NCT02574598

MK-3475 in Combination With Docetaxel vs Docetaxel Alone in Non-Small Cell Lung Cancer Patients

A Randomized Crossover, Phase II Clinical Trial of MK-3475 in Combination With Docetaxel Versus Docetaxel Alone in Patients With Non-Small Cell Lung Cancer (NSCLC) Previously Treated.

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 78 (actual)
• Sponsor: Instituto Nacional de Cancerologia de Mexico · Academic / Other
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

This is a phase II open-label randomized clinical trial of MK-3475 (Pembrolizumab) on previously treated non-small cell lung cancer (NSCLC) patients . This drug has shown to allow partial response according to the immune-related response criteria and the response evaluation criteria in solid tumors (RECIST). The main endpoint is to compare the overall response rate (ORR) of MK-3475 with docetaxel or docetaxel alone in patients with advanced NSCLC.

Detailed description

MK-3475 (MK-3475) is an IgG4 monoclonal antibody to PD1, which received a 'breakthrough therapy' designation for advanced melanoma from the FDA in January 2013. Preliminary results from the NSCLC cohort of a phase I dose expansion trial of MK-3475 were presented at the 2013 World Conference on Lung Cancer meeting. MK-3475 was administered intravenously every three weeks, and continued until disease progression based upon immune related response criteria (irRC) or unacceptable toxicity. IrRC take into account the potential for different patterns of response that can be seen with immunotherapy. Of the 38 patients with previously treated advanced NSCLC evaluable for efficacy, 9 (24 percent) achieved at least partial response by irRC. Standard oncology criteria for response (Response Evaluation Criteria In Solid Tumors, RECIST were available for 33 of these patients, with at least a partial response in seven patients (21 percent). Median overall survival was 51 weeks. Therapy was well tolerated, with one case of pneumonitis (grade 2) and one case of pulmonary edema (grade 3) reported. Tumor PDL1 expression (assessed with a different assay than that used for the trials evaluating Nivolumab and MPDL3280A; antibody used undisclosed) was available for 33 of the patients who had irRC assessments and 29 of those with standard oncology (RECIST) assessment. Of the 9 patients with PDL1 positivity and irRC response data, 6 achieved at least partial response (67 percent); of the 7 patients with PDL1 positivity and standard oncology response data, 4 achieved response (57 percent). Of note, 1 of 24 patients with PDL1 negativity achieved response by irRC; 2 of 22 patients with PDL1 negativity had response by standard oncology criteria (RECIST). Based upon these results, a randomized phase II trial comparing MK-3475 to standard salvage docetaxel in patients with advanced NSCLC has been launched (NCT01905657), however there is no study in which the synergistic activity of Docetaxel + MK-3475 were evaluated, this could open the possibility of using this drug concurrently with Docetaxel as standard therapy in patients with progression of the disease despite a double platinum-based regimen. Measure the expression levels of PD1/PD-L1/PD-L2 subpopulations tumor cells of patients with NSCLC who come to the clinic of the National Cancer Institute and relevant way, associating their role forecast and its potential as a biomarker, relating the PD-L1 levels with clinicopathologic characteristics of the patients studied.

Conditions

• Carcinoma, Non-Small-Cell Lung

Interventions

Type	Name	Description
DRUG	MK-3475	The dosing interval of pembrolizumab can be increased in case of toxicity.
DRUG	Docetaxel	Use on both arms as standard of care.

Timeline

• Start date: 2016-06-01
• Primary completion: 2019-10-01
• Completion: 2020-11-19
• First posted: 2015-10-14
• Last updated: 2021-01-06
• Results posted: 2020-12-14

Locations

1 site across 1 country: Mexico