A phase II study of dasatanib (BMS 354825) in recurrent or metastatic ckit-expressing adenoid cystic (ACC) and non-ACC malignant salivary glands tumors (MSGT).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6022-6022
Author(s):  
Stuart J. Wong ◽  
Ezra E.W. Cohen ◽  
Theodore Karrison ◽  
David N. Hayes ◽  
Merrill S. Kies ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Study Drug ◽  
Protein Product ◽  
Stage I ◽  
Stage Ii ◽  
Best Response ◽  
Grade 3

6022 Background: ACC is a rare disease, accounting for 1/3rd of MSGT, in which 90% of cases express the protein product of the ckit proto-oncogene. Dasatinib is a potent and selective inhibitor of five oncogenic PTKs/kinase families including ckit. We conducted a phase II study to determine the antitumor activity of dasatinib in ACC and non-ACC MSGT. Methods: In a two-stage design, adult patients (pts) with recent radiographic progressive, recurrent or metastatic ACC, + cKIT, were treated with dasatinib 70 mg PO BID. Pts with non-ACC MSGT of other histologic types, were treated as a separate cohort. Response was assessed every 8 wks by imaging using RECIST criteria. The study design stipulated enrollment of n=40 ACC patients (20 in stage I and 20 in stage II) and 25 non-ACC patients (14 in stage I and 11 in stage II). Results: Fifty-four pts were enrolled, 40 ACC and 14 non-ACC. One additional pt was a screen failure. Baseline data on 54 pts are: M:F = 28:26, median age 56.6 yrs (range 20-82), PS 0:1:2 = 24:28:2, prior radiation:chemotherapy = 44:21. The most frequent adverse events experienced (as % of pts, worst grade 2 or higher and at least possibly related to study drug) were: fatigue (28%), nausea (19%), headache (15%), lymphopenia (11%), dyspnea (11%), alanine aminotransferase increased (7%), anorexia (7%), vomiting (7%), alkaline phosphatase increased (6%), diarrhea (6%), and non-cardiac chest pain (6%). No grade 4 adverse events occurred and only 15 pts experienced a grade 3 adverse event (at least possibly attributed to study drug), primarily dyspnea (4 patients) and fatigue (3 patients). Significant cardiac toxicity was observed in one pt (grade 3 prolonged QT corrected interval). Among ACC pts, best response to dasatinib: 0 pts (0%) had PR, 21 pts (52%) had SD (range 2.8-13.8 months), 12 pts (30%) had PD, and 2 died prior to cycle 2. Median PFS was 4.8 mos. For 14 evaluable non-ACC pts, none had an objective response, triggering early stopping. 7 had SD (range 1.4-6.6 months), and 4 PD. Conclusions: Although there were no objective responses, dasatinib is well tolerated, with tumor stabilization achieved by 52% of ACC pts. Dasatinib demonstrated no activity in non-ACC MSGT. Clinical trial information: NCT00859937.

Phase II study of PX-866 in recurrent glioblastoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2051-2051
Author(s):  
Marshall W. Pitz ◽  
Mary Valeria MacNeil ◽  
David R. Macdonald ◽  
Ankineedu Saranya Kakumanu ◽  
Brian Thiessen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Glioblastoma ◽  
Pi3k Inhibitor ◽  
Stage I ◽  
Stage Ii ◽  
Response Data ◽  
Grade 3 ◽  
Recurrent Gbm

2051 Background: Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system. The majority of GBM have genetic changes that increase the activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway, critical for cell motility, proliferation, and survival. We present the interim results of PX-866, an oral PI3K inhibitor, in patients (pts) with recurrent GBM. Methods: Pts with histologically confirmed GBM at first recurrence after treatment with chemoradiation and adjuvant temozolomide are given PX-866 8 mg daily on this single-arm phase II study. MRI and clinical exam are done every 8 weeks to determine treatment response. The trial has a 2-stage design with dual endpoints of objective response and early progression (within 8 weeks). In Stage I, 15 pts are evaluated and if 0 responses and 10 or more early progressions are seen, enrolment will stop. Otherwise, Stage II will enrol another 15 pts for efficacy analysis. Tumour tissue is collected for analysis of potential markers of PI3K inhibitory activity (PTEN, EGFRvIII, PIK3CA mutations). Results: Seventeen pts have been enroled to date: 14 evaluable for response and 15 for toxicity. Median age was 54 years (range 35-70), with 7 females and 10 males. No pts had received treatment for recurrent GBM, and median time between initial diagnosis and study enrolment was 300 days (range: 113-447 days). Pts have received a median of one 8-week cycle of PX-866 (range: 1-4). Twelve pts have discontinued therapy, 9 due to disease progression and 3 due to grade 3/4 liver enzyme abnormalities. Other adverse effects have included fatigue (10 pts/1 grade 3), diarrhea (6 pts/3 grade 3), nausea (7 pts/0 grade 3), vomiting (6 pts/0 grade 3), lymphopenia (14 pts/3 grade 3). Stage I response data are premature; it is not yet known if the trial will continue to Stage II. Archival tissue is available on all patients and is undergoing analysis. Conclusions: This is one of the first trials of a PI3K inhibitor in pts with recurrent GBM. PX-866 has been relatively well tolerated. Stage I response data are premature; while it is not yet known if the criteria will be met to continue to Stage II, prolonged SD has been observed in some pts. The correlative biomarker assays underway will be important to understand this observation.

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

A phase II study of a novel anti-tubulin, E7389, in patients with advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7106-7106
Author(s):  
A. Das ◽  
A. Spira ◽  
N. Iannotti ◽  
M. Savin ◽  
E. Zang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Study Drug ◽  
Progression Free Survival ◽  
Large Cell ◽  
Median Number ◽  
Synthetic Analog ◽  
Open Label ◽  
Best Response

7106 Background: E7389, a synthetic analog of halichondrin B that was isolated from a marine sponge, has broad anti-proliferative activity at nanomolar levels and a unique profile of tubulin interactions. Methods: This is an open-label, single-arm, stratified phase II study of E7389 in patients with measurable, recurrent and/or metastatic NSCLC who progressed during or after platinum-based doublet chemotherapy. E7389 (1.4 mg/m2) was administered as a bolus IV on days 1, 8, and 15 of a 28-day cycle to 72 patients (cohort 1) in stratum I (55 taxane pretreated patients) and stratum II (17 taxane-naive patients) and on Days 1 and 8 of a 21-day cycle (cohort 2), providing an additional 22 patients in stratum I. The primary efficacy endpoint was objective response rate to E7389 monotherapy. Results: As of 9 December 2005, 94 evaluable patients received E7389. Nineteen tumors were classified as squamous cell carcinomas, 39 as adenocarcinomas, and 36 were large cell carcinomas or unclassified. The median number of cycles completed was 3. Fifteen patients completed 6 or more cycles and 75 patients underwent tumor assessments after cycle 2. Major toxicities related to study drug included myelosuppression, nausea, fatigue, dehydration, arthralgias, dyspnea, and peripheral neuropathy. Based on RECIST criteria, 6 partial responses (PR) were observed among 94 evaluable patients (PR rate = 6.4%, 95% CI: 2.8%, 12.8%). For 33 patients the best response was stable disease (SD rate = 35.1%, 95% CI: 25.5%, 45.1%). Disease control rate (PR + SD) was 41.5% (95% CI: 31.4%, 51.7%). For cohort 1, the 12-week progression free survival rate was 57.2%. As of 9 December 2005, median PFS time was 108 days (95% CI = 55, min-max = 1–239+). Cohort 2 is being followed to estimate their 12-week PFS. The correlation of beta tubulin isotype, stathmin, microtubule-associated protein 4 (MAP4) and tau protein mRNA expression with tumor responses is on-going. Conclusions: Based on this data, E7389 has been shown to be safe and effective in the treatment of NSCLC patients. Updated information and results of molecular correlations of responses will be presented. [Table: see text]

A phase II study of lapatinib in recurrent or metastatic EGFR and/or ErbB2 expressing adenoid cystic (ACC) and non-ACC malignant tumors of the salivary glands (MSGT)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5566-5566 ◽  
Author(s):  
M. Agulnik ◽  
E. E. Cohen ◽  
R. B. Cohen ◽  
E. X. Chen ◽  
S. J. Hotte ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Malignant Tumors ◽  
Objective Response ◽  
Therapeutic Index ◽  
Eligibility Criteria ◽  
Dual Inhibitor ◽  
Grade 3 ◽  
Present Trial

5566 Background: The limited therapeutic index of chemotherapy in recurrent or metastatic MSGT provides a strong rationale for the evaluation of molecularly targeted agents in this disease. Lapatinib is a dual inhibitor of EGFR and ErbB2 tyrosine kinase activity. Expression of ErbB2 and EGFR has been associated with biological aggressiveness and poor prognosis in MSGT, respectively. We conducted a phase II study to determine the antitumor activity of lapatinib in MSGT. Methods: The main study has a two-stage design in which patients (pts) with progressive, recurrent or metastatic ACC, and immunohistochemically expressing at least 1+ EGFR and/or 2+ ErbB2, were treated with lapatinib 1500 mg PO daily. Each cycle consists of 4 weeks of continuous dosing. Pts with non-ACC MSGT of other histologies, meeting identical eligibility criteria, were treated in this trial as a single-stage, separate cohort. Results: Of 57 pts screened for this study, 29/33 (88%) ACC and 22/24 (92%) non-ACC pts expressed EGFR and/or ErbB2. Thirty-eight pts have been accrued to the study to date (20 ACC/18 non-ACC). The remaining 13 pts who were screened positive either declined entry or were ineligible for other reasons. Baseline data on 34 pts are: M:F = 25:9, median age 56 (range 38–80), PS 0:1:2 = 16:17:1, prior radiation:chemotherapy = 30:18. After 92 cycles of therapy, the most frequent adverse events experienced (as % of cycles) were diarrhea (54%), pain (52%), fatigue (52%), lymphopenia (39%), anemia (38%), hyperglycemia (38%) and dyspnea (34%). No grade 4 adverse events have occurred and only 8 pts experienced a grade 3 adverse event, primarily pain and dyspnea. No significant cardiac toxicity has been observed. Among 14 ACC pts evaluable for response so far: 9 have SD (range 2–9 cycles), 3 PD, and 2 died prior to cycle 2. For 12 evaluable non-ACC pts: 8 have SD (range 2–9 cycles), and 4 PD. No pts have had an objective response. Conclusions: Although there are no objective responses to date, lapatinib is well tolerated, with tumor stabilization achieved by 64% of pts and 24/38 pts remain on treatment at present. Trial accrual of ACC pts into the first stage has been completed, the second stage will open if an objective response is seen. No significant financial relationships to disclose.

A phase II multicenter trial of the multitargeted kinase inhibitor sulfatinib in advanced medullary thyroid cancer (MTC) and radioiodine (RAI)-refractory differentiated thyroid cancer (DTC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6037-6037 ◽  
Author(s):  
Jiaying Chen ◽  
Qinghai Ji ◽  
Junning Cao ◽  
Dongmei Ji ◽  
Chunmei Bai ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Growth Factor ◽  
Disease Progression ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Stage I ◽  
Grade 3

6037 Background: Sulfatinib is an oral tyrosine kinase inhibitor targeting Vascular Endothelial Growth Factor Receptor (VEGFR), Fibroblast Growth Factor Receptor 1 (FGFR 1), and Colony Stimulating Factor 1 Receptor (CSF1R). In a proof of concept (PoC) phase II study, sulfatinib showed promising efficacy in patients (pts) with neuroendocrine tumors (NETs). Methods: This is an open label, two cohorts phase II study using Simon's two-stage design. In stage I, 15 pts will be enrolled in each cohort (advanced MTC or iodine-refractory DTC), and 10 more pts will be enrolled in a cohort in stage II if at least 2 PR observed in that cohort in stage I. Pts are required to have progressive disease in the past 12 months, but could not have received > 1 prior anti-angiogenesis therapy. Pts are treated with oral sulfatinib 300 mg once daily until disease progression, death, or intolerable toxicity. Primary endpoint is Objective Response Rate (ORR) by investigator per RECIST 1.1. Results: As of Dec 31 2016,the studyenrolled 18 pts (MTC: 6, DTC: 12), amongst whom 17 pts were efficacy evaluable. There were a total of 4 confirmed PRs, 1 in the MTC cohort and 3 in the DTC cohort, respectively. The others best response was stable disease (SD). 11 pts (61.1%) had dose interruption due to adverse events (AEs) and 5 pts (27.8%) had dose reduction. Two pts discontinued therapy (1 patient due to disease progression, another due to subject's decision). The most commonly reported AEs were proteinuria 72.2% (Grade 3-4: 22.2%), hypertriglyceridemia 50.0% (Grade 3-4: 0%), hypertension 44.4% (Grade 3-4: 16.7%), blood bilirubin increased 44.4% (Grade 3-4: 5.6%), and diarrhea 33.3% (Grade 3-4: 0%). No Grade 5 AE was reported by the time of data cut-off. Conclusions: Sulfatinib appears to be well tolerated in the pts with advanced MTC and RAI refractory DTC. Safety profile seems to be consistent to previous report, with mostly manageable AEs. Efficacy is encouraging in both indications. Further investigation is warranted. Clinical trial information: NCT02614495.

A phase II study of apatinib treatment for advanced biliary tract carcinoma after failure of the standard chemotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16684-e16684
Author(s):  
Chenchen Wang ◽  
Weijian Guo ◽  
Mingzhu Huang
Keyword(s):  
Adverse Events ◽  
Biliary Tract ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Formation ◽  
Biliary Tract Carcinoma ◽  
Efficacy Evaluation ◽  
Grade 3

e16684 Background: There is no standard second-line therapy for advanced biliary tract carcinoma (BTC). Apatinib, a VEGFR2 tyrosine kynase inhibitor, showed an inhibitary effect on tumor formation in BTC tumorgraft mouse model in previous study, with tolerable toxicity in clinical trials for other types of advanced cancer such as gastric cancer. We conducted an exploratory study to evaluate the efficacy and safety of apatinib in patients with advanced BTC. Methods: This is a single-center, single-arm phase II study (NCT03427242). The key inclusion criteria were:(1) histologically confirmed advanced or metastatic BTC; (2) Prior lack of response or intolerance to at least one chemotherapeutic regimens; (3) At least one measurable lesion as defined by RECIST 1.1; (4) No prior use of anti-angiogenic targeted drugs. Eligible patients received oral apatinib 500mg each day continuously until unacceptable toxicity or tumor progression. The primary endpoint was progression free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR) and treatment safety. Results: From Dec 1, 2017 to Jan 31, 2020, a total of 18 patients (12 males and 6 females) had been recruited, and 16 patients who had received the medication of apatinib were included in this analysis. Among these patients, 10 were previously treated with only first-line chemotherapy and 6 were treated with two or more lines of therapy. The median age was 65 (range 45-76) years old. Fourteen patients had received the efficacy evaluation after treatment. Two patients achieved partial response (PR, 14.3%), 6 patients with stable disease (SD, 42.9%),and 6 patients with progressive disease(PD). The ORR and DCR were 14.3% and 57.1%, respectively. At the last follow-up date on Jan 30, 2020, 4 patients are still on apatinib medication. The median PFS was 2.70 months (95% CI, 1.94 - 3.46), and the median OS was 7.03 months (95% CI, 3.16 - 10.9). Grade 3 or 4 adverse events were reported in 7 patients (43.8%). The detailed grade 3 or 4 adverse events were proteinuria in 5 patients, hand-foot syndrome in 2 patients, platelet count decrease in 1 patients, diarrhea in 1 patients and urine bilirubin in 1 patients (Table). Conclusions: For the patients with advanced biliary tract carcinoma, apatinib showed an anti-tumor activity with acceptable safety. Clinical trial information: NCT03427242 . [Table: see text]

scholarly journals Apatinib for patients with metastatic biliary tract carcinoma refractory to standard chemotherapy: results from an investigator-initiated, open-label, single-arm, exploratory phase II study

2021 ◽  
Vol 13 ◽  
pp. 175883592110390
Author(s):  
Chenchen Wang ◽  
Mingzhu Huang ◽  
Qirong Geng ◽  
Wenhua Li ◽  
Jinjia Chang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Biliary Tract ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Group Performance ◽  
Phase Ii Study ◽  
Objective Response ◽  
Biliary Tract Carcinoma ◽  
Grade 3

Background: There is no standard therapy for metastatic biliary tract carcinoma (BTC) refractory to first-line chemotherapy. Apatinib, a VEGFR2 tyrosine kynase inhibitor, showed an activity against BTC xenografts in preclinical models. We conducted an exploratory study to evaluate the efficacy and safety of apatinib in patients with metastatic BTC. Methods: This is a single-arm phase II study [ClinicalTrials.gov identifier: NCT03427242]. Eligible patients were aged 18 years or older; histologically confirmed metastatic BTC; refractory or intolerance to at least one chemotherapeutic regimen; no prior use of anti-angiogenic targeted drugs; Eastern Cooperative Oncology Group performance status of 0–2. Patients received oral apatinib 500 mg each day continuously until unacceptable toxicity or tumor progression. The primary endpoint was progress free survival (PFS). The secondary endpoint was overall survival (OS), objective response rate (ORR) and treatment safety. Results: A total of 22 patients were recruited. All of them received apatinib medication. The median age was 63 (44–75) years old. Twenty patients received efficacy evaluation after treatment. The objective response rate (ORR) and disease control rate (DCR) were 15.0% and 60.0%, respectively. The median PFS was 2.73 months [95% confidence interval (CI): 1.74–3.72 months], with 6 months PFS rate of 27.3% (95% CI: 8.7–45.9%). The median OS was 4.81 months (95% CI: 3.16–10.9 months), with 12 months OS rate of 36.4% (95% CI: 16.2–56.6%). Nine out of 22 patients (40.9%) had grade 3/4 adverse events. The most common grade 3/4 adverse events were hand-foot skin syndrome [three (13.6%) patients] and hypertension [two (9.1%) patients]. No treatment-related death occurred. Conclusions: For patients with metastatic BTC, apatinib showed an anti-tumor activity with acceptable safety, which deserves the further clinical trial. This trial was prospectively registered on ClinicalTrials.gov [NCT03427242]. Date of first patient enrollment: 26 January 2018. Date of registration (date of first posted): 9 February 2018.

ECOG-ACRIN 5162: A phase II study of osimertinib 160 mg in NSCLC with EGFR exon 20 insertions.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9513-9513 ◽  
Author(s):  
Zofia Piotrowska ◽  
Yating Wang ◽  
Lecia V. Sequist ◽  
Suresh S. Ramalingam
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Therapeutic Window ◽  
Clinical Activity ◽  
Eligibility Criteria ◽  
Grade 3 ◽  
Exon 20

9513 Background: EGFR exon 20 insertions (ins20), which comprise 4-10% of EGFR-mutant NSCLC, are generally refractory to first- and second-generation EGFR TKIs. While the clinical activity of the third-generation EGFR TKI osimertinib against EGFR ins20 is unknown, preclinical studies suggest its favorable therapeutic window may allow for inhibition of EGFR isn20 at clinically-achievable doses (Hirano, Oncotarget 2015). We report the results of EA5162, a single-arm, phase II study of osimertinib 160 mg in NSCLC pts with EGFR ins20 (NCT03191149). Methods: Pts with advanced NSCLC with an EGFR ins20 mutation identified by any local, CLIA-certified tissue assay were treated with osimertinib 160 mg daily until progression, intolerable toxicity or withdrawal. At least one prior line of therapy was required; stable, asymptomatic brain metastases were allowed. The primary endpoint was objective response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS) and overall survival. The estimated sample size was 19 patients. Results: 21 pts were enrolled between 4/2018 and 7/2019 (median age 65; 15 female, 6 male; median 2 prior therapies); 1 patient did not meet eligibility criteria due to laboratory studies obtained 1 day out of window. As of 1/21/20, 6 pts remain on treatment. Among the 20 eligible pts, the best response was PR in 4 pts and CR in one pt, for a confirmed ORR of 25%; 12 (60%) pts had SD. The median PFS was 9.7 months (95% CI, 4.07, NA), median duration of response (DOR) was 5.7 months (95% CI, 4.73, NA.) Grade > 3 treatment-related adverse events (TRAE) observed in > 1 pt included anemia (n=2), fatigue (n=2), prolonged QT interval (n=2.) One pt had grade 4 respiratory failure, there were no grade 5 TRAEs. One pt discontinued study treatment due to grade 3 anemia. Conclusions: Osimertinib 160mg daily is well-tolerated and showed clinical activity in EGFR ins20-mutant NSCLC with a response rate of 25%, disease control rate of 85%, and mPFS of 9.7 months. The adverse events with osimertinib 160 mg QD in this cohort were consistent with other reports of this regimen; grade 3 rash and diarrhea were not observed. Clinical trial information: NCT03191149 .

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

scholarly journals Pyrotinib in HER2-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study

2020 ◽  
Vol 38 (24) ◽  
pp. 2753-2761 ◽  
Author(s):  
Caicun Zhou ◽  
Xingya Li ◽  
Qiming Wang ◽  
Guanghui Gao ◽  
Yiping Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Unmet Need ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Grade 3

PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of pyrotinib in patients with HER2-mutant advanced NSCLC in a prospective, multicenter, open-label, single-arm, phase II study. PATIENTS AND METHODS Patients with stage IIIB or IV HER2-mutant lung adenocarcinoma who were previously treated with platinum-based chemotherapy were enrolled to receive pyrotinib at a dose of 400 mg/d for 21-day cycles. The primary end point was objective response rate per independent review committee (IRC). RESULTS Between October 20, 2016, and December 10, 2018, 60 patients received pyrotinib monotherapy. At baseline, 58 (96.7%) were stage IV, and 25 (41.7%) received at least 2 lines of prior chemotherapy. As of data cutoff on June 20, 2019, IRC-assessed objective response rate was 30.0% (95% CI, 18.8% to 43.2%). All subgroups of patients with different HER2 mutation types showed a favorable objective response rate. The objective response rates were similar between patients with and without brain metastases (25.0% v 31.3%). The median duration of response was 6.9 months (95% CI, 4.9 to 11.1 months). The median progression-free survival was 6.9 months (95% CI, 5.5 to 8.3 months) per IRC. The median overall survival was 14.4 months (95% CI, 12.3 to 21.3 months). Treatment-related adverse events of grade 3 or 4 occurred in 28.3% of patients, with the most common being diarrhea (20.0%; all grade 3). No treatment-related deaths were reported. CONCLUSION Pyrotinib showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with HER2-mutant NSCLC.

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