scholarly journals Pazopanib in Patients with Osteosarcoma Metastatic to the Lung: Phase 2 Study Results and the Lessons for Tumor Measurement

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Paul Frankel ◽  
Chris Ruel ◽  
An Uche ◽  
Edwin Choy ◽  
Scott Okuno ◽  
...  
Keyword(s):  
Doubling Time ◽  
Kinase Inhibitor ◽  
Common Adverse Event ◽  
Phase 2 ◽  
Primary Analysis ◽  
Tumor Doubling Time ◽  
Metastatic Osteosarcoma ◽  
Phase 2 Study ◽  
Study Results ◽  
Slow Growing

Background. This single-arm, multicenter, phase 2 study evaluated the safety and antitumor activity of pazopanib in patients with unresectable, pulmonary metastatic osteosarcoma. Patients and Methods. Patients with pulmonary metastatic osteosarcoma unresponsive to chemotherapy were eligible. Patients who received prior tyrosine kinase inhibitor therapy were excluded. Pazopanib at 800 mg once daily was administered for 28-day cycles. Tumor responses were evaluated by local radiology assessment 1 month prior to and after initiation of treatment to calculate tumor doubling time and after every even numbered cycle. The primary endpoints were progression-free survival at 4 months, concomitant with a demonstrated 30% increase in tumor doubling time relative to the pretreatment growth rate. Results. 12 patients (7 female) were enrolled. The study was terminated prematurely due to withdrawal of financial support by the sponsor. 8 subjects were eligible for the primary analysis, whereas 4 patients were in a predefined exploratory “slow-growing” cohort. In the “fast-growing” cohort, 3 of the 8 patients (37.5%) eligible for first-stage analysis were deemed “success” by the preplanned criteria, adequate to proceed to second-stage accrual. In addition, 1 of the 4 patients in the “slow-growing” cohort experienced a partial remission. Grade 1-2 diarrhea was the most common adverse event, and grade 3 events were infrequent. Conclusion. This study illustrates a novel method of demonstrating positive drug activity in osteosarcoma by increasing tumor doubling time, and this is further supported by a partial response in a patient with “slow-growing” disease. This trial is registered with NCT01759303.

scholarly journals Primary Analysis of ZUMA-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients (Pts) with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL)

2021 ◽  
Vol 27 (3) ◽  
pp. S67-S68
Author(s):  
Caron A. Jacobson ◽  
Julio C. Chavez ◽  
Alison R. Sehgal ◽  
Basem M. William ◽  
Javier Munoz ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase 2 ◽  
Primary Analysis ◽  
Non Hodgkin Lymphoma ◽  
Phase 2 Study

CTNI-21. PHASE 2 STUDY OF VAL-083 AND RADIOTHERAPY IN NEWLY DIAGNOSED MGMT-UNMETHYLATED GBM

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi63-vi64
Author(s):  
Zhong-ping Chen ◽  
Cheng-Cheng Guo ◽  
Yang Qun-ying ◽  
Jia-Wei Li ◽  
Shao-xiong Wu ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Radiation Treatment ◽  
Gene Promoter ◽  
Progression Free Survival ◽  
Common Adverse Event ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Phase 2 Study

Abstract Approximately 60% of glioblastoma multiforme (GBM) patients possess an unmethylated methylguanine DNA-methyltransferase (MGMT) gene promoter, which confers a limited clinical response to standard-of-care treatment with temozolomide (TMZ), resulting in shorter median survival when compared to patients with a methylated MGMT promoter. VAL-083 is a novel bi-functional DNA targeting agent that induces interstrand DNA cross-links at N7-guanine, leading to DNA double-strand breaks and ultimately cell death. VAL-083 circumvents MGMT-mediated TMZ resistance in vitro and in vivo. A Phase 2 study has been conducted to evaluate efficacy and safety of VAL-083 when administered concurrently with radiation therapy (RT) in newly diagnosed MGMT unmethylated GBM. The study was conducted in 2 stages: Stage 1 was a dose-escalation phase to confirm the dose of VAL-083 in this setting. Patients received VAL-083 at 20, 30, or 40 mg/m2/day x 3 days every 21 days along with standard radiation treatment (RT) (2 Gy/day, 5 days/week for 6 weeks). At the end of this stage, 30 mg/m2/day of VAL-083 in combination with RT was generally safe and well-tolerated. Stage 2 was an expansion phase to enroll up to 20 additional patients at the 30 mg/m2/day of VAL-083 in combination with RT. All patients have been enrolled, with a total of 29 patients in the study, and 25 patients receiving 30 mg/m2/day VAL-083. All 29 patients have completed treatment and patients are in the follow-up phase of the study. Consistent with our prior experience, myelosuppression was the most common adverse event. As of March 2021, 22/29 (75.9%) subjects had disease progression. The median progression free survival for all patients enrolled was 9.3 (95%CI: 6.4-12.0) months. Sixteen (16/29; 55.2%) patients had died, and median overall survival for all patients enrolled was 19.6 (95%CI: 14.0-22.4) months. Further safety and efficacy updates will be presented at the meeting. Clinicaltrials.gov identifier: NCT03050736.

scholarly journals Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing

2020 ◽  
Vol 8 (1) ◽  
pp. e000775 ◽  
Author(s):  
Danny Rischin ◽  
Michael R Migden ◽  
Annette M Lim ◽  
Chrysalyne D Schmults ◽  
Nikhil I Khushalani ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Antitumor Activity ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Phase 2 ◽  
Primary Analysis ◽  
Link Type ◽  
Phase 2 Study ◽  
Group 3 ◽  
Group 1

BackgroundCemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).MethodsThe primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability.ResultsFor Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan–Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%).ConclusionIn patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses.Trial registration numberClinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498

scholarly journals Phase 2 Study of CP-690,550, an Oral Janus Kinase Inhibitor, in Active Ulcerative Colitis

2011 ◽  
Vol 140 (5) ◽  
pp. S-110 ◽  
Author(s):  
William J. Sandborn ◽  
Subrata Ghosh ◽  
Julian Panes ◽  
Ivana Vranic ◽  
Chinyu Su ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Active Ulcerative Colitis ◽  
Phase 2 ◽  
Janus Kinase Inhibitor ◽  
Phase 2 Study

scholarly journals Peficitinib, an Oral Janus Kinase Inhibitor, in Moderate-to-severe Ulcerative Colitis: Results From a Randomised, Phase 2 Study

2018 ◽  
Vol 12 (10) ◽  
pp. 1158-1169 ◽  
Author(s):  
Bruce E Sands ◽  
William J Sandborn ◽  
Brian G Feagan ◽  
Gary R Lichtenstein ◽  
Hongyan Zhang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Phase 2 ◽  
Janus Kinase Inhibitor ◽  
Severe Ulcerative Colitis ◽  
Phase 2 Study
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