scholarly journals First‐in‐Class Selective HDAC6 Inhibitor ( ACY ‐1215) Has a Highly Favorable Safety Profile in Patients with Relapsed and Refractory Lymphoma

2021 ◽  
Author(s):  
Jennifer E. Amengual ◽  
Jennifer K. Lue ◽  
Helen Ma ◽  
Renee Lichtenstein ◽  
Bijal Shah ◽  
...  
Keyword(s):  
Safety Profile ◽  
Favorable Safety Profile ◽  
Hdac6 Inhibitor ◽  
Refractory Lymphoma ◽  
Favorable Safety

Safety of darolutamide (DARO) for nonmetastatic castration-resistant prostate cancer (nmCRPC) from extended follow-up in the phase III ARAMIS trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 239-239
Author(s):  
Matthew Raymond Smith ◽  
Karim Fizazi ◽  
Teuvo L. J. Tammela ◽  
Felipe Melo Cruz ◽  
Luke T. Nordquist ◽  
...  
Keyword(s):  
Safety Profile ◽  
Safety Data ◽  
Final Analysis ◽  
Phase Iii ◽  
Prolonged Treatment ◽  
Fracture Rate ◽  
Castration Resistant Prostate Cancer ◽  
Favorable Safety Profile ◽  
Risk Of Death ◽  
Favorable Safety

239 Background: DARO is a structurally distinct androgen receptor inhibitor (ARI) approved for treating nmCRPC. In ARAMIS, DARO significantly reduced the risk of death by 31% (HR = 0.69; 95% CI: 0.53-0.88; p = 0.003) and prolonged median metastasis-free survival vs placebo (PBO; 40.4 months vs 18.4 months; HR = 0.41; 95% CI: 0.34-0.50; p < 0.001). Adverse events (AEs) of interest commonly associated with ARI therapy, such as fatigue, falls, fractures, rash, mental impairment, and hypertension, as well as interactions between ARIs and concomitantly administered drugs, can impact patient daily life. In the final analysis of the double-blind (DB) period of the ARAMIS trial, DARO had a favorable safety profile, showing ≤2% difference vs PBO for most AEs of interest. Fatigue was the only AE with > 10% incidence with DARO. The incidence of permanent discontinuation due to AEs was also similar between DARO and PBO (8.9% vs 8.7%). Here we present safety data for prolonged treatment with DARO from the final analysis of the DB + open-label (OL) period of ARAMIS. Methods: Patients (pts) with nmCRPC (N = 1509) were randomized 2:1 to DARO or matched PBO while continuing androgen deprivation therapy. The data cut-off for the primary analysis of the DB period was September 3, 2018. Study unblinding occurred on November 30, 2018, after which pts in the DARO arm still receiving study treatment continued with OL DARO. The data cut-off for final analysis of the DB+OL period was November 15, 2019. Results: At the final analysis, the median treatment duration for pts randomized to DARO was 18.5 months for the DB period and 25.8 months for the DB+OL period. At the final cut-off date, 48.8% of patients in the DARO DB+OL group were still receiving DARO treatment. The increase in the incidence of any-grade AEs (85.7% vs 89.8%) and serious AEs (26.1% vs 32.1%) between the DB and DB+OL period was small. Between the DB and DB+OL periods, only minor numerical changes for ARI-associated AEs were observed. When the incidences were corrected for exposure, there were minimal differences between the DB and DB+OL period, e.g., the fracture rate was 3.4 vs 4.0 per 100 patient-years for the DB vs DB+OL periods, respectively. Fatigue was the only ARI-associated AE of interest that exhibited > 10% incidence in the DARO arm during the DB+OL period. The incidence of permanent discontinuation of DARO due to AEs increased slightly from 8.9% during the DB period to 10.5% during the DB+OL period; the incidence of discontinuation of PBO due to AEs during the DB period was 8.7%. Conclusions: With longer treatment exposure, DARO remained well-tolerated. In the DB+OL period, no new safety signals were observed. The expected increases in incidence of AEs between the DB and DB+OL periods largely disappeared when adjusted for the longer exposure, confirming the favorable safety profile of DARO with prolonged treatment. Clinical trial information: NCT02200614.

1504: 4F-PCC DEMONSTRATES FAVORABLE SAFETY PROFILE IN A RABBIT MODEL OF VENOUS THROMBOSIS

2016 ◽  
Vol 44 (12) ◽  
pp. 451-451
Author(s):  
Eva Herzog ◽  
Franz Kaspereit ◽  
Wilfried Krege ◽  
Baerbel Doerr ◽  
Marcel Mischnik ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Safety Profile ◽  
Rabbit Model ◽  
Favorable Safety Profile ◽  
Favorable Safety

scholarly journals Fosfomycin: A First-Line Oral Therapy for Acute Uncomplicated Cystitis

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
George G. Zhanel ◽  
Andrew J. Walkty ◽  
James A. Karlowsky
Keyword(s):  
Clinical Trials ◽  
Safety Profile ◽  
Cross Resistance ◽  
Adult Women ◽  
First Line ◽  
Favorable Safety Profile ◽  
E Coli ◽  
Acute Uncomplicated Cystitis ◽  
Uncomplicated Cystitis ◽  
Favorable Safety

Fosfomycin is a new agent to Canada approved for the treatment of acute uncomplicated cystitis (AUC) in adult women infected with susceptible isolates ofE. coliandEnterococcus faecalis. We reviewed the literature regarding the use of oral fosfomycin for the treatment of AUC. All English-language references from 1975 to October 2015 were reviewed. In Canada, fosfomycin tromethamine is manufactured as Monurol® and is available as a 3-gram single dose sachet. Fosfomycin has a unique chemical structure, inhibiting peptidoglycan synthesis at an earlier site compared toβ-lactams with no cross-resistance with other agents. Fosfomycin displays broad-spectrum activity against ESBL-producing, AmpC-producing, carbapenem-non-susceptible, and multidrug-resistant (MDR)E. coli. Resistance to fosfomycin inE. coliis rare (<1%). Fosfomycin is excreted unchanged in the urine by glomerular filtration with peak urinary concentration ~4000 µg/mL and remains at concentrations >100 µg/mL for 48 hours after a single 3-gram oral dose. No dosage adjustments are required in elderly patients, in pregnant patients, or in either renal or hepatic impairment. Fosfomycin demonstrates a favorable safety profile, and clinical trials have demonstrated efficacy in AUC that is comparable to ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Fosfomycin’s in vitro activity against common uropathogens, including MDR isolates, its favorable safety profile including pregnancy patients, drug interactions, and clinical trials data demonstrating efficacy in AUC, has resulted in Canadian, US, and European guidelines/authorities recommending fosfomycin as a first line agent for the treatment of AUC.

Preliminary results from a phase II study of ARQ 197 in patients with microphthalmia transcription factor family (MiT)-associated tumors

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10502-10502 ◽  
Author(s):  
J. Goldberg ◽  
G. D. Demetri ◽  
E. Choy ◽  
L. Rosen ◽  
A. Pappo ◽  
...  
Keyword(s):  
Safety Profile ◽  
Soft Part ◽  
Phase 1 ◽  
Favorable Safety Profile ◽  
Tumor Cell Migration ◽  
Anti Cancer ◽  
Arq 197 ◽  
Favorable Safety ◽  
Stage 1 ◽  
Cancer Activity

10502 Background: ARQ 197 is a selective, non-ATP competitive inhibitor of c-Met, a receptor tyrosine kinase implicated in tumor cell migration, invasion, and proliferation. The drug has demonstrated a favorable safety profile and preliminary anti-cancer activity in three phase 1 studies. MiT tumors include clear cell sarcoma (CCS), alveolar soft part sarcoma (ASPS), and translocation-associated renal cell carcinoma (TLA RCC) and are linked biologically by a shared activated transcriptional mechanism which directly upregulates c-Met. Tumors with this type of chromosomal abnormality are generally resistant to all approved therapies and, in the absence of complete surgical resection, prove invariably fatal. Methods: This is a multi-center, single arm, two-stage phase 2 trial in patients (pts) 13 years of age or older with MiT tumors. Initially pts received 120 mg ARQ 197 orally twice daily (bid). The protocol was amended in August 2008 to increase the dose to 360 mg bid. If either a complete response (CR) or a partial response (PR) were to be observed in the 23 pts in stage 1, the study would be advanced to stage 2 where 16 additional patients will be enrolled. Tumor responses are measured in 8-week intervals per RECIST criteria. Results: To date, 28 pts (19 females, 9 males; median age = 21; 7 CCS, 17 ASPS, 4 RCC) have been treated. One pt with CCS demonstrated a confirmed PR, 15 pts (10 ASPS, 2 CCS, 3 RCC) demonstrated stable disease (SD) for durations up to 29+ weeks, and 4 pts progressed. An overall response rate of 5% and a disease control rate (CR+PR+SD) of 80% were demonstrated among 20 pts who were evaluable for efficacy. The most common drug-related adverse events (AEs) have been fatigue (35.7%), nausea (35.7%), vomiting (21.4%), decreased hemoglobin (10.7%). and cough (10.7%). To date, only 3 drug-related Grade 3 or 4 AEs have been reported including anemia (2) and decreased neutrophil count (1). No drug-related serious AEs or deaths have been reported. Conclusions: To date, ARQ 197 has demonstrated an extremely favorable safety profile and preliminary evidence of anti-cancer activity in these young pts. The criterion for advancing the study from stage 1 to stage 2 has been met. Stage 2 enrollment is ongoing. Updated data on both dose levels will be presented. [Table: see text]

Long-term safety and efficacy analysis of abiraterone acetate (AA) plus prednisone (P) in metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy (COU-AA-302).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5009-5009
Author(s):  
Dana E. Rathkopf ◽  
Matthew R. Smith ◽  
Johann Sebastian De Bono ◽  
Christopher Logothetis ◽  
Neal Shore ◽  
...  
Keyword(s):  
Incidence Rate ◽  
Safety Profile ◽  
Castration Resistant Prostate Cancer ◽  
Prior Chemotherapy ◽  
Favorable Safety Profile ◽  
Post Hoc Analysis ◽  
Long Term Treatment ◽  
Favorable Safety ◽  
Post Hoc

5009 Background: AA, a CYP17 inhibitor, prolongs the lives of men with progressive pre- or post-chemotherapy treated mCRPC with a favorable safety profile (Rathkopf et al. ASCO-GU 2013. Abstr 5). This post hoc analysis examines the safety and tolerability of long-term treatment (≥ 24 mos) in study COU-AA-302. Methods: 1,088 pts were randomized 1:1 to AA 1000 mg + P 5 mg po BID vs placebo + P. Co-primary endpoints were radiographic progression-free survival (rPFS) and OS. Median times with 95% CI of the end points were estimated using the Kaplan-Meier (KM) method. Post hoc analysis of adverse events (AEs) was performed at pre-specified interim analysis (IA3) (55% OS events). Results: At a median follow-up = 27.1 mos (IA3): rPFS HR (95% CI) = 0.53 (0.45, 0.62), p < 0.0001 and OS was improved over P [0.79 (0.66, 0.96), p = 0.0151]; the latter did not reach the pre-specified efficacy boundary (p = 0.0035). All secondary endpoints favored the AA arm (Rathkopf et al. ASCO-GU 2013. Abstr 5). The incidence rate of selected AEs by duration of exposure is shown below (Table). There was no clinically relevant increase in the incidence rate of AEs with longer exposure using AA + P versus P alone; although pts on treatment for ≥ 24 mos may have had greater tolerability. The percentage of patients who came off study due to an AE was 8% (AA) versus 6% (P). Conclusions: The updated IA3 of COU-AA-302 in pts without prior chemotherapy confirms the delay in progression and prolongation of life with a favorable safety profile including pts treated for ≥ 24 mos with AA + P or P. Clinical trial information: NCT00887198. [Table: see text]

Larotrectinib efficacy and safety in adult TRK fusion cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3122-3122 ◽  
Author(s):  
David S. Hong ◽  
Shivaani Kummar ◽  
Anna F. Farago ◽  
Ulrik Niels Lassen ◽  
Jordan Berlin ◽  
...  
Keyword(s):  
Disease Progression ◽  
Safety Profile ◽  
Safety Data ◽  
Disease Status ◽  
Bone Sarcoma ◽  
Primary Diagnosis ◽  
Efficacy And Safety ◽  
Favorable Safety Profile ◽  
Duration Of Response ◽  
Favorable Safety

3122 Background: A broad range of pediatric and adult malignancies harbor TRK fusions involving the NTRK1, NTRK2, and NTRK3 genes. The highly-selective TRK inhibitor, larotrectinib, has previously shown a high overall response rate (ORR) and a favorable safety profile in patients (pts) with TRK fusion cancer. To better delineate efficacy in adults, as pediatric pts have a particularly high ORR, here we report updated efficacy and safety data from the adult subset of pts with TRK fusion cancer treated with larotrectinib. Methods: Adult pts (aged 18 or older) with TRK fusion cancer detected by local testing in 2 larotrectinib clinical trials (NCT02122913 and NCT02576431) were analyzed. Larotrectinib was administered 100 mg PO BID until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed by both investigator (INV) and independent assessment (IRC) using RECIST v1.1. Results: As of July 30, 2018, 83 adults (median age: 57 y, range 20–80 y) with TRK fusion cancer had been treated. Cancer types included salivary gland (23%) and thyroid cancer (19%), soft tissue sarcoma (14%), lung cancer (13%), colon cancer and melanoma (7% each), GIST (5%), and bone sarcoma, cholangiocarcinoma, and appendiceal, breast, and pancreas cancer (≤2% each). TRK fusions involved NTRK1 (40%), NTRK2 (2%), and NTRK3 (57%). 77% of pts had received prior systemic therapy (median lines: 2, range 0–10). In 74 pts evaluable per INV, the ORR was 76% with 9% CR, 57% confirmed PR, 9% PR pending confirmation, 12% SD, 11% PD, and 1% not determined; 9 pts were non-evaluable (NE) due to lack of post-baseline assessment. In 65 pts evaluable per IRC, the ORR was 68% with 17% CR, 51% PR, 15% SD, 12% PD, and 5% NE. With a median follow up of 17.2 and 17.5 mo per INV and IRC, respectively, the median duration of response had not been reached (ranges identical: 1.9+ to 38.7+ months). At data cutoff, 63% remained on treatment; 30% had discontinued due to disease progression. Adverse events were mostly grade 1–2. Conclusions: Larotrectinib demonstrated robust tumor-agnostic efficacy and a favorable safety profile in adult pts with TRK fusion cancer. These results support testing for TRK fusion cancer in pts with advanced solid tumors, regardless of site of primary diagnosis. Clinical trial information: NCT02122913 and NCT02576431.

scholarly journals Budesonide Foam Has a Favorable Safety Profile for Inducing Remission in Mild-to-Moderate Ulcerative Proctitis or Proctosigmoiditis

2015 ◽  
Vol 60 (11) ◽  
pp. 3408-3417 ◽  
Author(s):  
David T. Rubin ◽  
William J. Sandborn ◽  
Brian Bosworth ◽  
Salam Zakko ◽  
Glenn L. Gordon ◽  
...  
Keyword(s):  
Safety Profile ◽  
Ulcerative Proctitis ◽  
Favorable Safety Profile ◽  
Budesonide Foam ◽  
Favorable Safety
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