Exploratory study evaluating the potential of immune signature profiling for predicting response in patients with resectable Stage II, IIIA and select IIIB (T3N2 only) non-squamous Non-Small Cell Lung Cancer (NSCLC) to neoadjuvant ATEZOLIZUMAB plus Carboplatin/Nab Paclitaxel

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Heidelberg AöR, Universitaetsklinikum Heidelberg AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

22 Feb 2021 → ongoing

Decision date (initial)

2024-09-18

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516590-75-00

EudraCT number

2020-000388-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess response in patients with NSCLC undergoing neoadjuvant ATEZOLIZUMAB investigational treatment in combination with Carboplatin and nab-Paclitaxel before NSCLC curative intent surgery.

Secondary objectives 5

1. To evaluate response by tumor size
2. To evaluate response by PET-activity
3. To evaluate event-free survival
4. To evaluate overall survival
5. Feasibility to proceed to surgery after neoadjuvant immunochemotherapy

Conditions and MedDRA coding

Lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 20

1. Willing and able to sign a written informed consent form (ICF)
2. Informed consent, patients age ≥ 18-year-old including, signed and datedInformed consent, patients age ≥ 18-year-old including, signed and dated
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
4. Histologically confirmed NSCLC of non-squamous histology, cStage II, IIIA or select IIIB (T3N2 only); for T-status ≤ T3 allowed; for N2 patients only IIIa1-3 Robinson classification allowed
5. Deemed surgically resectable with curative intent by an attending thoracic surgeon after adequate staging including PET-CT
6. Adequate lung and cardiac function for intended lung resection according to German S3 regulation
7. Radiologically measurable disease as defined by response evaluation criteria in solid tumors RECIST v1.1
8. Sufficient availability of the tissue sample from primary tumor before start of neoadjuvant treatment
9. Females of child-bearing potential must agree to use, and be able to comply with, effective contraception (</=1% failure rate annually) without interruption, 28 days prior to starting therapy (including dose interruptions), and while on study medication or for a period of 120 days after the last dose of study medication
10. Females must have a negative serum pregnancy test (β -hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy.
11. Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following treatment discontinuation, even if he has undergone a successful vasectomy.
12. adequate renal, hepatic, and bone marrow function as defined below
13. Absolute neutrophil count (ANC) > 1500/μl
14. Platelet count ≥ 100000/μl
15. Hemoglobin ≥ 9 g/dl (can be post-transfusion)
16. International normalized ratio (INR) ≤ 1.4 in patients not receiving anticoagulation; for patients receiving respective anticoagulation an INR ≤3.0 allowed
17. Activated partial thromboplastin time (aPTT) ≤ 1.5 times upper limit of normal (ULN) in patients not receiving anticoagulation; for patients receiving respective anticoagulation a PTT ≤2.5 x ULN allowed
18. Bilirubin < 1.5 times x ULN (for patients with known Gilbert disease Bilirubin ≤ 3 times x ULN allowed)
19. ALT and AST < 2.5 times x ULN
20. Creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 60 ml/min for subjects with creatinine levels > 1.5 x ULN; for patients meeting the criterion of creatinine ≤ 1.5 x ULN also a calculated creatinine clearance of > 30 ml/min is mandatory

Exclusion criteria 24

1. Illness or condition that may interfere with a patient’s capacity to understand, follow, and/or comply with study procedures
2. Treatment in any other clinical trial within 30 days before screening.
3. NSCLC Stage cT4
4. NSCLC stage cN3 or cN2 IIIA4 (bulky or fixed multi-station N2 disease) according to Robinson classification
5. NSCLC of squamous cell histology
6. Any prior therapy for lung cancer (including systemic therapy, radiotherapy or major surgery)
7. Malignancies other than NSCLC within 5 years prior to study inclusion with the exception of malignancies with a negligible risk of metastasis or death (5-year OS > 90%) like localized prostate cancer, ductal carcinoma in situ, adequately treated carcinoma in situ of the cervix, Stage I uterine cancer or non-melanoma skin carcinoma
8. History of allogeneic tissue / solid organ transplant or allogeneic stem cell transplantation
9. Patients with active hepatitis B or C infections or a history of HIV infection
10. Pregnant or lactating women
11. Active autoimmune disease or history of severe autoimmune disease or immunodeficiency or a syndrome that requires systemic steroids or immunosuppressive agents
12. The following exceptions are granted: o patients with vitiligo, eczema, lichen simplex or resolved childhood asthma/atopy o subjects requiring intermittent use of bronchodilatators or local steroid injections o patients with hypothyreoidism stable on hormone replacement
13. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, and anti-tumor necrosis factor (anti- TNF) agents) within 2 weeks prior to Cycle 1, Day 1 (except lowdose steroids for adrenal failure or emesis prophylaxis)
14. History of idiopathic pulmonary fibrosis, interstitial lung disease, organizing pneumonia, drug-induced pneumonitis, or evidence of active pneumonitis on screening chest Computed Tomography (CT) scan
15. Prior treatment with cluster of differentiation 137 (CD137) agonist or immune checkpoint blockade therapies, anti-programmeddeath- 1 (anti-PD-1), and anti-PD-L1 therapeutic antibody
16. Live vaccine within 30 days prior to first dose of trial treatment
17. Cerebrovascular accident within the past 6 months
18. Severe infection or significant traumatic injury within the past 4 weeks
19. Clinically significant history of cardiovascular disease, including any of the following:
20. Myocardial infarction or unstable angina within the past 6 months
21. New York Heart Association class II, III-IV congestive heart failure
22. Poorly controlled cardiac arrhythmia despite medication, except rate-controlled atrial fibrillation
23. Known allergy or hypersensitivity to any component of the chemotherapy regimen
24. Patients who have been incarcerated or involuntarily institutionalized by court order or by the authorities, as well as patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Response to neoadjuvant immunochemotherapy with ATEZOLIZUMAB, Carboplatin and nab- Paclitaxel as determined by Major Pathologic Response (MPR) (≤10% residual viable tumor cells) (pathologic regression grading according to Junker criteria) rate

Secondary endpoints 5

1. Response rate as determined by Δ tumor size and Δ lymph node size according to RECIST 1.1 criteria
2. Response rate as determined by Δ PETactivity (standardized uptake value [SUV])
3. Event-free survival (EFS) ● calculated from start of 1st cycle of neoadjuvant treatment ● follow-up for 24 months after end of treatment visit; end of treatment visit takes place 6 weeks after surgery
4. Overall survival (OS) ● calculated from start of 1st cycle of neoadjuvant treatment ● follow-up for 24 months after end of treatment visit; end of treatment visit takes place 2-6 weeks after surgery
5. Number of patients attaining surgery as planned

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Heidelberg AöR

Sponsor organisation

Universitaetsklinikum Heidelberg AöR

Address

Im Neuenheimer Feld 672, Neuenheim Neuenheim

City

Heidelberg

Postcode

69120

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Heidelberg AöR

Contact name

Prof. Dr. med. Dirk Jäger

Public contact point

Organisation

Universitaetsklinikum Heidelberg AöR

Contact name

Prof. Dr. med. Dirk Jäger

Universitaetsklinikum Heidelberg AöR

Sponsor organisation

Universitaetsklinikum Heidelberg AöR

Address

Im Neuenheimer Feld 672, Neuenheim Neuenheim

City

Heidelberg

Postcode

69120

Country

Germany

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications