Recombinant humanized anti-PD-1 monoclonal antibody toripalimab in patients with metastatic urothelial carcinoma: Results of an open-label phase II clinical study Polaris-03.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5040-5040
Author(s):  
Xinan Sheng ◽  
Haige Chen ◽  
Bin Hu ◽  
Xudong Yao ◽  
Ziling Liu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Study ◽  
Urothelial Carcinoma ◽  
Clinical Response ◽  
Disease Progression ◽  
Phase Ii ◽  
Safety Profile ◽  
Clinical Activity ◽  
Phase Ii Clinical Study ◽  
Metastatic Urothelial Carcinoma

5040 Background: Patients with advanced metastatic urothelial carcinoma (UC) who experience disease progression after standard therapy have limited treatment options. Phase I study of toripalimab in subjects with heavily pretreated metastatic UC had demonstrated an acceptable safety profile and promising clinical activity. Here we report the safety and efficacy result of toripalimab in a phase II clinical study (POLARIS-03) in Chinese patients with metastatic urothelial carcinoma. (Clinical trial ID: NCT03113266). Methods: Metastatic UC Patients receive toripalimab 3 mg/kg Q2W until disease progression, unacceptable toxicity or voluntary withdrawal. Clinical response is assessed every 8 weeks. Tumor PD-L1 expression and other biomarkers will be evaluated for correlation with clinical response. Results: From May 2017 to September 2019, 204 patients were screened and the study enrollment was completed with 151 patients enrolled from 15 participating centers. The median age was 62 years and 66% were male. 87% patients had visceral metastasis. By the cut-off date of Jan 6, 2020, 92.1% (139/151) patients experienced treatment related adverse event (TRAE) and grade 3 and above TRAE occurred in 35.8% (54/151) patients. Most common TRAE included anemia, triglycerides increased, proteinuria, fatigue, and hyperglycemia. Treatment discontinuation due to a TRAE occurred in 6 (4.0%) patients, while dose delay due to a TRAE occurred in 23 (15.2%) patients. Three patients with major protocol deviations were excluded from efficacy analysis. Among 148 patients assessed by IRC per RECISTv1.1, 2 CR, 36 PR, and 30 SD were observed for an ORR of 25.7% and a DCR of 45.9%. The median DOR was 15.7 months. The median PFS was 1.9 months, and the median OS was estimated 20.8 months. PD-L1 expression results were obtained from 141 patients. PD-L1+ patients (n=46) had significant better ORR than PD-L1- patients (n=95), 41.3% versus 16.8% ( p<0.01). Conclusions: Toripalimab has demonstrated encouraging clinical activity in chemo-refractory UC patients with a manageable safety profile. Patients will be continuously monitored for safety and overall survival. Clinical trial information: NCT03113266 .

Recombinant humanized anti-PD-1 monoclonal antibody toripalimab in patients with metastatic urothelial carcinoma: Preliminary results of an open-label phase II clinical study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4554-4554
Author(s):  
Xinan Sheng ◽  
Haige Chen ◽  
Xin Yao ◽  
Yi Hu ◽  
Xudong Yao ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Study ◽  
Urothelial Carcinoma ◽  
Clinical Response ◽  
Disease Progression ◽  
Safety Profile ◽  
Clinical Activity ◽  
Safety And Efficacy ◽  
Phase Ii Clinical Study ◽  
Metastatic Urothelial Carcinoma

4554 Background: Patients with advanced metastatic urothelial carcinoma (UC) who experience disease progression after standard therapy have limited treatment options. Phase I studies of toripalimab in subjects with heavily pretreated metastatic UC have demonstrated an acceptable safety profile and promising clinical activity. Here we report the preliminary safety and efficacy result of toripalimab in a phase II clinical study in Chinese patients with refractory/metastatic urothelial carcinoma. (Clinical trial ID: NCT03113266). Methods: Metastatic UC Patients will receive toripalimab, also known as JS001, 3 mg/kg Q2W until disease progression or unacceptable toxicity. All patients with measurable disease will be assessed for clinical response every 8 weeks according to RECISTv1.1. Tumor PD-L1 expression and tumor mutational burden will be measured for correlation with clinical response. Results: From May 2017 to February 10, 2019, 79 patients were enrolled from 7 participating centers. The median age was 61 years with 57.5% male. By the cut-off date of Jan 20, 2019, common treatment related AEs were mostly grade 1 or 2, including anemia, hyperglycemia, ALT increased, AST increased and hypothyroidism. Among 65 evaluable patients, 2 complete responses, 18 partial responses, and 13 stable diseases were observed, for an objective response rate (ORR) of 30.8% and a disease control rate of 50.8%. 70% (14/20) responses were ongoing by the cut-off date. PD-L1 expression results were obtained from 56 subjects. PD-L1+ patients (n=16, 28.6%) had significant better ORR than PD-L1- patients (n=40), 62.5% versus 15.0% ( p<0.01). Conclusions: Toripalimab has demonstrated encouraging clinical activity in chemo-refractory UC patients and a manageable safety profile. Toripalimab elicited a favorable 62.5% ORR in PD-L1 positive patients, while PD-L1 negative patients also achieved a 15% ORR, including one complete response. Patients will be continuously monitored for additional safety and efficacy readouts (DOR, PFS and OS). Clinical trial information: NCT03113266.

Recombinant humanized anti-PD-1 monoclonal antibody toripalimab in patients with metastatic urothelial carcinoma: Preliminary results of an open-label phase II clinical study (POLARIS-03).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 504-504
Author(s):  
Xinan Sheng ◽  
Haige Chen ◽  
Bin Hu ◽  
Xudong Yao ◽  
Ziling Liu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Study ◽  
Urothelial Carcinoma ◽  
Clinical Response ◽  
Disease Progression ◽  
Safety Profile ◽  
Clinical Activity ◽  
Safety And Efficacy ◽  
Phase Ii Clinical Study ◽  
Metastatic Urothelial Carcinoma

504 Background: Patients with advanced metastatic urothelial carcinoma (UC) who experience disease progression after standard therapy have limited treatment options. Phase I studies of toripalimab in subjects with heavily pretreated metastatic UC have demonstrated an acceptable safety profile and promising clinical activity. Here we report the preliminary safety and efficacy result of toripalimab in a Phase II clinical study in Chinese patients with refractory/metastatic UC (Clinical trial ID: NCT03113266). Methods: Metastatic UC patients received toripalimab, also known as JS001, 3 mg/kg Q2W until disease progression or unacceptable toxicity. All patients with measurable disease were assessed for clinical response every 8 weeks according to RECISTv1.1. Tumor PD-L1 expression and tumor mutational burden was measured for correlation with clinical response. Results: From May 2017 to Sep 2019, 151 patients were enrolled from 15 participating centers. Patient enrollment was completed for this study. The median age was 62.0 years with 66.9% of the population being male. By the cut-off date of 21 Oct 2019, common treatment related AEs were mostly Grade 1 or 2, including anemia, blood triglycerides increased, fever, protein urine present and blood glucose increased. Among 128 efficacy evaluable patients, 4 complete responses, 25 partial responses, and 35 stable diseases were observed, for an objective response rate (ORR) of 22.7% and a disease control rate of 50.0%. 62.1% (18/29) of responses were ongoing at the cut-off date. PD-L1 expression results were obtained from 121 efficacy evaluable subjects. PD-L1+ patients (n = 39, 32.2%) had significant better ORR than PD-L1- patients (n = 82), 38.5% versus 13.4%. Conclusions: Toripalimab has demonstrated encouraging clinical activity in chemo-refractory UC patients and a manageable safety profile. Toripalimab elicited a favorable 38.5% ORR in PD-L1+ patients. Nevertheless PD-L1- patients also achieved a 13.4% ORR, including one complete response. Patients will be continuously monitored for additional safety and efficacy readouts (DOR, PFS and OS). Clinical trial information: NCT03113266.

Recombinant humanized anti-PD-1 monoclonal antibody (JS001) as salvage treatment for advanced gastric adenocarcinoma: Preliminary results of an open-label, multi-cohort, phase Ib/II clinical study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 108-108 ◽  
Author(s):  
Rui-hua Xu ◽  
Fenghua Wang ◽  
Nong Xu ◽  
Lin Shen ◽  
Guanghai Dai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Study ◽  
Clinical Response ◽  
Gastric Adenocarcinoma ◽  
Safety Profile ◽  
Gastroesophageal Junction ◽  
Chinese Patients ◽  
Positive Staining ◽  
Safety And Efficacy ◽  
Phase Ib

108 Background: Patients with gastric adenocarcinoma (GC) or gastroesophageal junction cancer (GEC) often present with advanced or metastatic disease, which has poor prognosis and limited treatment options and represent an important unmet medical need especially in China/Asia. JS001, a humanized recombinant IgG4 antibody against PD-1, selectively blocks the interactions of PD-1 with its ligands PD-L1 and PD-L2, and promotes antigen specific T-cell activation. A phase I study of JS001 in Chinese patients with heavily pretreated solid tumors has demonstrated an acceptable safety profile in doses up to 10 mg/kg Q2W. Here we report the safety and efficacy of JS001 in a phase Ib/II clinical study in Chinese patients with refractory/metastatic GC. (Clinical trial ID: NCT02915432) Methods: Refractory/metastatic GC Patients receive JS001 3 mg/kg Q2W until disease progression or unacceptable toxicity. All patients with measurable disease will be assessed for clinical response every 8 weeks according to the RECIST 1.1 criteria. Tumor PD-L1 expression as well as additional potential predictive biomarkers are monitored for correlation with clinical response. Results: Between Apr 19, 2017 and Sep 11, 2017, 48 GC pts (74.5% received at least 2 Lines of treatment) were enrolled into the study. Treatment related adverse events occurred were mostly grade 1 or 2. As of Sep 11, 2017, 25 GC pts have been evaluated for clinical efficacy. 5 PR (partial response) and 10 SD (stable disease) were observed (ORR 20% and DCR 60%). The PD-L1 expression positivity (defined as positive staining ³1% on Tumor Cell or on Immune Cell by SP142) in EC tumor was 14.3% (7/48). 3/5 (60%) PD-L1+ patients and 2/20 (10%) PD-L1 negative patients achieved partial responses. Conclusions: JS001 showed a promising preliminary clinical activity in heavily pre-treated metastatic GC pts with a manageable safety profile. Of the 25 evaluable GC patients by 9/11/2017, 5 PR and 10 SD were observed (ORR 20% and DCR 60%). Among PD-L1 positive patients (n=5), ORR was 60% and DCR 80%. Pts will be continuously monitored for safety and efficacy upon JS001 treatment. Clinical trial information: NCT02915432.

A phase II trial to evaluate pemetrexed clinical responses in relation to tumor methylthioadenosine phosphorylase (MTAP) gene status in patients with previously treated metastatic urothelial carcinoma.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 385-385 ◽  
Author(s):  
Omar Alhalabi ◽  
Matthew T Campbell ◽  
Rebecca Slack-Tidwell ◽  
Arlene O. Siefker-Radtke ◽  
Amishi Yogesh Shah ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Response Rate ◽  
Synthetic Lethality ◽  
Objective Response ◽  
The Cancer Genome Atlas ◽  
Dynamic Monitoring ◽  
Nucleotide Synthesis ◽  
Metastatic Urothelial Carcinoma

385 Background: According to The Cancer Genome Atlas, 26.8% of bladder tumors harbor homozygous deletion of the MTAP gene, which encodes for an essential enzyme for the salvage pathway of nucleotide synthesis. Pemetrexed is a well-known anti-folate agent that inhibits the de novo pathway of nucleotide synthesis. Therefore, we hypothesized that tumors with MTAP gene loss have a synthetic lethality to pemetrexed due to loss of both essential nucleotide synthesis pathways. We proposed a study to determine pemetrexed response rate in patients with MTAP-deficient metastatic urothelial carcinoma (mUC). Methods: We carried out a single-arm, open-label, phase II clinical trial with pemetrexed in patients with mUC and MTAP loss by immunohistochemistry. This is an interim analysis of results. Each patient receives pemetrexed (500 mg/m2) on day 1 of each 21-day cycle. Pemetrexed is continued until progression of disease (PD) and a repeat biopsy is obtained at that time. Pre- and post-treatment blood, urine and tumor samples are obtained for dynamic monitoring of immune and molecular correlates to clinical activity. Results: Six patients have been enrolled on this trial and all have received at least one previous treatment including a cisplatin-containing regimen in 5 (83%) patients and an immune checkpoint inhibitor in 4 (66%) patients. Of these 6 patients, 1 (17%) had complete response (CR); two (33%) had partial response (PR); 1 (17%) had stable disease; 1 (17%) was not evaluable; 1 (17%) had PD. Treatment was generally well tolerated with mostly grade 1 or 2 adverse events. Only 2 of 6 patients developed grade 3 anemia. Immunologic and molecular analyses are ongoing on all collected samples. Conclusions: Our study show that in heavily pretreated MTAP deficient mUC patients, pemetrexed is still an effective and well-tolerated therapy with an objective response rate (ORR=CR+PR) of 50%, which is higher than previously reported pemetrexed activity (ORR=8-28%) as first or second line treatment for mUC. Clinical trial information: NCT02693717.

Clinical response and biomarker analysis of POLARIS-02 a phase II study of toripalimab, a humanized IgG4 mAb against programmed death-1 (PD-1) in patients with metastatic nasopharyngeal carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6542-6542
Author(s):  
Fenghua Wang ◽  
Xiao-Li Wei ◽  
Jifeng Feng ◽  
Qi Li ◽  
Nong Xu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Response ◽  
Disease Progression ◽  
Treatment Options ◽  
Nasopharyngeal Cancer ◽  
Fold Increase ◽  
Clinical Activity ◽  
Standard Chemotherapy ◽  
Systemic Treatments ◽  
Biomarker Analysis

6542 Background: Metastatic nasopharyngeal cancer (mNPC) patients progressed after standard therapy have limited treatment options. This study is to evaluate the clinical efficacy and safety of toripalimab in mNPC patients refractory to standard chemotherapy treatment (Clinical trial ID: NCT02915432). Methods: Patients receive 3 mg/kg toripalimab Q2W via IV infusion until disease progression, unacceptable toxicity, or voluntary withdrawal. Clinical response is assessed every 8 weeks according to RECIST v1.1. Tumor PD-L1 expression, plasma EBV titer and other biomarkers will be evaluated for correlation with clinical response. Results: From Dec 2016 to Feb 2019, 190 mNPC patients were enrolled from 17 participating centers in China. The median age was 46 years with 83% male. Patients were heavily pretreated with a median of 2 lines of prior systemic treatments. By the cutoff date of Jan 17, 2020, 97% patients experienced treatment related adverse events (TRAE). Most common TRAE included anemia, hypothyroidism, AST increased, proteinuria and fever. Grade 3+ TRAE occurred in 28% patients. Among 190 patients assessed by Independent Review Committee per RECIST v1.1, 6 CR, 33 PR and 40 SD were observed for an ORR of 20.5% and a DCR of 41.6%. The median DOR was 12.9 months. The median PFS and median OS were 1.9 months and 18.6 months respectively. PD-L1+ patients (n=48) had higher ORR than PD-L1- patients (n=134), 27.1% versus 19.4%. By tumor histology, ORR was higher in keratinizing NPC (n=8) than non-keratinizing NPC (n=168), 62.5% versus 19.0%. 144 patients had valid plasma EBV titer measured every 28 days during the study. An average drop of 101-fold plasma EBV titer from baseline was observed in patients with objective responses. Patients with 2-fold+ drop in plasma EBV titer on day 28 (n=60) went on to have 48.3% ORR and 76.7% DCR, whereas patients with less than 2-fold drop (n=88) had 5.7% ORR and 25.0% DCR. 14 responding patients who later developed progressive disease had at least 2-fold+ increase of plasma EBV tier 3-months (median) before radiographic identification of disease progression. Conclusions: Toripalimab demonstrated encouraging clinical activity with a manageable safety profile in mNPC patients refractory to standard chemotherapy. Patients with 2-fold+ drops in plasma EBV titer on day 28 from baseline had favorable clinical response of 48.3% ORR, which might be used as a predictive biomarker. Clinical trial information: NCT02915432 .

scholarly journals A Phase II Clinical Trial of TRC105 (Anti-Endoglin Antibody) in Adults With Advanced/Metastatic Urothelial Carcinoma

2017 ◽  
Vol 15 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Andrea B. Apolo ◽  
Fatima H. Karzai ◽  
Jane B. Trepel ◽  
Sylvia Alarcon ◽  
Sunmin Lee ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Phase Ii Clinical Trial ◽  
Metastatic Urothelial Carcinoma

A phase II study of cabozantinib (XL184) in patients with advanced/metastatic urothelial carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS4589-TPS4589 ◽  
Author(s):  
Andrea Borghese Apolo ◽  
Howard L. Parnes ◽  
Ravi Amrit Madan ◽  
James L. Gulley ◽  
John Joseph Wright ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Metastatic Urothelial Carcinoma ◽  
Serum And Urine

TPS4589 Background: Accumulating evidence supports MET as a therapeutic target in urothelial carcinoma. Activated MET can promote angiogenesis and tumor growth by upregulating VEGF and may play a role in urothelial carcinoma pathogenesis. Cabozantinib inhibits primarily VEGFR2 and MET pathways. Cabozantinib has been approved by the FDA for the treatment of progressive metastatic medullary thyroid cancer, is in Phase 3 trials for metastatic castration-resistant prostate cancer and has demonstrated clinical activity in multiple solid tumors. We previously reported that shed MET levels in serum and urine of patients with urothelial carcinoma correlate with stage, presence of visceral metastases and urinary source and that cabozantinib is effective in reversing HGF-driven urothelial carcinoma cell growth and invasion. These data support the evaluation of cabozantinib in patients with metastatic urothelial carcinoma. Methods: This is a phase II study of oral cabozantinib 60mg daily given continuously in 28-day cycles. There are three study cohorts: [1] metastatic urothelial carcinoma [2] bone only metastatic urothelial carcinoma [3] metastatic non-urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis. A maximum of 55 subjects will be enrolled. Up to 45 patients will be accrued to cohort 1.The remainder will be enrolled on exploratory cohorts 2 & 3. A two-stage single-arm phase II design will be employed. The primary objective is to determine the objective response rate in patients with metastatic urothelial carcinoma who have progressed on prior chemotherapy. Secondary objectives include progression free survival, safety and toxicity, and overall survival. Exploratory objectives include tumor tissue Met expression, shed MET levels in serum and urine, immune subsets, genetic biomarkers, molecular markers of angiogenesis and circulating tumor cells, correlation with clinical response parameters. Finally we will explore treatment evaluation with FDG and NaF PET/CT compared to standard imaging. This study is supported by the Cancer Therapy Evaluation Program (CTEP). NCT01688999 Clinical trial information: NCT01688999.

Recombinant humanized anti-PD-1 monoclonal antibody (JS001) as salvage treatment for advanced esophageal squamous cell carcinoma: Preliminary results of an open-label, multi-cohort, phase Ib/II clinical study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 116-116 ◽  
Author(s):  
Rui-hua Xu ◽  
Fenghua Wang ◽  
Jianhua Shi ◽  
Ji Feng Feng ◽  
Lin Shen ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Squamous Cell Carcinoma ◽  
Clinical Study ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Response ◽  
Safety Profile ◽  
Chinese Patients ◽  
Safety And Efficacy ◽  
Phase Ib

116 Background: Patients with Esophageal squamous cell carcinoma (EC) often present with advanced and metastatic stage disease, which has poor prognosis and limited treatment options, and represent an important unmet medical need especially in China/Asia. JS001, a humanized recombinant IgG4 antibody against PD-1, selectively blocks the interactions of PD-1 with its ligands PD-L1 and PD-L2, and promotes antigen specific T-cell activation. A phase I study of JS001 in Chinese patients with heavily pretreated solid tumors has demonstrated an acceptable safety profile in doses up to 10 mg/kg Q2W. Here we report the safety and efficacy of JS001 in a phase Ib/II clinical study in Chinese patients with refractory/metastatic EC. (Clinical trial ID: NCT02915432) Methods: Refractory/metastatic EC Patients receive JS001 3 mg/kg Q2W until disease progression or unacceptable toxicity. All patients with measurable disease will be assessed for clinical response every 8 weeks according to the RECIST 1.1 criteria. Tumor PD-L1 expression as well as additional potential predictive biomarkers are monitored for correlation with clinical response. Results: Between Apr 19 2017 and Sep 11 2017, 56 EC pts (84.9% received at least 2 Lines of treatment) were enrolled into the study. Treatment related adverse events occurred were mostly grade 1 or 2. As of Sep 11 2017, 34 EC pts have been evaluated for clinical efficacy. Among these pts, 8 PR (partial response) and 14 SD (stable disease) were observed (ORR 23.5% and DCR 64.7%). The PD-L1 expression positivity (defined as positive staining ³1% on Tumor Cell [TC] or on Immune Cell [IC] by SP142) in EC tumor tissue was 21.4% (12/56). 2/10 (20%) PD-L1+ patients and 6/24 (25%) PD-L1 negative patients achieved partial responses. Conclusions: JS001 showed a promising preliminary clinical activity in heavily pre-treated metastatic EC pts with a manageable safety profile. Clinical response was not correlated with PD-L1 expression. Pts will be continuously monitored for safety and efficacy upon JS001 treatment. Clinical trial information: NCT02915432.

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