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

N

Nikolaj Frost MD

Status and phase

Enrolling
Phase 4

Conditions

Non-Small Cell Lung Cancer Metastatic

Treatments

Drug: Carboplatin
Drug: Pemetrexed
Drug: Atezolizumab
Drug: Nab paclitaxel
Drug: Pembrolizumab
Drug: Cisplatin

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT05689671
SAP131705
AIO-TRK-0122 (Other Identifier)
2022-002990-27 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

136 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)
  • 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
  • AST/ ALT and alkaline phosphatase ≤ 2.5 x ULN
  • 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) as well as azoospermic male patients do not require contraception

Exclusion criteria

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 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)
  • 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
  • Any chronic skin condition that does not require systemic therapy
  • 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:

  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • 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 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 design

136 participants in 2 patient groups

Pemetrexed-free Immunochemotherapy (Arm A)
Experimental group
Description:
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)
Treatment:
Drug: Nab paclitaxel
Drug: Atezolizumab
Drug: Carboplatin
Pemetrexed-based Immunochemotherapy (Arm B)
Active Comparator group
Description:
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)
Treatment:
Drug: Cisplatin
Drug: Pembrolizumab
Drug: Pemetrexed
Drug: Carboplatin

Trial contacts and locations

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Central trial contact

Nikolaj Frost, PD Dr.; Daniel Müller, Dr.

Data sourced from clinicaltrials.gov

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