Positive results from an ongoing phase II study of BIND-014 in non-small cell lung cancer showed that it has met the primary objective in the once-every-three-weeks arm, as measured by overall response rate. The data demonstrate that BIND-014 is well-tolerated with clinically meaningful anti-tumor activity at a lower dose than conventional docetaxel in patients with advanced or metastatic NSCLC.
BIND-014, sponsored by BIND Therapeutics Inc., also demonstrates promising anti-tumor activity in patients with tumors expressing KRAS mutations. An additional signal was observed in patients with squamous cell carcinomas. The data were presented at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain.
“We believe the activity and tolerability of BIND-014 demonstrated in this study suggest meaningful differentiation from the historical docetaxel experience, in both the broader NSCLC patient population and in two important groups of patients with high unmet medical need,” said Hagop Youssoufian, chief medical officer of BIND Therapeutics. “Based on these positive results, we plan to conduct additional global, multicenter phase II studies to confirm and expand the dataset on BIND-014 and to define an expeditious regulatory path for BIND-014.”
The Q3W dosing arm of the open label, multicenter, phase II study enrolled 40 patients with advanced metastatic NSCLC who were treated with 60 mg/m2 of BIND-014 on day 1 of a 21-day cycle.
Preliminary median overall survival was 6.2 months for all patients treated, 9.6 months in patients with KRAS mutant tumors and 11.1 months in patients with squamous cell carcinoma.
Five patients achieved a partial response with a median duration of response of 5.2 months and median progression free survival of 2.7 months. There was one unconfirmed partial response that was not included in the analysis per RECIST v1.1.
Nine patients were enrolled with a confirmed KRAS mutation and two of those nine experienced an objective response; median PFS in patients with KRAS mutant tumors was 2.7 months.
In nine patients with squamous cell carcinoma there were no confirmed objective responses; however, median PFS in patients with squamous cell carcinoma was 2.8 months. Prolonged (>4 cycles) disease control was also noted in six of nine patients with squamous histology.
The sponsor plans to initiate global, multicenter phase II studies of BIND-014 in patients with KRAS mutant NSCLC and in patients with NSCLC of squamous histology who have progressed on prior therapy. These studies aim to assess overall survival and additional endpoints to position BIND-014 for subsequent registration studies.
Based on the promising results of the Q3W arm presented today and the more patient-friendly once every three week dosing schedule, combined with the absence of a confirmed partial response in the first 22 patients enrolled on the Q1W schedule, the company will not continue enrollment on the weekly dosing schedule.
Opdivo Study Shows 41 Percent One-Year Survival In Patients With at Least Two Past Therapies
Results from CheckMate-063, a phase II single-arm, open-label study of Opdivo administered as a single agent in patients with advanced squamous cell non-small cell lung cancer who have progressed after at least two prior systemic treatments with 65 percent receiving three or more prior therapies, showed that 41 percent of Opdivo-treated patients were alive at one year.
The estimated one-year survival rate was 41 percent (95% CI = 31.6, 49.7) and median overall survival was 8.2 months (95% CI = 6.05, 10.91).
With approximately 11 months of minimum follow up, the study’s primary endpoint of objective response rate was 15 percent (95% CI = 8.7, 22.2) as assessed by an independent review committee using RECIST 1.1 criteria and the median duration of response was not reached.
The data were presented at the 2014 Chicago Multidisciplinary Symposium on Thoracic Oncology.
“The phase II findings from CheckMate-063 are encouraging as there are no effective treatment options for patients with refractory squamous cell lung cancer after their disease has progressed through two prior therapies,” said Suresh Ramalingam, professor and director of medical oncology at the Winship Cancer Institute of Emory University.
Checkmate-063, sponsored by Bristol-Myers Squibb, is a single arm, open-label study designed to assess advanced squamous cell NSCLC patients who progressed after both platinum-based therapy and at least one additional systemic therapy with an ECOG Performance Status of 0 or 1 who were treated with Opdivo (nivolumab) as a single agent 3mg/kg by intravenous infusion every two weeks until disease progression or treatment discontinuation (n=117).
Secondary endpoints included investigator-assessed ORR. Overall survival, PFS and efficacy by PD-L1 expression status were exploratory endpoints. Seventy-six percent of patients were within three months of completion of their most recent therapy. The best response to the most recent prior systemic therapy was progressive disease in 61 percent of patients.
An additional 26 percent of patients had stable disease with a median duration of six months (95% CI, 4.73, 10.91) giving a disease control rate (defined as partial response + stable disease) of 41 percent. For patients with quantifiable PD-L1 expression, responses were observed independent of PD-L1 status.
