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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 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%
Hyponatremia
19%
Hypophosphatemia
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
8%
Anorexia
8%
Hypoglycemia
8%
Acute kidney injury
8%
Death, NOS
8%
Periorbital edema
8%
Skin hypopigmentation
8%
Pain in extremity
8%
Cough
8%
Insomnia
8%
Alkaline phosphatase increased
8%
Dry mouth
8%
Sepsis
6%
Hypernatremia
6%
Metabolism and nutrition disorders - Other
6%
Blood and lymphatic system disorders - Other
6%
Renal and urinary disorders - Other
6%
Hypercalcemia
6%
Dehydration
6%
Musculoskeletal and connective tissue disorder - Other, Rhabdomyolysis
6%
Chills
6%
Hypotension
6%
Myalgia
6%
Arthralgia
6%
Upper respiratory infection
6%
Headache
6%
Sinusitis
6%
Generalized muscle weakness
6%
Gastrointestinal disorders - Other
6%
Gastroesophageal reflux disease
3%
Vaginal inflammation
3%
Confusion
3%
Pruritus
3%
Febrile neutropenia
3%
Flu like symptoms
3%
Hepatic failure
3%
Skin infection
3%
Fall
3%
Fracture
3%
Skin and subcutaneous tissue disorders - Other, Angular cheilitis, unilateral
3%
Adult respiratory distress syndrome
3%
Renal and urinary disorders - Other, Acute renal failure
3%
INR increased
100%
80%
60%
40%
20%
0%
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
~3780
Tremelimumab
2017
Completed Phase 2
~3070
Selumetinib
2010
Completed Phase 2
~2080

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.

Find a Location

Who is running the clinical trial?

M.D. Anderson Cancer CenterLead Sponsor
3,051 Previous Clinical Trials
1,798,817 Total Patients Enrolled
National Cancer Institute (NCI)NIH
13,879 Previous Clinical Trials
41,013,206 Total Patients Enrolled
Don L GibbonsPrincipal InvestigatorM.D. Anderson Cancer Center

Media Library

Durvalumab (PD-L1 Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT03581487 — Phase 1 & 2
Non-Small Cell Lung Cancer Research Study Groups: Arm I (intermittent selumetinib, durvalumab, tremelimumab), Arm II (continuous selumetinib, durvalumab, tremelimumab)
Non-Small Cell Lung Cancer Clinical Trial 2023: Durvalumab Highlights & Side Effects. Trial Name: NCT03581487 — Phase 1 & 2
Durvalumab (PD-L1 Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03581487 — Phase 1 & 2
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