NSCLC (Non-small Cell Lung Carcinoma), UC (Urothelial Cancer)
Conditions
Brief summary
This study evaluated the safety and tolerability of epacadostat (INCB024360) administered in combination with atezolizumab (MPDL3280A) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that were previously treated with platinum-based chemotherapy and Stage IV urothelial carcinoma who failed a platinum-based chemotherapy regimen. The study was conducted in two phases. The dose escalation phase did utilize a 3 + 3 design to identify the maximum tolerated dose (MTD) or a Pharmacologically Active Dose (PAD) of the combination. This was followed by a dose expansion phase, which was comprised of three cohorts. Expansion Cohorts 1 & 2 will further evaluate the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics at the dose identified in phase one. Expansion Cohort 3 will evaluate the change in biomarker expression following treatment with epacadostat as monotherapy followed by epacadostat and atezolizumab administered in combination.
Interventions
DRUGEpacadostat
Epacadostat tablets
DRUGAtezolizumab
Atezolizumab intravenously
Sponsors
Incyte Corporation
Hoffmann-La Roche
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects, age 18 years or older * Histologically or cytologically confirmed NSCLC * Stage IIIB or Stage IV NSCLC who are not candidates for multimodality treatment and have received at least 1 line of standard platinum-based therapy: * Prior systemic regimens must include at least 2 cycles of a platinum-based therapy and may include platinum therapy used as a radiosensitizer. Maintenance chemotherapy is allowed. * Tumors with driver mutations (epidermal growth factor receptor mutation positive or anaplastic lymphoma kinase fusion oncogene positive) should have had disease progression or been intolerant to the standard tyrosine-kinase inhibitor (TKI), and should include a second line TKI where such therapy is available and indicated. * Subjects initially treated with a platinum regimen for Stage IIIB disease who later develop metastatic disease and are re-treated with a platinum regimen are allowed. * Histologically or cytologically confirmed urothelial carcinoma. * Stage IV locally advanced or metastatic urothelial carcinoma with disease progression during or following platinum-containing chemotherapy or had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. * Presence of measurable disease per RECIST v1.1 * Availability of an adequate archival tumor specimen or willingness to undergo a pretreatment tumor biopsy. * Subjects enrolled in Expansion Cohort 3 must be willing to have 2 on-treatment tumor biopsies. * For males and females of child-bearing potential, willingness to use adequate birth control through 90 days after the last dose of epacadostat or atezolizumab.
Exclusion criteria
* Laboratory and medical history parameters not within protocol-defined range. * Current treatment with an investigational study drug or immunological-based agent for any reason, or receipt of anticancer medication within 21 days or 5 half-lives (whichever is longer) before first dose. * Prior treatment with immune checkpoint inhibitors (eg, anti-CTLA-4, anti-PD-1, anti-PD-L1, and any other antibody or drug specifically targeting T-cell co-stimulation) or an IDO inhibitor. * Prior monoclonal antibody within 4 weeks before study Day 1, or has not recovered from adverse events due to agents administered more than 4 weeks earlier. * Has an active or inactive autoimmune process. * Has a history of pneumonitis or idiopathic pulmonary fibrosis, or evidence of interstitial lung disease. * Prior radiotherapy within 2 weeks of therapy; Must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. * Untreated central nervous system (CNS) metastases or CNS metastases that have progressed after completion of radiotherapy. * Use of systemic corticosteroids ≤ 2 weeks before Cycle 1 Day 1. * Currently pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events (AEs) | Continuously for duration of study participation and up to 42 days after the last dose [approximately 8 months |
| Incidence of dose-limiting toxicities (DLTs) | 21 days following the first administration of atezolizumab and epacadostat |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Measured every 6 weeks for duration of study participation [approximately 8 months] | ORR determined by radiographic disease assessments per modified RECIST v1.1 |
| Durability of response | Measured every 6 weeks for duration of study participation [approximately 8 months] | Time from the earliest date of disease response until earliest date of disease progression based on modified RECIST v1.1 |
| Progression-free survival | Measured every 6 weeks for duration of study participation [approximately 8 months] | Time from date of enrollment until the earliest date of disease progression per modified RECIST v1.1 or death due to any cause, whichever is earlier. |
| Duration of disease control | Measured every 6 weeks for duration of study participation [approximately 8 months] | Time from first dose until report of disease progression for subjects who reported stable disease or better based on modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
Countries
United States
Contacts
STUDY_DIRECTORHiroomi Tada, MD
Incyte Corporation
Outcome results
None listed