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

NCT05689671 | Active Not Recruiting Phase 4

• 3 other identifiers: SAP1317052022-002990-27AIO-TRK-0122
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 36

Brief Summary

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.

Conditions

Non-Small Cell Lung Cancer Metastatic

Keywords

NSCLC; checkpoint inhibitors; immunochemotherapy

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  time from randomization to the date of death due to any case

  30 months

Secondary Outcomes (7)

• Objectice Response Rate (ORR)

  30 months

• Progression-Free Survival (PFS)

  30 months

• One-Year Overall Survival Rate

  30 months

• Time to Next Treatment or Death (TNTD)

  30 months

• Progression-Free Survival 2 (PFS2)

  30 months

Study Arms (2)

Pemetrexed-free Immunochemotherapy (Arm A)

EXPERIMENTAL

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; Drug: Nab paclitaxel; Drug: Carboplatin

Pemetrexed-based Immunochemotherapy (Arm B)

ACTIVE COMPARATOR

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: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed

Interventions

Atezolizumab DRUG

1200 mg i.v. q3w

Also known as: Tecentriq

Pemetrexed-free Immunochemotherapy (Arm A)

Nab paclitaxel DRUG

100 mg/m² i.v. qw

Also known as: Abraxane

Pemetrexed-free Immunochemotherapy (Arm A)

Carboplatin DRUG

AUC 5-6 i.v. q3w

Pemetrexed-free Immunochemotherapy (Arm A)

Pembrolizumab DRUG

200 mg i.v. q3w

Also known as: Keytruda

Pemetrexed-based Immunochemotherapy (Arm B)

Cisplatin DRUG

75 mg/m² i.v. q3w

Pemetrexed-based Immunochemotherapy (Arm B)

Pemetrexed DRUG

500 mg/m² i.v. q3w

Pemetrexed-based Immunochemotherapy (Arm B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• PD-L1 tumor proportion score (TPS) \< 50%, tested locally by QUiP®-certified immunohistochemistry
• ECOG performance status ≤ 1
• Measurable lesions according to RECIST v1.1
• Life expectancy ≥ 12 weeks
• Adequate hepatic, renal and bone marrow function
• Hemoglobin ≥ 8.0 g/dL
• Absolute neutrophil count ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Calculated creatine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation and/or creatinin ≤ 1,5x upper limit of normal (ULN)
• Serum bilirubin ≤ 1.5 x institutional ULN

You may not qualify if:

• 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)
• Patients having received:
• Systemic treatment for metastatic or locally advanced disease
• 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). 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.
• 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
• 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:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto's disease) stable on hormone replacement
• Patients with controlled Type I diabetes mellitus on an insulin regimen

Sponsors & Collaborators

• Nikolaj Frost MD: lead
• Roche Pharma AG: collaborator
• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: collaborator

Study Sites (36)

Klinikum St. Marien

Amberg, 92224, Germany

Location

Universitätsklinikum Augsburg

Augsburg, 86156, Germany

Location

MVZ Taunus GmbH

Bad Homburg, 61352, Germany

Location

Evangelische Lungenklinik Krankenhausbetriebs gGmbH

Berlin, 13125, Germany

Location

Evangelische Lungenklinik

Berlin, 13125, Germany

Location

Charité Universitätsmedizin

Berlin, 13353, Germany

Location

Helios Klinikum Emil von Behring

Berlin, 14165, Germany

Location

Klinikum Bielefeld

Bielefeld, 33604, Germany

Location

Kliniken der Stadt Köln GmbH

Cologne, 51109, Germany

Location

Technische Universität Dresden Medizinische Fakultät Carl Gustav Carus

Dresden, 01307, Germany

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

KEM Evang. Kliniken Essen-Mitte

Essen, 45136, Germany

Location

Klinikum Esslingen GmbH

Esslingen am Neckar, 73730, Germany

Location

Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

Universitätsklinikum Frankfurt am Main

Frankfurt am Main, 60590, Germany

Location

Asklepios Klinik Gauting GmbH

Gauting, 82131, Germany

Location

Universitätsmedizin Göttingen

Göttingen, 37075, Germany

Location

LungenClinic Großhansdorf GmbH

Großhansdorf, 22927, Germany

Location

Asklepios Klinkum Hamburg

Hamburg, 21075, Germany

Location

Thoraxklinik Heidelberg gGmbH

Heidelberg, 69126, Germany

Location

Lungenklinik Hemer

Hemer, 58675, Germany

Location

Thoraxzentrum Ruhrgebiet Ev. Krankenhaus Herne

Herne, 44651, Germany

Location

Helios Klinikum Krefeld

Krefeld, 47805, Germany

Location

ÜBAG- Medizinisches Versorgungszentrum Dr. Vehling-Kaiser GmbH

Landshut, 84036, Germany

Location

Klinikum Lippe GmbH

Lemgo, 32657, Germany

Location

Klinikum Ludwigsburg

Ludwigsburg, 71640, Germany

Location

UKSH, Campus Lübeck

Lübeck, 23538, Germany

Location

Medizinische Fakultät Mannheim der Universität Heidelberg

Mannheim, 68167, Germany

Location

LMU Klinikum

München, 80336, Germany

Location

Unversitätsklinikum Münster

Münster, 48149, Germany

Location

Überörtliche Gemeinschaftspraxis für Hämatologie und Onkologie

Münster, 48153, Germany

Location

Pius Hospital

Oldenburg, 26121, Germany

Location

MVZ für Hämatologie und Onkologie Ravensburg GmbH

Ravensburg, 88212, Germany

Location

Barmherzige Brüder Krankenhaus Regensburg

Regensburg, 93049, Germany

Location

Elblandkliniken Stiftung & Co. KG Elblandklinikum Riesa

Riesa, 01589, Germany

Location

Klinikum Stuttgart

Stuttgart, 70174, Germany

Location

Related Publications (1)

• 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.

  PMID: 32620471 BACKGROUND

Related Links

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

MeSH Terms

Interventions

atezolizumab; Taxes; Albumin-Bound Paclitaxel; Carboplatin; pembrolizumab; Cisplatin; Pemetrexed

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Coordination Complexes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Nikolaj Frost, PD Dr.

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Nikolaj Frost, PD Dr. med., Principal Investigator

Study Record Dates

• First Submitted: November 30, 2022
• First Posted: January 19, 2023
• Study Start: December 6, 2023
• Primary Completion: March 5, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (36)