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J. Zhou
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P2.04 - Clinical Design, Statistics and Clinical Trials (ID 705)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.04-003 - Phase II Trial of X-396 (Ensartinib) for Chinese Patients with ALK (+) Non–Small-Cell Lung Cancer Who Progressed on Crizotinib (ID 8849)
09:30 - 09:30 | Author(s): J. Zhou
- Abstract
Background:
Crizotinib has been established as the standard first-line treatment for patients with ALK-rearranged non-small-cell lung cancer. However, despite its superiority to chemotherapy, resistance occurs within approximately 12 months. New ALK-inhibitors are needed to overcome the resistance to crizotinib and to increase drug penetration to CNS. X-396 (ensartinib) is a novel, potent ALK tyrosine kinase inhibitor (TKI). Its phase I/II study showed X-396 is well-tolerated with favorable anti-tumor activities in both ALK TKI-naïve and crizotinib-resistant NSCLC patients, as well as patients with CNS metastases. The recommended phase II dose (RP2D) was established at 225 mg, once daily.
Method:
A phase II, multi-center study is evaluating the efficacy and safety of single-agent X-396 in Chinese patients with ALK (+) non–small-cell lung cancer after progression on crizotinib. Eligible patients will have documentation of a positive ALK rearrangement and progression on crizotinib. X-396 225 mg is orally administered until disease progression or intolerable toxicity. The primary endpoint is RECIST 1.1 response rate. Secondary endpoints include PFS, duration of response, and safety. The sample size is calculated using the test for inequality method, assuming that X396 have an ORR of 50% in patients with ALK-positive NSCLC, 15% higher than that from existing second-line therapy. Therefore, up to 144 patients will be enrolled with a significance level and power of 5% and 90%, respectively. Recruitment will be started on September, 2017.
Result:
Section not applicable
Conclusion:
Section not applicable
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-070 - A Phase II Study of Fruquintinib in Combination with Gefitinib in Stage IIIb/IV NSCLC Patients Harboring EGFR Activating Mutations (ID 8365)
09:30 - 09:30 | Author(s): J. Zhou
- Abstract
Background:
Seveal studies have demonstrated targeting EGFR mutations and tumor angiogenesis simultaneously has synergistic effect in the 1[st] line setting in EGFR mutant NSCLC. However, in JO25567 trial, the ≥grade 3 hypertension incidence with combination therapy was much higher (60%) when compared to historic incidence of hypertension with bevacizumab (10-15%). Considering relatively shorter half-lives for small molecule tyrosine kinase inhibitors, it might be a better choice to combine EGFR TKI and VEGFR TKI when it comes to hypertension management. Fruquintinib is a potent and highly selective oral kinase inhibitor targeting VEGFR and it has demonstrated favorable benefit-to-risk profile in third line treatment in NSCLC patients.Thus it is important to assess safety, tolerability and efficacy of this new combination in the 1[st] line setting in EGFR mutant NSCLC patients. NCT02976116
Method:
This is a single arm, open-label, multi-center study. All patients will receive gefitinib continuously at 250 mg qd. Fruquintinib will be given at 4 mg as starting dose for 3 weeks followed by 1 week off in the first 4-week cycle. Fruquintinib dose can be escalated to 5 mg with the same 4-week cycle if no ≥grade 3 adverse event (AE) or ≥grades 2 liver dysfunction occurs in the first cycle. Treatment continues until disease progression, unacceptable toxicity, or patient withdrawal. The primary objective is to assess the safety and tolerability of this combination. Key eligibility criteria include: histologically or cytologically confirmed NSCLC, ECOG PS 0-1, no prior systematic treatment, no brain metastasis. Key exclusion criteria include: known T790M mutation and bleeding history within 1 month before enrollment.
Result:
As of Jun 20, 2017, 9 patients have been enrolled and received at least one dose of fruquintinib and gefitinib. Six patients had L858R mutations, and three patients had exon 19 deletions. All patients reported AEs, but only one patient (11.1%) had grade 3 proteinuria. No SAE was reported. The most common AEs were increased ALT (3 [33.3%] patients), increased AST (3 [33.3%] patients), increased TBIL (3 [33.3%] patients), proteinuria (3 [33.3%] patients) and rash (3 [33.3%] patients). Fruquintinib dose reduction occurred in 3 patients due to grade 3 proteinuria, grade 2 increased ALT and grade 2 hemoptysis, respectively.
Conclusion:
The study is ongoing. As of the cut-off date, no unexpected toxicities were identified. The combination of fruquintinib and gefitinib showed an expected and manageable preliminary safety profile. Additional patients and follow-up data are required to further confirm the full potential of this combination treatment.
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P3.01-087 - Impact Factor Analysis for Efficacy and Prognosis of Anlotinib in NSCLC as Third-Line Treatment: Data from Trial ALTER 0303 (ID 9129)
09:30 - 09:30 | Author(s): J. Zhou
- Abstract
Background:
Anlotinib hydrochloride is a novel TKI targeting the VEGFR, FGFR, PDGFR and c-Kit. With the capability of inhibiting the tumor angiogenesis and tumor cell itself, anlotinib had showed significantly improvement in OS (9.63 vs. 6.30 months, HR=0.68, 95%CI 0.54-0.87, p=0.0018) and PFS (5.37 vs. 1.40 months, HR=0.26, 95%CI 0.21-0.33, p<0.0001) in ALTER 0303 study for refractory cancer, a randomized, double-blind, placebo-controlled Phase Ⅲ trial in China. Here, we report the main impact factors affecting the efficacy and prognosis of anlotinib based on the data from ALTER0303 to elucidate the most benefit population.
Method:
Analyzed data were collected from 294 patients that were enrolled in ALTER0303 trial and received anlotinib treatment between 4[th] March 2015 and 15[th] August 2016. The statistical analysis was conducted using SPSS19.0 software, in which the measuring and enumeration materials were described with Mean±SD and frequency/percentage respectively, Kaplan-Meier method was used for survival curves in survival analysis. Independent impact factors of OS and PFS were identified by univariate and multivariate analysis in Cox proportional hazards regression model (Significant level, α=0.05).
Result:
Several factors were discovered to be associated with the efficacy of Anlotinib treatment. The impact factors were presented in Tab1.Tab1. Impact factors for PFS and OS analyzed by Cox proportional hazards regression model Independent risk factor Independent protective factor PFS Ratio of granulocytes to lymphocytes at PD (HR=1.07, 95%CI 1.041-1.100, p<0.0001) Elevated ALP level (HR=1.553, 95%CI 1.142-2.112, p=0.005) Baseline sum of longest diameters of target lesions (HR=1.004, 95%CI 1.001-1.006, p=0.007) Elevated TSH level (HR= 0.555, 95%CI 0.422-0.730, p<0.0001) Hypercholesteremia (HR=0.720, 95%CI 0.534-0.971, p=0.031) Hypertension (HR=0.482, 95%CI 0.370-0.628, p<0.0001) Hand-foot skin reaction (HR=0.489, 95%CI 0.373- 0.643, p<0.0001) Elevated LDL level (HR=0.630, 95%CI 0.437-0.909, p=0.014) Age (HR=0.987, 95%CI 0.975-0.999, p=0.039) OS Ratio of granulocytes to lymphocytes at PD (HR=1.116, 95%CI 1.081-1.151, p<0.0001) Baseline sum of longest diameters of target lesions (HR=1.006, 95%CI 1.003-1.008, p<0.0001) ECOG PS≥2 at PD (HR=2.245, 95%CI 1.704- 3.508, p<0.0001) Elevated TSH level (HR=0.725, 95%CI 0.524- 1.005, p=0.053) Hypertriglyceridemia (HR=0.601, 95%CI 0.440-0.821, p<0.0001) Rash (HR=0.581, 95%CI 0.369-0.916, p=0.019) Female (HR=0.713, 95%CI 0.533-0.953, p=0.022)
Conclusion:
This analysis explored the possible impact factors of PFS and OS in Anlotinib treatment. Moreover, we provide real data for the prediction of Anlotinib efficacy and most benefit population through the baseline characteristics and variety of clinical index. However, further analysis in the larger scale study is still looking forward.
