A phase II trial of atezolizumab and bevacizumab in patients with advanced, progressive neuroendocrine tumors (NETs).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 619-619 ◽  
Author(s):  
Daniel M. Halperin ◽  
Suyu Liu ◽  
Arvind Dasari ◽  
David R. Fogelman ◽  
Priya Bhosale ◽  
...  
Keyword(s):  
Adverse Events ◽  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Yield Response ◽  
Clinical Activity ◽  
Prior Therapy ◽  
Pre Treatment

619 Background: Neuroendocrine tumors (NETs) are relatively rare and heterogeneous tumors arising throughout the aerodigestive tract, which are incurable and life-limiting when metastatic. Prior studies of checkpoint inhibitors in NET patients have yielded minimal evidence of efficacy. Historically, effective therapies for advanced, progressive NET yield response rates less than 10% and progression-free survival (PFS) durations of approximately 11 months, as compared to approximately 4.5 months with placebo. Methods: We undertook a phase II basket study of atezolizumab in combination with bevacizumab in patients with rare cancers, and present here the data from the pancreatic NET (pNET) cohort and extrapancreatic NET (epNET) cohort, each of which included 20 patients with grade 1-2 NET that was progressive under any prior therapy. Patients received 1200mg of atezolizumab and 15mg/kg of bevacizumab IV q 21 days. The primary endpoint was confirmed objective response by RECIST 1.1. Results: The confirmed objective response rate with this combination was 20% (95% CI 6-44%) in the pNET cohort and 15% (95% CI 3-38%) in the epNET cohort. The median PFS in the pNET cohort is 19.6 months (95% CI 10.6-NR), while it was 14.9 months (95% CI 6.1-NR) in the epNET cohort, 1-year PFS was 75% and 52%, respectively. The combination was well-tolerated in this patient population, with the most common related treatment-emergent adverse events being hypertension (47.5%), proteinuria (37.5%), and fatigue (35%). The most common related grade 3/4 adverse events were hypertension (20%) and proteinuria (7.5%). Conclusions: The combination of atezolizumab and bevacizumab demonstrated moderate clinical activity in patients with advanced NETs. As pre-treatment and on-treatment biopsies were obtained for all patients, correlations with immune infiltration, mutations, and transcriptome alterations should provide additional insight into the mechanisms of response and resistance. Clinical trial information: NCT03074513.

A phase II study of pembrolizumab in combination with palliative radiotherapy (RT) for hormone receptor-positive (HR+) metastatic breast cancer (MBC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1047-1047 ◽  
Author(s):  
Romualdo Barroso-Sousa ◽  
Ian E. Krop ◽  
Lorenzo Trippa ◽  
Zhenying Tan-Wasielewski ◽  
Tianyu Li ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Metastatic Breast ◽  
Palliative Radiotherapy ◽  
Progression Free Survival ◽  
Optimal Method ◽  
Neutrophil Lymphocyte Ratio ◽  
Ecog Ps

1047 Background: RT is frequently used for palliation in MBC. In animal models its use has been reported to induce distant (abscopal) tumor responses when combined with immune checkpoint inhibitors. Here, we report the safety and efficacy of palliative RT plus pembrolizumab in a phase II single-arm study in patients (pts) with HR+/HER2- MBC. Methods: Eligible pts had HR+/HER2- MBC, ECOG PS <2, indication for palliative RT, and ≥1 measurable lesion outside of the RT field; there was no limit on prior lines of therapy. A total RT dose of 20 Gray was delivered over 5 daily fractions. Pembrolizumab was given at 200 mg IV 2-7 days before day 1 of RT, then every 3 weeks until disease progression. The primary endpoint was objective response rate (ORR) outside the field of radiation by RECIST v1.1. Using the Simons “optimal” method, if ≥ 1/8 pts responded during the first stage, 19 more would be enrolled. If ≥ 3/27 responded, the null hypothesis (ORR=3%) would be rejected in favor of a 20% ORR. Predefined secondary endpoints included progression free survival (PFS) and toxicity. Analyses associating PD-L1 expression, tumor-infiltrating lymphocytes (TIL), and neutrophil/lymphocyte ratio (NLR) with outcomes were exploratory. Results: Eight women were enrolled into the first stage of the trial; no objective responses were seen, and the study was closed to further accrual. The median age was 59y (37-68y), 6 (75%) had ECOG PS 1, all had bone and 5 (63%) had liver metastases. The median number of prior cytotoxic therapies for MBC was 2 (range 0 to 8). While one patient had a PR by RECIST criteria, this patient experienced concurrent clinical progression. Two pts had SD < 16 weeks and 5 had PD as best response. The median PFS was 1.4 months (95% CI 0.4 – 2.1). All-cause adverse events occurred in 87.5% of pts (G3-4, 12.5%). TIL were available for 6 pts: 4 had ≤10%, and 2 > 10%. Among 5 pts with PD-L1 status available, 2 were positive. Six pts had NLR > 4. Conclusions: Pembrolizumab combined with RT was well-tolerated, and no unexpected adverse events were observed; however, clinical benefit of the combination was not demonstrated in this heavily pretreated HR+ population. Clinical trial information: NCT03051672.

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

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

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

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 Ramucirumab in Combination with Pembrolizumab in Treatment-Naïve Advanced Gastric or GEJ Adenocarcinoma: Safety and Antitumor Activity from the Phase 1a/b JVDF Trial

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2985
Author(s):  
Ian Chau ◽  
Nicolas Penel ◽  
Andres O. Soriano ◽  
Hendrik-Tobias Arkenau ◽  
Jennifer Cultrera ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Metastatic Setting ◽  
Duration Of Response ◽  
Treatment Naïve ◽  
Combined Positive Score ◽  
Grade 3

Ramucirumab (anti-VEGFR2) plus pembrolizumab (anti-PD1) demonstrated promising antitumor activity and tolerability among patients with previously treated advanced cancers, supporting growing evidence that combination therapies modulating the tumor microenvironment may expand the spectrum of patients who respond to checkpoint inhibitors. Here we present the results of this combination in first-line patients with metastatic G/GEJ cancer. Twenty-eight patients (≥18 years) with no prior systemic chemotherapy in the advanced/metastatic setting received ramucirumab (8 mg/kg days 1 and 8) plus pembrolizumab (200 mg day 1) every 3 weeks as part of JVDF phase 1a/b study. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). Tumors were PD-L1-positive (combined positive score ≥ 1) in 19 and -negative in 6 patients. Eighteen patients experienced grade 3 treatment-related adverse events, most commonly hypertension (14%) and elevated alanine/aspartate aminotransferase (11% each), with no grade 4 or 5 reported. The ORR was 25% (PD-L1-positive, 32%; PD-L1-negative, 17%) with duration of response not reached. PFS was 5.6 months (PD-L1-positive, 8.6 months; PD-L1-negative, 4.3 months), and OS 14.6 months (PD-L1-positive, 17.3 months; PD-L1-negative, 11.3 months). Acknowledging study design limitations, ramucirumab plus pembrolizumab had encouraging durable clinical activity with no unexpected toxicities in treatment-naïve biomarker-unselected metastatic G/GEJ cancer, and improved outcomes in patients with PD-L1-positive tumors.

A phase II study of GW786034 (pazopanib) in patients with recurrent or metastatic invasive breast carcinoma: Results after completion of stage I: A trial of the Princess Margaret Hospital Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1133-1133 ◽  
Author(s):  
S. K. Taylor ◽  
S. Chia ◽  
S. Dent ◽  
M. Clemons ◽  
P. Grenci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Progressive Disease ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Lesion Size ◽  
Grade 3

1133 Background: Pazopanib, an oral small molecule inhibitor of VEGFR, PDGFR, and KIT, has demonstrated activity in phase I, with a recommended phase II dose of 800 mg/d (Hurwitz H et al, J Clin Oncol. 2005;23[16 suppl]:3012.1). We evaluated the activity of single agent pazopanib in recurrent or metastatic breast cancer (MBC). Methods: In this 2-stage design, patients with recurrent or MBC received pazopanib 800 mg/d. The primary endpoint was objective response rate (ORR) of 20%. Response in 3 out of 18 patients was required to go to stage 2. Treatment was continued until progression. Results: 21 patients entered stage 1; 67% were ER positive and all were HER-2-negative. Prior lines of chemotherapy were 1 in 76% and 2 in 14%. Of the 19 evaluable patients, 2 patients remain on treatment. 14 (74%) stopped due to progressive disease, 2 (10%) due to adverse events, and 1 (5%) due to patient request. Best response was partial response (PR) in 1 (5%), stable disease (SD) in 11 (58%), and progressive disease in 7 (37%). Clinical benefit rate (CR, PR, or SD for ≥ 6 months) was 26%. Median time to progression (TTP) was 3.7 months (95% C.I. 1.7 months - not reached). 9 out of 18 patients (50%) with measurable target lesions had some decrease in target lesion size. Estimated progression-free survival at 3 months was 55%, and 28% at 6 months. Adverse events were grade 3/4 elevations in AST (14%) and ALT (10%), and grade 3 hypertension and neutropenia (14% each). Other common events were grade 1/2 lymphopenia, neutropenia, diarrhea, fatigue, skin hypopigmentation, hypertension, nausea, vomiting, anorexia, and headache. Conclusions: Pazopanib is well tolerated and demonstrates activity in pretreated breast cancer. While the target ORR of 20% has not been met, rates of SD and TTP are comparable to other active agents in this setting, and therefore pazopanib may be an interesting agent for future studies in breast cancer. [Table: see text]

A phase II study of single agent mocetinostat, an oral isotype-selective histone deacetylase (HDAC) inhibitor, in patients with diffuse large cell B-cell (DLBCL) and follicular (FL) lymphomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8535-8535 ◽  
Author(s):  
Michael Crump ◽  
Charalambos Andreadis ◽  
Sarit E. Assouline ◽  
David Rizzieri ◽  
Amanda Copeland ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Hdac Inhibitor ◽  
Single Agent ◽  
Objective Response ◽  
Study Drug ◽  
Clinical Activity ◽  
Duration Of Treatment ◽  
Open Label ◽  
Cardiac Symptoms

8535 Background: Mocetinostat (MGCD0103) is an orally available, isotype-selective, non-hydroxamate HDAC inhibitor targeting HDACs 1,2, 3 and 11 with single-agent activity in Hodgkin’s lymphoma and in AML and MDS (in combination with 5-azacitidine). More than 430 patients have been treated to date. Methods: This open-label, phase II trial enrolled patients with DLBCL and FL. Patients received mocetinostat at doses ranging from 70-110 mg 3x/wk every 28 days. Anticancer activity, safety, pharmacokinetics and pharmacodynamics were evaluated. Results: Sixty-nine patients with DLBCL (n=41) and FL (n=28) were enrolled for treatment at starting doses of 85-110 mg. Median age was 62 years (range: 32 to 81). Median duration of treatment was ~3 months (range: <1 to 24). Objective response rate in DLBCL and FL, respectively, was 7/41 (17%; including 2 unconfirmed PRs) and 3/28 (11%; including 1 CR). Median time to response was 2.0 mos (range 1.7-21.0) and 5.3 mos (range 4.3-6.0) respectively. Stable disease was achieved by 13/41 (32%) and 14/28 (50%), respectively, for a disease control rate of 49% and 61%, respectively. Mean duration of SD in patients with DBLCL was ~4.5 mos (range 2-12 mos), with 10 patients remaining stable for ≥3 mos. Among FL patients, mean duration of SD was approximately 4.1 mos (range 1.7-13 mos), with 9 patients remaining stable for ≥3 mos. The FL CR occurred in a 62-year-old female with paratracheal, subcarinal and portal target lesions who achieved a PR after 4 cycles and CR after 12 cycles that persisted through the remaining 4 mos on study. Study drug was discontinued for adverse events in 19/69 (28%). Fatigue, weight loss or anorexia were most common (n=4 each). A total of 26 drug-related SAEs were reported among 12 patients (17%; 1-6 events per pt). There were no drug related deaths. Enrollment is complete and final data will be presented. Conclusions: Single-agent mocetinostat has activity in DLBCL and FL. Fatigue, gastrointestinal, and cardiac symptoms are the most common adverse events resulting in discontinuation of dosing. Based on the acceptable tolerability and clinical activity further development is warranted. Clinical trial information: NCT00359086.

Phase II trial of afatinib in patients with advanced/metastatic urothelial carcinoma (UC) with genetic alterations in ERBB receptors 1-3 who failed on platinum-based chemotherapy (CT).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS540-TPS540 ◽  
Author(s):  
Albert Font Pous ◽  
Javier Puente ◽  
Daniel E. Castellano ◽  
Francisco X. Real ◽  
Miguel A. Climent ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Genetic Alterations ◽  
Erbb Receptors ◽  
Clinical Activity ◽  
Erbb Family ◽  
Platinum Based Chemotherapy ◽  
Biomarker Analysis

TPS540 Background: First-line treatment of patients (pts) with advanced/metastatic UC consists of platinum-based CT, with no well-established subsequent therapy for platinum-refractory disease. Although checkpoint inhibitors have shown promising results recently, targeted agents have generally not demonstrated significant clinical activity in this setting. Around 20% of UC harbor ERBB family genetic alterations, as such it may be a suitable therapeutic target (Knowles, Nat Rev Cancer 2015;15:25–41). The irreversible ERBB family blocker, afatinib, has shown activity in a Phase II trial in a subset of pts with UC who had ERBB2/ERBB3 aberrations (Choudhury, J Clin Oncol 2016;34:2165–71). This Phase II trial will evaluate afatinib in pts with UC molecularly selected for ERBB receptor alterations. Methods: This single-arm trial will assess the efficacy and safety of afatinib in pts with UC harboring ERBB2/ERBB3 mutations or ERBB2 amplification (Cohort A), or EGFR (ERBB1) amplification (Cohort B). Eligible pts are ≥18 years of age with ECOG PS 0–1, histologically confirmed advanced/metastatic UC of the bladder, upper tract or urethra, not amenable to surgery and progressing during or after platinum-based CT, with available archival tissue samples for pre-screening biomarker analysis. Pts will receive oral afatinib 40 mg/day until disease progression or discontinuation. Cohort A is enrolling in two stages, with Stage 2 enrollment based on anti-tumor activity observed. The primary endpoint is progression-free survival (PFS) rate at 6 months; secondary endpoints include objective response rate, PFS, overall survival, disease control rate, duration of response and tumor shrinkage. Trial objectives will be analyzed separately for the two cohorts. Safety and biomarker assessments will also be performed. The trial commenced in June 2016; as of October 4, 2017, 201 samples have been analyzed, with 24.3% and 8% of pts with genetic alterations potentially eligible for inclusion in Cohort A and B, respectively. To date, 12 pts have received study treatment in Cohort A and 6 in Cohort B; recruitment is ongoing. Clinical trial information: NCT02780687.

Assessment of the Fanconi anemia repair pathway as a predictor of clinical activity of pembrolizumab (PEM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2555-2555
Author(s):  
Miguel Angel Villalona-Calero ◽  
John Paul Diaz ◽  
Zuanel Diaz ◽  
Wenrui Duan ◽  
Eric Douglas Schroeder ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Solid Tumor ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Primary Objective ◽  
Clinical Activity ◽  
Functional Assay ◽  
Phase 2 Trial

2555 Background: Given the activity of immune checkpoint inhibitors (ICI) in mismatch repair deficient tumors, we evaluated if homologous recombination repair deficiency associates with solid tumor response to ICI. Methods: We conducted a phase 2 trial (NCT03274661) of PEM in metastatic solid tumor patients progressing on standard of care and for whom PEM had no FDA approved indication. We evaluated a triple stain (FANCD2foci/DAPI/Ki67) immunofluorescence functional assay of the Fanconi Anemia pathway (FATSI) in treated patients’ archived tumors as a correlative biomarker. Patients with microsatellite unstable tumors were not eligible. The primary objective was objective response rate (iORR, CR+PR) by Immune Response Criteria, with the hypothesis that patients with FATSI negative tumors will have better clinical outcome. Secondary objectives were progression free survival (PFS), 6 months PFS and survival. PEM was given every 3 weeks and computed tomography scans were performed every 6 weeks. We utilized a two-stage phase II trial design to detect an iORR ≥ 20% in the whole population tested vs. the null hypothesis that the true iORR ≤5%. If ≥ 2 of the first 20 evaluable patients had an objective response the trial proceeded to full accrual of 39 evaluable patients. Outcomes were evaluated according to FATSI staining. Results: 42 patients (40 evaluable) (35F,7M; median age 62[36-83]) enrolled. Median # of prior regimens was 2[1-7]. Primary Dx included ovarian/fallopian (13), endometrial (10), colorectal (3), cervix (2), pancreatic(2), vaginal (2) and 1 each of various others. No unexpected toxicities occurred. Response evaluation showed 2 CR, 5 PR, 11 SD, 22 PD and 2 NE (iORR 18%). FATSI tumor analyses results are available in 34 patients; 25 FATSI positive, 9 negative. 2 PR, 8 SD, 14 PD, 1 NE occurred among the FATSI (+) (iORR 8%) and 2 CR, 2 PR, 2 SD, 3 PD among the FATSI (-) patients (iORR 44%). mPFS and 6m-PFS were 54 days and 12% (3/25) in FATSI (+), versus 248 days and 56% (5/9) in FATSI (-) patients; p = 0.017. Conclusions: PEM has meaningful antitumor activity in non MSI-high malignancies with no current FDA approved indications. Evaluation of FATSI as a biomarker supports a biomarker selected population approach. Clinical trial information: NCT03274661.

Hcrn GU15-215: A phase II trial of atezolizumab (atezo) and bevacizumab (bev) in cisplatin-ineligible patients (pts) with advanced/unresectable urothelial cancer (UC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS5098-TPS5098
Author(s):  
Arjun Vasant Balar ◽  
Samuel Aaron Funt ◽  
Shilpa Gupta ◽  
Arkadiusz Z. Dudek ◽  
Alejandro Recio Boiles ◽  
...  
Keyword(s):  
Phase Ii ◽  
Nyha Class ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Solitary Kidney ◽  
Cross Sectional ◽  
Biomarker Analysis ◽  
Pre Treatment

TPS5098 Background: Atezolizumab is a standard of care in selected cisplatin-ineligible pts with advanced UC. VEGF targeted therapies have activity in advanced UC and may lead to immune synergy when combined with anti-PD-1/L1 therapy. This phase II study is investigating the combination of bevacizumab and atezolizumab in untreated cisplatin-ineligible pts with advanced UC. Methods: HCRN GU15-215 (NCT03272217) is a phase 2, multicenter single arm trial to evaluate the efficacy and safety of atezolizumab and bevacizumab in pts with advanced UC. Cisplatin-ineligible pts (defined as any of estimated CrCl < 60 cc/min, Grade ≥ 2 hearing loss or neuropathy, ECOG PS 2 or solitary kidney) with untreated, histologically confirmed locally advanced or metastatic UC irrespective of PD-L1 expression status and with sufficient pre-treatment tumor tissue available for biomarker analysis are eligible. Pts who have received perioperative chemotherapy are eligible, however prior treatment with a checkpoint inhibitor is excluded. Pts with NYHA Class II or greater heart failure, significant cerebrovascular or cardiac disease within 3 months, uncontrolled HTN, persistent gross hematuria, and GI obstruction or perforation within 6 months are excluded. 70 pts will receive treatment with atezolizumab 1200 mg IV plus bevacizumab 15 mg/kg IV every 21 days. All pts will undergo an on-treatment biopsy before cycle 2 if safe and feasible. Peripheral blood samples and stool samples will be collected before treatment and on-treatment for immune-relevant biomarker analyses. Cross-sectional imaging will be performed every 9 weeks on therapy for the first 12 months and then every 12 weeks thereafter to assess for response. Subjects will be eligible to continue treatment until RECIST v1.1 defined progression or unacceptable toxicity for up to 24 months. The primary endpoint is overall survival rate at 1 year and will be analyzed by the Kaplan Meier method. Key secondary endpoints include objective response rate, duration of response, disease control rate, progression-free survival and safety and toxicity as defined by CTCAE version 4.0. Clinical trial information: NCT03272217 .

scholarly journals Daily Oral Everolimus Activity in Patients With Metastatic Pancreatic Neuroendocrine Tumors After Failure of Cytotoxic Chemotherapy: A Phase II Trial

2010 ◽  
Vol 28 (1) ◽  
pp. 69-76 ◽  
Author(s):  
James C. Yao ◽  
Catherine Lombard-Bohas ◽  
Eric Baudin ◽  
Larry K. Kvols ◽  
Philippe Rougier ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Phase Ii ◽  
Progressive Disease ◽  
Objective Response ◽  
Neuron Specific Enolase ◽  
Progression Free Survival ◽  
Pancreatic Neuroendocrine Tumor ◽  
Clinical Activity ◽  
Open Label ◽  
Octreotide Lar

PurposeNo established treatment exists for pancreatic neuroendocrine tumor (NET) progression after failure of chemotherapy. Everolimus (RAD001), an oral inhibitor of mammalian target of rapamycin, in combination with octreotide has demonstrated encouraging antitumor activity in patients with NETs.Patients and MethodsThis open-label, phase II study assessed the clinical activity of everolimus in patients with metastatic pancreatic NETs who experienced progression on or after chemotherapy. Patients were stratified by prior octreotide therapy (stratum 1: everolimus 10 mg/d, n = 115; stratum 2: everolimus 10 mg/d plus octreotide long-acting release [LAR], n = 45). Tumor assessments (using Response Evaluation Criteria in Solid Tumors) were performed every 3 months. Chromogranin A (CgA) and neuron-specific enolase (NSE) were assessed monthly if elevated at baseline. Trough concentrations of everolimus and octreotide were assessed.ResultsBy central radiology review, in stratum 1, there were 11 partial responses (9.6%), 78 patients (67.8%) with stable disease (SD), and 16 patients (13.9%) with progressive disease; median progression-free survival (PFS) was 9.7 months. In stratum 2, there were two partial responses (4.4%), 36 patients (80%) with SD, and no patients with progressive disease; median PFS was 16.7 months. Patients with an early CgA or NSE response had a longer PFS compared with patients without an early response. Coadministration of octreotide LAR and everolimus did not impact exposure to either drug. Most adverse events were mild to moderate and were consistent with those previously seen with everolimus.ConclusionDaily everolimus, with or without concomitant octreotide LAR, demonstrates antitumor activity as measured by objective response rate and PFS and is well tolerated in patients with advanced pancreatic NETs after failure of prior systemic chemotherapy.

Sign in / Sign up

Export Citation Format

Share Document