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Clinical Trials in the USA / NCT06008093
Active, not recruiting Phase 2

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

NCT06008093 · tracked via the Priya Life Science USA tracker
Sponsor
AstraZeneca
Phase
Phase 2
Started
2024-04-04
Last updated
2026-07-02

Condition(s) studied

Carcinoma, Non-Small-Cell Lung

Investigational drug(s) / intervention(s)

DurvalumabTremelimumabPemetrexedPembrolizumabCarboplatinCisplatin

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.

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).

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.

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.

Carboplatin: Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.

Cisplatin: Participants will receive IV Carboplatin or IV Cisplatin on Day 1 of each 21-day cycle for 4 cycles as induction treatment.

Study 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

Sex
ALL
Min age
18 Years
Max age
130 Years
Healthy volunteers
No
Inclusion Criteria: * 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 Exclusion Criteria: * 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. * 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.

Primary outcome measure(s)

Trial sites (47)

FacilityCityRegionStatus
Research Site Beverly Hills California
Research Site La Jolla California
Research Site Los Alamitos California
Research Site Los Angeles California
Research Site Santa Monica California
Research Site Washington D.C. District of Columbia
Research Site Fort Lauderdale Florida
Research Site Jupiter Florida
Research Site Ocala Florida
Research Site Orlando Florida
Research Site St. Petersburg Florida
Research Site Atlanta Georgia
Research Site Atlanta Georgia
Research Site Honolulu Hawaii
Research Site Carterville Illinois
Research Site Urbana Illinois
Research Site Bethesda Maryland
Research Site Jamaica Plain Massachusetts
Research Site Saint Paul Minnesota
Research Site Kansas City Missouri
Research Site St Louis Missouri
Research Site Billings Montana
Research Site Grand Island Nebraska
Research Site Lincoln Nebraska
Research Site Albany New York
Research Site East Syracuse New York
Research Site New York New York
Research Site Shirley New York
Research Site Stony Brook New York
Research Site Syracuse New York
Research Site The Bronx New York
Research Site Cleveland Ohio
Research Site Cleveland Ohio
Research Site Cleveland Ohio
Research Site Columbus Ohio
Research Site Dayton Ohio
Research Site Norman Oklahoma
Research Site Pittsburgh Pennsylvania
Research Site Sioux Falls South Dakota
Research Site Memphis Tennessee

+ 7 more sites — see the full list on the official registry below.

On this site

📄 Imfinzi (durvalumab) drug profile → 📄 Keytruda (pembrolizumab) drug profile →

More AstraZeneca trials in the USA

Other trials for the same condition

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06008093 on ClinicalTrials.gov ↗ ← All trials in the USA