A Study to Investigate the Efficacy of Durvalumab Plus Tremelimumab in Combination With Chemotherapy Compared With Pembrolizumab in Combination With Chemotherapy in Metastatic NSCLC Patients With Non-squamous Histology Who Have Mutations and/or Co-mutations in STK11, KEAP1, or KRAS
NCT ID: NCT06008093
Last Updated: 2025-10-27
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE3
280 participants
INTERVENTIONAL
2024-04-04
2031-03-20
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Combination of Durvalumab and Tremelimumab as Maintenance Treatment in Patients With Non Squamous and Squamous (NSCLC)
NCT03319316
Study of Durvalumab + Tremelimumab With Chemotherapy or Durvalumab With Chemotherapy or Chemotherapy Alone for Patients With Lung Cancer (POSEIDON).
NCT03164616
A Study of Durvalumab Plus Tremelimumab With Chemotherapy in Untreated ES-SCLC
NCT03963414
Durvalumab and Tremelimumab ± Platinum-Based Chemotherapy in Patients With Metastatic Squamous or Non-Squamous NSCLC
NCT03057106
Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE)
NCT02542293
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
INFORMATION FOR TRIAL PARTICIPANTS:
Researchers are looking for a better way to treat people who have metastatic NSCLC and tumors with STK11, KEAP1, or KRAS genetic mutations. Most people learn they have NSCLC after it has already become metastatic, and it can no longer be treated with surgery.
Based on previous trials, researchers think durvalumab plus tremelimumab with chemotherapy could help participants more than the current standard treatment, which is pembrolizumab with chemotherapy. Durvalumab and tremelimumab are designed to work by helping the immune system recognize and kill cancer cells.
In this trial, researchers want to learn more about how well durvalumab plus tremelimumab with chemotherapy works in people with metastatic NSCLC and genetic mutations that can cause the cancer to be less responsive to treatment.
This trial is planned to have 280 participants. These participants will be randomly divided into one of two groups:
* One group will receive durvalumab plus tremelimumab with standard of care chemotherapy
* One group will receive pembrolizumab with standard of care chemotherapy
Durvalumab, tremelimumab, pembrolizumab, and chemotherapy are given as an injection over time into a vein, also called an IV infusion. Chemotherapy will be one of the following regimens: pemetrexed plus cisplatin or pemetrexed plus carboplatin.
This is an open-label trial. This means that each participant will know which trial treatment they receive, and the doctors and trial staff will also know.
Researchers will measure and compare:
* How long participants live during the trial
* How long participants live during the trial without their cancer getting worse
* How many participants' tumors respond to treatment
* How long participants' tumor responses last
* How long before participants need to start a different treatment type
Researchers will also keep track of all the medical problems participants have during the trial and monitor their safety.
Participants will stop receiving trial treatment if they no longer benefit from it or they stop participating for another reason.
Participants will visit their trial site every 3 to 4 weeks. At most visits, participants will:
* Have a physical exam and answer questions about any medications they are taking or any medical problems they have
* Receive their trial treatment
* Give blood and urine samples
* Have pictures of their tumors taken using CT or MRI scans
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm A: Durvalumab + Tremelimumab + Platinum-based Chemotherapy
Participants will receive durvalumab plus tremelimumab every 3 weeks (q3w) for four 21-day cycles in combination with chemotherapy followed by maintenance treatment period (durvalumab plus pemetrexed maintenance) every 4 weeks (q4w) until disease progression or unacceptable toxicity or treatment discontinuation. During the maintenance treatment period, participants will receive additional doses of tremelimumab at Cycle 6 (Week 16) and Cycle 28 (Week 104 - at Investigator's discretion) along with durvalumab and pemetrexed.
Durvalumab
Participants will receive intravenous (IV) Durvalumab q3w for four 21-day cycles as induction treatment. Durvalumab will also be given during the maintenance treatment period q4w until disease progression or unacceptable toxicity.
Tremelimumab
Participants will receive IV Tremelimumab q3w for four 21-days cycles as induction treatment. Tremelimumab will also be given during the maintenance therapy phase at week 16 and week 104 (at the investigators discretion).
Pemetrexed
Participants in Arm A and Arm B will receive IV pemetrexed q3w for four 21-day cycles as induction treatment. In the maintenance therapy phase, Treatment Arm A will receive Pemetrexed q4w, Treatment Arm B will receive Pemetrexed q3w until disease progression or unacceptable toxicity.
Carboplatin
Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.
Cisplatin
Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.
Arm B: Pembrolizumab + Platinum-based Chemotherapy
Participants will receive pembrolizumab regimen q3w for four 21-day cycles in combination with chemotherapy as induction treatment followed by maintenance treatment (pembrolizumab plus pemetrexed maintenance) q3w until disease progression or unacceptable toxicity or treatment discontinuation.
Pemetrexed
Participants in Arm A and Arm B will receive IV pemetrexed q3w for four 21-day cycles as induction treatment. In the maintenance therapy phase, Treatment Arm A will receive Pemetrexed q4w, Treatment Arm B will receive Pemetrexed q3w until disease progression or unacceptable toxicity.
Pembrolizumab
Participants will receive IV pembrolizumab q3w for four 21-days cycles as induction treatment. Pembrolizumab will also be given in the maintenance treatment phase q3w until disease progression or unacceptable toxicity or up to 24 months.
Carboplatin
Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.
Cisplatin
Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Durvalumab
Participants will receive intravenous (IV) Durvalumab q3w for four 21-day cycles as induction treatment. Durvalumab will also be given during the maintenance treatment period q4w until disease progression or unacceptable toxicity.
Tremelimumab
Participants will receive IV Tremelimumab q3w for four 21-days cycles as induction treatment. Tremelimumab will also be given during the maintenance therapy phase at week 16 and week 104 (at the investigators discretion).
Pemetrexed
Participants in Arm A and Arm B will receive IV pemetrexed q3w for four 21-day cycles as induction treatment. In the maintenance therapy phase, Treatment Arm A will receive Pemetrexed q4w, Treatment Arm B will receive Pemetrexed q3w until disease progression or unacceptable toxicity.
Pembrolizumab
Participants will receive IV pembrolizumab q3w for four 21-days cycles as induction treatment. Pembrolizumab will also be given in the maintenance treatment phase q3w until disease progression or unacceptable toxicity or up to 24 months.
Carboplatin
Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.
Cisplatin
Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Participants must have tumors with STK11 or KEAP1 or KRAS mutations. Co-mutations are also allowed.
* Participants must have tumors that lack activating epidermal growth factor receptor mutations and ALK fusions.
* No prior chemotherapy or any other systemic therapy for metastatic NSCLC. Participants who have received prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for advanced disease are eligible, provided that progression has occurred \> 6 months from end of last therapy.
* No prior exposure to immune-mediated therapy excluding therapeutic anti-cancer vaccines, within 6 months of randomization.
* WHO/ECOG performance status of 0 or 1 at enrollment and randomization.
* Minimum life expectancy ≥ 12 weeks at randomization.
* At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter with Computed Tomography (CT)/CT- Positron Emission Tomography or Magnetic Resonance Imaging and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines.
* Adequate organ and bone marrow function.
* Negative pregnancy test (urine or serum) for women of child-bearing potential
* Female participants must be 1 year post-menopausal, surgically sterile, or using one highly effective form of birth control
* Male and Female participants and their partners must use an acceptable method of contraception.
* Body weight of \> 30 kg
Exclusion Criteria
* Mixed small cell lung cancer and NSCLC histology.
* Major surgical procedure within 28 days prior to the first dose of the study intervention or an anticipated need for major surgery during the study.
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis \[requiring immunosuppressive systemic therapy, eg, methotrexate, steroids\], hypophysitis, uveitis, etc), autoimmune pneumonitis and autoimmune myocarditis. The following are exceptions to this criterion:
* Participants with vitiligo or alopecia.
* Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
* Any chronic skin condition that does not require systemic therapy.
* Participants without active disease in the last 5 years may be included but only after consultation with the Study Clinical Lead.
* Participants with celiac disease controlled by diet alone.
* Medical contraindication to platinum-based doublet chemotherapy.
* History of another primary malignancy except:
* Malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence
* Adequately resected non-melanoma skin cancer and curatively treated in situ disease.
* Persistent toxicities (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≥ 2) caused by previous anti-cancer therapy, alopecia and vitiligo are excluded toxicities.
* Participants with Grade ≤ 2 neuropathy can be considered based on Investigator's judgement. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by treatment with study intervention in the opinion of the Investigator may be included (eg, hearing loss).
* Spinal cord compression unless asymptomatic and stable.
* Participant meets the following:
\- Symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted based on the Investigator judgement with cardiologist consultation recommended.
* Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.
* No radiation therapy is allowed, unless it is 1) definitive radiation that had been administered at least 6 months prior, 2) palliative radiation to brain, with associated criteria for stability or lack of symptoms, or 3) palliative radiation to painful bony lesions (this must comprise less than 30% of the bone marrow)
* Patients with suspected brain metastases at screening should have an IV contrast-enhanced MRI (preferred) or IV contrast-enhanced CT/CT-PET of the brain prior to study entry. If brain metastases are detected patients must be treated before randomization. Randomization is only permitted if patients with brain metastases have:
* Confirmed stable condition
* Returned neurologically to baseline Brain metastases will not be recorded as RECIST target lesions at baseline.
* History of leptomeningeal carcinomatosis.
* Known to have tested positive for active tuberculosis infection
* Known active hepatitis infection, positive HCV antibody, HBsAg, or anti-HBc, at screening. Participants with a past or resolved HBV infection (defined as the presence of anti-HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if PCR is negative for HCV RNA. Participants co-infected with HBV and HCV, or co-infected with HBV and HDV, namely: HBV positive (presence of HBsAg and/or anti-HBcAb with detectable HBV DNA); AND
* HCV positive (presence of anti-HCV antibodies); OR
* HDV positive (presence of anti-HDV antibodies).
* Known human immunodeficiency virus (HIV) infection that is not well controlled.
* Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention. The following are exceptions to this criterion:
* Intranasal, inhaled, topical steroids or local steroid injections (eg, intra-articular injection).
* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
* Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication, premedication for chemotherapy) or a single dose for palliative purpose (eg, pain control).
* Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention.
* Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
* Participants with a known hypersensitivity to any of the study interventions or any of the excipients of the products.
* For females only: Currently pregnant (confirmed with positive pregnancy test) or breastfeeding, or who are planning to become pregnant.
Female participants should refrain from breastfeeding from enrolment throughout the study and until up to 14 months after the last dose of cisplatin or 180 days after pemetrexed or 90 days after tremelimumab or durvalumab or pembrolizumab, whichever is longer; and during treatment with carboplatin.
18 Years
130 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
AstraZeneca
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Research Site
Birmingham, Alabama, United States
Research Site
Anchorage, Alaska, United States
Research Site
Chandler, Arizona, United States
Research Site
Tucson, Arizona, United States
Research Site
Beverly Hills, California, United States
Research Site
Irvine, California, United States
Research Site
La Jolla, California, United States
Research Site
Loma Linda, California, United States
Research Site
Los Alamitos, California, United States
Research Site
Los Angeles, California, United States
Research Site
Los Angeles, California, United States
Research Site
Redding, California, United States
Research Site
Santa Monica, California, United States
Research Site
Denver, Colorado, United States
Research Site
Wheat Ridge, Colorado, United States
Research Site
Washington D.C., District of Columbia, United States
Research Site
Washington D.C., District of Columbia, United States
Research Site
Fort Lauderdale, Florida, United States
Research Site
Jupiter, Florida, United States
Research Site
Ocala, Florida, United States
Research Site
Orlando, Florida, United States
Research Site
St. Petersburg, Florida, United States
Research Site
Tampa, Florida, United States
Research Site
Tampa, Florida, United States
Research Site
Albany, Georgia, United States
Research Site
Atlanta, Georgia, United States
Research Site
Atlanta, Georgia, United States
Research Site
Atlanta, Georgia, United States
Research Site
Columbus, Georgia, United States
Research Site
Honolulu, Hawaii, United States
Research Site
Carterville, Illinois, United States
Research Site
Chicago, Illinois, United States
Research Site
Chicago, Illinois, United States
Research Site
Maywood, Illinois, United States
Research Site
Urbana, Illinois, United States
Research Site
Dyer, Indiana, United States
Research Site
Evansville, Indiana, United States
Research Site
Westwood, Kansas, United States
Research Site
Lexington, Kentucky, United States
Research Site
Louisville, Kentucky, United States
Research Site
Bethesda, Maryland, United States
Research Site
Jamaica Plain, Massachusetts, United States
Research Site
Worcester, Massachusetts, United States
Research Site
Detroit, Michigan, United States
Research Site
Farmington Hills, Michigan, United States
Research Site
Lansing, Michigan, United States
Research Site
Traverse City, Michigan, United States
Research Site
Saint Paul, Minnesota, United States
Research Site
Kansas City, Missouri, United States
Research Site
Kansas City, Missouri, United States
Research Site
St Louis, Missouri, United States
Research Site
St Louis, Missouri, United States
Research Site
Billings, Montana, United States
Research Site
Grand Island, Nebraska, United States
Research Site
Lincoln, Nebraska, United States
Research Site
Albany, New York, United States
Research Site
Clifton Park, New York, United States
Research Site
East Syracuse, New York, United States
Research Site
Mineola, New York, United States
Research Site
New Hyde Park, New York, United States
Research Site
New York, New York, United States
Research Site
New York, New York, United States
Research Site
New York, New York, United States
Research Site
New York, New York, United States
Research Site
Northport, New York, United States
Research Site
Shirley, New York, United States
Research Site
Stony Brook, New York, United States
Research Site
Syracuse, New York, United States
Research Site
The Bronx, New York, United States
Research Site
The Bronx, New York, United States
Research Site
Westbury, New York, United States
Research Site
Bismarck, North Dakota, United States
Research Site
Cleveland, Ohio, United States
Research Site
Cleveland, Ohio, United States
Research Site
Cleveland, Ohio, United States
Research Site
Columbus, Ohio, United States
Research Site
Dayton, Ohio, United States
Research Site
Maumee, Ohio, United States
Research Site
Perrysburg, Ohio, United States
Research Site
Toledo, Ohio, United States
Research Site
Norman, Oklahoma, United States
Research Site
Hershey, Pennsylvania, United States
Research Site
Philadelphia, Pennsylvania, United States
Research Site
Philadelphia, Pennsylvania, United States
Research Site
Pittsburgh, Pennsylvania, United States
Research Site
Providence, Rhode Island, United States
Research Site
Sioux Falls, South Dakota, United States
Research Site
Memphis, Tennessee, United States
Research Site
Memphis, Tennessee, United States
Research Site
Memphis, Tennessee, United States
Research Site
Nashville, Tennessee, United States
Research Site
Austin, Texas, United States
Research Site
Dallas, Texas, United States
Research Site
Dallas, Texas, United States
Research Site
Denton, Texas, United States
Research Site
Fort Worth, Texas, United States
Research Site
Houston, Texas, United States
Research Site
Houston, Texas, United States
Research Site
Kingwood, Texas, United States
Research Site
San Antonio, Texas, United States
Research Site
San Antonio, Texas, United States
Research Site
Charlottesville, Virginia, United States
Research Site
Fairfax, Virginia, United States
Research Site
Richmond, Virginia, United States
Research Site
Milwaukee, Wisconsin, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
D419ML00003
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.