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

Non-Small Cell Lung Cancer Metastatic Clinical Trial

— ANTELOPE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05689671
• Other study ID #: SAP131705
• Secondary ID: 2022-002990-27AI
• Status: Recruiting
• Phase: Phase 4
• Start date: December 6, 2023
• Est. completion date: October 2026

Study information

• Verified date: April 2024
• Source: Charite University, Berlin, Germany
• Contact: Nikolaj Frost, PD Dr.
• Phone: +49 30 450 565 005
• Email: nikolaj.frost[@]charite.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 136
• Est. completion date: October 2026
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

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 central nervous system (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)

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Non-Small Cell Lung Cancer Metastatic

Intervention

Drug:
• Atezolizumab
1200 mg i.v. q3w
• Nab paclitaxel
100 mg/m² i.v. qw
• Carboplatin
AUC 5-6 i.v. q3w
• Pembrolizumab
200 mg i.v. q3w
• Cisplatin
75 mg/m² i.v. q3w
• Carboplatin
AUC 5-6 i.v. q3w
• Pemetrexed
500 mg/m² i.v. q3w

Locations

Country	Name	City	State
Germany	Klinikum St. Marien	Amberg
Germany	MVZ Taunus GmbH	Bad Homburg
Germany	Charité Universitätsmedizin	Berlin
Germany	Evangelische Lungenklinik	Berlin
Germany	Evangelische Lungenklinik Krankenhausbetriebs gGmbH	Berlin
Germany	Helios Klinikum Emil von Behring	Berlin
Germany	Klinikum Bielefeld	Bielefeld
Germany	Technische Universität Dresden Medizinische Fakultät Carl Gustav Carus	Dresden
Germany	KEM Evang. Kliniken Essen-Mitte	Essen
Germany	Klinikum Esslingen GmbH	Esslingen
Germany	Krankenhaus Nordwest	Frankfurt
Germany	Universitätsklinikum Frankfurt am Main	Frankfurt am Main
Germany	Asklepios Klinik Gauting GmbH	Gauting
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	LungenClinic Großhansdorf GmbH	Großhansdorf
Germany	Asklepios Klinkum Hamburg	Hamburg
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg
Germany	Lungenklinik Hemer	Hemer
Germany	Kliniken der Stadt Köln GmbH	Köln
Germany	Helios Klinikum Krefeld	Krefeld
Germany	ÜBAG- Medizinisches Versorgungszentrum Dr. Vehling-Kaiser GmbH	Landshut
Germany	Klinikum Lippe GmbH	Lemgo
Germany	UKSH, Campus Lübeck	Lübeck
Germany	Klinikum Ludwigsburg	Ludwigsburg
Germany	Medizinische Fakultät Mannheim der Universität Heidelberg	Mannheim
Germany	LMU Klinikum	München
Germany	Überörtliche Gemeinschaftspraxis für Hämatologie und Onkologie	Münster
Germany	Unversitätsklinikum Münster	Münster
Germany	Pius Hospital	Oldenburg
Germany	Barmherzige Brüder Krankenhaus Regensburg	Regensburg
Germany	Elblandkliniken Stiftung & Co. KG Elblandklinikum Riesa	Riesa

Sponsors (3)

Lead Sponsor	Collaborator
Nikolaj Frost MD	Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest, Roche Pharma AG

Country where clinical trial is conducted

Germany, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	time from randomization to the date of death due to any case	30 months
Secondary	Objectice Response Rate (ORR)	proportion of subjects with best response of complete or partial response (CR & PR) according to RECIST v1.1	30 months
Secondary	Progression-Free Survival (PFS)	time from randomization until progression defined by RECIST v1.1 or death due to any cause	30 months
Secondary	One-Year Overall Survival Rate	percentage of patients alive at 12 months after randomization	30 months
Secondary	Time to Next Treatment or Death (TNTD)	time from initial study randomization to the start of next subsequent treatment or death, whichever occurs first	30 months
Secondary	Progression-Free Survival 2 (PFS2)	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
Secondary	Health-related quality of life 1 (HRQoL)	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)
Secondary	Health-related quality of life 2 (HRQoL)	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)

External Links

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