The study consists of an open-label, safety run-in to confirm the safety of INCB039110 in
combination with erlotinib in subjects with nonsquamous non-small cell lung cancer (NSCLC)
that is Stage IIIB, Stage IV, or recurrent whose tumors have EGFR activating mutations.
Subjects in the safety run-in will receive open-label INCB039110 and erlotinib.
In the second part of the study, subjects will be enrolled and randomized to receive
erlotinib (open-label) and either INCB039110 or placebo in a blinded manner. The dose of
INCB039110 administered will be determined from the data produced in the safety run-in
Treatment will consist of repeating 21-day cycles. Subjects will take erlotinib tablets
daily and INCB039110/placebo will be self-administered daily during the entire cycle.
- Histologically or cytologically confirmed diagnosis of nonsquamous NSCLC that is
Stage IIIB, Stage IV, or recurrent (including Stage II).
- Documented evidence of an activating mutation in EGFR in tumor samples (exon 19
deletions or point mutation L858R in exon 21 or point mutations at codon 719).
- A mGPS of 1 or 2 as defined below:
- Criteria: C-reactive protein >10 mg/L AND albumin 35 g/L Score-1
- Criteria: C-reactive protein >10 mg L AND albumin <35 g/L Score-2
- Radiographically measurable or evaluable disease.
- Life expectancy of at least 12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Adequate renal, hepatic, and bone marrow function demonstrated by protocol-specified
laboratory parameters at the screening visit.
- Known presence of the T790M mutation in EGFR in tumor samples
- Candidates for curative radiation therapy or surgery.
- Previous systemic chemotherapy for advanced disease, including EGFR inhibitor
therapy, except subjects who received 1 cycle of chemotherapy while waiting to
receive EGFR results, who may enroll provided that 21 days have elapsed from end of
chemotherapy to the day to the baseline radiographic measurement prior to Cycle 1 Day
- Distinct or suspected, or history of, pulmonary fibrosis or ILD.
- Current or previous other malignancy within 2 years of study entry, except cured
basal or squamous cell skin cancer, superficial bladder cancer, prostate
intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive
indolent or Stage I malignancy without sponsor approval.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Part 1: Determination of the dose of INCB039110 that is safe and tolerable in combination with erlotinib as measured by the number of dose-limiting toxicities (DLTs) observed in the evaluation cohort.
Part 2: Overall Survival (OS)
Part 2: Progression-free survival (PFS)