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)

Conditions: NSCLC (Non-small Cell Lung Carcinoma); UC (Urothelial Cancer)

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.