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.
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 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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
280
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.
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).
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.
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.
Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.
Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.
Research Site
Birmingham, Alabama, United States
WITHDRAWNResearch Site
Anchorage, Alaska, United States
RECRUITINGResearch Site
Chandler, Arizona, United States
WITHDRAWNResearch Site
Tucson, Arizona, United States
RECRUITINGOverall survival (OS)
OS is defined as the time from randomization until death due to any cause in all participants. The measure of interest is the hazard ratio with corresponding 95% CI.
Time frame: From randomization until death, withdrawal of consent, or the end of the study (approximately 84 months)
OS in subset of randomized participants with STK11 or KEAP1 mutations and/or co-mutations
OS is defined as the time from randomization until death due to any cause in participants with STK11 or KEAP1 mutations and/or co-mutations. The measure of interest is the hazard ratio with corresponding 95% CI.
Time frame: From randomization until death, withdrawal of consent, or the end of the study (approximately 84 months)
Overall survival at 12 months
OS is defined as the time from randomization until death due to any cause in all participants. The measure of interest is survival rate with corresponding 95% CI at 12 months landmark.
Time frame: At 12 months
Overall survival at 24 months
OS is defined as the time from randomization until death due to any cause in all participants. The measure of interest is survival rate with corresponding 95% CI at 24 months landmark.
Time frame: At 24 months
Overall survival at 12 months in subset of randomized participants with STK11 or KEAP1 mutation and/or co mutations
OS is defined as the time from randomization until death due to any cause. The measure of interest is survival rate with corresponding 95% CI at 12 months landmark.
Time frame: At 12 months
Overall survival at 24 months in subset of randomized participants with STK11 or KEAP1 mutation and/or co mutations
OS is defined as the time from randomization until death due to any cause. The measure of interest is survival rate with corresponding 95% CI at 24 months landmark.
Time frame: At 24 months
Overall survival in subset of randomized participants whose PD-L1 status is PD-L1 TC < 1%
OS is defined as the time from randomization until death due to any cause. The measure of interest is the hazard ratio with corresponding 95% CI.
Time frame: From randomization until death, withdrawal of consent, or the end of the study (approximately 84 months)
Overall survival at 12 months in subset of randomized participants whose PD-L1 status is PD-L1 TC < 1%
OS is defined as the time from randomization until death due to any cause. The measure of interest is survival rate with corresponding 95% CI at 12 months landmark.
Time frame: At 12 months
Overall survival at 24 months in subset of randomized participants whose PD-L1 status is PD-L1 TC < 1%
OS is defined as the time from randomization until death due to any cause. The measure of interest is survival rate with corresponding 95% CI at 24 months landmark.
Time frame: At 24 months
Progression-free survival (PFS)
PFS is defined as the time from randomization until the date of confirmed PD (per Response Evaluation Criteria in Solid Tumours, Version 1.1 \[RECIST 1.1\] as assessed by the Investigator) or death due to any cause (in the absence of progression) in all participants. The measure of interest is the HR and the corresponding 95% CI.
Time frame: From randomization until disease progression, death, withdrawal of consent, or end of study (approximately 84 months)
Objective response rate (ORR)
ORR is defined as the proportion of participants with a confirmed objective tumour response (complete response \[CR\] or partial response \[PR\]) as determined by the investigator per RECIST 1.1 in all participants who have measurable disease at baseline. The measures of interest are the relative risk and common risk difference with corresponding 95% CI.
Time frame: From randomization until disease progression, or the last evaluable assessment in the absence of progression (approximately 84 months)
Duration of response (DOR)
DOR is defined as the time from the date of first documented confirmed response until the date of documented progression (per RECIST 1.1, as assessed by the Investigator) or death due to any cause (in the absence of disease progression) in all participants who have confirmed objective response. The measure of interest is the median duration of response and corresponding 95% CI.
Time frame: From first documented response until documented progression (approximately 84 months)
Time to First Subsequent Therapy (TFST)
TFST is defined as the time from randomization until the start date of the first subsequent anti-cancer therapy after discontinuation of randomized study intervention, or death due to any cause in all participants. The measure of interest is the HR and the corresponding 95% CI.
Time frame: From randomization until the start date of the first subsequent anti-cancer therapy after discontinuation of randomized study intervention or death [approx. up to 84 months]
Number of participants with adverse events (AEs)
To assess the safety and tolerability of durvalumab plus tremelimumab plus chemotherapy compared with pembrolizumab plus chemotherapy in participants with non-squamous histology who have metastatic NSCLC with mutations and/or co-mutations in STK11, KEAP1, or KRAS.
Time frame: From screening until the follow-up period is completed [approx. up to 84 months]
AstraZeneca Clinical Study Information Center
CONTACT
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Research Site
Beverly Hills, California, United States
RECRUITINGResearch Site
Irvine, California, United States
RECRUITINGResearch Site
La Jolla, California, United States
RECRUITINGResearch Site
Loma Linda, California, United States
RECRUITINGResearch Site
Los Alamitos, California, United States
RECRUITINGResearch Site
Los Angeles, California, United States
RECRUITING...and 95 more locations