Comparative Study of Atezolizumab, Carboplatin, and Nab-Paclitaxel Versus Pembrolizumab, Platinum, and Pemetrexed in Metastatic TTF-1 Negative Lung Adenocarcinoma
- Trial ID
- 2023-505054-17-00
- Protocol
- ANTELOPE
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare **survival** outcomes in patients with metastatic TTF-1 negative lung adenocarcinoma receiving a combination of atezolizumab, carboplatin, and nab-paclitaxel versus those receiving pembrolizumab, platinum, and pemetrexed. This comparison is clinically relevant as it aims to determine the most effective treatment regimen for improving survival in this patient population, which is critical for guiding therapeutic decisions in clinical practice.
Participants
The clinical trial involves participants diagnosed with **metastatic TTF-1 negative lung adenocarcinoma**. The study population includes both male and female subjects, aged 18 years and older, with a focus on individuals who have histologically or cytologically confirmed metastatic stage IV non-squamous non-small cell lung cancer (NSCLC). Participants are required to have a negative local testing for TTF-1, as well as negative molecular testing for EGFR mutations and ALK rearrangements. The trial includes individuals with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial population was selected based on specific inclusion criteria, including adequate hepatic, renal, and bone marrow function, and a life expectancy of at least 12 weeks. Both male and female participants of childbearing potential are required to use effective contraception during the study and for a specified period after the last dose of the investigational medicinal product. The sponsor has not provided information regarding the total number of participants in the trial. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, ensuring that ethical considerations are in place for their participation.
Plans and Procedures
The clinical trial is designed to evaluate the **overall survival** of patients with **metastatic TTF-1 negative lung adenocarcinoma** receiving different treatment regimens. This is a randomized, double-blind, controlled trial comparing the efficacy of **atezolizumab**, **carboplatin**, and **nab-paclitaxel** versus **pembrolizumab**, **platinum**, and **pemetrexed**. The trial is categorized as a low-intervention Phase IV study, with all investigational medicinal products being market-approved and used in accordance with their marketing authorization. The trial is expected to run from July 2023 to January 2026, with a maximum treatment period of 12 months for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as adequate hepatic, renal, and bone marrow function, and negative molecular testing for EGFR mutations and ALK rearrangements. Following the screening, participants will be randomized to receive one of the treatment regimens. Regular follow-up visits will be scheduled to monitor the participants' health status, treatment adherence, and any adverse events. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination.
The expected length of participant involvement is up to 12 months, with conditions for early termination including the discovery of EGFR mutations or ALK rearrangements, or if the participant is unable to comply with the study protocol. Participants will receive their treatments via **intravenous infusion**, with dosages tailored to the specific regimen. The trial aims to ensure that all procedures align with local clinical practices, minimizing additional risks or burdens to participants beyond standard care.
Treatment
The clinical trial involves the administration of several **antineoplastic** agents, each with specific dosing regimens and administration routes. **Pemetrexed** is provided as a solution for infusion, with a maximum daily and total dose of 500 mg/m². It is administered via **intravenous infusion** over a treatment period of up to 12 weeks. The dosing schedule is designed to ensure optimal therapeutic levels while monitoring for potential adverse effects.
**Cisplatin** is also administered as a solution for infusion, with a maximum daily and total dose of 75 mg/m². This agent is delivered through **intravenous infusion** and is part of the treatment regimen for up to 12 weeks. The administration schedule is carefully monitored to maintain efficacy and minimize toxicity.
**Atezolizumab** is provided as a solution for infusion, with a maximum daily and total dose of 1200 mg. It is administered via **intravenous infusion** over a 12-week period. The dosing regimen is structured to achieve sustained therapeutic levels, with regular monitoring to ensure patient safety and compliance.
**Paclitaxel albumin-bound** is administered as a powder for suspension for solution, with a maximum daily and total dose of 100 mg/m². This formulation is delivered through **intravenous infusion** and is included in the treatment protocol for up to 12 weeks. The dosing schedule is designed to optimize therapeutic outcomes while monitoring for potential side effects.
**Carboplatin** is provided as a solution for infusion, with a maximum daily and total dose of 6 units (as per the specific dosing unit used in the study). It is administered via **intravenous infusion** over a 12-week treatment period. The administration is carefully monitored to ensure efficacy and minimize adverse reactions.
**Pembrolizumab** is administered as a solution for infusion, with a maximum daily and total dose of 200 mg. This agent is delivered through **intravenous infusion** and is part of the treatment regimen for up to 12 weeks. The dosing schedule is structured to maintain therapeutic levels, with regular monitoring to ensure patient safety and adherence to the protocol.
Efficacy
Efficacy in the clinical trial titled "ANTELOPE – Atezolizumab/Carboplatin/nab-Paclitaxel vs. Pembrolizumab/Platinum/Pemetrexed in metastatic TTF-1 negative lung adenocarcinoma" will be primarily assessed by measuring **Overall Survival (OS)**. This endpoint is chosen to compare the survival rates of patients receiving the combination of atezolizumab, carboplatin, and nab-paclitaxel against those receiving pembrolizumab, platinum, and pemetrexed. The trial is designed to evaluate the efficacy of these treatment regimens in patients with metastatic stage IV non-squamous non-small cell lung cancer (NSCLC) that is TTF-1 negative.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patient has provided written informed consent
- Patient* 18 years or older at time of signing the informed consent form
- Histologically or cytologically confirmed metastatic stage IV non-squamous NSCLC
- Negative local testing for TTF-1
- Negative molecular testing for EGFR mutations and ALK rearrangements (tested locally). Exception: In specific individual cases, treatment can be initiated prior to receiving molecular diagnostics after consulting with the sponsor, if the local principal investigator assesses the likelihood of an EGFR mutation or ALK fusion to be negligible. However, this should only be done in exceptional cases if the patient has particularly high demand for treatment. If it is subsequently found that patients are positive for EGFR mutations and/or ALK rearrangements, they must be withdrawn from the study immediately and must not receive any further study medication. Instead, patients should receive adequate SOC therapy outside the study. Awaiting results for molecular testing remains standard procedure for patient inclusion.
- PD-L1 tumor proportion score (TPS) < 50%**
- ECOG performance status ≤ 1
- Measurable lesions according to RECIST v1.1
- Life expectancy ≥ 12 weeks
- Adequate hepatic, renal and bone marrow function a) Hemoglobin ≥ 8.0 g/dL b) Absolute neutrophil count ≥ 1.5 x 109/L c) Platelets ≥ 100 x 109/L d) Calculated creatine clearance ≥ 50 mL/min as determined by the Cockgraft-Gault equation and/or creatine ≤ 1,5x upper limit of normal (ULN) e) Serum bilirubin ≤ 1.5 x institutional ULN f) AST/ ALT and alkaline phosphatase ≤ 2.5 x ULN g) International normalized ratio (INR)/ Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PTT is within therapeutic range of intended use of anticoagulants
- The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
- Female patients who are considered as woman of childbearing potential (WOCBP) must use any contraceptive method with a failure rate of less than 1% per year during the treatment as well as up to 6 months after the last dose of study treatment. Male patients who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year during the treatment as well as at least 6 months after the last dose of IMP. Female patients who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile, see section 5.1.5) as well as azoospermic male patients do not require contraception
Exclusion Criteria
- Mixed histology (small-cell and non-small cell or non-squamous and squamous; patients exhibiting the latter expression pattern may be eligible if the non-squamous part predominates)
- Patients having received: a. Systemic treatment for metastatic or locally advanced disease b. prior PD-1/PD-L1 immunotherapies (prior treatment with CD137 agonists or immune checkpoint blockade therapies, including, but not limited to, anti-cytotoxic T lymphocyte associated protein 4 [anti-CTLA-4], anti T cell immunoreceptor with Ig and tyrosine-based inhibition motif domains [anti-TIGIT], anti-PD-1 and anti-PD-L1 therapeutic antibodies)
- Symptomatic, neurologically unstable CNS metastases or requiring increasing doses of steroids to manage CNS symptoms within 2 weeks prior to study entry (maximal acceptable dose must be ≤ 10 mg of prednisolone)
- Leptomeningeal disease
- History of interstitial lung disease
- Severe infection within 2 weeks prior to study entry. Clinical signs must have been resolved to CTCAE grade ≤ 1
- Active infection with hepatitis B or C virus (HBV, HCV), human immunodeficiency virus (HIV) or Mycobacterium tuberculosis
- Known additional malignancies other than NSCLC, either untreated or having required active treatment within the past 3 years, with the exception of malignancies with a negligible risk of metastasis or death (e.g. 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. Other similar cases can be considered after discussion with the lead investigators
- Significant cardiovascular disease (≥ NYHA 3)
- Active or prior documented autoimmune or inflammatory disorders (including but not limited to diverticulitis [with the exception of diverticulosis], celiac disease, systemic lupus erythematosus, Sarcoidosis, or Wegener’s syndrome [granulomatosis with polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis). The following are exceptions to this criterion: a. Patients with vitiligo or alopecia b. Patients with hypothyroidism (e.g., following Hashimoto’s disease) stable on hormone replacement c. Patients with controlled Type I diabetes mellitus on an insulin regimen d. Any chronic skin condition that does not require systemic therapy e. Patients without active disease in the last 5 years may be included but only after consultation with the study physician
- Current or prior use of immunosuppressive medication within 14 days before the first dose of atezolizumab/pembrolizumab. The following are exceptions to this criterion: a. Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra articular injection) b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent c. Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
- Live vaccine within 30 days prior to first dose of trial treatment
- Known allergy or contraindication against to or hypersensitivity to any component of the chemotherapy regimen or to atezolizumab or pembrolizumab or any constituents of the products
- Any co-existing medical condition that in the investigator’s judgement will substantially increase the risk associated with the patient’s participation in the study.
- Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 01 Jul 2023 | 136 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
PEMETREXED | Test | — | INTRAVENIOUS INFUSION | 500 | 12 | SUB09655MIG |
CISPLATIN | Test | — | INTRAVENIOUS INFUSION | 75 | 12 | SUB07483MIG |
PEMBROLIZUMAB | Test | — | INTRAVENIOUS INFUSION | 200 | 12 | SUB167136 |
PACLITAXEL ALBUMIN-BOUND | Test | — | INTRAVENIOUS INFUSION | 100 | 12 | SUB127678 |
ATEZOLIZUMAB | Test | — | INTRAVENIOUS INFUSION | 1200 | 12 | SUB178312 |
CARBOPLATIN | Test | — | INTRAVENIOUS INFUSION | 6 | 12 | SUB06614MIG |