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 .

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: 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 (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) in patients with refractory/metastatic nasopharyngeal carcinoma: Interim results of an open-label phase II clinical study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6017-6017 ◽  
Author(s):  
Fenghua Wang ◽  
Xiao-Li Wei ◽  
Ji Feng Feng ◽  
Qi Li ◽  
Nong Xu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Response ◽  
Phase Ii ◽  
Copy Number ◽  
Objective Response ◽  
Nasopharyngeal Cancer ◽  
Dna Copy Number ◽  
Open Label ◽  
Open Label Phase ◽  
Ebv Dna

6017 Background: Metastatic nasopharyngeal cancer (NPC) patients progressed afterstandardtherapy have limited treatment options. Toripalimab, also known as JS001, a humanized IgG4 antibody specific for human PD-1, has been approved for 2nd line treatment of metastatic melanoma in China. Here we report the results from a phase IIstudy in metastatic NPC patients treated with toripalimab.(Clinical trial ID: NCT02915432). Methods: This multi-center, open-label, phase II registration study is designed to evaluate the safety and efficacy of toripalimab in metastaticNPC patients who have failed systemic treatment. Toripalimabis given at 3 mg/kg IV Q2W until disease progression or intolerable toxicity.Tumor PD-L1 expression, plasma EBV DNA level and other biomarkerswill be correlatedwith clinical response. Results: Enrollment of 190chemo-refractory metastatic NPCpatients was completed by Feb 2019 from 17 participating centers. The median age was 46 years, with 89.5% patients received at least 2 lines of prior systemic therapies. Treatment related adverse events (TRAE)occurred in 92% patients, which were mostly grade 1 or 2.Common TRAE includedanemia, hypothyroidism, AST increased, proteinuria, pyrexia, cough, constipation, ALT increased, hypoalbuminemia and pruritus.Grade 3 or higherTRAEoccurred in 25% patients.By the cut-off date of Jan 7 2019, among 135 evaluable patients, 3 complete responses, 31 partial responses and 40 stable diseaseswere observed for an objective response rate (ORR) of 25.2% and a disease control rate of 54.8%. PD-L1 expression results were obtained from 125 patients and 45.6% (57/125) were PD-L1+.PD-L1+ patientsachieved slightly higherORR than PD-L1- patients, 29.8% versus 22.1%. In addition, an average drop of 47-fold plasma EBV DNA copy number was observed in responding patients, which typically proceeded the radiographic identification of clinical benefit. Conclusions: Toripalimab has demonstrated a manageable safety profileand encouraging clinical activity in the largest check-point blockade study in NPC to date. A change in plasma EBV DNA copy number might serve as a predictive marker for favorable clinical response. Patients will be continuously monitored for additional safety and survival readouts. Clinical trial information: NCT02915432.

METex14 ctDNA dynamics & resistance mechanisms detected in liquid biopsy (LBx) from patients (pts) with METex14 skipping NSCLC treated with tepotinib.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9012-9012
Author(s):  
Paul K. Paik ◽  
Remi Veillon ◽  
Enriqueta Felip ◽  
Alexis Cortot ◽  
Hiroshi Sakai ◽  
...  
Keyword(s):  
Clinical Response ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Clinical Activity ◽  
Molecular Response ◽  
Resistance Mutations ◽  
Data Set ◽  
Biomarker Analysis ◽  
Treatment Data ◽  
Never Smokers

9012 Background: In the VISION study, tepotinib in METex14 skipping NSCLC pts (Cohort A) had robust and durable clinical activity. Serial LBx samples were collected for biomarker analyses, presented herein. Methods: LBx samples taken at baseline (BL), Week 6, 12, & end of treatment (EOT) were analyzed using Guardant360® CDx (73 genes). Investigator (INV)-assessed clinical outcome was evaluated per BL biomarker profiles and by molecular response (MR; defined as > 75% depletion from BL in METex14 variant allele frequency [VAF] ctDNA confirmed in 2 consecutive samples) or molecular progression (MP; defined as VAF increase > 0 from BL). Acquired resistance was investigated in EOT samples, following progression per INV. Results: LBx pts (n = 99) had a median age of 72 yrs (range 49–88), 53% were male, 44% never smokers, 85% had adenocarcinoma. INV ORR was 53% (95% CI 42, 63); ORR in 1L (n = 44) was 59% (43, 74) & ≥2L (n = 55) was 47% (33, 61). 94 pts had BL biomarker profiles; these were similar in 1L and ≥2L pts, except EGFR amp: 1/43 1L [2%] vs 8/51 ≥2L [16%]. Outcomes were not impacted by location/type of METex14 alteration. 1 pt with concomitant MET M1250T mutation had a PFS of 17.3 months. A trend towards better efficacy was seen in pts with concomitant MET amp (6 responses in 8 pts). Response to tepotinib occurred both in pts with wt or mutant TP53; however, there was a trend for longer mDOR in pts with wt TP53 (18.3 [95% CI 9.7, ne] vs 7.1 [4.7, 10.9] months) and mPFS (9.5 [6.7, 19.7] vs 5.1 [2.8, 6.9] months). Concomitant oncogenic mutations were rare, with no responses in 3 pts with KRAS, NRAS alterations and 3 responses in 5 pts with PI3K/AKT alterations. 65 pts had 2 consecutive on-treatment samples: 46 (71%) had confirmed MR, 5 (8%) had confirmed MP, 14 (22%) had no change in VAF or lacked confirmation. MR was associated with clinical response and MP was associated with no response/short PFS (Table). 52 pts with progression had EOT LBx samples. Emerging MET resistance mutations (Y1230H/C & D1228H/N) occurred in 7 (13%) pts, all responders and 5/7 had PFS > 10 months. Analyses on non-MET-driven resistance mechanisms will be presented. Conclusions: LBx biomarker analysis from the largest on-treatment data set for a MET inhibitor in METex14 skipping NSCLC, showed that ctDNA depletion in METex14 VAF is associated with improved clinical response in pts treated with tepotinib. This suggests serial LBx could help us to monitor response/non-response, understand resistance, and guide trials that test escalation/de-escalation strategies to improve outcomes and maximize QOL. Clinical trial information: NCT02864992. [Table: see text]

Tisotumab vedotin versus investigator’s choice chemotherapy in second- or third-line recurrent or metastatic cervical cancer (innovaTV 301/ENGOT-cx12/GOG 3057, trial in progress).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5596-TPS5596
Author(s):  
Ignace Vergote ◽  
Bradley J. Monk ◽  
Robert L. Coleman ◽  
Leslie M. Randall ◽  
Keiichi Fujiwara ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cervical Cancer ◽  
Cell Death ◽  
Disease Progression ◽  
Treatment Options ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

TPS5596 Background: Doublet chemotherapy (paclitaxel plus either platinum or topotecan) with bevacizumab (if eligible) is recommended for first-line treatment of recurrent (not amenable to curative therapy) or metastatic cervical cancer (r/mCC; Tewari 2014). In the second-line setting, there are limited data for currently available treatment options. Tisotumab vedotin (TV) is an investigational antibody-drug conjugate (ADC) composed of a tissue factor (TF)-directed human monoclonal antibody covalently linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. TV is directed to cells expressing TF and releases MMAE upon internalization, resulting in cell cycle arrest and apoptotic cell death. TV has anti-tumor activity on multiple tumor types and kills tumor cells by direct cytotoxicity, bystander cytotoxicity, antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and in a manner consistent with immunogenic cell death. In a recent phase 2 pivotal trial (innovaTV 204), TV demonstrated a clinically meaningful objective response rate (ORR) of 24% and median duration of response (DOR) of 8.3 months, as well as a manageable and tolerable safety profile with most adverse events being mild to moderate, in r/mCC patients with disease progression on or after chemotherapy. These findings support further investigation of TV in patients with r/mCC who progress on available first-line treatment options. Methods: The innovaTV 301 trial (NCT04697628) is a global, randomized, open-label, phase 3 clinical trial evaluating the efficacy and safety of TV in patients with previously treated r/mCC. Eligible patients must be ≥18 years, have r/mCC, and have experienced disease progression after receiving 1-2 prior lines of therapy (either standard of care systemic chemotherapy doublet or platinum-based therapy [if eligible; paclitaxel+cisplatin+bevacizumab, paclitaxel+carboplatin+bevacizumab, or paclitaxel+topotecan/nogitecan+bevacizumab]). Approximately 482 patients will be randomized 1:1 to receive 21-day cycles of either TV (2.0 mg/kg IV once every 3 weeks) or investigator’s choice of chemotherapy: topotecan (1 or 1.25 mg/m2 IV; Day 1 [D1] to D5 of each cycle), vinorelbine (30 mg/m2 IV; D1 and D8 of each cycle), gemcitabine (1000 mg/m2 IV; D1 and D8 of each cycle), irinotecan (100 or 125 mg/m2 IV; weekly for 28days, then every 42 days), or pemetrexed (500 mg/m2 IV, D1 of each cycle). The primary endpoint of this trial is overall survival. Key secondary endpoints are progression-free survival, ORR, time to response, DOR, safety, and quality of life outcomes. The study is currently enrolling and will have sites open in the US, EU, Japan, Latin America, Taiwan, Singapore, and South Korea. Clinical trial information: NCT04697628.

Effect of continuation of bevacizumab following disease progression in patients with metastatic colorectal cancer on survival

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15143-e15143
Author(s):  
G. F. Samelis ◽  
A. Tsiakou ◽  
M. Karamanidi ◽  
M. Pelechrini ◽  
A. Zaganides ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Clinical Activity ◽  
Line Treatment ◽  
First Line ◽  
Standard Chemotherapy ◽  
Multiple Line ◽  
Co Morbidity

e15143 Background: The management of patients with metastatic colorectal cancer (mCRC) has evolved dramatically over the last decade, with several “targeted” agents having entered the treatment arena. Multiple-line treatment is now considered as an important step towards the optimal therapeutic strategy for this patient population. Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown clinical activity in patients with mCRC when used either as a first-line or second-line treatment. Currently, there is limited information in the literature on the use of bevacizumab combination chemotherapy in multiple lines with regimens including irinotecan and oxaliplatin, in mCRC patients who have progressed. Methods: We evaluated the efficacy and safety of bevacizumab in combination with standard chemotherapy (irinotecan, capecitabine, oxaliplatin, cetuximab) in 21 patients with metastatic colorectal cancer with a median age of 69 (range: 47–85) years old with PS: 0–1, included in the study. The metastatic sites were liver in 13 patients, liver and lung in 4 patients, lung in 2 patients, intra-abdominal in 1 patient and urinary-bladder in 1 patient. Bevacizumab treatment was continuously dispensed after disease progression and only other combined drugs were altered. Subgroup analysis was performed in terms of age, site of metastases, spread and co-morbidity. Results: The median age of the patients included in the analysis was 69 years (range 47–85). Progression free survival (PFS) was 17 months in first line setting (overall survival (OS) not reached yet) o, and for the age group >69 and <69 it was 23 and 16 months respectively (p=0.4565). Overall survival for the <69 years old was 36 months. Anemia (all grades) was reported in 90.6% of the patients, while hemorrhage and thrombosis were reported in 28.6% and 14.3% respectively. Conclusions: Multiple line treatment in advanced colorectal cancer, including bevacizumab combined with standard chemotherapy, may improve OS (median: 23+ months) with an acceptable toxicity profile in patients with mCRC. However, further research through well-designed randomized studies is warranted to appraise the beneficial risk- benefit ratio of such an approach. No significant financial relationships to disclose.

FRACTION (Fast Real-time Assessment of Combination Therapies in Immuno-Oncology)-gastric cancer (GC): A randomized, open-label, adaptive, phase 2 study of nivolumab in combination with other immuno-oncology (IO) agents in patients with advanced GC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4137-TPS4137 ◽  
Author(s):  
Praveen Aanur ◽  
Martin Gutierrez ◽  
Ronan Joseph Kelly ◽  
Jaffer A. Ajani ◽  
Geoffrey Yuyat Ku ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rapid Development ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
New Combination ◽  
Clinical Activity ◽  
Phase 2 ◽  
Open Label

TPS4137 Background: Nivolumab, a fully human IgG4 mAb that targets programmed death-1, alone and in combination with ipilimumab, a fully human IgG1 mAb that targets cytotoxic T-lymphocyte antigen 4, has demonstrated encouraging clinical activity in patients with advanced GC. These data support the rationale that nivolumab in combination with other IO agents or targeted therapies may improve treatment outcomes in patients with advanced GC. Given the rapid development of novel IO agents, traditional studies cannot efficiently evaluate all possible IO-IO and IO-targeted therapy combinations. FRACTION is an innovative clinical trial program with a rolling, adaptive platform design that allows for the addition of new combination regimens, as well as withdrawal of ineffective regimens. Here we describe the study concept, key design components, and the first IO treatment combinations of FRACTION-GC, a phase 2, randomized, open-label, adaptive study in advanced GC (NCT02935634). Methods: Patients with advanced GC or gastroesophageal junction (GEJ) cancer will be enrolled based on prior IO treatment and randomized to receive nivolumab plus BMS-986016 (fully human IgG4 mAb that targets lymphocyte activation gene 3) or nivolumab plus ipilimumab. Enrollment is continuous and may offer patients consecutive treatment options based on their treatment exposure and response. The primary endpoints are objective response rate, duration of response, and progression-free survival rate at 24 weeks. The secondary endpoint is safety. Comprehensive biomarker analyses will also be performed. New treatment combinations will be added over time to explore their potential benefits and to provide a continuous flow of treatment options for patients whose cancer progresses on existing treatments. In this way, FRACTION-GC is envisioned to accelerate the development of the next generation of IO combinations for patients with metastatic GC and GEJ cancer. Clinical trial information: NCT02935634.

Overall survival and biomarker analysis of a phase Ib combination study of toripalimab, a humanized IgG4 mAb against programmed death-1 (PD-1) with axitinib in patients with metastatic mucosal melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10007-10007 ◽  
Author(s):  
Xinan Sheng ◽  
Xieqiao Yan ◽  
Zhihong Chi ◽  
Lu Si ◽  
Chuanliang Cui ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Response ◽  
Mucosal Melanoma ◽  
Phase 2 Trial ◽  
Voluntary Withdrawal ◽  
Biomarker Analysis ◽  
Tumor Mutational Burden ◽  
Treatment Naïve ◽  
Grade 3 ◽  
Endothelial Growth Factor

10007 Background: Metastatic mucosal melanoma responds poorly to PD-1 blockade therapy in comparison with cutaneous melanoma. Vascular endothelial growth factor (VEGF) is indicated to play an important immunosuppressive role in mucosal melanoma. Combination of VEGF inhibition with PD-1 blockade might provide therapeutic opportunities. Toripalimab was approved as a second-line treatment for metastasis melanoma in Dec 2018. This study is to evaluate the safety and clinical efficacy of toripalimab combined with axitinib for the treatment of metastatic mucosal melanoma. (Clinical trial ID: NCT03086174). Methods: Patients with metastatic melanoma receive 1 or 3 mg/kg toripalimab Q2W in combination with 5 mg axitinib BID until disease progression, unacceptable toxicity, or voluntary withdrawal. Clinical response is assessed every 8 weeks according to RECISTv1.1. Tumor PD-L1 expression, tumor mutational burden (TMB), and gene expression profile (GEP) will be evaluated for correlation with clinical response. Results: From April 2017 to April 2018, 33 patients were enrolled in the study. No DLT or treatment related death was observed. 97% patients experienced treatment related AE (TRAE) and 39.4% patients experienced Grade 3-4 TRAEs. Most common TRAEs include diarrhea, proteinuria, hand and foot syndrome and hypothyroidism. Only one patient discontinued treatment due to TRAE. Among 29 treatment naïve mucosal melanoma patients, 14 PR and 11 SD were observed for an ORR of 48.3% and a DCR of 86.2%. The median DOR was 13.7 months. The median PFS was 7.5 months and the median OS was 20.7 months. PD-L1 expression or TMB had no significant differences in responders versus non-responders. In contrast, GEP scores of eight selected immune-related and four angiogenesis-related genes showed strong correlation with clinical response, whereas previous published immune related signature or angiogenesis signature alone had no correlation. Conclusions: Toripalimab combined with axitinib is a promising treatment option for metastatic mucosal melanoma. GEP scores of selected immune-related and angiogenesis-related genes might predict the response to the combination. A randomized 3-arm Phase 2 trial has been initiated to compare toripalimab plus axitinib with toripalimab or axitinib alone. Clinical trial information: NCT03086174.

Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 824-824 ◽  
Author(s):  
Jordan Berlin ◽  
David S. Hong ◽  
John F. Deeken ◽  
Valentina Boni ◽  
Do-Youn Oh ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Treatment Options ◽  
Safety Data ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Receptor Kinase ◽  
Efficacy And Safety ◽  
Prior Therapy ◽  
Gi Cancer ◽  
Best Response

824 Background: Tropomyosin receptor kinase (TRK) fusions arise from rearrangements of the neurotrophic tyrosine receptor kinase ( NTRK) 1, 2, or 3 genes and an unrelated gene, creating constitutively active oncogenic drivers that have been detected in a range of adult and pediatric malignancies, but are generally rare in patients with gastrointestinal (GI) cancer. Larotrectinib is a selective TRK inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. Here, we report efficacy and safety data for patients with TRK fusion GI tumors. Methods: Patients with a TRK fusion GI cancer treated with larotrectinib in a phase II clinical trial, NAVIGATE (NCT02576431), were included in this analysis. Larotrectinib was administered at 100 mg twice daily, until disease progression, unacceptable toxicity, death, or withdrawal. Response was assessed by the investigator using RECIST v1.1. Results: As of February 19, 2019, 14 patients with TRK fusion GI cancer (median age 68 y, range 32–84 y) were enrolled. GI tumor types were colon (8), cholangiocarcinoma (2), pancreas (2), appendix (1), and hepatic (1). Fusions involved NTRK1 (n = 12) and NTRK3 (n = 2). Nine patients had ≥2 prior lines of therapy. The best response on last prior therapy was 1 partial response (PR). Overall best responses on larotrectinib were: colon cancer, 4 patients had a PR and 4 had stable disease (SD); pancreatic cancer, 1 patient had a PR and 1 had SD; cholangiocarcinoma, 1 patient had a PR and 1 had progressive disease; appendix cancer, 1 patient had SD; response in 1 patient with hepatic cancer was not determined. Median time to response was 1.8 months (range 1.7–2.1). With 5 patients ongoing and censored, the median progression free survival was 5.3 months (95% CI 2.2–9.0). Median overall survival was 33.4 months (95% CI 2.8–36.5). Larotrectinib was well tolerated, with most adverse events being grade 1 or 2. Conclusions: Although the sample size is limited, there is evidence of clinical activity with larotrectinib in TRK fusion GI cancer, with a manageable safety profile. TRK fusion GI cancer may represent an under-diagnosed subset of patients with viable treatment options. Clinical trial information: NCT02576431.

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