Phase 2 study of the CDK4 inhibitor abemaciclib in dedifferentiated liposarcoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11004-11004 ◽  
Author(s):  
Mark Andrew Dickson ◽  
Andrew Koff ◽  
Sandra P. D'Angelo ◽  
Mrinal M. Gounder ◽  
Mary Louise Keohan ◽  
...  
Keyword(s):  
Partial Response ◽  
Primary Endpoint ◽  
Study Drug ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Cancer Center ◽  
Phase 2 ◽  
Prior Therapy ◽  
Phase 2 Study ◽  
Cdk4 Inhibitor

11004 Background: The oncogene cyclin-dependent kinase 4 (CDK4) is amplified in > 90% of de-differentiated liposarcomas (DDLS). We previously demonstrated that treatment with the CDK4 inhibitor palbociclib results in favorable progression-free survival (PFS) in DDLS. Abemaciclib is a newer and more potent CDK4 inhibitor. This single-arm phase 2 study was designed to test the activity of abemaciclib in DDLS. Methods: Participants were adults with advanced DDLS, measurable disease by RECIST 1.1, any (or no) priory therapy, and progression by RECIST in the 6 months prior to study entry. The primary endpoint was PFS at 12 weeks. Based on historical data, promising drugs have 12-week PFS of ≥ 40% and not promising ≤ 20%. This study would be positive if 12-week PFS was ≥ 60%. The study was approved by the Institutional Review Board of Memorial Sloan-Kettering Cancer Center and all patients provided written informed consent. The study was registered at Clinicaltrials.gov (NCT02846987) and study drug was provided by Eli-Lilly. Results: Treatment was abemaciclib 200 mg by mouth twice daily continuously. 30 patients were treated and 29 were evaluable for the primary endpoint. Patient characteristics: Median age 62 (range 39-88), 60% male. Lines of prior therapy: 0 (50%); 1 (33%); ≥ 2 (17%). The observed PFS at 12 weeks was 76% (95% CI 57-90%). Median PFS was 30.4 weeks (95% CI 28.9-NE). There was one partial response. A further 3 patients had > 10% decrease in tumor size by RECIST but did not meet the criterion for partial response. Grade 3-4 toxicity included anemia (37%), neutropenia (20%), thrombocytopenia (17%) and diarrhea (7%). Conclusions: This study met its primary endpoint. In patients with advanced progressive DDLS, abemaciclib treatment results in favorable PFS and objective tumor response with manageable toxicity. Updated response data and results of paired tumor biopsies will be presented. Clinical trial information: NCT02846987.

Combination ibrutinib (Ibr) and venetoclax (Ven) for the treatment of mantle cell lymphoma (MCL): Primary endpoint assessment of the phase 2 AIM study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7520-7520 ◽  
Author(s):  
Constantine Si Lun Tam ◽  
Andrew Warwick Roberts ◽  
Mary Ann Anderson ◽  
Sarah-Jane Dawson ◽  
Rodney J Hicks ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Phase Iii ◽  
Phase 2 ◽  
Prior Therapy ◽  
Pet Ct ◽  
Phase 2 Study ◽  
Mantle Cell ◽  
Starting Dose ◽  
Grade 3

7520 Background: Both ibr and ven have activity in relapsed/refractory (R/R) MCL, but complete remissions (CR) are attained in <25% with either. We sought to determine the activity of the combination in an investigator-initiated, phase 2 study. Methods: Enrolment of 24 patients (pts) with R/R (n=23) or frontline (n=1) MCL completed in 09/16. Pts received 4 weeks of ibr (560mg/d), followed by introduction of ven (weekly ramp-up to target 400mg/d). The primary endpoint was CR rate at week 16, as assessed by PET/CT, BMAT, flow & molecular MRD, and endoscopy (if baseline gut involvement). Response was calculated separately with and without knowledge of the PET result by IWG criteria (Cheson JCO 2007), in order to compare with published studies (ibr, 9% CR at wk16; ven, best CR rate 21%). Results: Median age of pts was 68 (range, 47-81) years. For the R/R pts (n=23), median lines of prior therapy was 2 (1-6), 48% were refractory to last treatment, and 30% had failed previous autologous SCT. As of data cutoff on Jan 11 2017, 18 pts remain on therapy, and 6 stopped treatment due to progressive disease (4), adverse event (1) or unrelated death (1). At week 16, ORR was 71% (63% CR) and 80% of complete responders were flow-cytometry negative in the marrow (sensitivity 10-3 to 10-4). Using CT without PET, the comparison responses were CR 42%, CRu 17%, PR 17% (ORR 78%). After a median follow-up of 8.3 (range 1.4-17.7) months, the 8-month estimates of PFS and OS months are 74% and 81%. Adverse events ≥20%, irrespective of attribution, were fatigue (71%), diarrhea (67%), nausea (50%), URTI (38%), gastro-esophageal reflux (33%), neutropenia (33%), cough (25%) and bruising (21%); with the exception of neutropenia (25% grade 3-4), these were predominantly grade 1-2 in severity. Tumour lysis syndrome occurred in 2 pts with high tumour burden, leading to revision of the protocol ven starting dose from 50mg, to 20mg/d. Conclusions: The combination of ibr and ven was tolerable and achieved CR rate of 63% at week 16 in pts with MCL. The efficacy results compare favorably with historical results, and warrant further phase III investigation. Clinical trial information: NCT02471391.

Phase 2, two-group, two-stage study of avelumab in patients (pts) with microsatellite stable (MSS), microsatellite instable (MSI), and polymerase epsilon (POLE) mutated recurrent/persistent endometrial cancer (EC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5502-5502 ◽  
Author(s):  
Panagiotis A. Konstantinopoulos ◽  
Joyce F. Liu ◽  
Weixiu Luo ◽  
Carolyn N. Krasner ◽  
Jeffrey Joseph Ishizuka ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Eligibility Criteria ◽  
Prior Therapy ◽  
Primary Endpoints ◽  
Phase 2 Study ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Mmr Proteins

5502 Background: This non-randomized phase 2 study evaluated the PD-L1 inhibitor avelumab in two cohorts of EC: i) MSI/ POLE cohort including ECs with immunohistochemical (IHC) loss of expression of at least one of the mismatch repair (MMR) proteins and/or documented mutation in the exonuclease domain of POLE and ii) MSS cohort including ECs with normal IHC expression of all MMR proteins. Methods: Eligibility criteria included measurable disease, unlimited prior therapies, and any EC histology. Co-primary endpoints were confirmed objective response (OR) and progression-free survival rate at 6 months (PFS6). Avelumab 10 mg/kg IV was given every 2 weeks until progression or unacceptable toxicity. In the 1st stage, 16 pts were enrolled in each cohort; if there were ≥2 ORs or ≥2 PFS6 responses, accrual would continue to the 2nd stage with enrollment of 19 additional pts. Overall, if there are ≥4 ORs or ≥8 PFS6 responses, avelumab would be considered worthy of further study in each cohort. Results: As of 12/2018, 33 pts were enrolled. The MSS cohort was closed at the 1st stage due to futility; of 16 pts in the MSS cohort, only 1 pt exhibited an OR and PFS6 response [ORR and PFS6 rate 6.25% (95% CI 0.16%-30.2%)]. Conversely, the MSI/POLE cohort reached the primary endpoint of 4 ORs after accrual of only 17 pts. Two pts in the MSI/POLE cohort did not initiate protocol therapy and were excluded from all analyses. Of 15 pts in the MSI/POLE cohort, 4 pts exhibited OR [1CR+3PRs, OR rate (ORR) 26.7% (95% CI 7.8%-55.1%)] and 6 pts (including the 4 pts with OR) exhibited PFS6 responses [PFS6 rate 40.0% (95% CI 16.3%-66.7%)], 4 ongoing and 3 approaching 2 yrs. Twenty-two pts (71%) reported treatment related toxicities, 6 patients (19%) G3 toxicities; there were no treatment-related G4 and G5 toxicities. In the MSI/POLE cohort, 5 of 6 PFS6 responses were observed in pts with ≥3 lines of prior therapy (p = 0.011) and in tumors who were PD-L1 negative by IHC. Further correlative work will be reported at the meeting. Conclusions: In EC pts stratified by MSI/POLE status, MSI vs MSS status appears to be correlated with avelumab response even in PD-L1 negative tumors. Responses in the MSI/POLE cohort were more frequent in more heavily pretreated patients, a finding that warrants further investigation. Clinical trial information: NCT02912572.

Phase 2 study of tremelimumab plus durvalumab for previously-treated malignant pleural mesothelioma (MPM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8549-8549 ◽  
Author(s):  
Deepti Venkatraman ◽  
Adrienne Anderson ◽  
Subba Digumarthy ◽  
Patrick H. Lizotte ◽  
Mark M. Awad
Keyword(s):  
Primary Endpoint ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Flow Cytometric ◽  
Phase 2 Study ◽  
Duration Of Response ◽  
Previously Treated ◽  
Pre Treatment

8549 Background: Treatment options are limited for patients (pts) with MPM who experience disease progression after first-line pemetrexed-based chemotherapy. This study was designed to explore the activity of combined CTLA-4 + PD-L1 immune checkpoint inhibition using tremelimumab plus durvalumab in previously-treated MPM. Methods: We conducted a phase 2 study of tremelimumab 75 mg plus durvalumab 1500 mg administered intravenously every 4 weeks for four cycles followed by durvalumab maintenance every 4 weeks. Eligible pts had previously received pemetrexed-based platinum doublet chemotherapy and had measurable disease using modified RECIST criteria for mesothelioma. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS), and duration of response (DoR) as well as safety and tolerability of this combination. A Simon two-stage design was employed to enroll up to 40 patients if 4 or more responses were observed among the first 19 study patients. Pre-treatment, on-treatment, and optional post-progression biopsies underwent flow cytometric immunoprofiling for correlative studies. Results: Among 19 pts enrolled in this study, the best objective response was a confirmed partial response in one patient (5%), stable disease in 9 pts (47%), progressive disease in 8 pts (42%), and not evaluable in one patient. At a median follow-up of 7.1 months, the median PFS was 2.8 months (95% CI 2.04-5.72), and the median OS was 7.8 months (95% CI 6.24-not reached). Of 17 PD-L1 evaluable cases, 10 (59%) were PD-L1 negative, and 7 (41%) had a PD-L1 tumor proportion score of ≥1%. Treatment was generally well-tolerated and there were no treatment-related study discontinuations or deaths. Flow cytometric immunologic changes over the course of treatment associated with disease control will be presented. Conclusions: Tremelimumab + durvalumab was well-tolerated in unselected pts with previously-treated MPM. This study did not meet its primary endpoint. Additional strategies are necessary to develop novel immunotherapeutics and biomarkers of response in MPM. Clinical trial information: NCT03075527.

scholarly journals Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3016-3024 ◽  
Author(s):  
Xavier C. Badoux ◽  
Michael J. Keating ◽  
Xuemei Wang ◽  
Susan M. O'Brien ◽  
Alessandra Ferrajoli ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Final Analysis ◽  
Patient Characteristics ◽  
Lymphocytic Leukemia ◽  
Prior Exposure ◽  
Chromosome 17 ◽  
Prior Therapy ◽  
Previously Treated Patients ◽  
First Relapse ◽  
Previously Treated

Abstract Optimal management of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) is dictated by patient characteristics, prior therapy, and response to prior therapy. We report the final analysis of combined fludarabine, cyclophosphamide, and rituximab (FCR) for previously treated patients with CLL and identify patients who benefit most from this therapy. We explore efficacy of FCR in patients beyond first relapse, patients with prior exposure to fludarabine and alkylating agent combinations, and patients with prior exposure to rituximab. The FCR regimen was administered to 284 previously treated patients with CLL. Patients were assessed for response and progression by 1996 National Cancer Institute–Working Group (NCI-WG) criteria for CLL and followed for survival. The overall response rate was 74%, with 30% complete remission. The estimated median overall survival was 47 months and median progression-free survival for all patients was 21 months. Subgroup analyses indicated that the following patients were most suitable for FCR treatment: patients with up to 3 prior treatments, fludarabine-sensitive patients irrespective of prior rituximab exposure, and patients without chromosome 17 abnormalities. FCR is an active and well-tolerated therapy for patients with relapsed CLL. The addition of rituximab to FC improved quality and durability of response in this patient population.

Eribulin and gemcitabine in previously treated patients with advanced liposarcoma or leiomyosarcoma: A multicenter, single-arm, phase 2-trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11516-11516
Author(s):  
Chang Gon Kim ◽  
Jin-Hee Ahn ◽  
Jeong Eun Kim ◽  
Jee Hung Kim ◽  
Min Kyung Jeon ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Alternative Hypothesis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Histologic Types

11516 Background: Eribulin and gemcitabine have shown encouraging efficacy in soft-tissue sarcoma (STS) as a monotherapy. Here, we evaluated the activity and safety of combined use of eribulin and gemcitabine in two most common histologic types of STS, liposarcoma and leiomyosarcoma. Methods: In this non-randomized, multi-center phase 2 study, patients were included if they had progressive disease after one or two prior chemotherapy including doxorubicin. Patient were given eribulin 1.4 mg/m2 and gemcitabine 1,000 mg/m2 on day1 and day 8 every 3 weeks. The primary endpoint was progression-free survival rate at 12 weeks (PFSR12wks) with null and alternative hypothesis of PFSR12wks≤20.0% and ≥40.0%, respectively. Results: Of 37 patients included, 22 had leiomyosarcoma, and 15 had liposarcoma. At 12-weeks after treatment, 16 and (72.7%) 11 (73.3%) patients in leiomyosarcoma and liposarcoma were progression-free. Overall PFSR12wks was 73.0%, satisfying the primary endpoint. Objective response rate, disease control rate, median progression-free survival, and median overall survival were 16.2%, 78.4%, 23.9 weeks, and 88.9 weeks, without any statistical differences according to histologic subtypes. No new safety signals and treatment-related death were observed. Conclusions: Eribulin and gemcitabine showed promising activity and manageable safety profile in patients with STS of liposarcoma and leiomyosarcoma histology. Updated outcomes for ongoing patients will be presented. Clinical trial information: NCT03810976.

scholarly journals A Randomized Phase 2 Study of ADXS11-001 Listeria monocytogenes–Listeriolysin O Immunotherapy With or Without Cisplatin in Treatment of Advanced Cervical Cancer

2018 ◽  
Vol 28 (4) ◽  
pp. 764-772 ◽  
Author(s):  
Partha Basu ◽  
Ajay Mehta ◽  
Minish Jain ◽  
Sudeep Gupta ◽  
Rajnish V. Nagarkar ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Listeria Monocytogenes ◽  
Adverse Events ◽  
Progression Free Survival ◽  
Combination Group ◽  
Listeriolysin O ◽  
Phase 2 ◽  
Safety And Efficacy ◽  
Treatment Groups ◽  
Phase 2 Study

ObjectivesA global unmet medical need exists for effective treatments for persistent, recurrent, or metastatic cervical cancer, as patients have a short life expectancy. Recently, immunotherapies have shown promising survival benefits for patients with advanced forms of cancer. Axalimogene filolisbac (ADXS11-001), aListeria monocytogenesimmunotherapy with a broad effect on the immune system, is under investigation for treatment of human papillomavirus–associated cancers including cervical cancer.MethodsThis phase 2 study evaluated the safety and efficacy of ADXS11-001, administered with or without cisplatin, in patients with recurrent/refractory cervical cancer following prior chemotherapy and/or radiotherapy. A total of 109 patients were treated, and 69 were evaluable for tumor response at equal to or more than 3 months postbaseline.ResultsMedian overall survival (OS) was comparable between treatment groups (ADXS11-001: 8.28 months; 95% confidence interval [CI], 5.85–10.5 months; ADXS11-001 + cisplatin: 8.78 months; 95% CI, 7.4–13.3 months). The 12- and 18-month milestone OS rates were 30.9% versus 38.9%, and 23.6% versus 25.9% for each group, respectively (34.9% and 24.8% combined). Median progression-free survival (6.10 vs 6.08 months) and the overall response rate (17.1% vs 14.7%) were similar for both groups. ADXS11-001 was generally well tolerated; adverse events were predominantly mild to moderate in severity and not related to treatment. More adverse events were reported in the combination group (429 vs 275).ConclusionsThese promising safety and efficacy results, including the encouraging 12-month 34.9% combined OS rate, warrant further investigation of ADXS11-001 for treatment of recurrent/refractory cervical cancer.

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 using oral thalidomide-cyclophosphamide-prednisone for idiopathic multicentric Castleman disease

Blood ◽  
2019 ◽  
Vol 133 (16) ◽  
pp. 1720-1728 ◽  
Author(s):  
Lu Zhang ◽  
Ai-lin Zhao ◽  
Ming-hui Duan ◽  
Zhi-yuan Li ◽  
Xin-xin Cao ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Progression Free Survival ◽  
Castleman Disease ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Multicentric Castleman Disease ◽  
End Point ◽  
Phase 2 Study ◽  
Grade 3

Abstract Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder. The anti–interleukin 6 (IL-6) therapy siltuximab is not available everywhere, and is not effective for over one-half of patients. Alternative treatment approaches are urgently needed. In the first iMCD clinical trial directed against a target other than IL-6 signaling, we investigated a thalidomide-cyclophosphamide-prednisone (TCP) regimen in newly diagnosed iMCD patients. This single-center, single-arm, phase 2 study enrolled 25 newly diagnosed iMCD patients between June 2015 and June 2018. The TCP regimen (thalidomide 100 mg daily for 2 years; oral cyclophosphamide 300 mg/m2 weekly for 1 year; prednisone 1 mg/kg twice a week for 1 year) was administered for 2 years or until treatment failure. The primary end point was durable tumor and symptomatic response for at least 24 weeks. Twelve patients (48%) achieved the primary end point with no relapse, 3 patients (12%) demonstrated stable disease, and 10 patients (40%) were evaluated as treatment failure. Even when considering all patients, there were significant (P &lt; .05) improvements in median symptom score, IL-6 level, hemoglobin, erythrocyte sedimentation rate, albumin, and immunoglobulin G. Among responders, the median levels of all evaluated parameters significantly improved, to the normal range, after treatment. The regimen was well tolerated. One patient died of pulmonary infection and 1 patient had a grade 3 adverse event (rash); 2 patients died following disease progression. Estimated 1-year progression-free survival and overall survival were 60% and 88%, respectively. The TCP regimen is an effective and safe treatment of newly diagnosed iMCD patients, particularly when siltuximab is unavailable. This trial was registered at www.clinicaltrials.gov as #NCT03043105.

scholarly journals 1477. A Randomized Phase 2 Study of Cefepime Combined with the Novel Extended Spectrum β-Lactamase Inhibitor Enmetazobactam in Hospitalized Adults with Complicated Urinary Tract Infections (cUTI) Including Acute Pyelonephritis (AP)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S539-S539
Author(s):  
Yehuda Carmeli ◽  
Philipp Knechtle ◽  
Jeff Hardenberg ◽  
Mathias Knecht
Keyword(s):  
Study Drug ◽  
Generation Cephalosporin ◽  
Double Blind Study ◽  
The Novel ◽  
Phase 2 ◽  
Double Blind ◽  
Extended Spectrum ◽  
Phase 2 Study ◽  
Dosing Regimens ◽  
Tract Infections

Abstract Background Third-generation cephalosporin (3GC)-resistant Enterobacteriaceae has been classified as critical priority pathogens. The novel extended-spectrum β-lactamase (ESBL) inhibitor enmetazobactam (formerly AAI101; EMT) in combination with cefepime (FEP) is currently being developed as a carbapenem-sparing treatment of serious Gram-negative infections in settings with a high prevalence of 3GC-resistant Enterobacteriaceae. We report here the results from a phase 2 study that assessed safety, tolerability, and pharmacokinetics of FEP-EMT in patients with cUTI/AP. Methods Forty-five patients were enrolled in a randomized, multicenter, double-blind study of hospitalized adults with cUTI/AP. Patients received dosing regimens of FEP or FEP-EMT IV therapy q8h by 2 hours infusion (table) for 7 to 10 days with a 28-day follow-up. Efficacy was evaluated in the microbiological-modified ITT (µMITT) population. Safety was monitored in patients who received at least 1 dose of study drug. Clinical cure was designated as the resolution of cUTI symptoms present at study entry. Plasma and urine PK were determined from all patients. Results The study drugs were well tolerated in each cohort, with similar % adverse events and no new or unexpected safety concerns (table). Two discontinuations were due to allergic dermatitis. The microbiological- and clinical responses at test-of-cure for the combined FEP-EMT group were 83.3% (20/24) and 95.8% (23/24) compared with responses in the combined FEP group of 73.3% (11/15) and 93.3% (14/15), respectively (table). The most common baseline pathogens were Escherichia coli (66.7%) and Klebsiella pneumoniae (23.1%): 28.2% of isolates produced ESBLs with eradication rates for the combined FEP-EMT group of 85.7% (6/7) and for the combined FEP group of 75.0% (3/4). FEP and EMT PK were best described by a 2-compartment, linear PK model. Both agents exhibited half-lives of 2.3 hours. Creatinine clearance had a significant covariate effect on FEP and EMT, consistent with predominant renal excretion of both agents. Conclusion Results from this phase 2 study justify advancement to phase 3 studies to evaluate the safety and efficacy of FEP-EMT in patients with cUTI/AP. Disclosures All authors: No reported disclosures.

scholarly journals LB3. Exebacase (EXE) Reduced Length of Stay and 30-Day Readmission Rates for US Patients with Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia Including Endocarditis Compared with Standard of Care Antibiotics (SoC) Alone in a Phase 2 Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S994-S994
Author(s):  
Cara Cassino ◽  
Cara Cassino ◽  
Hemal Shah ◽  
Joy Lipka-Diamond ◽  
Anita F Das
Keyword(s):  
Staphylococcus Aureus ◽  
Length Of Stay ◽  
Study Drug ◽  
Standard Of Care ◽  
The United States ◽  
Controlled Study ◽  
Phase 2 ◽  
Readmission Rates ◽  
Phase 2 Study ◽  
Study Results

Abstract Background Exebacase, a lysin (cell wall hydrolase), is the first direct lytic agent to report Phase 2 study results in Staphylococcus aureus bacteremia including endocarditis. Among MRSA patients enrolled in this randomized, double-blind, placebo, controlled study, EXE used in addition to standard of care antibiotics (SoC), had 42.8% higher clinical responder rates (CRRs) compared SoC alone. We sought to determine whether these differences in CRRs translated into reductions in health resource utilization (HRU) in this population of critically ill, hospitalized patients. Methods The microbiological intent-to-treat population included 116 patients (71 EXE, 45 SoC) with documented S. aureus who received a single 2-hour infusion of blinded study drug dosed based on target attainment. The primary efficacy endpoint was CRR at Day 14. Diagnoses and clinical outcomes were determined by a blinded Adjudication Committee. HRU including length of stay (LOS), and 30-day hospital readmission rates (HRR) for all causes (AC) and for S. aureus (SA) were evaluated in MRSA patients who were alive at the time of discharge. Results The average patient was white, male and ~56 years old (67.8%). Twenty-seven EXe patients (38.0%) and 16 SoC patients (35.6%) had MRSA. All but 2 MRSA patients (1 EXE, 1 SoC) were enrolled in the United States. The Day 14 CRR were 70.4% for EXE and 60.0% for SoC groups (p=0.314) overall. In a prespecified analysis of MRSA patients, the CRR with EXE was 74.1% vs. 31.3% with SoC (P = 0.010). Among MRSA patients who received study drug, incidence of treatment emergent adverse events (TEAEs) was balanced between groups (24 (88.9%) in EXE and 15 (98.3%) in SoC) as were serious TEAEs (17(63.0%) in EXE, 12 (75%) in SoC). 1 EXE and 2 SoC US MRSA patients died in hospital. Among US MRSA patients discharged alive from the hospital, the median LOS after study drug was 6 vs. 10 days for EXE and SoC, respectively. Thirty-day AC HRR were 16% vs. 30.8%, for EXE vs. SoC, respectively, and 30-day SA HRR were 8% vs. 15.4%, respectively. Conclusions Exebacase used in addition to SoC was associated with a reduction in length of hospital stay and 30-day readmission rates for all causes and for S. aureus compared with SoC alone in patients being treated for MRSA bacteremia/endocarditis. Disclosures Cara Cassino, MD, ContraFect Corporation (Employee), Hemal Shah, PharmD, Boehringer Ingelheim (Consultant), ContraFect Corp (Consultant), DBV Technologies (Consultant), Mylan specialty (Consultant), Nabriva (Consultant), Joy Lipka-Diamond, MS, ContraFect Corporation (Consultant), Anita F. Das, PhD, Achaogen (Consultant), AntiobioTx (Consultant), Boston Pharmaceuticals (Consultant), Cempra (Consultant), ContraFect Corporation (Consultant), Iterum Therapeutics (Consultant), Nabriva (Consultant), Paratek (Consultant), Tetraphase (Consultant), UTILITY (Consultant), Wockhardt (Consultant).

Sign in / Sign up

Export Citation Format

Share Document