Multicenter, open-label phase II study of daily oral regorafenib for chemotherapy-refractory, metastatic and locally advanced angiosarcoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11561-11561
Author(s):  
Mark Agulnik ◽  
Steven Ian Robinson ◽  
Scott H. Okuno ◽  
Brittany Siontis ◽  
Steven Attia ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Study ◽  
Performance Status ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Open Label ◽  
Tie2 Receptor ◽  
Open Label Phase

11561 Background: Angiosarcoma has a particularly poor prognosis with 5-year overall survival rates of approximately 30-40%. Treatment of locally advanced and metastatic angiosarcoma is inadequate. Data strongly suggest concurrent, potent inhibition of VEGFR and Tie2 represents an attractive therapeutic strategy in angiosarcoma. Regorafenib displays potent VEGFR and Tie2 receptor inhibition and also possesses activity against additional potential targets in angiosarcoma including PDGFRs, RAF, KIT and FGFR, amongst others. Methods: A multicenter phase II study of regorafenib in patients with locally advanced or metastatic angiosarcoma was conducted through the Midwest Sarcoma Trials Partnership. Adequate performance status, organ function, measurable disease (RECIST 1.1) and 1-4 prior therapies were required. Regorafenib 160 mg PO daily was given in 28-day cycles (21 days on, 7 days off) until disease progression (PD) or unacceptable toxicity. The primary endpoint was progression-free survival (PFS), assessed at 16 weeks. Secondary endpoints include overall response rate (ORR), clinical benefit rate (CBR), OS, and safety and tolerability. A Simon 2-stage design was used. Results: After final enrollment of the second stage, a total of 31 pts were enrolled at 6 sites, 23 are evaluable for response. Median age was 65 (range 30-91); 50% were female, 67.7% had metastatic disease. PFS at 4 months is 52.2% with a median PFS and OS of 3.55 and 11.4 months. 1 confirmed CR and 2 PR, 12 SD and 8 PD were observed. ORR and CBR are 14.29 and 65.2%, respectively. No uncommon grade 3-4 adverse events were observed. 6 pts were non-evaluable due to refusal of further therapy and 2 patients progressed prior to first evaluation. Conclusions: Regorafenib was well tolerated in this study of pretreated patients with angiosarcomas and met its primary endpoint with a median PFS > 45% at 4 months. Treatment was feasible and did not reveal any previously unreported toxicities. Efficacy outcomes were complicated by early withdrawals of patients. RECIST responses were encouraging and regorafenib has a clinically meaningful 4-month PFS. Clinical trial information: NCT02048722 .

Regomune: A phase II study of regorafenib + avelumab in solid tumors—Results of the biliary tract cancer (BTC) cohort.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4096-4096
Author(s):  
Sophie Cousin ◽  
Carine A. Bellera ◽  
Jean Philippe Guégan ◽  
Thibault Mazard ◽  
Carlos A. Gomez-Roca ◽  
...  
Keyword(s):  
Phase Ii ◽  
Adaptive Design ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Treatment Interruption ◽  
Clinical Activity ◽  
Open Label

4096 Background: Regorafenib (R) has shown promising efficacy in patients (pts) with BTC refractory to standard chemotherapy. Anti-PD1/PD-L1 antibodies have only limited clinical activity. Synergy between R and anti–PD-1/PD-L1 antibodies has been shown in pre-clinical solid tumor models. Methods: This is a single-arm open-label multicentric phase II trial (Bayesian adaptive design) assessing the efficacy and safety of R (160 mg QD 3weeks/4) + avelumab (A) (10 mg/kg every 2 weeks) combination in BTC pts. The primary endpoint was the objective response rate under treatment, based on central review according to RECIST 1.1. Secondary endpoints included: 1-year progression free survival (PFS), 1-year overall survival (OS), and Safety using NCI-CTCAE v5.0. Correlative studies were planned from pts tumor samples obtained at baseline. Results: Between Nov. 2018 and Nov. 2019, 34 BTC pts were enrolled in 4 centers. Median age was 63 (range 36 – 80). Median follow-up was 9.8 months. Median number of previous treatment lines for metastatic or locally advanced disease was: 2 (range 1 – 4). Twenty-nine (85.3%) pts experienced at least 1 dose modification or treatment interruption of R or A due to an adverse event (AE) related to the treatment. The most common grade 3/4 AEs were : Hypertension (17.6%), Fatigue (14.7%), and maculo-papular rash (11.8%). No death was related to the treatment. Among the 29 pts with at least one imaging tumor assessment, 4 (13.8%) achieved a partial response, and 11 (37.9%) demonstrated stable disease including 10 (34.5%) pts with tumor shrinkage. Fourteen pts (48.3%) had progressive disease. The median PFS and OS were 2.5 months (95%CI 1.9 – 5.5) and 11.9 months (95%CI 6.2 – NA) respectively. Baseline tumor samples were available for 27 pts. High IDO and PD-L1 expression at baseline was associated with better outcome. Conclusions: The R+A combination is associated with significant anti-tumor activity with promising survival rates in this heavily pre-treated population. Full Biomarkers analyses will be presented at the meeting. Clinical trial information: NCT03475953.

Silmitasertib (CX-4945) in combination with gemcitabine and cisplatin as first-line treatment for patients with locally advanced or metastatic cholangiocarcinoma: A phase Ib/II study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 312-312
Author(s):  
Mitesh J. Borad ◽  
Li-Yuan Bai ◽  
Ming-Huang Chen ◽  
Joleen M. Hubbard ◽  
Kabir Mody ◽  
...  
Keyword(s):  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Preliminary Evidence ◽  
Phase Iii ◽  
Response To Treatment ◽  
Open Label ◽  
Phase Ib ◽  
Open Label Phase ◽  
Almost All

312 Background: Silmitasertib (CX-4945), an oral small molecule inhibitor of casein kinase 2 (CK2), has exhibited preclinical antitumor activity and strong synergism with gemcitabine + cisplatin. We investigated the safety and efficacy of silmitasertib in combination with gemcitabine + cisplatin in patients with unresectable cholangiocarcinoma (CCA). Methods: S4-13-001 is a multicenter, open-label, phase Ib/II study of silmitasertib in combination with gemcitabine + cisplatin in patients with locally advanced or metastatic CCA. The phase Ib portion included dose-escalation, expansion, and exploratory cohorts of silmitasertib with doses ranging from 200 to 1000 mg bid (6 days for the escalation/expansion cohorts and 10 and 21 days’ continuous dosing for the exploratory cohorts). In the phase II portion patients received silmitasertib 1000 mg bid for 10 days in combination with gemcitabine + cisplatin on days 1 & 8 over a 21-day cycle. In this interim analysis, we present findings from the combined population of patients from the phase Ib and II portions of the study. Response to treatment was assessed by RECIST v1.1 every 6 weeks. Primary efficacy outcome measure was progression-free survival (PFS). ClinicalTrials.gov (NCT02128282). Results: A total of 87 patients were enrolled and received silmitasertib in the phase Ib (n=50) and phase II (n=37) portions of the study. Of these, 55 patients were evaluable for efficacy with details as follows: median PFS 11.1 (95% CI 7.6–14.7) months; median overall survival (OS) 17.4 (95% CI 13.4–25.7) months; overall response rate (ORR) 32.1%; and disease control rate (DCR) 79.3%. Almost all patients (79/87; 90.8%) evaluable for safety reported ≥1 treatment-related adverse event (TEAE). The most common TEAEs (all grades) with silmitasertib were diarrhea (65.5%), nausea (50.6%), vomiting (33.3%), fatigue (31.0%), and anemia (21.8%). The most common grade ≥3 TEAEs were diarrhea (13.8%), neutropenia (11.5%), nausea (9.2%), anemia (8.0%), and thrombocytopenia (8.0%). Eleven patients (12.6%) discontinued treatment due to TEAEs. Conclusions: Silmitasertib in combination with gemcitabine + cisplatin yields promising preliminary evidence of efficacy in patients with locally advanced or metastatic CCA. Based on these data a randomized phase III trial is planned. Clinical trial information: NCT02128282.

Docetaxel-carboplatin chemotherapy in combination with cetuximab in patients with locally advanced or metastasized non-small cell lung cancer (NSCLC): Interim results of the nonrandomized phase II study TaxErb

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19062-e19062
Author(s):  
J. R. Fischer ◽  
F. Griesinger ◽  
T. Fink ◽  
E. Buchholz ◽  
T. Salm ◽  
...  
Keyword(s):  
Phase Ii ◽  
Partial Remission ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
Benefit Risk Assessment

e19062 Background: Combination chemotherapy with carboplatin-docetaxel has been shown to be effective and safe for patients with locally advanced or metastasized NSCLC. The monoclonal anti-EGRF antibody cetuximab has the potential to improve response rates and survival without a substantial increase in toxicity when given in combination with chemotherapy. Methods: Open, non-controlled phase II study with a planned sample size of 70 pts. Pts with locally advanced or metastasized NSCLC, ECOG performance status ≤ 2 and no prior systemic chemotherapy were treated with carboplatin AUC5 (d 1) q4w for 4–6 cycles and docetaxel 35 mg/m2 (d1, 8, 15) q4w; cetuximab 400 / 250 mg/m2 (d 1) q1w until progression or intolerable toxicity (12 month max.). The primary endpoint was response rate defined as complete or partial remission according to RECIST. Secondary endpoints were toxicity, 1 year survival, median and progression free survival. Results: Subject of the interims analysis were 27 pts (25 stage IV, 2 stage IIIb). ECOG 0/1/2 was 33.3%/59.3%/3.7% (1 no data). 63% had prior surgery, 93% prior radiotherapy and all had adjuvant or inductive chemotherapy. Pts received a mean of 3 ± 1.4 cycles docetaxel-carboplatin-cetuximab. 49 adverse events were grade 1–2 and 12 grade 3–5. Skin toxicity (49%; 95%CI: 30%-68%; 41% G1/2, 8% G3/4), dyspnoea (35%; 95%CI: 17%-53%) and diarrhoea (23%; 95%CI: 7 %-39%; 19% G1/2, 4% G3) were most frequent. 11 pts (41%) had toxicity leading to dose reduction. 0 pts had complete and 11 pts had partial remission resulting in a response rate of 40.7% (95%CI: 22%-59%) based on intention to treat. 6 pts had stable disease (22.2%; 95%CI: 7%-38%). 5 pts were not evaluable for response. Conclusions: The combination of carboplatin-docetaxel-cetuximab has an overall acceptable tolerability. With a preliminary response rate of 40.7% the benefit risk assessment was found to be favourable and the study was continued. [Table: see text]

A multicohort phase II study of durvalumab plus tremelimumab for the treatment of patients (PTS) with advanced neuroendocrine neoplasms (NENs) of gastroenteropancreatic (GEP) or lung origin (the DUNE trial-GETNE1601-).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4146-TPS4146
Author(s):  
Ignacio Matos Garcia ◽  
Enrique Grande ◽  
Rocio Garcia-Carbonero ◽  
Carlos Lopez ◽  
Alexandre Teule ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Tumor Growth Rate ◽  
Neuroendocrine Neoplasms ◽  
Low Grade ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Tumor Load

TPS4146 Background: NENs include a heterogeneous group of tumors with different behavior. Despite immunomodulators such as interferon are approved for the management of grade 1-2 NENs, the low mutation tumor load and PD-1/PDL-1 expression have limited the development of immune check-point inhibitors in this setting. The rational for immunotherapy in high grade NENs is stronger compared with low grade NENs based on the results observed in small cell lung cancer. However, the combination of an antiPDL-1 and antiCTLA-4 could increase the probability of success regardless of tumor growth rate, mutational tumor load or PDL-1 expression in low grade NENs. Methods: This prospective, multi-center, open label, phase II study (EudraCT:2016-002858-20) will evaluate the efficacy and safety of durvalumab plus tremelimumab in 126 pts within four different cohorts, including well-moderately differentiated lung NENs (Cohort 1), grade 1-2 gastrointestinal NENs (Cohort 2), grade 1-2 pancreatic NENs (Cohort 3) and grade 3 GEP NENs (Cohort 4). To optimize the efficacy of immunotherapy in low grade NENs, pts included in the trial must have progressed to all standard approved therapy in each setting, including somatostatin analogues, targeted agents and chemotherapy for lung and GEP grade 1-2 NENs up to 4 prior lines. For pts included in cohort 4, progression to standard platinum-based chemotherapy is mandatory. All pts will receive durvalumab 1500 mg every 28 days for 12 months, and tremelimumab 75 mg Q4W up to 4 doses/cycles. Retreatment is allowed after disease progression in the follow-up period. The primary endpoint of the study for cohorts 1-3 is disease control rate at 9 months including the percentage of pts achieving complete response, partial response, or stable disease according to RECIST v1.1; Median overall survival will be the primary endpoint for cohort 4. Primary endpoints will be assessed by investigators and confirmed by central radiological review. Secondary endpoints include median progression-free survival, safety and tolerability and a wide panel of biomarkers in blood samples and tumor tissue. Clinical trial information: 2016-002858-20.

Randomized, open-label, phase II study comparing five-weekly S-1 plus cisplatin (SP) with tri-weekly capecitabine plus cisplatin (XP) in chemotherapy-naïve patients with HER2 negative advanced gastric cancer (AGC): OGSG 1105 HERBIS-4A trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 102-102
Author(s):  
Atsushi Takeno ◽  
Youichi Makari ◽  
Shunji Endo ◽  
Jin Matsuyama ◽  
Ryohei Kawabata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Open Label ◽  
Group 13 ◽  
Common Grade ◽  
Open Label Phase ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
To Receive

102 Background: This phase II study aimed to investigate the safety and efficacy of XP compared to SP in the first-line treatment of HER2 negative AGC. Methods: Patients were randomly assigned to receive either SP (S-1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/ m2 on day 8, every 5 weeks) or XP (capecitabine 1,000 mg/m2 twice daily for 14 days plus cisplatin 80 mg/m2 on day 1, every 3 weeks). Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), and adverse events. Results: 84 eligible patients were randomly assigned to receive SP ( N = 41) or XP ( N = 43). No statistical difference was observed in overall RR between the SP and XP groups [51.2% (95% CI, 35.1% to 67.1%) vs. 53.5% (95% CI, 37.7% to 68.8%), P = 1.000]. Despite not significant, however, SP vs. XP showed a trend toward better PFS [median, 5.9 months vs. 4.1 months; hazard ratio (HR), 0.763; 95% CI, 0.462 to 1.259; P = .284] and OS (median, 13.5 months vs. 10.0 months; HR, 0.776; 95% CI, 0.485 to 1.244; P = .290). This trend in the SP vs. XP comparison was more pronounced in TTF (median, 4.5 months vs. 3.1 months; HR, 0.651; 95% CI, 0.421 to 1.006; P = .052). Common grade 3 to 4 hematological toxicities were neutropenia and anemia (SP group, 23% and 23%; XP group, 35% and 28%). Grade 3-4 anorexia and hyponatremia were more frequently seen in the XP group (31% and 16%) compared to the SP group (13% and 5%). Treatment-related deaths occurred in one patient (2.3%) in the XP group. Conclusions: XP failed to demonstrate the superior efficacy over SP. Higher incidence of severe toxicities by XP suggests SP as the standard 1st line chemotherapy for HER2 negative AGC in Japan. Clinical trial information: UMIN000006755.

A randomized noncomparative phase II study of maintenance therapy with multiepitope vaccine Tedopi (OSE2101) ± nivolumab or FOLFIRI after induction chemotherapy (CT) with FOLFIRINOX in patients (Pts) with advanced pancreatic ductal adenocarcinoma (aPDAC) (TEDOPaM–PRODIGE 63 GERCOR D17-01 study).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4160-TPS4160
Author(s):  
Cindy Neuzillet ◽  
Vincent Hautefeuille ◽  
Aurélien Lambert ◽  
Marie-Line Garcia-Larnicol ◽  
Dewi Vernerey
Keyword(s):  
Maintenance Therapy ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Vaccine Antigen ◽  
New Combination ◽  
Ductal Adenocarcinoma ◽  
Open Label

TPS4160 Background: FOLFIRINOX (5-fluorouracil [5FU], folinic acid [FA], irinotecan [Iri], and oxaliplatin [Ox]) is a standard 1st-line treatment in fit Pts with aPDAC. Anti-PD-1/PD-L1 as single agents have failed in PDAC so far and new combination immunotherapies are needed. Tedopi (OSE2101) is a multiple neoepitope vaccine restricted to HLA-A2 positive Pts, targeting 5 tumor-associated antigens (CEA, HER2, MAGE2, MAGE3, TP53) that are frequently expressed in PDAC. This study aims to assess the efficacy and safety of Tedopi alone and in combination with anti-PD-1 nivolumab, or FOLFIRI as maintenance therapy in Pts with aPDAC after FOLFIRINOX induction CT. Methods: TEDOPaM - PRODIGE 63 is a 3-arm, Fleming 2-stage, open-label, randomized, non-comparative phase II study. 156 Pts with locally advanced or metastatic, pathologically proven PDAC; ECOG performance status 0-1; HLA-A2 genotype; controlled disease (objective response or stable disease) after 8 cycles of (modified) FOLFIRINOX; and adequate organ functions, are randomized (1:1:1, stratified on center, tumor stage, and best response to FOLFIRINOX) into 3 arms: Clinical trial information: NCT03806309. In Arms B and C, FOLFIRI is reintroduced at disease progression or unacceptable toxicity. Primary endpoint: overall survival rate at M12. Secondary endpoints: progression-free survival (CT-scan Q8W), duration of disease control, safety, objective response rate, RECIST v1.1/iRECIST comparison, HRQoL (EORTC QLQ-C30), Q-TWiST. An interim analysis is planned after inclusion of 20 Pts in each arm. Translational research will be performed on tumor tissue (initial FFPE biopsy and optional re-biopsy at inclusion): RNAseq (cancer and stroma), mutation burden, MMR status, immune infiltrates; and in blood (before and on-treatment): cytokine panel, PBMC phenotyping, vaccine-antigen specific T-cells, TCR repertoire, and extracellular vesicles, to explore biomarkers and pharmacodynamics effects of Tedopi ± nivolumab. Enrollment (12th Feb 2019): 1. ClinicalTrials Registration: NCT03806309.[Table: see text]

Multicenter phase II study of triplet combination chemotherapy with paclitaxel, cisplatin, and S-1 for advanced gastric cancer (OGSG 0703).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 124-124
Author(s):  
Kazumasa Fujitani ◽  
Yutaka Kimura ◽  
Hiroshi Imamura ◽  
Masahiro Gotoh ◽  
Shohei Iijima ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Phase Ii Study ◽  
Performance Status ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Statistical Hypothesis ◽  
Multicenter Phase

124 Background: Docetaxel combined with cisplatin and 5-fluorouracil is active in advanced gastric cancer, but not generally accepted because of its substantial toxicities. We conducted a multicenter phase II study of triplet combination using paclitaxel, cisplatin and S-1 (PCS) as first-line treatment for advanced gastric cancer. Methods: Patients with previously untreated, locally advanced or metastatic measurable gastric cancer, a performance status < 2, age of 20-75 years, and adequate organ functions were given intravenous paclitaxel at 70 mg/m2 and cisplatin at 30 mg/m2 on days 1 and 15, plus oral S-1 at 40 mg/m2 b.i.d. on days 1 to 21, followed by 2-week rest, repeated every 5 weeks. Treatment was continued until disease progression or unacceptable toxicity occurred, or the patient refused the therapy. Study endpoints included overall response rate (ORR) as primary, progression free survival (PFS), overall survival (OS), and toxicity. Sample size of 40 patients was determined to reject the ORR of 55% under the expectation of 75% with a power of 80% and a one-sided α of 5%. Results: A total of 52 patients were enrolled in this study, among whom 49 were assessable for efficacy and 51 assessable for toxicity. ORR was 46.9% (95% CI: 32.5-61.7%). The median PFS and median OS were 5.4 months (95% CI: 4.1-7.0) and 11.5 months (95% CI: 7.3-16.1), respectively. Frequent grade 3/4 toxicities were neutropenia (51%), leucopenia (25%), anemia (20%), hyponatremia (16%), anorexia (14%), diarrhea (8%) and fatigue (8%). There was no treatment-related death. Conclusions: Triplet combination chemotherapy with PCS demonstrated superior feasibility with promising antitumor activity, though which did not meet the statistical hypothesis, for advanced gastric cancer.

CTIM-30. PHASE II TRIAL OF PEMBROLIZUMAB IN RECURRENT AND RESIDUAL HIGH-GRADE MENINGIOMAS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi57-vi57
Author(s):  
Priscilla Brastianos ◽  
Albert Kim ◽  
Anita Giobbie-Hurder ◽  
Eudocia Quant Lee ◽  
Nancy Wang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
High Grade ◽  
Open Label ◽  
Free Survival ◽  
Significance Level ◽  
Open Label Phase ◽  
Immunosuppressive Tumor Microenvironment

Abstract INTRODUCTION High-grade meningiomas are associated with significant neuro-cognitive morbidity and a poor prognosis. Systemic therapies, to date, have demonstrated minimal efficacy. We recently found that high-grade meningiomas harbor an immunosuppressive tumor microenvironment and that programmed cell death-ligand 1 (PD-L1) expression may contribute to the aggressive phenotype of these tumors. Therefore, we conducted a single-arm, open-label phase II trial evaluating efficacy of pembrolizumab, a PD-1 inhibitor, in a cohort of 24 patients with recurrent and progressive grade II and III meningiomas. METHODS The primary endpoint was the rate of progression-free survival at 6 months. The trial distinguished between 6-month PFS (PFS-6) rates of 26% vs. 52%. If at least 10 patients demonstrated a 6-month PFS, among the 24 patients, the agent would be considered worthy of further study. This design has at least 88% power using an exact binomial test with a one-sided significance level of 0.1. RESULTS Between November 2017 to December 2019, twenty-four patients were enrolled. The majority of the patients in our cohort were heavily pre-treated; prior to enrolling to the study, twenty patients underwent more than one surgical resection and twelve patients had received more than one round of radiotherapy. Our study met its primary endpoint and achieved a 6-month progression-free survival rate of 0.50 (90% exact CI: 0.32-0.68) and a median PFS of 8.3 months (90% CI: 4.1-12.9 months). For the twelve patients who achieved the PFS-6 primary endpoint, median PFS from the start of treatment was 17.3 months (90% CI: 9.7 – 24.3 months). Four patients had grade-3 or higher adverse events that were at least possibly treatment-related, including colitis, skin infection, encephalopathy and transaminitis. CONCLUSION Our study achieved its primary endpoint. These results suggest that pembrolizumab exerts promising activity on these tumors and results in prolonged PFS compared to historical controls.

scholarly journals Phase II Study of Vorinostat for Treatment of Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma

2011 ◽  
Vol 29 (9) ◽  
pp. 1198-1203 ◽  
Author(s):  
Mark Kirschbaum ◽  
Paul Frankel ◽  
Leslie Popplewell ◽  
Jasmine Zain ◽  
Maria Delioukina ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Open Label ◽  
Mantle Cell ◽  
Open Label Phase

Purpose We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma. Patients and Methods In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability. Results All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue. Conclusion Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted.

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