scholarly journals Correction to: Selinexor in combination with topotecan in patients with advanced or metastatic solid tumors: Results of an open-label, single-center, multi-arm phase Ib study

2021 ◽  
Author(s):  
Kyaw Zin Thein ◽  
Sarina A. Piha-Paul ◽  
Apostolia Tsimberidou ◽  
Daniel D. Karp ◽  
Filip Janku ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Single Center ◽  
Open Label ◽  
Phase Ib

scholarly journals Selinexor in combination with topotecan in patients with advanced or metastatic solid tumors: Results of an open-label, single-center, multi‐arm phase Ib study

2021 ◽  
Author(s):  
Kyaw Zin Thein ◽  
Sarina A. Piha-Paul ◽  
Apostolia Tsimberidou ◽  
Daniel D. Karp ◽  
Filip Janku ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Single Center ◽  
Open Label ◽  
Phase Ib

Selinexor in combination with weekly paclitaxel in patients with advanced or metastatic solid tumors: Results of an open label, single-center, multiarm phase 1b study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5565-5565
Author(s):  
Shannon Neville Westin ◽  
Siqing Fu ◽  
Apostolia Maria Tsimberidou ◽  
Sarina Anne Anne Piha-Paul ◽  
Fechukwu Akhmedzhanov ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Solid Tumors ◽  
Clinical Benefit ◽  
Nuclear Export ◽  
Nuclear Accumulation ◽  
Weekly Paclitaxel ◽  
Clinical Activity ◽  
Single Center ◽  
Open Label ◽  
Phase 1B

5565 Background: Selinexor is a first-in-class novel, oral potent selective inhibitor of nuclear export (SINE) which blocks Exportin-1 (XPO1) leading to nuclear accumulation and activation of tumor suppressor proteins and prevention of translation of proto-oncogenes. Weekly paclitaxel is a standard chemotherapy regimen used in various tumor types. Preclinical models show that selinexor with paclitaxel exerts antitumor activity against multiple solid tumors. Our objective was to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of selinexor and weekly paclitaxel. Methods: This was an open label, single-center, multi-arm phase 1b study utilizing a “3 + 3” design and a “basket type” expansion. Selinexor (twice weekly orally) and weekly paclitaxel (80mg IV 2 week on, 1 week off) was employed as one of 13 parallel arms. Two dose levels (DL) of selinexor were explored: DL1 selinexor 60mg; DL2 selinexor 80mg. Patients (pts) with advanced or metastatic solid tumors were eligible if they had adequate bone marrow and organ function. There was no limit on prior lines of therapy. Efficacy was evaluated using RECIST 1.1. Progression free survival (PFS) was defined as time from treatment until disease progression or death. Results: Of 35 pts treated, all were evaluable for toxicity, and 31 (88%) were evaluable for response. Pt diagnoses included ovarian (n = 28), breast (n = 4), prostate (n = 2), and cervical (n = 1) cancer. Pts had a median of four prior therapies (range 1-10), and 47% had a prior taxane. All pts with ovarian cancer had platinum resistant/refractory disease; high grade serous histology was most common. There were no DLTs and DL1 was chosen as the RP2D given its long term tolerability. 97% of pts had at least one treatment-emergent adverse event (TEAE) and the most common TEAEs were anemia (74%), nausea (57%), fatigue (51%), leukopenia (51%), neutropenia (49%), thrombocytopenia (46%), and vomiting (31%). The most prevalent grade ≥ 3 TEAE were neutropenia (46%), anemia (31%), leukopenia (17%), and fatigue (9 %). Partial responses (PR) were noted in 4 pts (13%); 10 pts (32%) achieved stable disease for > 4 months for a clinical benefit rate (CBR) of 45%. 16 pts (47%) had prior exposure to a taxane, including 1 pt who achieved PR. Among 24 evaluable pts with ovarian cancer, response rate was 17%, CBR was 58%, and PFS was 6.83 months (95% CI 3.73, not reached (NR)). Median duration of clinical benefit in ovarian cancer was 7.57 months (95% CI: 4.43, NR). Conclusions: Oral selinexor in combination with weekly paclitaxel demonstrated promising clinical activity with manageable toxicity, and further evaluation with once weekly selinexor is warranted. This combination should be considered for further exploration in a randomized study, especially in ovarian malignancies. Clinical trial information: NCT02419495.

scholarly journals 565P Selinexor in combination with topotecan in patients with advanced or metastatic solid tumours: Results of an open label, single-center, multi-arm phase Ib study

2020 ◽  
Vol 31 ◽  
pp. S486
Author(s):  
K.Z. Thein ◽  
A.M. Tsimberidou ◽  
S. Piha-Paul ◽  
F. Janku ◽  
D.D. Karp ◽  
...  
Keyword(s):  
Solid Tumours ◽  
Single Center ◽  
Open Label ◽  
Phase Ib

Results of a phase Ib study of ARQ 092 in combination with carboplatin (C) plus paclitaxel (P), or with P in patients (pts) with solid tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2524-2524 ◽  
Author(s):  
Nehal Lakhani ◽  
Anthony W. Tolcher ◽  
Drew W. Rasco ◽  
Amita Patnaik ◽  
Timothy J. O'Rourke ◽  
...  
Keyword(s):  
Platelet Count ◽  
Antitumor Activity ◽  
Solid Tumors ◽  
Neutrophil Count ◽  
Single Agent ◽  
Mucosal Inflammation ◽  
Akt Inhibitor ◽  
Open Label ◽  
Phase Ib

2524 Background: ARQ 092 is an oral, potent AKT inhibitor with single agent antitumor activity. P or P+C is the standard therapy or the therapy of choice for pts with various solid tumors. ARQ 092 potentiated antitumor activity of P in in vivo xenograft models, providing the rationale for this study. Methods: This is an open-label, phase Ib study of ARQ 092+C+P (CP Arm) or ARQ 092+P (P Arm) in pts with advanced solid tumors to determine safety and tolerability of these 2 combinations. Blood samples are collected for PK. Results: Enrollment into CP Arm has been completed with 13 pts (15% male; median age 62 years, 4 ovarian, 9 others) being treated in 2 dose cohorts (see table and results below). Enrollment into P Arm is ongoing. Data from P Arm (80 mg/m2 weekly) will be presented during the meeting. In CP Arm, 3 DLTs were observed in 2 pts (both received ARQ 092 at 200 mg BID, 1 day/week) including grade (G) 4 neutrophil count decreased, G 4 thrombocytopenia and G 3 diarrhea. ARQ 092-related adverse events (AEs) in ≥10% pts included diarrhea 69%, fatigue 54%, hyperglycemia 31%, maculopapular rash 31%, nausea 23%, mucosal inflammation 23%, anemia 15%, platelet count decreased 15% and hypokalemia 15%. Paclitaxel- and/or carboplatin-related AEs in ≥10% pts included fatigue 77%, alopecia 62%, thrombocytopenia 39%, platelet count decreased 39%, nausea 31%, lymphocyte count decreased 31%, neutrophil count decreased 31%, white blood cell count decreased 31%, anemia 23%, mucosal inflammation 23%, hypomagnesaemia 23%, peripheral sensory neuropathy 23%, neutropenia 15%, vomiting 15% and hypokalemia 15%. Two ovarian pts previously treated with CP achieved complete response (mutant AKT) and partial response (AKT mutation unknown) respectively and 3 pts (Gastroesophageal, pancreatic, ovarian mixed mullerian) experienced stable diseases for >12 weeks. PK data will be presented during the meeting. Conclusions: Encouraging anticancer activity was demonstrated in heavily pretreated ovarian cancer pts, but full dose CP was not tolerated by most patients. Clinical trial information: NCT02476955. [Table: see text]

A phase Ib/II, multicenter, open-label study of DSP-7888 dosing emulsion in combination with immune checkpoint inhibitors (CPI) nivolumab or pembrolizumab in adult patients (pts) with advanced solid tumors, including platinum-resistant ovarian cancer (PROC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6099-TPS6099
Author(s):  
Makoto Origuchi ◽  
Chris Korth ◽  
Zhonggai Li ◽  
Edgar E. Braendle
Keyword(s):  
Ovarian Cancer ◽  
Solid Tumors ◽  
Phase Ii ◽  
Metastatic Cancer ◽  
Objective Response ◽  
Clinical Activity ◽  
Induction Phase ◽  
Advanced Solid Tumors ◽  
Open Label ◽  
Phase Ib

TPS6099 Background: DSP-7888 is a therapeutic cancer vaccine composed of two synthetic peptides derived from Wilms’ tumor 1 (WT1) to promote both cytotoxic and helper T-lymphocyte-mediated immune responses against WT1-expressing tumors. WT1 is overexpressed in various solid tumors, including ovarian cancer. Combining cancer vaccines like DSP-7888 with a CPI may reduce resistance to immunomodulators and improve clinical benefit. A phase Ib/II study is being conducted to evaluate DSP-7888 in combination with a CPI in pts with advanced solid tumors, including PROC (NCT03311334). Methods: This phase Ib/II, open-label, multicenter, two-part dose-search/dose-expansion study investigates DSP-7888 + nivolumab or pembrolizumab in pts with advanced solid tumors (phase Ib), including PROC (phase II). The phase Ib primary objectives are safety, tolerability, and identification of the recommended phase II dose (RP2D). The phase II primary objective is evaluation of objective response rate (ORR); secondary objectives are clinical activity, safety, and tolerability. Pts aged ≥18 years with unresectable, metastatic cancer approved for treatment with nivolumab (phase Ib, Arm 1, n=6–12, 7 enrolled) or pembrolizumab (phase Ib, Arm 2, n=6–12, 6 enrolled), or with PROC (phase II) are eligible. Phase II will enroll ~40 pts into two groups based on programmed death-ligand 1 status (combined positive score of ≥10 [Group 1] or <10 [Group 2]). Clinical activity will be assessed continuously using Bayesian analysis and actual enrollment may increase by ~20 pts/group based on this analysis. Pts in phase II will receive DSP-7888 intradermally (RP2D from phase Ib) once a week (wk) for 6 wks in the induction phase then every 3 wks in the maintenance phase. Beginning Day 1, pembrolizumab will be administered intravenously every 3 wks. In phase II, objective disease will be assessed every 6 wks for 24 wks, then every 12 wks until progression. Endpoints include ORR (per RECIST v1.1) (primary), duration of response, disease control rate (DCR), progression-free survival (PFS), 6-month PFS rate (per RECIST v1.1), and overall survival, immune (i)ORR, iDCR, and iPFS (per iRECIST) (secondary). Exploratory endpoints include blood and tumor tissue biomarkers. Safety and tolerability, assessed by adverse events, will be evaluated throughout the duration of the study and follow-up. This study is currently recruiting patients. Clinical trial information: NCT03311334.

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