NCT06008093

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

A Phase IIb, 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: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 130 Years
• Healthy volunteers: Not accepted

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.

Detailed description

A trial to learn if durvalumab plus tremelimumab with chemotherapy is safe and how well it works compared to pembrolizumab with chemotherapy in participants with metastatic non-small cell lung cancer with certain genetic mutations. 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 100 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 without their cancer getting worse * How long participants live during the trial * 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, at trial close, or if 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

• Carcinoma, Non-Small-Cell Lung

Interventions

Type	Name	Description
DRUG	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 clinical progression or confirmed RECIST 1.1- defined radiological progression as assessed by the investigator, unacceptable toxicity, withdrawal of participant consent, or EOS, whichever comes first.
DRUG	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).
DRUG	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 clinical progression or confirmed RECIST 1.1- defined radiological progression as assessed by the investigator, unacceptable toxicity, withdrawal of participant consent, or EOS, whichever comes first.
DRUG	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 clinical progression or confirmed RECIST 1.1- defined radiological progression as assessed by the investigator, unacceptable toxicity, withdrawal of participant consent, or EOS, whichever comes first.
DRUG	Carboplatin	Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.
DRUG	Cisplatin	Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.

Timeline

• Start date: 2024-04-04
• Primary completion: 2026-12-08
• Completion: 2027-12-23
• First posted: 2023-08-23
• Last updated: 2026-03-30

Locations

47 sites across 1 country: United States

Regulatory

• FDA-regulated drug study