Pemetrexed-free vs. Pemetrexed-based Immunochemotherapy in Metastatic TTF-1 Negative Lung Adenocarcinoma (ANTELOPE)

March 6, 2026 updated by: Nikolaj Frost MD

Atezolizumab/Carboplatin/Nab-Paclitaxel vs. Pembrolizumab/Platinum/Pemetrexed in Metastatic TTF-1 Negative Lung Adenocarcinoma

This is an open-label randomized, controlled, multicenter, phase II trial with two arms. Patients with metastatic TTF-1 negative, treatment-naive lung adenocarcinoma without actionable genomic alterations are randomized in a 1:1 manner to investigate the efficiency of atezolizumab, carboplatin and nab-paclitaxel (Arm A) versus pembrolizumab, cis-/carboplatin and pemetrexed (Arm B) as first-line treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Thyroid transcription factor 1 (TTF-1) is expressed in the majority of lung adenocarcinoma and has a clear prognostic value. Pemetrexed-based immunochemotherapy is a standard of care for advanced lung adenocarcinoma. However, real-world data suggest that TTF-1 negative patients might derive superior outcome using pemetrexed-free regimens. The aim of this study is to compare a pemetrexed-free (Arm A) vs. a pemetrexed-based immunochemotherapy (Arm B) as first-line treatment for metastatic TTF-1 negative lung adenocarcinoma without actionable genomic alterations.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
136

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Germany
      • Amberg, Germany, 92224
        • Klinikum St. Marien
      • Augsburg, Germany, 86156
        • Universitatsklinikum Augsburg
      • Bad Homburg, Germany, 61352
        • MVZ Taunus GmbH
      • Berlin, Germany, 14165
        • Helios Klinikum Emil von Behring
      • Berlin, Germany, 13353
        • Charité Universitätsmedizin
      • Berlin, Germany, 13125
        • Evangelische Lungenklinik
      • Berlin, Germany, 13125
        • Evangelische Lungenklinik Krankenhausbetriebs gGmbH
      • Bielefeld, Germany, 33604
        • Klinikum Bielefeld
      • Cologne, Germany, 51109
        • Kliniken der Stadt Köln GmbH
      • Dresden, Germany, 01307
        • Technische Universität Dresden Medizinische Fakultät Carl Gustav Carus
      • Essen, Germany, 45122
        • Universitätsklinikum Essen
      • Essen, Germany, 45136
        • KEM Evang. Kliniken Essen-Mitte
      • Esslingen am Neckar, Germany, 73730
        • Klinikum Esslingen GmbH
      • Frankfurt, Germany, 60488
        • Krankenhaus Nordwest
      • Frankfurt am Main, Germany, 60590
        • Universitätsklinikum Frankfurt am Main
      • Gauting, Germany, 82131
        • Asklepios Klinik Gauting GmbH
      • Großhansdorf, Germany, 22927
        • LungenClinic Großhansdorf GmbH
      • Göttingen, Germany, 37075
        • Universitätsmedizin Göttingen
      • Hamburg, Germany, 21075
        • Asklepios Klinkum Hamburg
      • Heidelberg, Germany, 69126
        • Thoraxklinik Heidelberg gGmbH
      • Hemer, Germany, 58675
        • Lungenklinik Hemer
      • Herne, Germany, 44651
        • Thoraxzentrum Ruhrgebiet Ev. Krankenhaus Herne
      • Krefeld, Germany, 47805
        • Helios Klinikum Krefeld
      • Landshut, Germany, 84036
        • ÜBAG- Medizinisches Versorgungszentrum Dr. Vehling-Kaiser GmbH
      • Lemgo, Germany, 32657
        • Klinikum Lippe GmbH
      • Ludwigsburg, Germany, 71640
        • Klinikum Ludwigsburg
      • Lübeck, Germany, 23538
        • UKSH, Campus Lübeck
      • Mannheim, Germany, 68167
        • Medizinische Fakultät Mannheim der Universität Heidelberg
      • München, Germany, 80336
        • LMU Klinikum
      • Münster, Germany, 48149
        • Unversitätsklinikum Münster
      • Münster, Germany, 48153
        • Überörtliche Gemeinschaftspraxis für Hämatologie und Onkologie
      • Oldenburg, Germany, 26121
        • Pius Hospital
      • Ravensburg, Germany, 88212
        • MVZ für Hämatologie und Onkologie Ravensburg GmBH
      • Regensburg, Germany, 93049
        • Barmherzige Brüder Krankenhaus Regensburg
      • Riesa, Germany, 01589
        • Elblandkliniken Stiftung & Co. KG Elblandklinikum Riesa
      • Stuttgart, Germany, 70174
        • Klinikum Stuttgart

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patient has provided written informed consent
  2. Patient* 18 years or older at time of signing the informed consent form
  3. Histologically or cytologically confirmed metastatic stage IV non-squamous NSCLC
  4. Negative local testing for TTF-1

  5. 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.

  6. PD-L1 tumor proportion score (TPS) < 50%, tested locally by QUiP®-certified immunohistochemistry
  7. ECOG performance status ≤ 1
  8. Measurable lesions according to RECIST v1.1
  9. Life expectancy ≥ 12 weeks

  10. Adequate hepatic, renal and bone marrow function

    1. Hemoglobin ≥ 8.0 g/dL
    2. Absolute neutrophil count ≥ 1.5 x 109/L
    3. Platelets ≥ 100 x 109/L
    4. Calculated creatine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation and/or creatinin ≤ 1,5x upper limit of normal (ULN)
    5. Serum bilirubin ≤ 1.5 x institutional ULN
    6. AST/ ALT and alkaline phosphatase ≤ 2.5 x ULN
    7. 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
  11. 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.
  12. 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) as well as azoospermic male patients do not require contraception

Exclusion Criteria:

  1. Mixed histologies (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)

  2. Patients having received:

    1. Systemic treatment for metastatic or locally advanced disease
    2. 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)
  3. 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). Patients with asymptomatic, incidentally detected CNS metastases may be enrolled. Palliative radiotherapy for asymptomatic brain metastases (and any other, non-brain metastases, e.g. bone metastases) may be conducted after study entry.
  4. Leptomeningeal disease
  5. History of interstitial lung disease
  6. Severe infection within 2 weeks prior to study entry. Clinical signs must have been resolved to CTCAE grade ≤ 1
  7. Active infection with hepatitis B or C virus (HBV, HCV), human immunodeficiency virus (HIV) or Mycobacterium tuberculosis
  8. Known additional malignancies other than NSCLC, either untreated or having required active treatment within the past 3 years
  9. Significant cardiovascular disease (≥ NYHA 3)

  10. 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:

    1. Patients with vitiligo or alopecia
    2. Patients with hypothyroidism (e.g., following Hashimoto's disease) stable on hormone replacement
    3. Patients with controlled Type I diabetes mellitus on an insulin regimen
    4. Any chronic skin condition that does not require systemic therapy
    5. Patients without active disease in the last 5 years may be included but only after consultation with the study physician

  11. Current or prior use of immunosuppressive medication within 14 days before the first dose of atezolizumab/pembrolizumab. The following are exceptions to this criterion:

    1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra articular injection)
    2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
    3. Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
  12. 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
  13. Live vaccine within 30 days prior to first dose of trial treatment
  14. Known allergy or hypersensitivity to any component of the chemotherapy regimen or to atezolizumab or pembrolizumab or any constituents of the products
  15. 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.
  16. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Pemetrexed-free Immunochemotherapy (Arm A)
Atezolizumab 1200 mg q3w, carboplatin AUC 5-6 q3w, nab-paclitaxel 100 mg/m2 qw (administered for 4 cycles with subsequent maintenance with atezolizumab monotherapy 1200 mg q3w until loss of clinical benefit or occurrence of unacceptable toxicity)
Drug: Atezolizumab
1200 mg i.v. q3w
Other Names:
  • Tecentriq
Drug: Nab paclitaxel
100 mg/m² i.v. qw
Other Names:
  • Abraxane
Drug: Carboplatin
AUC 5-6 i.v. q3w
Active Comparator: Pemetrexed-based Immunochemotherapy (Arm B)
Pembrolizumab 200 mg q3w, cisplatin 75 mg/m2 q3w OR carboplatin AUC 5-6 (each) q3w, pemetrexed 500 mg/m2 q3w (administered for 4 cycles with subsequent maintenance with pembrolizumab 200 mg AND pemetrexed 500 mg/m2 (each) q3w until loss of clinical benefit or occurrence of unacceptable toxicity)
Drug: Carboplatin
AUC 5-6 i.v. q3w
Drug: Pembrolizumab
200 mg i.v. q3w
Other Names:
  • Keytruda
Drug: Cisplatin
75 mg/m² i.v. q3w
Drug: Pemetrexed
500 mg/m² i.v. q3w

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 30 months
time from randomization to the date of death due to any case
30 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Objectice Response Rate (ORR)
Time Frame: 30 months
proportion of subjects with best response of complete or partial response (CR & PR) according to RECIST v1.1
30 months
Progression-Free Survival (PFS)
Time Frame: 30 months
time from randomization until progression defined by RECIST v1.1 or death due to any cause
30 months
One-Year Overall Survival Rate
Time Frame: 30 months
percentage of patients alive at 12 months after randomization
30 months
Time to Next Treatment or Death (TNTD)
Time Frame: 30 months
time from initial study randomization to the start of next subsequent treatment or death, whichever occurs first
30 months
Progression-Free Survival 2 (PFS2)
Time Frame: 30 months
time from initial study randomization to second disease progression or death from any cause to assess efficacy post-trial-treatment anti-cancer therapy
30 months
Health-related quality of life 1 (HRQoL)
Time Frame: Assessed after randomization at cycle 1 day 1, after completion of cycle 4 (each cycle is 21 days) of the chemoimmunotherapy and at progressive disease (if occurring within the maximum time frame of 30 months)
assessed with the QoL questionnaire QLQ-C30 on general health conditions in lung cancer patients using numeric scales ranging from 1-4. Lower numbers indicate no, higher numbers high agreement.
Assessed after randomization at cycle 1 day 1, after completion of cycle 4 (each cycle is 21 days) of the chemoimmunotherapy and at progressive disease (if occurring within the maximum time frame of 30 months)
Health-related quality of life 2 (HRQoL)
Time Frame: Assessed after randomization at cycle 1 day 1, after completion of cycle 4 (each cycle is 21 days) of the chemoimmunotherapy and at progressive disease (if occurring within the maximum time frame of 30 months)
assessed with the lung cancer symptom-specific QoL questionnaire QLQ-LC13 using numeric scales ranging from 1-4. Lower numbers indicate no, higher numbers high agreement.
Assessed after randomization at cycle 1 day 1, after completion of cycle 4 (each cycle is 21 days) of the chemoimmunotherapy and at progressive disease (if occurring within the maximum time frame of 30 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nikolaj Frost MD

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Roche Pharma AG
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Nikolaj Frost, PD Dr., Charite University, Berlin, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 6, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 5, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 30, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 18, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 19, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 10, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 6, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SAP131705
  • 2022-002990-27 (EudraCT Number)
  • AIO-TRK-0122 (Other Identifier: Arbeitsgemeinschaft Internistische Onkologie)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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