGH

17%

MYALGIA

17%

CONSTIPATION

17%

DYSPNEA

17%

CHILLS

13%

HEADACHE

13%

RASH MACULO-PAPULAR

13%

DIZZINESS

13%

PRURITUS

10%

LUNG INFECTION

10%

SINUS TACHYCARDIA

10%

ALLERGIC REACTION

10%

ANXIETY

10%

ANEMIA

10%

SKIN AND SUBCUTANEOUS TISSUE DISORDERS - OTHER, SPECIFY

10%

URTICARIA

10%

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - OTHER, SPECIFY

10%

EDEMA LIMBS

DEPRESSION

FLU LIKE SYMPTOMS

HYPONATREMIA

URINARY TRACT INFECTION

FLUSHING

HYPERTHYROIDISM

VOICE ALTERATION

PLEURAL EFFUSION

HYPERGLYCEMIA

DYSPEPSIA

PAIN

LYMPHOCYTE COUNT DECREASED

VOMITING

FEVER

FLATULENCE

CREATININE INCREASED

NECK PAIN

PRODUCTIVE COUGH

EAR AND LABYRINTH DISORDERS - OTHER, SPECIFY

PELVIC PAIN

TUMOR PAIN

HYPOTHYROIDISM

HEMORRHOIDS

TREMOR

ESOPHAGITIS

CONJUNCTIVITIS

DEHYDRATION

GAIT DISTURBANCE

BLURRED VISION

INSOMNIA

BLOATING

PRESYNCOPE

PARESTHESIA

DRY MOUTH

GASTROESOPHAGEAL REFLUX DISEASE

SORE THROAT

BRONCHOSPASM

HYPOMAGNESEMIA

MOVEMENTS INVOLUNTARY

PERIPHERAL MOTOR NEUROPATHY

ACUTE KIDNEY INJURY

NASAL CONGESTION

PAIN OF SKIN

PNEUMONITIS

DRY SKIN

FLASHING LIGHTS

HYPOTENSION

SINUSITIS

HEARING IMPAIRED

MALAISE

ALKALINE PHOSPHATASE INCREASED

OSTEONECROSIS OF JAW

NEUTROPHIL COUNT DECREASED

THROMBOEMBOLIC EVENT

RASH ACNEIFORM

SOMNOLENCE

HYPERTENSION

MUSCLE WEAKNESS LOWER LIMB

SYNCOPE

VAGINAL INFECTION

PAIN IN EXTREMITY

DYSPHAGIA

POSTNASAL DRIP

COLITIS

HOT FLASHES

RESPIRATORY FAILURE

GASTROINTESTINAL DISORDERS - OTHER, SPECIFY

ALLERGIC RHINITIS

SEPSIS

WEIGHT GAIN

100%

80%

60%

40%

20%

Study treatment Arm

Imprime PGG 4 mg/kg

Imprime PGG 2 mg/kg

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: MK-3475 + GemcitabineExperimental Treatment2 Interventions

200mg MK-3475 200 given by IV infusion every 3 weeks, for 2 years, or until disease progression and Gemcitabine 1250 mg/m2 iv Days 1, 8 every 3 weeks, for maximum 6 cycles.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

MK-3475

2014

Completed Phase 2

~1350

Gemcitabine

2017

Completed Phase 3

~1920

0 / 10Eligibility 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

Common treatments for Non-Small Cell Lung Cancer (NSCLC) often involve immune checkpoint inhibitors such as Pembrolizumab. Pembrolizumab works by inhibiting the PD-1 receptor, a protein on T cells that normally helps keep these cells from attacking other cells in the body, including cancer cells. By blocking PD-1, Pembrolizumab enhances the immune system's ability to detect and destroy cancer cells. This mechanism is significant for NSCLC patients as it offers a targeted approach to boost the body's natural defenses against cancer, potentially leading to better treatment outcomes and prolonged survival.

Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11).