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.

Efficacy and safety evaluation of HLX10 (a recombinant humanized anti-PD-1 monoclonal antibody) combined with albumin-bound paclitaxel in patients with advanced cervical cancer who have progressive disease or intolerable toxicity after first-line standard chemotherapy: A single-arm, open-label, phase 2 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17510-e17510
Author(s):  
Lingying Wu ◽  
Xiumin Li ◽  
Jing Wang ◽  
Lijing Zhu ◽  
Ruifang An ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Adverse Events ◽  
Cancer Patients ◽  
Advanced Cervical Cancer ◽  
Phase 2 ◽  
First Line ◽  
Standard Chemotherapy ◽  
Open Label ◽  
Phase 2 Study ◽  
Line Standard

e17510 Background: Limited effective treatments are available for advanced cervical cancer patients who progress after first-line chemotherapy. Historic data indicate PD-1 antibodies have significant activity in advanced cervical cancer patients. This study was designed to determine the efficacy and safety of HLX10 (a recombinant humanized anti-PD-1 monoclonal antibody) plus albumin-bound paclitaxel in patients with advanced cervical cancer who have progressed on or are intolerant to first-line standard chemotherapy. Methods: This is an ongoing single-arm, open-label, multicenter, two-stage phase 2 study (NCT04150575). 143 eligible patients aged between 18 and 75, with histologically or cytologically diagnosed cervical cancer and positive PD-L1 expression (combined positive score [CPS] ≥1) were planned to be enrolled and given intravenous infusion of HLX10 (4.5 mg/kg) plus albumin-bound paclitaxel (260 mg/m2) every 3 weeks. Stage one (N = 20) was a safety run-in and preliminary efficacy exploration study with primary endpoints of adverse events, serious adverse events and objective response rate (ORR, assessed by IRRC per RECIST v1.1). In this stage, after all patients completed two tumor evaluations (every 6 weeks), a safety evaluation and a preliminary evaluation of anti-tumor efficacy were conducted to determine whether to proceed to the second stage (N = 123). Stage two is a single-arm, open-label, multicenter, phase 2 study with primary endpoint of ORR assessed by IRRC per RECIST v1.1. Results: Here we report the stage one results (safety and preliminary efficacy) of HLX10 in advanced cervical cancer patients. By cut-off date Oct 14, 2020, 21 eligible patients with median age of 50 (range: 31–65) and average CPS of 39.33 were enrolled; the median follow-up duration was 4.34 months. 71.4% patients had ECOG PS 1. The ORR assessed by IRRC and investigators were 52.4% (95% CI: 29.8%, 74.3%) and 42.9% (95% CI: 21.8%, 66.0%), respectively. The most common grade 3 or worse treatment-emergent adverse events (TEAEs) were decreased neutrophil counts (n = 7, 33.3%), decreased white blood cell count (n = 6, 28.6%) and anemia (n = 4, 19.0%). No TEAEs leading to drug discontinuation were observed. One death (multiple organ dysfunction syndrome) possibly related to treatment was reported. Conclusions: Stage one results demonstrated a manageable safety profile and encouraging efficacy (ORR 52.4%) of HLX10 plus albumin-bound paclitaxel in advanced cervical cancer patients who have progressive disease or intolerable toxicity to first-line standard chemotherapy, representing a novel potential treatment option that warranted further investigation. Clinical trial information: NCT04150575.

A retrospective study of anlotinib in patients with cervical cancer after chemoradiotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17509-e17509
Author(s):  
Liu Tan ◽  
Alan Chu ◽  
Yu Yang ◽  
Jinjin Yuan ◽  
Ge Hou ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Retrospective Study ◽  
Adverse Events ◽  
Objective Response ◽  
Progression Free Survival ◽  
Combination Group ◽  
Tyrosine Kinase Receptor ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Antiangiogenic Drug

e17509 Background: Anlotinib is a novel small molecule antiangiogenic drug, which can inhibit multiple tyrosine kinase receptor activity. Its antitumor activity has been proved in various cancers, including gynecological tumors. This retrospective study explored the efficacy and safety of anlotinib monotherapy or anlotinib combined chemotherapy in cervical cancer patients who have disease progressed or metastasis after chemoradiotherapy. Methods: 28 patients with cervical cancer admitted to the Second Affiliated Hospital of Zhengzhou University were enrolled. These patients who had received radiotherapy and at least one line chemotherapy had tumor progression or metastasis. 13 patients received anlotinib monotherapy (12mg/d from day 1 to day 14 in a 21-day cycle) and 15 patients received chemotherapy combined with the anlotinib. Treatment was continued until disease progression or death or intolerable adverse events. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS) and safety. Results: As of Dec 31 2020, no one was lost follow up. 2 patients were still under treatment, and 26 patients were evaluable. 1 CR, 6 PR, 13 SD, 6 PD, yielding the ORR of 26.92%, and the DCR of 76.92%. The median PFS for receiving anlotinib monotherapy was 4.57 (95% CI, 3.85-5.29) months, and 8.47 (95% CI, 5.09-11.85) months for combination group. The most common adverse events (AEs)were grade 1, including hypertension (46.43%), anemia (42.85%) and fatigue (39.29%). Grade 3 AEs were hypertension(10.71%) and anemia(7.14%). No higher grade AEs occurred. Conclusions: Anlotinib is safe and effective for patients with advanced cervical cancer after chemoradiotherapy, and it is well tolerated.

scholarly journals A Randomized Phase 2 Study of VT-1161 for the Treatment of Acute Vulvovaginal Candidiasis

2020 ◽  
Author(s):  
Stephen R Brand ◽  
Jack D Sobel ◽  
Paul Nyirjesy ◽  
Mahmoud A Ghannoum ◽  
Robert J Schotzinger ◽  
...  
Keyword(s):  
Adverse Events ◽  
Vulvovaginal Candidiasis ◽  
Phase 2 ◽  
Serious Adverse Events ◽  
Once Daily ◽  
Treatment Groups ◽  
Phase 2 Study ◽  
Dose Levels ◽  
To Receive

Abstract Background Acute vulvovaginal candidiasis (VVC) is common among women, but current azole antifungal treatments are often associated with safety and resistance issues. VT-1161 (oteseconazole) is an oral agent with increased selectivity for fungal CYP51. In this phase 2 clinical study, we evaluated the efficacy and safety of VT-1161 vs fluconazole in participants with moderate to severe acute VVC. Methods Participants presenting with an acute episode of VVC (n = 55) were randomized to receive VT-1161 300 mg once daily (q.d.) for 3 days, 600 mg q.d. for 3 days, or 600 mg twice daily (b.i.d.) for 3 days or to receive a single dose of fluconazole 150 mg (FDA-approved dose to treat acute VVC). Participants were followed for 6 months. The primary outcome was the proportion of participants with therapeutic (clinical and mycological) cure at day 28. Results A larger proportion of participants in the per-protocol population experienced therapeutic cure in the VT-1161 300 mg q.d. (75.0%), VT-1161 600 mg q.d. (85.7%), and VT-1161 600 mg b.i.d. (78.6%) groups vs the fluconazole group (62.5%); differences were not statistically significant. At 3 and 6 months, no participants in the VT-1161 groups vs 28.5% and 46.1% in the fluconazole group, respectively, had evidence of mycological recurrence. No serious adverse events or treatment-emergent adverse events leading to discontinuation were reported. Conclusions The majority of participants across all treatment groups achieved therapeutic cure at day 28. VT-1161 was well tolerated at all dose levels through 6 months of follow-up. Clinical Trials Registration NCT01891331.

scholarly journals Phase 2 study of TAS-117, an allosteric akt inhibitor in advanced solid tumors harboring phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog gene mutations

2021 ◽  
Author(s):  
Jii Bum Lee ◽  
Minkyu Jung ◽  
Seung Hoon Beom ◽  
Gun Min Kim ◽  
Hye Ryun Kim ◽  
...  
Keyword(s):  
Adverse Events ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Phosphatidylinositol 3 Kinase ◽  
Akt Inhibitor ◽  
Viral Oncogene ◽  
Phase 2 Study ◽  
Grade 3 ◽  
Viral Oncogene Homolog ◽  
Phosphatidylinositol 3

SummaryTAS-117 is a potent and selective allosteric pan-v-akt murine thymoma viral oncogene homolog (Akt) inhibitor. We conducted a single-arm single-center phase 2 study of TAS-117 in heavily treated patients with tumors refractory to systemic chemotherapy and harboring phosphatidylinositol 3-kinase (PI3K)/Akt mutations. Patients with gastrointestinal (GI) cancers were orally administered 16 mg TAS-117 daily, and those with non-GI tumors were administered 24 mg on a 4 days on/3 days off schedule. The primary endpoint was overall response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), PFS ratio, safety, and tolerability. Thirteen patients were enrolled: eight with non-GI (breast, ovarian, endometrial, and non-small cell lung) and five with GI (colon, rectal, gastric, and gallbladder) cancers. Ten patients were treated with TAS-117 after ≥ 4 lines of therapy. Twelve patients showed PIK3 catalytic subunit alpha (PIK3CA) mutations; one harbored an Akt1E17K mutation. The median treatment duration was 1.4 months; the median number of treatment cycles was 2. The ORR was 8 %, and DCR was 23 %. The median PFS and OS were 1.4 and 4.8 months, respectively. Grade 3–4 treatment-related adverse events were anorexia (grade 3, 8 %) and hyperglycemia (grade 3, 8 %; grade 4, 8 %).Grade 3–4 treatment-related adverse events occurred in 27 % of grade 3 anorexia (9 %) and hyperglycemia (grade 3, 8 %; grade 4, 9\%). TAS-117 showed limited antitumor activity and manageable toxicity. Clinical efficacy was observed in patients with ovarian cancer harboring PIK3CA E545K mutations and in patients with breast cancer harboring PIK3CA H1047R and Akt1E17K mutations.Trial registration: This study was retrospectively registered with ClinicalTrial.gov (NCT03017521 on January 11, 2017).

scholarly journals Safety and Efficacy of Gevokizumab in Patients with Behçet’s Disease Uveitis: Results of an Exploratory Phase 2 Study

2016 ◽  
Vol 25 (1) ◽  
pp. 62-70 ◽  
Author(s):  
Ilknur Tugal-Tutkun ◽  
Sibel Kadayifcilar ◽  
Moncef Khairallah ◽  
Sung Chul Lee ◽  
Pinar Ozdal ◽  
...  
Keyword(s):  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Phase 2 ◽  
Safety And Efficacy ◽  
Behcet's Disease ◽  
Phase 2 Study

scholarly journals Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study

2021 ◽  
Author(s):  
Takeshi Kato ◽  
Yoshinori Kagawa ◽  
Yasutoshi Kuboki ◽  
Makio Gamoh ◽  
Yoshito Komatsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Therapeutic Option ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Wild Type ◽  
Open Label ◽  
Safety And Efficacy ◽  
Multicentre Phase

Abstract Background We aimed to assess the safety and efficacy of combination treatment with panitumumab plus trifluridine/tipiracil (FTD/TPI) in patients with wild-type RAS metastatic colorectal cancer (mCRC) who were refractory/intolerant to standard therapies other than anti-epidermal growth factor receptor therapy. Methods APOLLON was an open-label, multicentre, phase 1/2 trial. In the phase 1 part, 3 + 3 de-escalation design was used to investigate the recommended phase 2 dose (RP2D); all patients in the phase 2 part received the RP2D. The primary endpoint was investigator-assessed progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and safety. Results Fifty-six patients were enrolled (phase 1, n = 7; phase 2, n = 49) at 25 Japanese centres. No dose-limiting toxicities were observed in patients receiving panitumumab (6 mg/kg every 2 weeks) plus FTD/TPI (35 mg/m2 twice daily; days 1–5 and 8–12 in a 28-day cycle), which became RP2D. PFS rate at 6 months was 33.3% (90% confidence interval [CI] 22.8–45.3). Median PFS, OS, ORR, DCR, and TTF were 5.8 months (95% CI 4.5–6.5), 14.1 months (95% CI 12.2–19.3), 37.0% (95% CI 24.3–51.3), 81.5% (95% CI 68.6–90.8), and 5.8 months (95% CI 4.29–6.21), respectively. Neutrophil count decreased (47.3%) was the most common Grade 3/4 treatment-emergent adverse event. No treatment-related deaths occurred. Conclusion Panitumumab plus FTD/TPI exhibited favourable anti-tumour activity with a manageable safety profile and may be a therapeutic option for pre-treated mCRC patients.

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