Carcinoma, Non-Small-Cell LungPhase 2TRITONNCT06008093
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 2 study testing Durvalumab, Tremelimumab and Pemetrexed in people with Carcinoma, Non-Small-Cell Lung, run by AstraZeneca at 47 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Durvalumab, Tremelimumab and Pemetrexed
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 47 sitesUnited States
- Study dates
- 4 Apr 2024to 5 Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- Any evidence of acute or uncontrolled diseases or history of allogeneic organ transplant.
- Mixed small cell lung cancer and NSCLC histology.
- 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.
- 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:
- Participants with vitiligo or alopecia.
- Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
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- Any chronic skin condition that does not require systemic therapy.
- Participants without active disease in the last 5 years may be included but only after consultation with the Study Clinical Lead.
- Participants with celiac disease controlled by diet alone.
- Medical contraindication to platinum-based doublet chemotherapy.
- History of another primary malignancy except:
- 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
- Adequately resected non-melanoma skin cancer and curatively treated in situ disease.
- Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≥ 2) caused by previous anti-cancer therapy, alopecia and vitiligo are excluded toxicities.
- 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).
- Spinal cord compression unless asymptomatic and stable.
- Participant meets the following:
- Symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted based on the Investigator judgement with cardiologist consultation recommended.
- 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.
- 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)
- Patients with suspected brain metastases at screening should have an 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:
- Confirmed stable condition
- Returned neurologically to baseline Brain metastases will not be recorded as RECIST target lesions at baseline.
- History of leptomeningeal carcinomatosis.
- Known to have tested positive for active tuberculosis infection
- 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
- HCV positive (presence of anti-HCV antibodies); OR
- HDV positive (presence of anti-HDV antibodies).
- Known human immunodeficiency virus (HIV) infection that is not well controlled.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids or local steroid injections (eg, intra-articular injection).
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
- Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication, premedication for chemotherapy) or a single dose for palliative purpose (eg, pain control).
- Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention.
- Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
- Participants with a known hypersensitivity to any of the study interventions or any of the excipients of the products.
- For females only: Currently pregnant (confirmed with positive pregnancy test) or breastfeeding, or who are planning to become pregnant.
- Female participants should refrain from breastfeeding from enrolment throughout the study and until up to 14 months after the last dose of cisplatin or 180 days after pemetrexed or 90 days after tremelimumab or durvalumab or pembrolizumab, whichever is longer; and during treatment with carboplatin.
Trial locations and contacts
47 sites in 1 country.
47 sites in 1 country
United States47 sites
Research Site
Albany, New York, 12206
Research Site
Atlanta, Georgia, 30318
Research Site
Atlanta, Georgia, 30322
Research Site
Bethesda, Maryland, 20817
Research Site
Beverly Hills, California, 90211
Research Site
Billings, Montana, 59102
Research Site
Carterville, Illinois, 62918
Research Site
Cleveland, Ohio, 44111
Research Site
Cleveland, Ohio, 44124
Research Site
Cleveland, Ohio, 44195
Research Site
Columbus, Ohio, 43210
Research Site
Dallas, Texas, 75246
Research Site
Dayton, Ohio, 45459
Research Site
Denton, Texas, 76210
Research Site
East Syracuse, New York, 13057
Research Site
Fairfax, Virginia, 22031
Research Site
Fort Lauderdale, Florida, 33308
Research Site
Grand Island, Nebraska, 68803
Research Site
Honolulu, Hawaii, 96813
Research Site
Houston, Texas, 77030
Research Site
Houston, Texas, 77090
Research Site
Jamaica Plain, Massachusetts, 02130
Research Site
Jupiter, Florida, 33458
Research Site
Kansas City, Missouri, 64132
Research Site
Kingwood, Texas, 77339
Research Site
La Jolla, California, 92093
Research Site
Lincoln, Nebraska, 68506
Research Site
Los Alamitos, California, 90720
Research Site
Los Angeles, California, 90034
Research Site
Memphis, Tennessee, 38120
Research Site
New York, New York, 10032
Research Site
Norman, Oklahoma, 73072
Research Site
Ocala, Florida, 34474
Research Site
Orlando, Florida, 32804
Research Site
Pittsburgh, Pennsylvania, 15212
Research Site
Richmond, Virginia, 23298
Research Site
Saint Paul, Minnesota, 55101
Research Site
Santa Monica, California, 90404
Research Site
Shirley, New York, 11967
Research Site
Sioux Falls, South Dakota, 57105
Research Site
St Louis, Missouri, 63128
Research Site
St. Petersburg, Florida, 33705
Research Site
Stony Brook, New York, 11790
Research Site
Syracuse, New York, 13210
Research Site
The Bronx, New York, 10461
Research Site
Urbana, Illinois, 61801
Research Site
Washington D.C., District of Columbia, 20007
About this study
Official title: 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)
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.
Read the 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
- Being tested
- Durvalumab, Tremelimumab, Pemetrexed, Pembrolizumab, Carboplatin
- Keywords
- 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)
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736 & IMFINZI®
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.
TremelimumabDrug
Also called IMJUDO®
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).
PemetrexedDrug
Also called Background Platinum-based Chemotherapy
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.
PembrolizumabDrug
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.
CarboplatinDrug
Also called Background Platinum-based Chemotherapy
Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.
CisplatinDrug
Also called Background Platinum-based Chemotherapy
Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Durvalumab + Tremelimumab + Platinum-based Chemotherapy | Experimental | 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 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. 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. Receives: Drug: Durvalumab; Drug: Tremelimumab; Drug: Pemetrexed; Drug: Carboplatin; Drug: Cisplatin |
| Arm B: Pembrolizumab + Platinum-based Chemotherapy | Experimental | 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 for up to 24 months, 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. Receives: Drug: Pemetrexed; Drug: Pembrolizumab; Drug: Carboplatin; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS) in randomized participants
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. The measure of interest is the hazard ratio (HR) and the corresponding 95% confidence interval (CI).
Measured: From randomization until death, withdrawal of consent, or the end of the study (approximately 48 months)
PFS at 6 months
PFS is defined as the time from randomization until the date of confirmed PD (per RECIST 1.1 as assessed by the Investigator) or death due to any cause. The measure of interest is the PFS rate and the corresponding 95% CI at 6 months.
Measured: From randomization until death, withdrawal of consent, or the end of the study (approximately 48 months)
PFS at 12 months
PFS is defined as the time from randomization until the date of confirmed PD (per RECIST 1.1 as assessed by the Investigator) or death due to any cause. The measure of interest is the PFS rate and the corresponding 95% CI at 12 months.
Measured: From randomization until death, withdrawal of consent, or the end of the study (approximately 48 months)
Secondary outcomes (9)
Overall survival (OS) at 12 months
OS is defined as the time from randomization until death due to any cause. The measure of interest is the OS rate with corresponding 95% CI at 12 months landmark.
Measured: At 12 months
OS at 24 months
OS is defined as the time from randomization until death due to any cause. The measure of interest is the OS rate with corresponding 95% CI at 24 months landmark.
Measured: At 24 months
OS at 12 months in subset of randomized participants with STK11, KEAP1 or KRAS mutation and/or co mutations
OS is defined as the time from randomization until death due to any cause. The measure of interest is the OS rate with corresponding 95% CI at 12 months landmark.
Measured: At 12 months
OS at 24 months in subset of randomized participants with STK11, KEAP1 or KRAS mutation and/or co mutations
OS is defined as the time from randomization until death due to any cause. The measure of interest is the OS rate with corresponding 95% CI at 24 months landmark.
Measured: At 24 months
OS in randomized participants
OS is defined as the time from randomization until death due to any cause. The measure of interest is the HR with corresponding 95% CI.
Measured: From randomization until death, withdrawal of consent, or the end of the study (approximately 48 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]) per RECIST 1.1, as assessed by the Investigator. The measures of interest is common risk difference with corresponding 95% CI.
Measured: From randomization until disease progression, or the last evaluable assessment in the absence of progression (approximately 48 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 all randomized participants as randomized (FAS) who have confirmed objective response. The measure of interest is the median duration of response and the corresponding 95% CI.
Measured: From first documented response until documented progression (approximately 48 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 intervention, or death due to any cause. The measure of interest is the median TFST and the corresponding 95% CI.
Measured: From randomization until the start date of the first subsequent anti-cancer therapy after discontinuation of randomized study intervention or death (approximately 48 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.
Measured: From screening until the follow-up period is completed (approximately 48 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2023
- Study start4 Apr 2024
- Primary completion27 Oct 2026 (estimated)
- Study completion5 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase IIb 2-arm, parallel randomized open label multicenter study
- Masking
- None (open label)
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06008093
- Sponsor's protocol ID
- D419ML00003
- Acronym
- TRITON
- Status last verified
- Oct 2026
- First submitted
- 17 Aug 2023
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
Publications
Skoulidis F, Borghaei H, Garon EB, Leal TA, Kaufman J, Liu SV, Nadler E, Patel SP, Peters S, Ricciuti B, Gautam A, Emeribe U, Luciani-Silverman L, Heymach JV. Rationale and design for a phase IIIb trial of first-line tremelimumab plus durvalumab versus pembrolizumab, in combination with chemotherapy, in patients with non-squamous metastatic non-small-cell lung cancer and mutations or co-mutations in STK11, KEAP1, or KRAS: the TRITON study. Ther Adv Med Oncol. 2025 Nov 6;17:17588359251386611. doi: 10.1177/17588359251386611. eCollection 2025.
PubMed 41209621
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT06008093
- Acronym / sponsor ID
- TRITON / D419ML00003
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Keywords
- 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)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 103 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 4 Apr 2024 (actual)
- Primary completion
- 27 Oct 2026 (estimated)
- Study completion
- 5 Jan 2028 (estimated)
- First posted
- 23 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase IIb 2-arm, parallel randomized open label multicenter study
| Arm | Type | Receives |
|---|---|---|
| Arm A: Durvalumab + Tremelimumab + Platinum-based Chemotherapy | Experimental | Drug: Durvalumab, Drug: Tremelimumab, Drug: Pemetrexed, Drug: Carboplatin, Drug: CisplatinParticipants 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 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. 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. |
| Arm B: Pembrolizumab + Platinum-based Chemotherapy | Experimental | Drug: Pemetrexed, Drug: Pembrolizumab, Drug: Carboplatin, Drug: CisplatinParticipants 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 for up to 24 months, 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. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (38 listed)
- Any evidence of acute or uncontrolled diseases or history of allogeneic organ transplant.
- Mixed small cell lung cancer and NSCLC histology.
- 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.
- 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:
- Medical contraindication to platinum-based doublet chemotherapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurvalumabAlso: MEDI4736 & IMFINZI®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 | Arm A: Durvalumab + Tremelimumab + Platinum-based Chemotherapy |
| TremelimumabAlso: IMJUDO®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 | Arm A: Durvalumab + Tremelimumab + Platinum-based Chemotherapy |
| PemetrexedAlso: Background Platinum-based ChemotherapyParticipants 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 | Arm A: Durvalumab + Tremelimumab + Platinum-based Chemotherapy, Arm B: Pembrolizumab + Platinum-based Chemotherapy |
| PembrolizumabParticipants 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 | Arm B: Pembrolizumab + Platinum-based Chemotherapy |
| CarboplatinAlso: Background Platinum-based ChemotherapyParticipants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment. | Drug | Arm A: Durvalumab + Tremelimumab + Platinum-based Chemotherapy, Arm B: Pembrolizumab + Platinum-based Chemotherapy |
| CisplatinAlso: Background Platinum-based ChemotherapyParticipants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment. | Drug | Arm A: Durvalumab + Tremelimumab + Platinum-based Chemotherapy, Arm B: Pembrolizumab + Platinum-based Chemotherapy |
Primary outcome
Progression-free survival (PFS) in randomized participants
Time frame: From randomization until death, withdrawal of consent, or the end of the study (approximately 48 months)
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. The measure of interest is the hazard ratio (HR) and the corresponding 95% confidence interval (CI).
PFS at 6 months
Time frame: From randomization until death, withdrawal of consent, or the end of the study (approximately 48 months)
PFS is defined as the time from randomization until the date of confirmed PD (per RECIST 1.1 as assessed by the Investigator) or death due to any cause. The measure of interest is the PFS rate and the corresponding 95% CI at 6 months.
PFS at 12 months
Time frame: From randomization until death, withdrawal of consent, or the end of the study (approximately 48 months)
PFS is defined as the time from randomization until the date of confirmed PD (per RECIST 1.1 as assessed by the Investigator) or death due to any cause. The measure of interest is the PFS rate and the corresponding 95% CI at 12 months.
9 secondary outcomes
Overall survival (OS) at 12 months
Time frame: At 12 months
OS at 24 months
Time frame: At 24 months
OS at 12 months in subset of randomized participants with STK11, KEAP1 or KRAS mutation and/or co mutations
Time frame: At 12 months
OS at 24 months in subset of randomized participants with STK11, KEAP1 or KRAS mutation and/or co mutations
Time frame: At 24 months
OS in randomized participants
Time frame: From randomization until death, withdrawal of consent, or the end of the study (approximately 48 months)
Objective response rate (ORR)
Time frame: From randomization until disease progression, or the last evaluable assessment in the absence of progression (approximately 48 months)
Duration of response (DOR)
Time frame: From first documented response until documented progression (approximately 48 months)
Time to First Subsequent Therapy (TFST)
Time frame: From randomization until the start date of the first subsequent anti-cancer therapy after discontinuation of randomized study intervention or death (approximately 48 months)
Number of participants with adverse events (AEs)
Time frame: From screening until the follow-up period is completed (approximately 48 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
- Derived from this study: PubMed 41209621Skoulidis F, Borghaei H, Garon EB, Leal TA, Kaufman J, Liu SV, Nadler E, Patel SP, Peters S, Ricciuti B, Gautam A, Emeribe U, Luciani-Silverman L, Heymach JV. Rationale and design for a phase IIIb trial of first-line tremelimumab plus durvalumab versus pembrolizumab, in combination with chemotherapy, in patients with non-squamous metastatic non-small-cell lung cancer and mutations or co-mutations in STK11, KEAP1, or KRAS: the TRITON study. Ther Adv Med Oncol. 2025 Nov 6;17:17588359251386611. doi: 10.1177/17588359251386611. eCollection 2025.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
47 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Durvalumab, Tremelimumab and Pemetrexed in people with Carcinoma, Non-Small-Cell Lung, run by AstraZeneca at 47 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) in randomized participants (time frame: From randomization until death, withdrawal of consent, or the end of the study (approximately 48 months)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06008093, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.