A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC)

JRCT ID: jRCT2021220007

Registered date:19/05/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: LOCALLY ADVANCED, UNRESECTABLE, STAGE III NON-SMALL CELL LUNG CANCER
• Date of first enrollment: 01/11/2022
• Target sample size: 320
• Countries of recruitment: Costa Rica,Japan,Poland,Japan,Unites States,Japan,Australia,Japan,China,Japan,Colombia,Japan,Hong Kong,Japan,Korea,Japan,Thailand,Japan,Taiwan,Japan,Singapore,Japan,Canada,Japan,Chile,Japan,United Kingdom,Japan,New Zealand,Japan,Turkey,Japan
• Study type: Interventional

Intervention(s)

Alectinib: Alectinib 600 mg will be administered PO twice a day
Entrectinib: Entrectinib 600 mg will be administered PO once a day
Pralsetinib: Pralsetinib 400 mg will be administered PO once a day
Durvalumab: Durvalumab 1500 mg will be received by IV infusion every 4 weeks

Outcome(s)

Primary Outcome

Efficacy
Progression-Free Survival (PFS)

Secondary Outcome

Safety, Efficacy
- Time-to-confirmed deterioration (TTCD)
- European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ)-C30 Questionnaires
- European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ)-LC13 Scores
- Percentage of participants with adverse events (AEs)
- Time to central nervous system (CNS) progression [ Time Frame: From randomization to the first occurrence of disease progression in the CNS as determined by BICR per RECIST v1.1]
- Distant metastasis-free survival (DMFS) [ Time Frame: From randomization to the first occurrence of distant metastasis or death (whichever occurs first) as determined by BICR per RECIST v1.1
- Objective response rate (ORR), defined as the percentage of participants with measurable disease who attain a complete response (CR) or partial response (PR) as determined by the investigator per RECIST v1.1
- PFS [ Time Frame: From randomization to the first documented disease progression as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurs first
- Duration of response (DOR) [ Time Frame: From the first documented CR or PR to the first documented disease progression or death (whichever occurs first) as determined by the investigator per RECIST v1.1
- ORR, defined as the percentage of participants with measurable disease who attain a CR or PR as determined by BICR per RECIST v1.1
- DOR [ Time Frame: From the first documented CR or PR to the first documented disease progression or death (whichever occurs first) as determined by BICR per RECIST v1.1]
- Overall survival (OS) [ Time Frame: From randomization to death from any cause]
- Time to CNS progression [ Time Frame: From randomization to the first occurrence of disease progression in the CNS as determined by the investigator per RECIST v1.1]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

*Inclusion Criteria (All Cohorts):
- Body weight >/= 30 kg at screening
- Willingness and ability to use the electronic device(s) or application(s) for the electronic patient-reported outcome (PRO)
- Whole-body positron emission tomography/computed tomography scan (PET/CT) (from the base of skull to mid-thighs) for the purposes of staging, 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
- 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
- Confirmed availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen
- Documented tumor PD-L1 status (TC score < 1% vs. >/= 1% vs. unknown) as determined: centrally with the SP263 IHC assay on the confirmed available FFPE tumor specimen; locally, with the SP263 (preferred) or 22C3 IHC assays
- 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, as defined by the protocol
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm, as defined by the protocol

*Inclusion criteria specific to Cohort A1:
- Documented ALK fusion positivity by an eligible result from: centralized multiplex molecular testing of tumor tissue at the Sponsor's designated central laboratory under Study BX43361 or available results from a Sponsor pre-approved local, appropriately validated ALK fusion test on tumor tissue performed in a Clinical Laboratory Improvement Amendments certified or equivalent laboratory

*Inclusion criteria specific to Cohort A2:
- Documented ROS1 fusion positivity by an eligible result from: centralized multiplex molecular testing of tumor tissue at the Sponsor's designated central laboratory under Study BX43361 or available results from a Sponsor pre-approved local, appropriately validated ROS1 fusion test on tumor tissue performed in a Clinical Laboratory Improvement Amendments certified or equivalent laboratory
- Ability to swallow entrectinib intact, without chewing, crushing, or opening the capsules

*Inclusion criteria specific to Cohort A3:
- Documented RET fusion positivity by an eligible result from: centralized multiplex molecular testing of tumor tissue at the Sponsor's designated central laboratory under Study BX43361 or available results from a Sponsor pre-approved local, appropriately validated RET fusion test on tumor tissue performed in a Clinical Laboratory Improvement Amendments certified or equivalent laboratory

Exclude criteria

Only all Cohorts (Excerpt):
- Any history of previous NSCLC and/or any history of prior treatment for NSCLC (patients must be newly diagnosed with unresectable Stage III disease)
- Any evidence of Stage IV disease
- If a pleural effusion is present, the following criteria must be met to exclude malignant involvement (T4 disease): when pleural fluid is visible on both the CT scan and chest X-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative; participants with exudative pleural effusions are excluded regardless of cytology; participants 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 a known or likely oncogenic-driver mutation in the EGFR gene, as identified by site local testing or Sponsor central testing
- Liver disease, characterized by any of the following: impaired excretory function (e.g., hyperbilirubinemia), synthetic function, or other conditions of decompensated liver disease, such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices or active viral or active autoimmune, alcoholic, or other types of acute hepatitis
- Positive hepatitis B surface antigen (HBsAg) test at screening
- Participants known to be positive for hepatitis C virus (HCV) antibody (Ab) are excluded with the following exception: participants who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution are eligible
- HIV infection: participants are excluded if not well-controlled as defined by the protocol
- Known active tuberculosis
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest CT scan
- Grade >/= 2 pneumonitis from prior cCRT or sCRT
- Any Grade > 2 unresolved toxicity from prior cCRT or sCRT
- Any gastrointestinal disorder that may affect absorption of oral medications
- Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Prior allogeneic stem cell or solid organ transplantation
- Any prior Grade >/= 3 immune-mediated adverse event or any unresolved Grade > 1 immune-mediated adverse event while receiving any previous immunotherapy agent other than immune checkpoint blockade agents

Related Information

• Primary Sponsor: Ahmadur Rahman, M.B.B.S.
• Secondary ID(s): NCT05170204