Lung Cancer, Advanced or Metastatic Non-Small-Cell Lung Cancer, Resectable Non-Small-Cell Lung Cancer
Conditions
Brief summary
The goal of this platform clinical trial is to test how well novel treatment combinations work in participants with lung cancer. Substudy-01 will compare the different novel combinations versus standard of care in participants with metastatic (cancer that has spread) non-small-cell lung cancer (NSCLC) who have not been treated before. Substudy-02 will compare the different novel combination versus standard of care in participants with cancer that has progressed after receiving previous treatment for metastatic NSCLC. Substudy-03 will compare the different novel combinations versus standard of care in participants with resectable stage II-III NSCLC. The primary objectives of this study are: Substudy-01 and Substudy-02: To evaluate the objective response rate (ORR) assessed per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Substudy-03: To evaluate the efficacy of treatment combinations based on complete pathological response (pCR) rate.
Interventions
DRUGZimberelimab (ZIM)
Administered intravenously
Administered intravenously
Administered intravenously
DRUGEtrumadenant (ETRUMA)
Administered orally
DRUGCarboplatin
Administered intravenously
DRUGCisplatin
Administered intravenously
DRUGPemetrexed
Administered intravenously
DRUGPaclitaxel
Administered intravenously
DRUGNab-paclitaxel
Administered intravenously
DRUGDocetaxel
Administered intravenously
DRUGNivolumab
Administered intravenously
Sponsors
Gilead Sciences
Arcus Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: All Substudies: * Histologically or cytologically documented non-small-cell lung cancer (NSCLC). * No known actionable genomic alterations for which targeted therapies are available. * Eastern cooperative oncology group (ECOG) performance status score of 0 or 1. * Measurable disease per response evaluation criteria in solid tumors. * Adequate hematologic and end-organ function. * Individuals of childbearing potential who engage in heterosexual intercourse must agree to use specified method(s) of contraception. Substudy 01: All Experimental arms * Stage IV NSCLC. * For individuals with nonsquamous histology: Epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alteration negative. * PD-L1 status by central confirmation. * No prior systemic treatment for metastatic NSCLC. Substudy 02: All Experimental arms * Stage IV NSCLC. * In individuals with nonsquamous histology and actionable EGFR, ALK, or other known genomic alterations must have received treatment with at least 1 targeted therapy to the appropriate genomic alteration. Substudy 03: All Experimental arms * Previously untreated individuals with resectable (Stage II, IIIA, IIIB (T\[3-4\]N2) NSCLC (per American Joint Committee on Cancer (AJCC) Edition 8). * Planned surgery must comprise of lobectomy, sleeve lobectomy, or bi-lobectomy. * PD-L1 status by central confirmation. * For individuals with nonsquamous histology: Epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alteration negative. Key
Exclusion criteria
All Substudies: * Mixed small-cell lung cancer and NSCLC histology. * Active second malignancy. * Active autoimmune disease. * History of or current non-infectious pneumonitis/interstitial lung disease. * Active serious infection within 4 weeks prior to study treatment. Substudy 01 and 02 * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. * Received previous anticancer therapy within 4 weeks prior to enrollment. Substudy 03: All Experimental arms * NSCLC previously treated with systemic therapy or radiotherapy. * Received prior treatment with any anti-PD-(L)-1 or other immune checkpoint inhibitors (CPIs). Note: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Substudies 01 and 02: Objective Response Rate (ORR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Up to 5 years | ORR is defined as the proportion of participants achieving a complete response (CR) or partial response (PR) as confirmed at least 4 weeks after the first detection of response. |
| Substudy 03: Complete Pathological Response (pCR) Rate | Up to 5 years | pCR is defined as the percentage of participants having an absence of residual invasive cancer in resected lung specimens and lymph nodes as assessed by local pathology review. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Substudies: Percentage of Participants Experiencing Clinical Laboratory Abnormalities | First dose date up to 24 months plus 100 days | — |
| Substudies 01 and 02: Progression-free Survival (PFS) According to RECIST Version 1.1 | Up to 5 years | PFS is defined as the time from the date of randomization until disease progression (PD) or death, whichever comes first. |
| Substudies 01 and 02: Duration of response (DOR) According to RECIST Version 1.1 | Up to 5 years | DOR is defined as the time from the first response (CR or PR) until the first documented PD, or death, whichever comes first. |
| All Substudies: Overall survival (OS) | Up to 5 years | OS is defined as the time from the date of randomization until death from any cause. |
| Substudy 03: Major Pathological Response (MPR) Rate | Up to 5 years | MPR rate is defined as the percentage of participants with ≤ 10% residual tumor in lung and lymph nodes at surgery as evaluated by local pathology review. |
| Substudy 03: Event-Free Survival (EFS) | Up to 5 years | Event-Free Survival (EFS) is defined as the time from randomization until any of the following events: any progression precluding surgery or preventing completion of surgery, progression or recurrence of disease after surgery (local or distant), as assessed by investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), or death due to any cause, whichever occurs first. Participants who do not undergo surgery for reasons other than progression will be considered to have had an event at progression or at death. |
| All Substudies: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) and Related TEAEs | First dose date up to 24 months plus 100 days | — |
Countries
Brazil, Hong Kong, Israel, South Korea, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTGilead Clinical Study Information Center
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed