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MO18 - NSCLC - Targeted Therapies IV (ID 116)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
MO18.02 - Preliminary clinical safety and activity of MK-3475 monotherapy for the treatment of previously treated patients with non-small cell lung cancer (NSCLC) (ID 2416)
16:15 - 17:45 | Author(s): E.B. Garon
Currently approved cytotoxic chemotherapies for previously treated patients with NSCLC demonstrate few objective responses, which are generally of short duration, with limited impact on progression-free survival and overall survival. Programmed death-1 (PD-1) is an inhibitory T-cell co-receptor whose activation by interaction with its ligands, PD-L1 or PD-L2, can lead to suppression of antitumor immunity. Preclinical and clinical data indicate that this pathway is important in NSCLC.MK-3475 is a humanized monoclonal IgG4 antibody against PD-1.
MK-3475 was administered at 10 mg/kg every three weeks to patients with NSCLC previously treated with two systemic regimens. At least one measurable tumor lesion, ECOG performance status of zero or one, and adequate laboratory function were required for eligibility. A new tumor biopsy no earlier than 60 days before the first dose of MK-3475 was required for study entry. Imaging assessments per investigators were performed every nine weeks until confirmed disease progression utilizing the immune-related response criteria (irRC). Independent central review of images was assessed with RECIST v1.1. PD-L1 expression on the pretreatment tumor sample was determined by immunohistochemistry. A cut-point associated with the Youden Index of the receiver-operating characteristic curve for PD-L1 staining was identified.
Between April 2012 and September 2012, thirty-eight patients were enrolled. Median age was 63 years (range, 34-85 years), with 42% men and 42% with an ECOG performance status of zero. Previously treated, stable brain metastases were allowed and were present in 10%. Seven patients had an EGFR mutation, eight patients had a KRAS mutation, and one patient had an ALK gene rearrangement in their tumor. Fifty percent of patients experienced drug-related adverse events; the most common were fatigue, rash, and pruritus (16% each). The incidence of diarrhea was 13% (only grade 1 or 2 reported). One case of a drug-related grade 3-4 adverse event (grade 3 pulmonary edema: 3%) was seen. There were no drug-related fatalities. Using investigator-assessed irRC, the objective response rate (ORR; confirmed and unconfirmed) was 24%, including squamous and nonsquamous subtypes. Similar results were obtained using RECIST v1.1, yielding an ORR (confirmed and unconfirmed) of 21%. Most responses by irRC were observed by the time of first planned assessment at Week 9. The median duration of response by irRC has not been reached, with a median duration of follow-up of 9 months (minimum, 6 months). As of June 2013, seven of the nine responding patients by irRC continue on therapy. Pretreatment tumor PD-L1 expression was a statistically significant predictor of response. In patients with evaluable tumor PD-L1 expression, all confirmed responses by RECIST v1.1 (and irRC) occurred in patients with tumors strongly positive for PD-L1.
MK-3475 is generally well tolerated in previously treated patients with advanced NSCLC and provides durable objective responses. An additional cohort of patients whose tumors express PD-L1 is enrolling; preliminary safety and efficacy data, including PFS and OS, will be reported further at the World Conference on Lung Cancer 2013.
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