What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) involving MEK inhibitors like Selumetinib and immune checkpoint inhibitors such as Durvalumab and Tremelimumab have several known side effects. MEK inhibitors can cause fatigue, nausea, and increased liver function tests. Immune checkpoint inhibitors, which enhance the immune response against cancer, often lead to immune-related adverse events such as colitis, dermatitis, hepatitis, and endocrinopathies. Additionally, patients may experience fatigue, rash, and diarrhea. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

For the treatment of Non-Small Cell Lung Cancer (NSCLC), the FDA has approved several immune checkpoint inhibitors. Pembrolizumab (Keytruda) is a PD-1 inhibitor approved for use in combination with chemotherapy or as monotherapy for patients with high PD-L1 expression. Nivolumab (Opdivo) and Atezolizumab (Tecentriq) are other PD-1/PD-L1 inhibitors approved for NSCLC. Durvalumab (Imfinzi), a PD-L1 inhibitor, is approved for use after chemoradiation in stage III NSCLC. While Tremelimumab, a CTLA-4 inhibitor, is not yet approved for NSCLC, it is being studied in combination with Durvalumab. Selumetinib, a MEK inhibitor, has not shown significant benefit in NSCLC in clinical trials and is not FDA-approved for this indication.

What other types of research exist?

Promising novel alternatives for NSCLC treatment in 2024 include: 1) Pembrolizumab and Nivolumab, which are PD-1 inhibitors with proven efficacy and potentially fewer side effects compared to CTLA-4 inhibitors. 2) Atezolizumab, another PD-L1 inhibitor, which has shown effectiveness in various trials. 3) Lenvatinib, a multi-kinase inhibitor that targets multiple pathways involved in tumor growth and angiogenesis. These alternatives offer different mechanisms of action and have shown promising results in clinical trials.

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PD-L1 Inhibitor

Triple Drug Therapy for Non-Small Cell Lung Cancer

Phase 1 & 2

Waitlist Available

Led By Don L Gibbons

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

Total body weight > 30 kg

Have adequate renal function, with a glomerular filtration rate (GFR) of >= 50 ml/min by the Cockcroft-Gault formula or by 24 hour urine collection

Must not have

History of organ transplant requiring therapeutic immunosuppression

Have refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would adversely affect the absorption / bioavailability of the orally administered study medication

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of three drugs to treat advanced lung cancer. Selumetinib blocks cancer cell growth, while durvalumab and tremelimumab help the immune system fight the cancer. Durvalumab and tremelimumab are already used together with other treatments for certain types of lung cancer. The goal is to see if this combination works better than current treatments.

Who is the study for?

This trial is for adults with stage IV non-small cell lung cancer or recurrent disease not suitable for curative therapy. Participants must have adequate organ function, measurable disease, no prior treatment with certain inhibitors, and agree to use contraception. Those with stable brain metastases treated without steroids may qualify.

What is being tested?

The study tests the combination of selumetinib (blocks tumor growth enzymes) with durvalumab and tremelimumab (monoclonal antibodies that boost the immune system against cancer). It aims to determine the best dose of selumetinib and assess how well this trio works together in advanced lung cancer.

What are the potential side effects?

Potential side effects include immune-related reactions affecting organs, infusion-related symptoms, fatigue, digestive issues like diarrhea or nausea, blood abnormalities such as low counts leading to increased infection risk. Specific side effects from selumetinib could involve vision changes or heart rhythm disturbances.

Eligibility Criteria

Inclusion Criteria

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

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I weigh more than 30 kilograms.

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My kidneys work well, with a filtration rate of at least 50 ml/min.

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My lung cancer cannot be cured with surgery or radiation.

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My cancer can be biopsied, and I am willing to have one.

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My kidneys are functioning well enough to filter waste.

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My cancer's KRAS mutation status has been tested.

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My cancer has worsened after treatment.

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I am fully active or can carry out light work.

Exclusion Criteria

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

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I have had an organ transplant and take medicine to lower my immune response.

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I have severe nausea, vomiting, or gut issues that affect medication absorption.

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My weight is 30 kg or less.

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I do not have any serious ongoing illnesses that would affect my participation in the study.

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I have been treated with a MEK, Ras, or Raf inhibitor before.

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I am not allergic to selumetinib, durvalumab, tremelimumab, or similar medications.

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I have had eye conditions like RPED/CSR or retinal vein occlusion, or I have high eye pressure/glaucoma.

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I have a heart condition that could affect my safety in the trial.

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I do not have a stomach or bowel problem that affects how I absorb medicine.

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I am not currently on any cancer treatments like chemotherapy or immunotherapy.

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I have been diagnosed with tuberculosis in the past.

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 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

Maximum tolerated dose (MTD) (dose-escalation phase)

Progression free survival time (PFS) (dose expansion phase)

Secondary study objectives

Disease control rate (complete response + partial response + stable disease)

Incidence of adverse events

Overall survival (OS)

Side effects data

From 2012 Phase 2 trial • 37 Patients • NCT01085214

75%

Diarrhea

50%

Fatigue

47%

Anemia

47%

Rash acneiform

44%

Hypoalbuminemia

44%

Edema, limbs

39%

Aspartate aminotransferase increased

33%

Neutrophil count decreased

33%

White blood cell decreased

31%

Nausea

31%

Vomiting

28%

Platelet count decreased

25%

CPK increased

25%

Hypomagnesemia

22%

Hypertension

19%

Hypophosphatemia

19%

Hyponatremia

19%

Hypocalcemia

19%

Edema, face

17%

Dry skin

17%

Alanine aminotransferase increased

14%

Skin and subcutaneous tissue disorders - Other

14%

Hypokalemia

14%

Creatinine increased

14%

Back pain

14%

Dyspnea

14%

Lymphocyte count decreased

11%

Pain

11%

Fever

11%

Localized edema

11%

Peripheral sensory neuropathy

11%

Hyperkalemia

11%

Dizziness

11%

Abdominal pain

Anorexia

Hypoglycemia

Acute kidney injury

Death, NOS

Periorbital edema

Skin hypopigmentation

Pain in extremity

Cough

Insomnia

Alkaline phosphatase increased

Dry mouth

Sepsis

Hypernatremia

Metabolism and nutrition disorders - Other

Blood and lymphatic system disorders - Other

Renal and urinary disorders - Other

Hypercalcemia

Dehydration

Musculoskeletal and connective tissue disorder - Other, Rhabdomyolysis

Chills

Hypotension

Myalgia

Arthralgia

Upper respiratory infection

Headache

Sinusitis

Generalized muscle weakness

Gastrointestinal disorders - Other

Gastroesophageal reflux disease

Vaginal inflammation

Confusion

Pruritus

Febrile neutropenia

Flu like symptoms

Hepatic failure

Skin infection

Fall

Fracture

Skin and subcutaneous tissue disorders - Other, Angular cheilitis, unilateral

Adult respiratory distress syndrome

Renal and urinary disorders - Other, Acute renal failure

INR increased

100%

80%

60%

40%

20%

Study treatment Arm

AZD6244 (Selumetinib) Treatment

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm II (continuous selumetinib, durvalumab, tremelimumab)Experimental Treatment3 Interventions

Participants receive selumetinib PO BID on days 1-28 and durvalumab IV over 60 minutes on day 1. Participants also receive tremelimumab IV over 60 minutes on day 1 for courses 1-4. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (intermittent selumetinib, durvalumab, tremelimumab)Experimental Treatment3 Interventions

Participants receive selumetinib PO BID on days 1-7 and 15-21 and durvalumab intravenously (IV) over 60 minutes on day 1. Participants also receive tremelimumab IV over 60 minutes on day 1 for courses 1-4. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Durvalumab

2017

Completed Phase 2

~3750

Tremelimumab

2017

Completed Phase 2

~3070

Selumetinib

2010

Completed Phase 2

~2080

0 / 20Eligibility 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) include targeted therapies and immunotherapies. Selumetinib, a MEK inhibitor, blocks enzymes needed for cell growth, targeting specific pathways often mutated in cancer cells. Durvalumab and Tremelimumab are monoclonal antibodies that enhance the immune response against cancer by inhibiting immune checkpoints (PD-L1 and CTLA-4, respectively). This allows the immune system to better recognize and attack cancer cells. These mechanisms are important for NSCLC patients as they provide a strategic approach to inhibit tumor growth and enhance immune-mediated tumor destruction.

EGFR TKI combination with immunotherapy in non-small cell lung cancer.Selumetinib with and without erlotinib in KRAS mutant and KRAS wild-type advanced nonsmall-cell lung cancer.Identification of common predictive markers of in vitro response to the Mek inhibitor selumetinib (AZD6244; ARRY-142886) in human breast cancer and non-small cell lung cancer cell lines.