RECRUITING

A Study to Investigate the Efficacy of Durvalumab Plus Tremelimumab in Combination With Chemotherapy Compared With Pembrolizumab in Combination With Chemotherapy in Metastatic Non-Small Cell Lung Cancer (NSCLC) Patients

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of the study is to assess 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.

Official Title

A Phase IIIb, Randomized, Multicenter, Open-label Study to Assess the Efficacy of Durvalumab Plus Tremelimumab Versus Pembrolizumab in Combination With Platinum-Based Chemotherapy for First-Line Treatment in Metastatic Non-Small Cell Lung Cancer Patients With Non-Squamous Histology Who Have Mutations and/or Co-mutations in STK11, KEAP1, or KRAS (TRITON).

Quick Facts

Study Start:2024-04-04
Study Completion:2031-03-20
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06008093

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 130 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Histologically or cytologically documented Stage IV non-squamous NSCLC not amenable to curative surgery or radiation.
  2. * Participants must have tumors with STK11 or KEAP1 or KRAS mutations. Co-mutations are also allowed.
  3. * Participants must have tumors that lack activating epidermal growth factor receptor mutations and ALK fusions.
  4. * 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.
  5. * No prior exposure to immune-mediated therapy excluding therapeutic anti-cancer vaccines, within 12 months to randomization.
  6. * WHO/ECOG performance status of 0 or 1 at enrollment and randomization.
  7. * Minimum life expectancy ≥ 12 weeks at randomization.
  8. * 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.
  9. * Adequate organ and bone marrow function:
  10. * Negative pregnancy test (urine or serum) for women of child-bearing potential
  11. * Female participants must be 1 year post-menopausal, surgically sterile, or using one highly effective form of birth control
  12. * Male and Female participants and their partners must use an acceptable method of contraception.
  13. * Body weight of \> 30 kg
  1. * Any evidence of acute or uncontrolled diseases or history of allogeneic organ transplant.
  2. * Mixed small cell lung cancer and NSCLC histology.
  3. * 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.
  4. * 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:
  5. * Participants with vitiligo or alopecia.
  6. * Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
  7. * Any chronic skin condition that does not require systemic therapy.
  8. * Participants without active disease in the last 5 years may be included but only after consultation with the Study Clinical Lead.
  9. * Participants with celiac disease controlled by diet alone.
  10. * Medical contraindication to platinum-based doublet chemotherapy.
  11. * History of another primary malignancy except:
  12. * 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
  13. * Adequately resected non-melanoma skin cancer and curatively treated in situ disease.
  14. * Persistent toxicities (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≥ 2) caused by previous anti-cancer therapy, alopecia and vitiligo are excluded toxicities.
  15. * 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).
  16. * Spinal cord compression unless asymptomatic and stable.
  17. * Participant meets the following:
  18. * 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.
  19. * 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)
  20. * Patients with suspected brain metastases at screening should have an intravenous (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:
  21. * Confirmed stable condition
  22. * Returned neurologically to baseline Brain metastases will not be recorded as RECIST target lesions at baseline.
  23. * History of leptomeningeal carcinomatosis.
  24. * Known to have tested positive for active tuberculosis infection
  25. * 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
  26. * HCV positive (presence of anti-HCV antibodies); OR
  27. * HDV positive (presence of anti-HDV antibodies).
  28. * Known human immunodeficiency virus (HIV) infection that is not well controlled.
  29. * Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention. The following are exceptions to this criterion:
  30. * Intranasal, inhaled, topical steroids or local steroid injections (eg, intra-articular injection).
  31. * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
  32. * Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication, premedication for chemotherapy) or a single dose for palliative purpose (eg, pain control).
  33. * Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention.
  34. * Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
  35. * Participants with a known hypersensitivity to any of the study interventions or any of the excipients of the products.
  36. * For females only: Currently pregnant (confirmed with positive pregnancy test) or breast-feeding, or who are planning to become pregnant.

Contacts and Locations

Study Contact

AstraZeneca Clinical Study Information Center
CONTACT
1-877-240-9479
information.center@astrazeneca.com

Study Locations (Sites)

Research Site
Birmingham, Alabama, 35233
United States
Research Site
Anchorage, Alaska, 99508
United States
Research Site
Chandler, Arizona, 85224
United States
Research Site
Tucson, Arizona, 85724
United States
Research Site
Irvine, California, 92618
United States
Research Site
La Jolla, California, 92093
United States
Research Site
Loma Linda, California, 92357
United States
Research Site
Los Alamitos, California, 90720
United States
Research Site
Los Angeles, California, 90034
United States
Research Site
Los Angeles, California, 90095
United States
Research Site
Redding, California, 96001
United States
Research Site
Santa Monica, California, 90404
United States
Research Site
Aurora, Colorado, 80012
United States
Research Site
Wheat Ridge, Colorado, 80033
United States
Research Site
Washington, District of Columbia, 20007
United States
Research Site
Washington, District of Columbia, 20010
United States
Research Site
Fort Lauderdale, Florida, 33308
United States
Research Site
Jupiter, Florida, 33458
United States
Research Site
Ocala, Florida, 34474
United States
Research Site
Orlando, Florida, 32804
United States
Research Site
Saint Petersburg, Florida, 33705
United States
Research Site
Tampa, Florida, 33607
United States
Research Site
Tampa, Florida, 33612
United States
Research Site
Albany, Georgia, 31701
United States
Research Site
Atlanta, Georgia, 30303
United States
Research Site
Atlanta, Georgia, 30318
United States
Research Site
Atlanta, Georgia, 30322
United States
Research Site
Columbus, Georgia, 31904
United States
Research Site
Carterville, Illinois, 62918
United States
Research Site
Chicago, Illinois, 60607
United States
Research Site
Chicago, Illinois, 60612
United States
Research Site
Maywood, Illinois, 60153
United States
Research Site
Urbana, Illinois, 61801
United States
Research Site
Dyer, Indiana, 46311
United States
Research Site
Evansville, Indiana, 47713
United States
Research Site
Westwood, Kansas, 66205
United States
Research Site
Lexington, Kentucky, 40502
United States
Research Site
Bethesda, Maryland, 20817
United States
Research Site
Jamaica Plain, Massachusetts, 02130
United States
Research Site
Worcester, Massachusetts, 01655
United States
Research Site
Detroit, Michigan, 48201
United States
Research Site
Farmington Hills, Michigan, 48334
United States
Research Site
Lansing, Michigan, 48912
United States
Research Site
Traverse City, Michigan, 49684
United States
Research Site
Saint Paul, Minnesota, 55101
United States
Research Site
Kansas City, Missouri, 64111
United States
Research Site
Kansas City, Missouri, 64132
United States
Research Site
Saint Louis, Missouri, 63110
United States
Research Site
Billings, Montana, 59102
United States
Research Site
Grand Island, Nebraska, 68803
United States
Research Site
Lincoln, Nebraska, 68506
United States
Research Site
Albany, New York, 12208
United States
Research Site
Bronx, New York, 10461
United States
Research Site
Bronx, New York, 10469
United States
Research Site
Clifton Park, New York, 12065
United States
Research Site
Mineola, New York, 11501
United States
Research Site
New Hyde Park, New York, 11042
United States
Research Site
New Hyde Park, New York, 11042
United States
Research Site
New York, New York, 10016
United States
Research Site
New York, New York, 10028
United States
Research Site
New York, New York, 10032
United States
Research Site
Northport, New York, 11768
United States
Research Site
Shirley, New York, 11967
United States
Research Site
Stony Brook, New York, 11790
United States
Research Site
Syracuse, New York, 13210
United States
Research Site
Bismarck, North Dakota, 58501
United States
Research Site
Cleveland, Ohio, 44111
United States
Research Site
Cleveland, Ohio, 44124
United States
Research Site
Cleveland, Ohio, 44195
United States
Research Site
Columbus, Ohio, 43210
United States
Research Site
Dayton, Ohio, 45459
United States
Research Site
Toledo, Ohio, 43623
United States
Research Site
Norman, Oklahoma, 73072
United States
Research Site
Oklahoma City, Oklahoma, 73120
United States
Research Site
Hershey, Pennsylvania, 17033
United States
Research Site
Philadelphia, Pennsylvania, 19111
United States
Research Site
Philadelphia, Pennsylvania, 19131
United States
Research Site
Providence, Rhode Island, 02906
United States
Research Site
Sioux Falls, South Dakota, 57105
United States
Research Site
Memphis, Tennessee, 38103
United States
Research Site
Memphis, Tennessee, 38104
United States
Research Site
Nashville, Tennessee, 37212
United States
Research Site
Austin, Texas, 78745
United States
Research Site
Dallas, Texas, 75246
United States
Research Site
Dallas, Texas, 75246
United States
Research Site
Denton, Texas, 76210
United States
Research Site
Fort Worth, Texas, 76104
United States
Research Site
Houston, Texas, 77030
United States
Research Site
Houston, Texas, 77090
United States
Research Site
Kingwood, Texas, 77339
United States
Research Site
San Antonio, Texas, 78229
United States
Research Site
Charlottesville, Virginia, 22908
United States
Research Site
Fairfax, Virginia, 22031
United States
Research Site
Richmond, Virginia, 23298
United States
Research Site
Milwaukee, Wisconsin, 53233
United States

Collaborators and Investigators

Sponsor: AstraZeneca

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-04-04
Study Completion Date2031-03-20

Study Record Updates

Study Start Date2024-04-04
Study Completion Date2031-03-20

Terms related to this study

Keywords Provided by Researchers

  • Mutation
  • Metastatic Non-Small Cell Lung Cancer
  • Kelch-Like ECH-Associated Protein 1 (KEAP1)
  • Kirsten rat sarcoma virus (KRAS)
  • Programmed death-ligand 1 (PD-L1)
  • Serine/threonine kinase 11 (STK11)

Additional Relevant MeSH Terms

  • Carcinoma, Non-Small-Cell Lung