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
Lung Cancer
Unknown Primary
18 - 130 Years, Male and Female
D419ML00003 (primary)
NCI-2024-00168
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.
Objectives
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 chemotherapy
- One group will receive pembrolizumab with 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 be in this trial for up to approximately 4 years. They 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
Eligibility
- 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 12 months to 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
Treatment Sites in Georgia
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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