HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric adenocarcinoma: A phase II clinical trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4524-4524
Author(s):  
Yan Song ◽  
Ning Li ◽  
Lan Mu ◽  
Shu Zhang ◽  
Qingxia Fan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Monoclonal Antibody ◽  
Phase Ii ◽  
Remission Rate ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
First Line ◽  
Intravenous Drip ◽  
Line Chemotherapy

4524 Background: Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes. We investigated HX008, an Anti-PD1 Antibody, with irinotecan in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and/or fluoropyrimidine. Methods: This study is a multicenter, open, phase II clinical study of recombinant humanized anti-pd-1 monoclonal antibody HX008 injection plus Irinotecan that was conducted at 11 hospitals in China. Eligible patients are adults with histologically confirmed advanced gastric or gastro-oesophageal junction cancer. Subjects participating in this study are required to submit a archived tumor tissue specimen or newly obtained biopsy of tumor lesions at the site of no previous radiotherapy and peripheral blood (2mL) for detection of PD-L1 and MSI/MMR expression. The samples will be tested for expression of PD-L1 and MMR by immunohistochemistry (IHC) in the central laboratory, and MSI levels will be determined by polymerase chain reaction (PCR) and gel electrophoresis. Subjects received PD-1 monoclonal antibody HX008 at 200mg (d1, intravenous drip, once every 3 weeks) plus irinotecan at 160mg/m2 (d1, intravenous drip, 60 ~ 120min, once every 2 weeks). Response was assessed every 6 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. Primary endpoints was objective remission rate (ORR). Results: Between October 2018 and September 2019, a total of 58 patients with advanced gastric or gastro-oesophageal junction cancer were enrolled in this study. Median (range) age was 61 (27-71) years, and most patients were male (72.4%). Among 53 patients who were evaluated, 15 (28.3%) experienced objective response and 22 (41.5%) experienced stable disease (SD). The median progression free survival (PFS) was 5.4 months, the one-year survival rate was 71.3%. The most common treatment-related adverse events of grade 3 or 4 included neutropenia(31.0%), anemia(15.5%), loss of appetite (6.9%), vomiting(5.2%), nausea(3.4%), diarrhea (1.7%) and fatigue (1.7%). There were no treatment-related deaths. Conclusions: HX008 injection plus Irinotecan demonstrated promising activity and manageable safety in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine. Clinical trial information: NCT03704246 .

Apatinib for locoregionally recurrent or metastatic nasopharyngeal carcinoma after failure of first-line chemotherapy: A multicenter, phase II trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6030-6030
Author(s):  
Wei Jiang ◽  
Jinghui Liang ◽  
Yufei Pan ◽  
Xiaolan Ruan ◽  
Rui Cai ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Multicenter Phase ◽  
Hand Foot Syndrome ◽  
Secondary Endpoints ◽  
Line Chemotherapy

6030 Background: Concordant programs for patients with nasopharyngeal carcinoma (NPC) who failed to first-line chemotherapy after locoregional recurrence or metastasis are not yet available. Here, we investigated the efficacy and safety of apatinib as an second-line treatment in these patients. Methods: In this multicenter, phase II trial, patients of NPC with disease progression after failure of first-line chemotherapy were treated with apatinib (500mg/d).The primary endpoint of this study was objective response rate (ORR), secondary endpoints included progression free survival (PFS), overall survival (OS) and toxicity. Results: Between January and December 2017, 33 patients were finally enrolled onto the analysis from three centers in China. The baseline characteristics were summarized in Table. Of the 12 patients achieved a partial response and no complete responses were observed, yielding an ORR of 36.3%. Additionally, 6 patients (18.2%) experienced stable disease of at least 5 months in duration, and the disease control rate was 54.5%. At a median follow-up time of 14 months (range 1-22), median PFS was 5.0 months (95% CI, 2.3 to 7.7). The median OS had not reached, and the 1-year OS rate was 83.1%. The most common adverse events (grade 1 to 2) related to apatinib were hypetension (42.4%), hand-foot syndrome (54.5%), proteinuria (12.1%) and oral ulcer (24.2%). Conclusions: Apatinib showed a well therapeutic effect and a manageable safety profile for patients of advanced NPC after previous chemotherapy. Further study in combination with chemotherapy and other targeted agents in patients with NPC is warranted. Baseline demographic and disease characteristics. Clinical trial information: NCT03130270. [Table: see text]

scholarly journals Phase II study of metronomic treatment with daily oral vinorelbine as first-line chemotherapy in patients with advanced/metastatic HR+/HER2− breast cancer resistant to endocrine therapy: VinoMetro—AGO-B-046

2021 ◽  
Author(s):  
Slavomir Krajnak ◽  
Thomas Decker ◽  
Lukas Schollenberger ◽  
Christian Rosé ◽  
Christian Ruckes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Open Label ◽  
Oral Vinorelbine ◽  
Her2 Breast Cancer ◽  
Line Chemotherapy

Abstract Purpose Metronomic chemotherapy (MCT) is an increasingly used treatment option in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced/metastatic breast cancer (MBC) after failure of endocrine-based therapies. Methods VinoMetro was a multicentre, open-label, single-arm, phase II study of metronomic oral vinorelbine (VRL; 30 mg/day) as a first-line chemotherapy (CT) in patients with HR+/HER2− MBC after endocrine failure. The primary endpoint was the clinical benefit rate (CBR) at 24 weeks. Results Between January 2017 and April 2019, nine patients were enrolled. The CBR was 22.2% (90% confidence interval [CI] 4.1–55.0), p = 0.211. The median progression-free survival (PFS) was 12.0 weeks (95% CI 11.3–12.7). Grade 3–4 adverse events (AEs) occurred in 22.2% of patients. One patient died of febrile neutropenia. Conclusion VinoMetro (AGO-B-046) was closed early after nine patients and occurrence of one grade 5 toxicity in agreement with the lead institutional review board (IRB). Metronomic dosing of oral VRL in HR+/HER2− MBC as first-line CT after failure of endocrine therapies showed only limited benefit in this population. Trial registration number and date of registration ClinicalTrials.gov Identifier: NCT03007992; December 15, 2016.

scholarly journals Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial

2017 ◽  
Vol 35 (29) ◽  
pp. 3315-3321 ◽  
Author(s):  
Maria E. Cabanillas ◽  
Jonas A. de Souza ◽  
Susan Geyer ◽  
Lori J. Wirth ◽  
Michael E. Menefee ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Phase Ii ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Multikinase Inhibitor

Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib. Patients and Methods Patients with RAI-refractory disease with Response Evaluation Criteria in Solid Tumor (RECIST) measurable disease and evidence of progression on prior VEGFR-targeted therapy were enrolled in this single-arm phase II study. The cabozantinib starting dose was 60 mg/day orally but could be escalated to 80 mg if the patient did not experience a response. Patients underwent tumor assessment according to RECIST v1.1 every 8 weeks. In this study, if at least five of 25 response-evaluable patients had an objective response, cabozantinib would be considered a promising agent in this patient population. Results Twenty-five patients were enrolled. The median age was 64 years, and 64% of patients were men. Twenty-one patients had received only one prior VEGFR-targeted therapy (sorafenib, pazopanib, or cediranib), and four patients had received two such therapies. The most common treatment-related adverse events were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. One drug-related death was noted. Of the 25 patients, 10 (40%) had a partial response, 13 (52%) had stable disease, and two (8%) had nonevaluable disease. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. Conclusion Cabozantinib demonstrated clinically significant, durable objective response activity in patients with RAI-refractory DTC who experienced disease progression while taking prior VEGFR-targeted therapy.

Anlotinib combined with pemetrexed and carboplatin as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC): ALTER L012.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21040-e21040
Author(s):  
Qiming Wang ◽  
Xiuli Yang ◽  
Tianjiang Ma ◽  
Qiumin Yang ◽  
Chenghui Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Treatment Naïve ◽  
Nsclc Patients ◽  
First Line Treatment

e21040 Background: The anti-angiogenic drug bevacizumab combined with chemotherapy has achieved positive results in previous studies. In particular, the median progression-free survival (PFS) for EGFR-negative patients was increased to 8.3 months in the BEYOND study. Unlike bevacizumab, anlotinib is a novel multitarget tyrosine kinase inhibitor and can be conveniently orally administered. In the phase III trial ALTER 0303, anlotinib significantly improved overall survival (OS) and PFS in advanced NSCLC patients. This exploratory study aims to establish the efficacy and safety of anlotinib in combination with pemetrexed and carboplatin as first-line treatment in advanced non-squamous NSCLC. Methods: This is a multi-center, single-arm clinical trial. Adults with treatment-naive, histologically confirmed stage IIIB-IV non-squamous NSCLC, ECOG 0-1, and without known sensitizing EGFR/ALK alterations are included. Patients received anlotinib (12 mg p.o., QD, d1 to 14, 21 days per cycle) combined with pemetrexed (500 mg/m2, iv, d15-21, Q3W) + carboplatin (AUC = 5, iv, d15-21, Q3W) for 4 cycles followed by anlotinib and pemetrexed maintenance until disease progression (PD). The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: Between Mar 2019 and Dec 2020, 40 patients were enrolled in six centers and 31 of them have received at least one tumor assessment. Median age was 62 (33, 75); 66.7% male, 11.1% brain metastasis. At data cutoff (Dec 31, 2020), patients were followed up for a median of 8.26 months. Median PFS was 10.5 months (95% CI: NE, NE); ORR was 67.7% (0 CR, 21 PR), DCR was 96.8% (0 CR, 21 PR, 9 SD) and median OS was NE. The most common Grade ≥ 3 AEs were hypertension 22.2%, neutropenia 19.44%, myelosuppression 11.1%, thrombocytopenia 8.33%, leukopenia 5.56%, hand-foot syndrome 5.56% and there were no Grade 5 toxicities. Conclusions: This study finds that anlotinib plus pemetrexed and carboplatin can significantly improve PFS and ORR compared to standard chemotherapy for treatment-naive non-squamous NSCLC patients. The combination was well tolerated, and the AEs were manageable. The follow-up time is not sufficient, and the OS outcomes need further evaluation. Clinical trial information: NCT03790228.

scholarly journals Promising Immunotherapy in Metastatic Testicular Sex Cord Stromal Tumours After First-Line Chemotherapy

2022 ◽  
Vol 12 ◽  
Author(s):  
Bingqing Shang ◽  
Chuanzhen Cao ◽  
Weixing Jiang ◽  
Hongzhe Shi ◽  
Xingang Bi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Chemotherapy Resistance ◽  
Progression Free Survival ◽  
Retroperitoneal Lymph Node Dissection ◽  
First Line ◽  
Experienced Grade ◽  
Line Chemotherapy

BackgroundTesticular sex cord stromal tumours (TSCSTs) are rare, with few studies focusing on the metastatic TSCST prognosis. The value of treatments, including radical orchiectomy (RO) and retroperitoneal lymph node dissection (RPLND), in preventing metastasis is controversial. Additionally, metastatic TSCSTs are resistant to chemotherapy. We aimed to assess the effectiveness and safety of immunotherapy in metastatic TSCSTs after first-line chemotherapy.MethodsWe retrospectively screened patients with testicular tumours undergoing testis surgery between January 2005 and January 2019. Patients with TSCSTs who had undergone testis-sparing surgery (TSS) or RO were identified. The malignant type was defined as metastasis confirmed by pathology. Treatment responses, progression-free survival (PFS), overall survival (OS) and safety were analysed.ResultsAmong the 494 testicular tumour patients who received TSS or RO, 11 (2.2%) patients with histologically proven TSCSTs were identified. At the last follow-up, 7 patients survived without tumours, and 4 patients developed metastasis and received first-line cisplatin-based chemotherapy, with 1 of them achieving an objective response. Their PFS times were 1.5, 2.2, 9.0, and 17.0 months, respectively. Two patients received immune checkpoint inhibitors (ICIs) after developing chemotherapy resistance and achieved a partial response up to the last follow-up; one of them experienced Grade 1 adverse events, and the other experienced Grade 2 adverse events during immunotherapy. The median OS time of the 4 patients with metastatic TSCSTs was 32 months.ConclusionsTSCSTs are rare, and most are benign with a good prognosis. ICIs represent a promising option for improving clinical outcomes in metastatic TSCSTs.

scholarly journals The Efficacy of Ramucirumab in the Treatment of Gastric or Gastroesophageal Junction Cancer: A Meta-Analysis of RCTs

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hongqiong Yang ◽  
Yaojun Zhou ◽  
Liangzhi Wang ◽  
Tianyi Gu ◽  
Mengjia Lv ◽  
...  
Keyword(s):  
Response Rate ◽  
Meta Analysis ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
First Line ◽  
Free Survival ◽  
Gastroesophageal Junction Cancer ◽  
Line Chemotherapy

Five electronic databases were searched for eligible records. Outcomes were presented and analyzed according to the objective response rate (ORR), progression-free survival (PFS) rate, and overall survival (OS) rate. Five records involving 2,024 participants were included in the study. The pooled analysis of OS and PFS were longer with ramucirumab (RAM) therapy than without RAM for OS (odds ratio OR = 0.90 , 95% confidence interval CI = 0.82 – 1.00 , p = 0.05 ) and PFS ( OR = 0.74 , 95 % CI = 0.57 – 0.96 , p = 0.02 ). Moreover, compared with the current first-line chemotherapy, the OS ( OR = 0.93 , 95 % CI = 0.83 – 1.04 , p = 0.19 ) and PFS ( OR = 0.82 , 95 % CI = 0.64 – 1.06 , p = 0.13 ) results were not significantly higher with RAM. The ORRs of the patients in the RAM therapy groups were significantly higher than those in the groups without RAM ( OR = 1.40 , 95 % CI = 1.14 – 1.73 , p = 0.001 ).

Comparing the clinical efficacies of anti-PD-1 antibody monotherapy and anti-PD-1 and anti-CTLA-4 combination therapy as first-line immunotherapy in Japanese advanced acral melanoma: A retrospective, multicenter study (JAMP-neo study).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9542-9542
Author(s):  
Yasuhiro Nakamura ◽  
Yukiko Kiniwa ◽  
Hiroshi Kato ◽  
Osamu Yamasaki ◽  
Takeo Maekawa ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Clinical Efficacy ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
First Line ◽  
Acral Melanoma ◽  
Kaplan Meier ◽  
Melanoma Patients ◽  
Clinical Records

9542 Background: Anti-PD-1 antibody monotherapy (PD1) has been commonly used for patients with advanced acral melanoma (AM). However, recent studies have demonstrated the limited clinical efficacy of PD1 in AM compared to non-acral cutaneous melanoma, particularly in nail apparatus melanoma. Although advanced AM patients are strong candidates for first-line anti-PD-1 and anti-CTLA-4 combination therapy (PD1+CTLA4), data on the clinical efficacy of PD1+CTLA4 in AM are lacking. Thus, we aimed to compare the clinical efficacies of PD1+CTLA4 and PD1 in Japanese advanced AM patients. Methods: We retrospectively reviewed the clinical records of advanced AM patients treated with PD1+CTLA4 or PD1 as first-line immunotherapy at 23 Japanese institutions. Clinical response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Survival was estimated using Kaplan-Meier analysis. Toxicity was assessed according to CTCAE 4.0. Results: A total of 192 patients (median age, 72 years) with advanced AM (palm and sole melanoma, 135; nail apparatus melanoma, 57) were included in the study. PD1+CTLA4 and PD1 were used as first-line immunotherapy in 39 and 153 patients, respectively. The baseline demographics and characteristics were similar between the PD1+CTLA4 and PD1 groups, except for age (median age 67.3 vs. 73.2; P = 0.005). The objective response rate (ORR) in PD1+CTLA4 was significantly higher than that of the PD1 group (38.5% vs. 16.3%; P = 0.047). The median progression-free survival (PFS) and overall survival (OS) in the PD1+CTLA4 group tended to be longer than those of the PD1 group, but the differences were not significant (median PFS 7.3 months vs. 4.5 months; P = 0.19, median OS 43.6 months vs. 18.2 months; P = 0.19). In the subgroup analysis of the palm and sole melanoma cohorts, no significant differences in ORR, PFS, and OS were observed between the PD1+CTLA4 and PD1 groups (ORR 31% vs. 20.8%; P = 0.67, median PFS 5.3 months vs. 5.9 months; P = 0.87, median OS not reached vs. 22.3 months; P = 0.66). Meanwhile, the nail apparatus melanoma cohort in the PD1+CTLA4 group exhibited significantly higher ORR, and longer PFS and OS than the PD1 group (ORR 60% vs 6.1%; P < 0.001; median PFS 19.6 months vs 3.8 months; P = 0.008, median OS 43.6 months vs 13.5 months; P = 0.049). Due to immune-related adverse events in all cohorts, the treatment cessation rate was higher in the PD1+CTLA4 group than the PD1 group (59% vs. 11.8%). Conclusions: PD1+CTLA4 was clinically more efficacious than PD 1 in advanced AM patients. Notably, advanced nail apparatus melanoma patients were strong candidates for first-line PD1+CTLA4.

scholarly journals Phase II California Cancer Consortium Trial of Gemcitabine-Eribulin Combination in Cisplatin-Ineligible Patients With Metastatic Urothelial Carcinoma: Final Report (NCI-9653)

2019 ◽  
Vol 37 (29) ◽  
pp. 2682-2688 ◽  
Author(s):  
Sarmad Sadeghi ◽  
Susan G. Groshen ◽  
Denice D. Tsao-Wei ◽  
Rahul Parikh ◽  
Amir Mortazavi ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Median Number ◽  
Final Report ◽  
Curative Surgery ◽  
Metastatic Urothelial Carcinoma

PURPOSE Patients with metastatic urothelial carcinoma are often ineligible for cisplatin-based treatments. A National Cancer Institute Cancer Therapy Evaluation Program–sponsored trial assessed the tolerability and efficacy of a gemcitabine-eribulin combination in this population. METHODS Patients with treatment-naïve advanced or recurrent metastatic urothelial carcinoma of the bladder, ureter, or urethra not amenable to curative surgery and not candidates for cisplatin-based therapy were eligible. Cisplatin ineligibility was defined as creatinine clearance less than 60 mL/min (but ≥ 30 mL/min), grade 2 neuropathy, or grade 2 hearing loss. Treatment was gemcitabine 1,000 mg/m2 intravenously followed by eribulin 1.4 mg/m2, both on days 1 and 8, repeated in 21-day cycles until progression or unacceptable toxicity. A Simon two-stage phase II trial design was used to distinguish between Response Evaluation Criteria in Solid Tumors, version 1.1 objective response rates of 20% versus 50%. RESULTS Between June 2015 and March 2017, 24 eligible patients with a median age of 73 years (range, 62 to 88 years) underwent therapy. Performance status of 0, 1, or 2 was seen in 11, 11, and two patients, respectively. Sites of disease included: lymph nodes, 16; lungs, nine; liver, seven; bladder, five; bones, two. Median number of cycles received was four (range, one to 16). Of 24 patients, 12 were confirmed responders; the observed objective response rate was 50% (95% CI, 29% to 71%). Median overall survival was 11.9 months (95% CI, 5.6 to 20.4 months), and median progression-free survival was 5.3 months (95% CI, 4.5 to 6.7 months). The most common treatment-related any-grade toxicities were fatigue (83% of patients), neutropenia (79%), anemia (63%), alopecia (50%), elevated AST (50%), and constipation, nausea, and thrombocytopenia (42% each). CONCLUSION Gemcitabine-eribulin treatment response and survival for cisplatin-ineligible patients compare favorably to other regimens. Additional research is needed.

Sign in / Sign up

Export Citation Format

Share Document