Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma

2016 ◽  
Vol 34 (12) ◽  
pp. 1330-1338 ◽  
Author(s):  
Sofie Wilgenhof ◽  
Jurgen Corthals ◽  
Carlo Heirman ◽  
Nicolas van Baren ◽  
Sophie Lucas ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Adverse Events ◽  
Disease Control ◽  
Phase Ii ◽  
Tumor Response ◽  
Phase Ii Study ◽  
Advanced Melanoma ◽  
Disease Control Rate ◽  
Skin Reactions ◽  
Autologous Monocyte

Purpose Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic mRNA (TriMixDC-MEL) are immunogenic and have antitumor activity as a monotherapy in patients with pretreated advanced melanoma. Ipilimumab, an immunoglobulin G1 monoclonal antibody directed against the cytotoxic T-lymphocyte-associated protein 4 receptor that counteracts physiologic suppression of T-cell function, improves the overall survival of patients with advanced melanoma. This phase II study investigated the combination of TriMixDC-MEL and ipilimumab in patients with pretreated advanced melanoma. Patients and Methods Thirty-nine patients were treated with TriMixDC-MEL (4 × 106 cells administered intradermally and 20 × 106 cells administered intravenously) plus ipilimumab (10 mg/kg every 3 weeks for a total of four administrations, followed by maintenance therapy every 12 weeks in patients who remained progression free). Six-month disease control rate according to the immune-related response criteria served as the primary end point. Results The 6-month disease control rate was 51% (95% CI, 36% to 67%), and the overall tumor response rate was 38% (including eight complete and seven partial responses). Seven complete responses and one partial tumor response are ongoing after a median follow-up time of 36 months (range, 22 to 43 months). The most common treatment-related adverse events (all grades) consisted of local DC injection site skin reactions (100%), transient post–DC infusion chills (38%) and flu-like symptoms (84%), dermatitis (64%), hepatitis (13%), hypophysitis (15%), and diarrhea/colitis (15%). Grade 3 or 4 immune-related adverse events occurred in 36% of patients. There was no grade 5 adverse event. Conclusion The combination of TriMixDC-MEL and ipilimumab is tolerable and results in an encouraging rate of highly durable tumor responses in patients with pretreated advanced melanoma.

Interim results of a phase II study of the mTOR inhibitor everolimus in patients with pretreated metastatic gastric and esophageal adenocarcinoma.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 80-80
Author(s):  
Zev A. Wainberg ◽  
Ravi Patel ◽  
Brian DiCarlo ◽  
David J Park ◽  
Frederic C. Kass ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Supportive Care ◽  
Disease Control ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Best Supportive Care ◽  
Disease Control Rate ◽  
Upper Gi ◽  
Grade 3

80 Background: There is increased evidence that cancers of the upper GI tract are comprised of distinct epidemiological and molecular entities that may respond differently to anti-cancer therapy in Asian patients compared to North American patients. Everolimus, an oral inhibitor of the mammalian target of rapamycin (mTOR) showed clinical promise in a phase II study in Japanese patients with pre-treated metastatic gastric cancer with a disease control rate of 56% (Doi et al, JCO, 2010). This study evaluates the efficacy and safety of everolimus in patients with pre-treated metastatic gastric and esophagus cancers in a US population. Methods: Patients with advanced upper GI adenocarcinomas who experienced disease progression despite 1-2 prior regimens were treated with everolimus 10 mg PO daily. The primary endpoint was disease control rate (DCR; CR+PR+SD). Secondary end points included progression free survival (PFS), toxicity, overall survival (OS) and translational correlatives of the mTOR pathway. Results: Of the 40 patients enrolled to date, 19 have gastric, 7 have esophagus and 14 have tumors from the GEJ. 32 patients are evaluable to date: median age of 59 (range 36-79), all patients had an ECOG of 0 or 1; 11 (34%) received 1 prior regimen and 21 (64%) received 2 prior regimens. We observed 0 responses with 44% of evaluable patients having stable disease. Median overall survival was 5.6 months (95% CI: 3.2-7.6) and PFS was 1.8 months (95% CI: 1.6-2.2). 89% of all adverse events were grade 1-2, and 11% were grade 3-4. Grade 3-4 related adverse events include: fatigue (24%), thrombocytopenia (22%), anemia (9%). Updated results of translational correlatives with the mTOR pathway will be presented. Conclusions: We did not achieve the same degree of overall survival or disease control as in the Japanese study which may reflect differences in the locations of the primary tumor or underlying geographic variation. However, OS is significantly better than best supportive care reported in a recent randomized European trial (Thuss-Patience PC et al, Eur J Cancer 2011). Results of the randomized Phase III trial of everolimus vs best supportive care in this patient population are pending.

Phase II study of autologous mRNA electroporated dendritic cells (TriMixDC-MEL) in combination with ipilimumab in patients with pretreated advanced melanoma.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 3014-3014 ◽  
Author(s):  
Bart Neyns ◽  
Sofie Wilgenhof ◽  
Jurgen Corthals ◽  
Carlo Heirman ◽  
Kris Thielemans
Keyword(s):  
Dendritic Cells ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Melanoma

Phase II study of dacarbazine for metastatic colorectal cancer: Final results with MGMT analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3581-3581
Author(s):  
Alessio Amatu ◽  
Andrea Sartore Bianchi ◽  
Catia Moutinho ◽  
Katia Bencardino ◽  
Erica Bonazzina ◽  
...  
Keyword(s):  
Dna Repair ◽  
Disease Control ◽  
Phase Ii ◽  
Dna Methyltransferase ◽  
Phase Ii Study ◽  
Alkylating Agents ◽  
Promoter Hypermethylation ◽  
Disease Control Rate ◽  
Double Blind ◽  
Base Pair Mismatch

3581 Background: O6-methylguanine-DNA-methyltransferase (MGMT) is a DNA repair protein removing mutagenic and cytotoxic adducts from O6-guanine in DNA. Approximately 40% of colorectal cancers (CRCs) display MGMT deficiency due to promoter hypermethylation leading to silencing of the gene. Alkylating agents, such as dacarbazine, exert their antitumor activity by DNA methylation at the O6–guanine site, inducing base pair mismatch, therefore activity of dacarbazine could be enhanced in CRCs lacking MGMT. We conducted a phase II study with dacarbazine in CRCs who had failed standard therapies (oxaliplatin, irinotecan, fluoropyrimidines, and cetuximab or panitumumab if KRAS wild type). Methods: All patients had tumor tissue assessed for MGMT as promoter hypermethylation in double-blind for treatment outcome. Patients received dacarbazine 250 mg/m2 i.v. qd for 4 consecutive days q21 until PD or intolerable toxicity. We employed a Simon two-stage design to determinate if the ORR would be ≥ 10%. Secondary endpoints included association of response, PFS and disease control rate with MGMT status. Results: Sixty-eight patients were enrolled from May 2011 to March 2012. Patients received a median of 3 cycles of dacarbazine [range 1-12]. Grade 3-4 toxicities included: fatigue (41%), nausea/vomiting (29%), constipation (25%), platelet count decrease (19%), anemia (18%). Overall, 2 patients (3%) achieved partial response (PR) and 8 patients (12%) had stable disease (SD). Disease control rate (PR+SD) was significantly associated with MGMT promoter hypermethylation in the corresponding tumors. Conclusions: Objective clinical responses to dacarbazine in metastatic CRC patients are confined to those tumors harbouring epigenetic inactivation of the DNA repair enzyme MGMT. Clinical trial information: 2011-002080-21.

DOCOX: A phase II trial with docetaxel and oxaliplatin as a second-line systemic therapy for patients with advanced and/or metastatic adenocarcinoma of the pancreas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4034-4034
Author(s):  
Thomas Jens Ettrich ◽  
Goetz von Wichert ◽  
Thomas M. Gress ◽  
Patrick Michl ◽  
Michael Geissler ◽  
...  
Keyword(s):  
Disease Control ◽  
Phase Ii ◽  
Tumor Response ◽  
Phase Ii Trial ◽  
Systemic Treatment ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
Disease Control Rate ◽  
Line Treatment ◽  
Free Survival

4034 Background: In Europe and the USA, pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of cancer-related death. For patients with metastatic disease, palliative cytostatic systemic treatment is the only option. There is no established standard for 2nd-line treatment. Fluoropyrimidines either alone or in combination with Oxaliplatin or other chemotherapeutic agents are increasingly used. There are interesting data regarding the combination of Gemcitabine with Oxaliplatin or Docetaxel with respect to progression free survival (PFS) and tumor response in 1st-line. For the first time, the DocOx-trial investigates the combination of Oxaliplatin with Docetaxel as 2nd-line treatment after progression under palliative first-line systemic treatment with Gemcitabine. Methods: Prospective, single arm, non-randomized, multicenter, Simon´s two stage phase II trial using Docetaxel (75 mg/m2, 60 min, d 1) plus Oxaliplatin (80 mg/m2, 120 min, d 2, qd 22). Duration of the trial is scheduled up to 8 cycles. Primary endpoint: tumor response (RR) according to RECIST 1.0. Secondary endpoints: PFS, OS, safety/toxicity, QoL/clinical benefit. Results: Here we present the data on response rate (RR), median progression free survival (mPFS) and median overall survival (mOS) as of February 4th, 2013. Data represents the Intention to treat-analysis of the 44 patients included between 2009 and 2012. 5 patients did not obtain any treatment. RR was 16% (7 partial remissions, no complete remission) with a disease control rate (DCR) of 48% after the first two treatment cycles. Median PFS was 7 weeks ( 95%-CI: 6-16 w.) and median OS after start of 2nd-line therapy was 36 weeks ( 95%-CI: 19-55 w.). Conclusions: In this single-arm 2nd-line trial for the treatment of PDAC, the combination of Doxcetaxel and Oxaliplatin shows very promising results compared to other 2nd-line-protocols such as OFF. Some patients seem to benefit particularly as indicated by long periods of treatment in this setting. Even after 8 cycles of treatment with DocOx, partial response was observed in 2 patients and stable disease in another 6 patients corresponding a disease control rate of 18%. Clinical trial information: NCT00690300.

A phase II study of oxaliplatin reintroduction in patients pretreated with oxaliplatin and irinotecan for advanced colorectal cancer (RE-OPEN study): Reports of interim analysis.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 580-580 ◽  
Author(s):  
Mitsukuni Suenaga ◽  
Nobuyuki Mizunuma ◽  
Satoshi Matsusaka ◽  
Eiji Shinozaki ◽  
Masato Ozaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Phase Ii ◽  
Stable Disease ◽  
Interim Analysis ◽  
Tumor Response ◽  
Phase Ii Study ◽  
Complete Response ◽  
Open Label ◽  
Study Characteristics

580 Background: Re-introduction of oxaliplatin for patients with metastatic colorectal cancer refractory to standard chemotherapy regimens including oxaliplatin, irinotecan and fluorouracil (5-FU) was thought to be effective approach, but has not been prospectively explored. Thus, we performed a single arm, open-label phase II study (UMIN ID: 000004884). Methods: Patients with prior chemotherapy including oxaliplatin and irinotecan, achieved tumor response or stable disease during prior oxaliplatin-based therapy, and six months or over from confirmed progression disease during previous oxaliplatin-based therapy were eligible for this study. Patients received FOLFOX regimens every two weeks. Primary endpoint was disease control rate (DCR) after 12 weeks of treatment. Tumor response was evaluated by RECIST v1.1, and DCR was defined as complete response, partial response or stable disease. This trial followed a Simon’s two-stage minimax design. Interim analysis of efficacy was planned after 12 weeks of treatment in 18 patients (Step I). If disease control were confirmed in more than five patients, 15 patients would be newly enrolled in Step II. Results: Between 01-2011 and 07-2012, 18 patients were enrolled in Step I of this study. Characteristics of patients were as follows (N=18): median age, 61 yrs (range 35-75 yrs); male/female, 11/7; ECOG PS0, 94.4%; and colon/rectum, 8/10. All patients were assigned to receive mFOLFOX6 regimen. Disease control was observed in seven patients. There was no benefit in nine patients. Two patients refused to continue treatment and one patient gave up treatment due to oxaliplatin related allergic reaction. According to the interim analysis, DCR after 12 weeks of treatment was 38.9%. There were no severe adverse events and treatment related deaths. Conclusions: In interim analysis, initial efficacy of reintroduction of oxaliplatin after 12 weeks of FOLFOX regimen was confirmed. Step II part of this study is currently ongoing. Clinical trial information: UMIN000004884.

Phase II study of bevacizumab in combination with S-1 plus cisplatin in patients with advanced nonsquamous non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18037-e18037
Author(s):  
Reiko Yoshino ◽  
Kyoichi Kaira ◽  
Yoshio Tomizawa ◽  
Toshifumi Kazama ◽  
Akihiro Yoshii ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Disease Control ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Small Cell ◽  
Small Cell Lung ◽  
Ecog Ps

e18037 Background: Cisplatin combined with S-1 is an active regimen for patients with advanced non-small cell lung cancer (NSCLC). Although the addition of bevacizumab to platinum based regimens significantly improved outcome, it remains unknown about the safety and efficacy of first-line cisplatin plus S-1 with bevacizumab. Therefore, we conducted a phase II study to evaluate the efficacy and tolerability of bevacizumab in combination with S-1 plus cisplatin regimen in patients with advanced non-squamous NSCLC. Methods: Patient with ages ranging from 20 to 74 years, non-squamous NSCLC, no prior systemic therapy, no brain metastases and ECOG PS 0-1 were enrolled. Patients received cisplatin 60mg/m2 and bevacizumab 15mg/kg on day 1 of each cycle, and S-1 80mg/m2 orally twice daily for 14 days every 21 days. After 4-6 courses, patients were continued on bevacizumab until progression disease (PD). Primary end point was response rate (RR). Secondary end points included overall survival (OS), PFS, time to treatment failure (TTF), and safety. Results: Twenty-nine patients were enrolled in this study. Median age was 67 years (range: 42 to 74); male/female=17(58%)/12(42%); ECOG PS 0/ 1 = 18 (62%) / 11(38%); stageIIIB/IV=3(10%)/26(90%); adeno / NSCLC = 26 (90%) / 3 (10%). The median courses of the induction therapy was 4 (range: 2 to 6), and that of the maintenance therapy was 3 courses (range: 1 to 15). Response rate (RR) was 65.5%, and disease control rate (DCR) was 100%. Median PFS was 5.39 months (95%CI, 125-265 days). Hematological adverse events reaching grade 3 or 4 were leukocytopenia (6.8%), neutropenia (20.9%), anemia (3.4%), thrombocytopenia (6.9%), and febrile neutropenia (3.4%). Nonhematological toxicities of grade3/4 were hypertension (17.2%), appetite loss (3.4%), mucositis oral (3.4%), alkaline phosphatase elvation (3.4%), serum amylase elevation (3.4%), and hyponatremia (3.4%). Seven patients delayed the start of next course because of adverse events. Conclusions: Bevacizumab in combination with S-1 plus cisplatin was effective in disease control and well-tolerated regimen for the treatment of patients with advanced non-squamous NSCLC.

scholarly journals RECIST and iRECIST criteria for the evaluation of nivolumab plus ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the GERCOR NIPICOL phase II study

2020 ◽  
Vol 8 (2) ◽  
pp. e001499
Author(s):  
Romain Cohen ◽  
Jaafar Bennouna ◽  
Aurélia Meurisse ◽  
Christophe Tournigand ◽  
Christelle De La Fouchardière ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Mismatch Repair ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Disease Control Rate ◽  
Recist 1.1

BackgroundImmune checkpoint inhibitors (ICIs) are highly effective in patients with microsatellite instability/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC). Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria may underestimate response to ICIs due to the pseudoprogression phenomenon. The GERCOR NIPICOL phase II study aimed to evaluate the frequency of pseudoprogressions in patients with MSI/dMMR mCRC treated with nivolumab and ipilimumab.MethodsPatients with MSI/dMMR mCRC previously treated with fluoropyrimidines, oxaliplatin, and irinotecan with/without targeted therapies received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four cycles then nivolumab 3 mg/kg every 2 weeks until progression or a maximum of 20 cycles. Computed tomography scan tumor assessments were done every 6 weeks for 24 weeks and then every 12 weeks. The primary endpoint was disease control rate at 12 weeks according to RECIST 1.1 and iRECIST by central review.ResultsOf 57 patients included between December 2017 and November 2018, 48.0% received ≥3 prior lines of chemotherapy, 18.0% had BRAFV600E mutation, and 56.0% had Lynch syndrome-related cancer. Seven patients (12.0%) discontinued treatment due to adverse events; one died due to a treatment-related adverse event. The disease control rate (DCR) at 12 weeks was 86.0% with RECIST 1.1% and 87.7% with iRECIST. Two pseudoprogressions (3.5%) were observed, at week 6 and at week 36, representing 18% of patients with disease progression per RECIST 1.1 criteria. With a median follow-up of 18.4 months, median progression-free survival (PFS) and overall survival (OS) were not reached. The 12-month PFS rate was 72.9% with RECIST 1.1% and 76.5% with iRECIST. The 12-month OS rate was 84%. Overall response rate was 59.7% with both criteria. RAS/BRAF status, sidedness, Lynch syndrome, and other baseline parameters were not associated with PFS.ConclusionPseudoprogression is rare in patients with MSI/dMMR mCRC treated with nivolumab and ipilimumab. This combined ICI therapy confirms impressive DCR and survival outcomes in these patients.Trial registration numberNCT03350126.

A phase II open-label, multicenter, study to evaluate the efficacy and safety of rivoceranib in subjects with recurrent or metastatic adenoid cystic carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6597-TPS6597
Author(s):  
Hyunseok Kang ◽  
Alan Loh Ho ◽  
Jameel Muzaffar ◽  
Daniel W. Bowles ◽  
Sung-Bae Kim ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Disease Control ◽  
Adenoid Cystic Carcinoma ◽  
Clinical Oncology ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Disease Control Rate ◽  
Open Label ◽  
Adenoid Cystic ◽  
Patient Reported

TPS6597 Background: Adenoid cystic carcinoma (ACC) is a rare salivary gland malignancy, also found in other secretory gland sites (tracheobronchial tree, esophagus, breast, lungs, prostate, uterine cervix and vulva). Initial disease is typically treated with surgical resection and radiation, but recurrent or metastatic disease remain to be a significant challenge. There is no standard systemic therapy option for advanced ACC, although recent studies with tyrosine kinase inhibitors have shown moderate objective response and disease stabilization rates. Rivoceranib (also known as apatinib) is a potent selective inhibitor of VEGFR-2 and has been evaluated in a single arm phase II study of 59 recurrent or metastatic ACC patients in China and has demonstrated an (ORR) of 47.1% and disease control rate of 98.1. Methods: This is a phase II, open-label, multicenter[HGJ3], single arm clinical trial of oral rivoceranib (700 mg daily) in patients with recurrent or metastatic ACC of any anatomic site, not amenable to curative surgery or radiotherapy to confirm activity of rivoceranib. Subjects must have at least one evaluable lesion by RECIST v1.1 and have evidence of disease progression within the 6 months prior to study entry. Fifty-five subjects will be enrolled at 7 US sites and 4 South Korean sites. The primary endpoint is ORR assessed by investigators with a target ORR of 25% to detect a difference of 15% from the historical ORR of 10% at 1-year (this achieves 80% power with a 5% significance level). Secondary endpoints include overall survival, disease control rate, progression free survival at 6, 12 and 24 months and time to progression. Exploratory objectives include correlation between ORR and the presence of MYB/MYB-L1 fusion, pharmacokinetics evaluation, and patient-reported quality of life assessments by FACT-G. This study is open and enrolling at the time of submission. References: 1. Tchekmedyian V, Sherman EJ, Dunn L, et al. Phase II Study of Lenvatinib in Patients With Progressive, Recurrent or Metastatic Adenoid Cystic Carcinoma. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2019;37:1529-37. 2. Zhu G, Zhang L, Li R, Dou S, Yang W, Zhang C. Phase II trial of apatinib in patients with recurrent and/or metastatic adenoid cystic carcinoma of the head and neck: Updated analysis. Journal of Clinical Oncology 2018;36:6026. Clinical trial information: NCT04119453 .

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