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

NCT ID: NCT05689671

Last Updated: 2025-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

136 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-06

Study Completion Date

2026-10-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non-Small Cell Lung Cancer Metastatic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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)

Group Type EXPERIMENTAL

Atezolizumab

Intervention Type DRUG

1200 mg i.v. q3w

Nab paclitaxel

Intervention Type DRUG

100 mg/m² i.v. qw

Carboplatin

Intervention Type DRUG

AUC 5-6 i.v. q3w

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)

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type DRUG

200 mg i.v. q3w

Cisplatin

Intervention Type DRUG

75 mg/m² i.v. q3w

Carboplatin

Intervention Type DRUG

AUC 5-6 i.v. q3w

Pemetrexed

Intervention Type DRUG

500 mg/m² i.v. q3w

Interventions

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Atezolizumab

1200 mg i.v. q3w

Intervention Type DRUG

Nab paclitaxel

100 mg/m² i.v. qw

Intervention Type DRUG

Carboplatin

AUC 5-6 i.v. q3w

Intervention Type DRUG

Pembrolizumab

200 mg i.v. q3w

Intervention Type DRUG

Cisplatin

75 mg/m² i.v. q3w

Intervention Type DRUG

Carboplatin

AUC 5-6 i.v. q3w

Intervention Type DRUG

Pemetrexed

500 mg/m² i.v. q3w

Intervention Type DRUG

Other Intervention Names

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Tecentriq Abraxane Keytruda

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Roche Pharma AG

INDUSTRY

Sponsor Role collaborator

Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

OTHER

Sponsor Role collaborator

Nikolaj Frost MD

OTHER

Sponsor Role lead

Responsible Party

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Nikolaj Frost MD

Nikolaj Frost, PD Dr. med., Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Nikolaj Frost, PD Dr.

Role: PRINCIPAL_INVESTIGATOR

Charite University, Berlin, Germany

Locations

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Klinikum St. Marien

Amberg, , Germany

Site Status RECRUITING

Universitätsklinikum Augsburg

Augsburg, , Germany

Site Status RECRUITING

MVZ Taunus GmbH

Bad Homburg, , Germany

Site Status RECRUITING

Evangelische Lungenklinik Krankenhausbetriebs gGmbH

Berlin, , Germany

Site Status RECRUITING

Evangelische Lungenklinik

Berlin, , Germany

Site Status RECRUITING

Charité Universitätsmedizin

Berlin, , Germany

Site Status RECRUITING

Helios Klinikum Emil von Behring

Berlin, , Germany

Site Status RECRUITING

Klinikum Bielefeld

Bielefeld, , Germany

Site Status RECRUITING

Kliniken der Stadt Köln GmbH

Cologne, , Germany

Site Status RECRUITING

Technische Universität Dresden Medizinische Fakultät Carl Gustav Carus

Dresden, , Germany

Site Status RECRUITING

Universitätsklinikum Essen

Essen, , Germany

Site Status RECRUITING

KEM Evang. Kliniken Essen-Mitte

Essen, , Germany

Site Status RECRUITING

Klinikum Esslingen GmbH

Esslingen am Neckar, , Germany

Site Status RECRUITING

Krankenhaus Nordwest

Frankfurt, , Germany

Site Status RECRUITING

Universitätsklinikum Frankfurt am Main

Frankfurt am Main, , Germany

Site Status RECRUITING

Asklepios Klinik Gauting GmbH

Gauting, , Germany

Site Status RECRUITING

Universitätsmedizin Göttingen

Göttingen, , Germany

Site Status RECRUITING

LungenClinic Großhansdorf GmbH

Großhansdorf, , Germany

Site Status RECRUITING

Asklepios Klinkum Hamburg

Hamburg, , Germany

Site Status RECRUITING

Thoraxklinik Heidelberg gGmbH

Heidelberg, , Germany

Site Status RECRUITING

Lungenklinik Hemer

Hemer, , Germany

Site Status RECRUITING

Thoraxzentrum Ruhrgebiet Ev. Krankenhaus Herne

Herne, , Germany

Site Status RECRUITING

Helios Klinikum Krefeld

Krefeld, , Germany

Site Status RECRUITING

ÜBAG- Medizinisches Versorgungszentrum Dr. Vehling-Kaiser GmbH

Landshut, , Germany

Site Status RECRUITING

Klinikum Lippe GmbH

Lemgo, , Germany

Site Status RECRUITING

Klinikum Ludwigsburg

Ludwigsburg, , Germany

Site Status RECRUITING

UKSH, Campus Lübeck

Lübeck, , Germany

Site Status RECRUITING

Medizinische Fakultät Mannheim der Universität Heidelberg

Mannheim, , Germany

Site Status RECRUITING

LMU Klinikum

München, , Germany

Site Status RECRUITING

Unversitätsklinikum Münster

Münster, , Germany

Site Status RECRUITING

Überörtliche Gemeinschaftspraxis für Hämatologie und Onkologie

Münster, , Germany

Site Status RECRUITING

Pius Hospital

Oldenburg, , Germany

Site Status RECRUITING

MVZ für Hämatologie und Onkologie Ravensburg GmbH

Ravensburg, , Germany

Site Status RECRUITING

Barmherzige Brüder Krankenhaus Regensburg

Regensburg, , Germany

Site Status RECRUITING

Elblandkliniken Stiftung & Co. KG Elblandklinikum Riesa

Riesa, , Germany

Site Status RECRUITING

Klinikum Stuttgart

Stuttgart, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Nikolaj Frost, PD Dr.

Role: CONTACT

+49 30 450 565 005

Daniel Müller, Dr.

Role: CONTACT

+49 69 7601 125

Facility Contacts

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Ludwig Fischer von Weikersthal, Dr. med.

Role: primary

Björn Hackanson, Dr.

Role: primary

Migle Link, Dr. med.

Role: primary

Christian Grohé, Prof. Dr.

Role: primary

Christian Grohé, Prof. Dr.

Role: primary

Nikolaj Frost, Dr.

Role: primary

Jens Kollmeier, Dr.

Role: primary

Martin Görner, Dr.

Role: primary

Carolin Groß-Ophoff-Müller, Dr. med.

Role: primary

Felix Saalfeld, Dr.

Role: primary

Marcel Wiesweg, Dr.

Role: primary

Sebastian Ertl, Dr.

Role: primary

Martin Faehling, PD Dr.

Role: primary

Akin Atmaca, PD DR.

Role: primary

Martin Sebastian, Dr. med.

Role: primary

Niels Reinmuth, Prof. Dr.

Role: primary

Tobias Overbeck, Dr.

Role: primary

Martin Reck, Prof. Dr.

Role: primary

Claas Wesseler, Dr.

Role: primary

Farastuk Bozorgmehr, Dr.

Role: primary

Karsten Schulmann, PD Dr. med.

Role: primary

Daniel Christoph, PD Dr. med.

Role: primary

Benoit Krämer

Role: primary

Florian Kaiser, Dr.

Role: primary

Christian Constantin, Dr.

Role: primary

Matthias Ulmer, Dr.

Role: primary

Sabine Bohnert, Dr.

Role: primary

Melanie Janning, Dr.

Role: primary

Amanda Tufman, Prof. Dr.

Role: primary

Annalen Bleckmann, Prof. Dr.

Role: primary

Rüdiger Liersch, PD Dr.

Role: primary

Frank Griesinger, Prof. Dr.

Role: primary

Tobias Dechow, Prof. Dr.

Role: primary

Veronika Berberich, Dr.

Role: primary

Jörg Schubert, Prof. Dr.

Role: primary

Markus Knott

Role: primary

References

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Frost N, Zhamurashvili T, von Laffert M, Klauschen F, Ruwwe-Glosenkamp C, Raspe M, Brunn M, Ochsenreither S, Temmesfeld-Wollbruck B, Suttorp N, Grohe C, Witzenrath M. Pemetrexed-Based Chemotherapy Is Inferior to Pemetrexed-Free Regimens in Thyroid Transcription Factor 1 (TTF-1)-Negative, EGFR/ALK-Negative Lung Adenocarcinoma: A Propensity Score Matched Pairs Analysis. Clin Lung Cancer. 2020 Nov;21(6):e607-e621. doi: 10.1016/j.cllc.2020.05.014. Epub 2020 May 22.

Reference Type BACKGROUND
PMID: 32620471 (View on PubMed)

Related Links

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https://www.aio-portal.de/studie/176--antelope.html

Study description on the webpage of the "Oncology in Internal Medicine Working Group" (AIO) within the German Cancer Society

Other Identifiers

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2022-002990-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AIO-TRK-0122

Identifier Type: OTHER

Identifier Source: secondary_id

SAP131705

Identifier Type: -

Identifier Source: org_study_id

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