Trial Results

Syros Announces New Preclinical Ovarian Cancer Study

April 23, 2018

Syros Pharmaceuticals announced new preclinical data showing that SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor currently in a Phase I trial in patients with advanced solid tumors, demonstrated potent anti-tumor activity in multiple models of heavily pretreated ovarian cancer. The ongoing Phase I trial of SY-1365 is a multi-center, open-label trial enrolling patients with advanced solid tumors. The primary objective of the trial is to assess the safety and tolerability of escalating doses of SY-1365, with the goal of establishing a maximum tolerated dose and a recommended Phase II dose and regimen. The dose-escalation phase is open and expected to enroll approximately 35 solid tumor patients for whom standard curative or palliative measures do not exist or are no longer effective. SY-136 showed induced cell death in numerous ovarian cancer cell lines and inhibited tumor growth in 10 of the 17 treatment-relapsed ovarian PDX models studied, including inducing complete regressions. Syros expects to open the expansion phase of the trial in mid-2018.

Bristol-Myers Squibb Announces Initial Results from the Phase III Study
Bristol-Myers Squibb announced initial results from the pivotal Phase III study, CheckMate -227, evaluating the Opdivo (nivolumab) 3 mg/kg plus low-dose Yervoy (ipilimumab, 1 mg/kg) combination in first-line advanced non-small cell lung cancer (NSCLC) patients with high tumor mutational burden. CheckMate -227 is an open-label Phase III trial evaluating Opdivo-based regimens versus platinum-doublet chemotherapy. In the study, the combination demonstrated a superior benefit for the co-primary endpoint of progression-free survival (PFS) versus chemotherapy (HR 0.58; 97.5 percent CI: 0.41 to 0.81; p=0.0002). The PFS benefit was observed regardless of PD-L1 expression levels and in both squamous and non-squamous tumor histology. Of all randomized TMB-evaluable patients, 444 (44 percent) had TMB ≥10 mut/Mb, including 139 patients randomized to Opdivo plus Yervoy and 160 patients randomized to chemotherapy. In the trial, TMB was assessed using the validated assay, FoundationOne CDx. Additionally, overall survival was observed with the combination versus chemotherapy in patients with high TMB. There are two co-primary endpoints in Part 1 for the Opdivo plus Yervoy combination: overall survival (OS) in patients whose tumors express PD-L1 (assessed in patients enrolled in Part 1a) and progression-free survival (PFS) in patients with high tumor mutational burden (TMB) ≥10 mut/Mb across the PD-L1 spectrum (assessed in patients enrolled across Parts 1a and 1b). The primary endpoint in Part 2 is OS.

Novocure Reports Positive Results from STELLAR Phase II Trial
NovoCure announced positive top-line results from its STELLAR phase II pilot trial in mesothelioma demonstrating clinically meaningful improvements in overall survival and progression free survival among patients who received Tumor Treating Fields. Plus standard of care chemotherapy, pemetrexed and cisplatin or carboplatin, compared to historical control data of patients who received standard of care chemotherapy alone. The final data exceeded the results of the interim analysis. The STELLAR trial is a phase II pilot single-arm, open-label, multi-center trial consisting of 80 patients with unresectable, previously untreated malignant pleural mesothelioma. The one-year survival rate of patients treated with Tumor Treating Fields combined with pemetrexed and cisplatin or carboplatin was 80 percent (compared to 50 percent in pemetrexed and cisplatin-alone historical controls). Median progression free survival in the Tumor Treating Fields-treated group was 7.3 months (compared to 5.7 months in pemetrexed and cisplatin-alone historical controls) and one-year survival rate was 79.7 percent (compared to 50.3 percent in pemetrexed and cisplatin-alone historical controls). No device-related serious adverse events had been reported to date.

Esketamine Demonstrated Improvements in Depressive Symptoms
The Janssen Pharmaceutical Companies of Johnson & Johnson announced that data from a Phase II proof of concept clinical study of esketamine nasal spray showed that treatment with esketamine resulted in a statistically significant, clinically meaningful improvement in depressive symptoms at four hours, including a measure of suicidal ideation, in patients with major depressive disorder who were at imminent risk for suicide, compared to placebo. This 12-week Phase IIa, randomized, double-blind, placebo-controlled, multicenter study conducted in the U.S. enrolled 68 adults. The participants were randomized in a 1:1 ratio to one of the two treatments: esketamine nasal spray 84 mg (N=36) plus standard of care or placebo nasal spray (N=32) plus standard of care. The study consisted of a screening evaluation performed within 24 to 48 hours prior to the Day 1 dose, immediately followed by a 25-day double-blind treatment phase (Day 1 to 25) with twice-weekly dosing sessions, and a 56-day follow up phase (Day 26 to Day 81). A statistically significant difference in the MADRS total score favoring esketamine was also seen at 24 hours (p=0.015; effect size=0.65), but not at the double-blind endpoint. The most common (>20 percent) treatment-emergent adverse events during the double-blind phase were (TEAEs) were: nausea (37.1 percent), dizziness (34.3 percent), unpleasant taste (31.4 percent), dissociation (31.4percent), headache (31.4 percent), and vomiting (20.0 percent).