Clinical trial NCT02298153: A Study of Atezolizumab (MPDL3280A) in Combination With Epacadostat (INCB024360) in Subjects With Previously Treated Stage IIIB or Stage IV Non-Small Cell Lung Cancer and Previously Treated Stage IV Urothelial Carcinoma (ECHO-110)
Official title: A Phase 1 Study of Atezolizumab in Combination With Epacadostat in Subjects With Previously Treated Stage IIIB or Stage IV Non-Small Cell Lung Cancer and Previously Treated Stage IV Urothelial Carcinoma (ECHO-110)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: NSCLC (Non-small Cell Lung Carcinoma)
UC (Urothelial Cancer)
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
name: Genentech, Inc.
First posted: 2014-11-21
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate 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 have been previously treated with platinum-based chemotherapy and Stage IV urothelial carcinoma who have failed a platinum-based chemotherapy regimen. The study will be conducted in two phases. The dose escalation phase will utilize a 3 + 3 design to identify the maximum tolerated dose (MTD) or a Pharmacologically Active Dose (PAD) of the combination. This will be followed by a dose expansion phase, which will be 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: Continuously for duration of study participation and up to 42 days after the last dose [approximately 8 months
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: 21 days following the first administration of atezolizumab and epacadostat
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Measured every 6 weeks for duration of study participation [approximately 8 months]
measure: Durability of response
timeFrame: Measured every 6 weeks for duration of study participation [approximately 8 months]
measure: Progression-free survival
timeFrame: Measured every 6 weeks for duration of study participation [approximately 8 months]
measure: Duration of disease control
timeFrame: Measured every 6 weeks for duration of study participation [approximately 8 months]
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Pinnacle Oncology Hematology
state: Arizona
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Boston
country: United States
facility: Harvard-Mass General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Incyte Corporation
name: Hiroomi Tada, MD
role: STUDY_DIRECTOR
References: