Trial Title:
NeoTRACK - Dissection of IO Efficacy in NSCLC by Longitudinal tracKing
NCT ID:
NCT05825625
Condition:
Non-small Cell Lung Cancer
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Atezolizumab
Conditions: Keywords:
Non-small Cell Lung Cancer
NSCLC
neoadjuvant
surgery
perioperative
immunotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
single-arm phase II trial combining chemotherapy with tiragolumab and atezolizumab as
neoadjuvant and adjuvant treatment for surgical NSCLC
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
Atezolizumab 1,200 mg by IV infusion Q3W.
Arm group label:
Platinum-based chemotherapy in combination with atezolizumab and tiragolumab
Other name:
Tecentriq
Intervention type:
Drug
Intervention name:
Tiragolumab
Description:
Tiragolumab by IV infusion Q3W.
Arm group label:
Platinum-based chemotherapy in combination with atezolizumab and tiragolumab
Other name:
no other name available
Summary:
Prospective, non-randomized, open-label, single-arm phase II trial to investigate the
feasibility and efficacy of combining chemotherapy with tiragolumab and atezolizumab as
neoadjuvant and adjuvant treatment for surgical NSCLC patients.
Detailed description:
The present study is a prospective, investigator-initiated, single-arm, open-label phase
II trial. Patients with non-small cell lung cancer of clinical stage II, IIIA and IIIB
(T3N2 only) will receive 2 cycles platinum-based standard of care chemotherapy in
combination with anti-TIGIT antibody tiragolumab and the anti-PD-L1 antibody atezolizumab
followed by curative intent surgery. After surgery, patients not achieving pCR will
receive additional 2 cycles chemotherapy in combination with tiragolumab and
atezolizumab, followed by tiragolumab/atezolizumab only for up to one year (max 16
cycles) or until intolerable toxicity, disease progression or patients' request, whatever
occurs first. Patients with pCR will receive the IO-IO antibodies only (without
additional chemotherapy). The objective of this study is to investigate the feasibility,
efficacy and safety of combining chemotherapy with tiragolumab and atezolizumab as
neoadjuvant and adjuvant treatment for surgical NSCLC patients. Efficacy outcomes will be
correlated to the accompanying in-depth translational analyses, which aim to understand
the role of the tumor microenvironment in response to IO-IO therapies and to identify
biomarkers that may be associated with response and resistance.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Has provided written informed consent
2. Patient* 18 years or older at time of signing informed consent form
3. Histologically confirmed NSCLC of squamous or non-squamous histology
4. Resectable clinical stage II, IIIA and IIIB (T3N2 only) NSCLC (according to UICC 8)
5. Adequate disease staging by PET and/or CT as per SOC (performed ≤ 42 days prior
initiation of the study treatment)
6. At least 1 measurable lesion according to RECIST v1.1
7. ECOG performance status ≤ 1
8. Adequate lung and cardiac function for curative intend lung resection (R0) according
to German S3 guideline
9. Eligibility to receive a platinum-based neoadjuvant chemotherapy
10. 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.
11. The patient is willing and able to provide liquid and tissue samples for the
accompanying translation project.
12. Adequate bone marrow and renal function including the following:
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count ≥ 1.0 x 109/L
- Platelets ≥ 75 x 109/L
- Calculated creatinine clearance ≥ 30 mL/min as determined by the
Cockcroft-Gault equation
13. Adequate hepatic function (with stenting for any obstruction, if required) including
the following:
- Serum bilirubin ≤ 3 x institutional upper limit of normal (ULN)
- AST (SGOT) / ALT (SGPT) and alkaline phosphatase ≤ 2.5x ULN
14. Female patients who are considered as women of childbearing potential (WOCBP) must
have a negative urine or serum pregnancy test within 7 days prior to start of trial.
15. Female patients who are considered as WOCBP must use any contraceptive method with a
failure rate of less than 1% per year during the treatment as well as up to 5 months
after the last dose of IMP. 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 5 months after the last dose of IMP. Female patients
who are not of childbearing potential (i.e., who are postmenopausal or surgically
sterile, see section 5.1.5) as well as azoospermic male patients do not require
contraception.
Exclusion Criteria:
1. Treatment in any other clinical trial with an investigational product within 30 days
before screening
2. Clinical stage I, IIIB (T4N2), IIIC, nodal NSCLC stage cN3 and stage IV NSCLC
3. Positive testing of activating (TKI-responsive) EGFR-mutation, ROS1-mutation or
known ALK fusion oncogene
4. Expected pneumonectomy at baseline to achieve curative intend resection
5. Any concurrent chemotherapy, investigational product (IMP), biologic, or hormonal
therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer
related conditions (e.g. hormone replacement therapy) is acceptable.
6. Malignancies other than NSCLC within 3 years prior to study inclusion with the
exception of malignancies with a negligible risk of metastases 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, in-situ bladder cancer
treated by BCG-Instillation, or non-melanoma skin carcinoma
7. History of allogeneic tissue / solid organ transplant or allogeneic stem cell
transplantation
8. History of active primary immunodeficiency.
9. Clinical diagnosis of active tuberculosis.
10. Positive testing for hepatitis B virus surface antigen (HBV sAg) or hepatitis C
virus (HCV) RNA indicating acute or chronic infection. Patients with a past or
resolved HBV infection (defined as the presence of hepatitis B core antibody
[anti-HBc] and absence of HBsAg) are eligible. Patients positive for HCV antibody
are eligible only if polymerase chain reaction is negative for HCV RNA.
11. Positive testing for human immunodeficiency virus (HIV) or known acquired
immunodeficiency syndrome (AIDS).
12. Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 5 months after the last dose of atezolizumab/tiragolumab.
13. 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.
14. Active, uncontrolled inflammatory bowel disease [e.g. ulcerative colitis or Crohn's
disease]. Patients in stable remission for more than 1 year may be included.
15. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, uncontrolled cardiac arrhythmia, interstitial lung disease,
gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
situations that would limit compliance with study requirement, substantially
increase risk of incurring AEs or compromise the ability of the patient to give
written informed consent.
16. Current or prior use of immunosuppressive medication within 14 days before the first
dose of atezolizumab/tiragolumab. 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)
17. 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
18. 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.
19. Prior treatment with CD137 agonist or immune checkpoint blockade therapies, such as
anti-TIGIT, anti-PD-1 and anti-PD-L1 therapeutic antibody
20. Live vaccine within 30 days prior to first dose of trial treatment
21. Known allergy or hypersensitivity to any component of the chemotherapy regimen or to
the IMP or any constituents of the products
22. 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.
23. Patient who has been incarcerated or involuntarily institutionalized by court order
or by the authorities.
24. Patients who are unable to consent because they do not understand the nature,
significance and implications of the clinical trial and therefore cannot form a
rational intention in the light of the facts
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Universitätsklinikum Essen (AöR)-Westdeutsches Tumorzentrum Essen
Address:
City:
Essen
Zip:
45147
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Martin Schuler, Prof. Dr.
Facility:
Name:
Thoraxklinik Heidelberg
Address:
City:
Heidelberg
Zip:
69126
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Florian Eichhorn, Dr.
Start date:
May 26, 2023
Completion date:
February 1, 2030
Lead sponsor:
Agency:
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Agency class:
Other
Collaborator:
Agency:
Thoraxklinik-Heidelberg gGmbH
Agency class:
Other
Collaborator:
Agency:
Roche Pharma AG
Agency class:
Industry
Source:
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05825625
