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)

Status: Recruiting
Location: See all (105) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 130
Healthy Volunteers: f
View:

• Histologically or cytologically documented Stage IV non-squamous NSCLC not amenable to curative surgery or radiation.

• 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

Locations
United States
Alaska
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Anchorage
Alabama
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Birmingham
Arizona
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Chandler
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Tucson
California
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Beverly Hills
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Irvine
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La Jolla
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Loma Linda
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Los Alamitos
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Los Angeles
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Los Angeles
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Redding
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Santa Monica
Colorado
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Denver
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Wheat Ridge
Washington, D.c.
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Washington D.c.
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Washington D.c.
Florida
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Fort Lauderdale
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Jupiter
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Ocala
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Orlando
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St. Petersburg
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Tampa
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Tampa
Georgia
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Albany
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Atlanta
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Atlanta
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Atlanta
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Columbus
Hawaii
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Honolulu
Illinois
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Carterville
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Chicago
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Chicago
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Maywood
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Urbana
Indiana
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Dyer
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Evansville
Kansas
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Westwood
Kentucky
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Lexington
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Louisville
Massachusetts
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Jamaica Plain
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Worcester
Maryland
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Bethesda
Michigan
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Detroit
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Farmington Hills
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Lansing
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Traverse City
Minnesota
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Saint Paul
Missouri
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Kansas City
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Kansas City
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St Louis
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St Louis
Montana
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Billings
North Dakota
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Bismarck
Nebraska
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Grand Island
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Lincoln
New York
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Albany
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Clifton Park
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East Syracuse
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Mineola
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New Hyde Park
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New York
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New York
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New York
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New York
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Northport
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Shirley
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Stony Brook
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Syracuse
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The Bronx
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The Bronx
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Westbury
Ohio
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Cleveland
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Cleveland
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Cleveland
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Columbus
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Dayton
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Maumee
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Perrysburg
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Toledo
Oklahoma
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Norman
Pennsylvania
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Hershey
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Philadelphia
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Philadelphia
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Pittsburgh
Rhode Island
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Providence
South Dakota
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Sioux Falls
Tennessee
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Memphis
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Memphis
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Memphis
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Nashville
Texas
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Austin
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Dallas
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Dallas
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Denton
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Fort Worth
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Houston
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Houston
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Kingwood
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San Antonio
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San Antonio
Virginia
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Charlottesville
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Fairfax
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Richmond
Wisconsin
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Milwaukee
Contact Information
Primary
AstraZeneca Clinical Study Information Center
information.center@astrazeneca.com
1-877-240-9479
Time Frame
Start Date: 2024-04-04
Estimated Completion Date: 2031-03-20
Participants
Target number of participants: 280
Treatments
Experimental: 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.
Experimental: 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.
Sponsors
Leads: AstraZeneca

This content was sourced from clinicaltrials.gov

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