A PHASE I-III, MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF MULTIPLE THERAPIES IN COHORTS OF PATIENTS SELECTED ACCORDING TO BIOMARKER STATUS, WITH LOCALLY ADVANCED, UNRESECTABLE, STAGE III NON-SMALL CELL LUNG CANCER
- Conditions
- NSCLC non small cell lung cancer10038666
- Registration Number
- NL-OMON53740
- Lead Sponsor
- Roche Nederland B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 3
Age >=18 years Body weight >=30 kg Whole-body positron emission
tomography/computed tomography scan (PET/CT) performed prior and within 42 days
of the first dose of cCRT or sCRT Histologically or cytologically documented
locally advanced, unresectable Stage III NSCLC of either squamous or
non-squamous histology (Version 8, American Joint Committee on Cancer/Union for
International Cancer Control NSCLC staging system (Amin et al. 2017). Prior
receipt of at least two prior cycles of platinum-based chemotherapy given
concurrently with radiotherapy (cCRT); or at least two prior cycles of
platinum-based chemotherapy given prior to radiotherapy (sCRT) The RT component
in the cCRT or sCRT must have been at a total dose of radiation of 60 (± 10%)
Gy (54 Gy to 66 Gy) administered by intensity-modulated radiotherapy
(preferred) or three dimension (3D)-conforming technique No disease progression
during or following platinum-based cCRT or sCRT Life expectancy >= 12 weeks
Documented tumor PD-L1 status Eastern Cooperative Oncology Group Performance
Status of 0, 1, or 2 • Adequate hematologic and end-organ function • For women
of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraception, and agreement to refrain from
donating eggs, during the treatment period and for at least 90 days after the
final dose of alectinib or durvalumab (Cohort A1 only) Confirmed availability
of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen
Documented ALK fusion positivity (Cohort A1 only)
Any history of previous NSCLC and/or any history of prior treatment for NSCLC
Any evidence of Stage IV disease If pleural effusion is present the following
criteria must be met to exclude malignant involvement (T4 disease): When
pleural fluid is visible on both the computed tomography scan and chest X-ray,
a pleuracentesis is required to confirm that the pleural fluid is cytologically
negative. Patients with exudative pleural effusions are excluded regardless of
cytology. Patients with effusions that are minimal (i.e., not visible on chest
X-ray) that are too small to safely tap are eligible NSCLC known to have one or
more of the following ALK point mutations, as identified by site local testing
or Sponsor central testing: I1171X (where X is any other amino acid), V1180L,
G1202R (Cohort A1). NSCLC known to have a known or likely oncogenic-driver
mutation in the EGFR gene, as identified by site local testing or Sponsor
central testing Liver disease Positive hepatitis B surface antigen test at
screening Patients known to be positive for hepatitis C virus antibody HIV
infection, patients are excluded if HIV is not adequately controlled (specific
criteria apply). Known active tuberculosis Presence of clinically symptomatic
interstitial lung disease or interstitial pneumonitis, including radiation
pneumonitis Grade >= 2 pneumonitis from prior cCRT or sCRT Symptomatic
bradycardia (Cohort A1) Any gastrointestinal (GI) disorder that may affect
absorption of oral medications Any other disease, metabolic dysfunction,
physical examination finding, or clinical laboratory finding that
contraindicates the use of an investigational drug, may affect the
interpretation of the results, or may render the patient at high risk from
treatment complications Active or history of autoimmune disease or immune
deficiency History of idiopathic pulmonary fibrosis, organizing pneumonia,
drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active
pneumonitis on the screening chest CT scan History of malignancy other than
NSCLC within 5 years prior to screening Any concurrent chemotherapy,
immunotherapy, biologic, or hormonal therapy for cancer Major surgical
procedure, within 4 weeks prior to initiation of study treatment, or
anticipation of need for a major surgical procedure during the study Severe
infection within 4 weeks prior to initiation of study treatment, including, but
not limited to, hospitalization for complications of infection, bacteremia, or
severe pneumonia Treatment with systemic immunostimulatory agents Treatment
with live, attenuated vaccine Treatment with investigational therapy within 28
days prior to initiation of study treatment Treatment with therapeutic oral or
IV antibiotics within 2 weeks prior to initiation of study treatment Treatment
with systemic immunosuppressive medication Prior treatment with ALK inhibitors.
Prior treatment with CD137 agonists or immune checkpoint blockade therapies
Prior allogeneic stem cell or solid organ transplantation History of
hypersensitivity to alectinib, durvalumab, or any of their excipients.
Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study or the follow-up period of an
interventional study Any condition that, in the opinion of the investigator,
would
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>For all cohorts, the primary efficacy endpoint is blinded independent central<br /><br>review (BICR)-assessed progression-free survival (PFS), as defined as the time<br /><br>from the randomization (or from first IMP intake) to the first documented<br /><br>disease progression according to RECIST v1.1 or death from any cause, whichever<br /><br>occurs first.<br /><br>The difference between the treatment arms will be assessed and tested for the<br /><br>following hypothesis: the survival distribution function of the treatment arm<br /><br>is the same as for the durvalumab treatment arm versus the alternative that the<br /><br>two distributions are different.<br /><br><br /><br>See protocol page 95, cohort A1 page 196, 200-201</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints:<br /><br>- Time to CNS progression (blinded independent central review and Investigator,<br /><br>per RECIST)<br /><br>- distant metastasis-free survival (blinded independent central review)<br /><br>- Progression Free Survival (Investigator per RECIST)<br /><br>- objective response rate, duration of response (blinded independent central<br /><br>review and Investigator, per RECIST)<br /><br>- Overall Survival (descriptive)<br /><br>- Safety<br /><br>- Time to confirmed deterioration of the disease<br /><br><br /><br>See protocol cohort A1 page 196, 200-201</p><br>