scholarly journals Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors

2014 ◽  
Vol 22 (1) ◽  
pp. 1-9 ◽  
Author(s):  
M Cives ◽  
P L Kunz ◽  
B Morse ◽  
D Coppola ◽  
M J Schell ◽  
...  
Keyword(s):  
Phase Ii ◽  
Somatostatin Receptor ◽  
Favorable Effect ◽  
Clinical Activity ◽  
Receptor Subtypes ◽  
Open Label ◽  
Radiographic Response ◽  
Somatostatin Receptor Subtypes ◽  
Grade 3 ◽  
Long Acting

Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA) with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR1,2,3) and 5 (SSTR5). Results from preclinical studies indicate that pasireotide can inhibit neuroendocrine tumor (NET) growth more robustly than octreotidein vitro. This open-label, phase II study assessed the clinical activity of pasireotide in treatment-naïve patients with metastatic grade 1 or 2 NETs. Patients with metastatic pancreatic and extra-pancreatic NETs were treated with pasireotide LAR (60 mg every 4 weeks). Previous systemic therapy, including octreotide and lanreotide, was not permitted. Tumor assessments were performed every 3 months using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), overall radiographic response rate (ORR), and safety. Twenty-nine patients were treated with pasireotide LAR (60 mg every 4 weeks) and 28 were evaluable for response. The median PFS was 11 months. The most favorable effect was observed in patients with low hepatic tumor burden, normal baseline chromogranin A, and high tumoral SSTR5expression. Median OS has not been reached; the 30-month OS rate was 70%. The best radiographic response was partial response in one patient (4%), stable disease in 17 patients (60%), and progressive disease in ten patients (36%). Although grade 3/4 toxicities were rare, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia including 14% grade 3 hyperglycemia. Although pasireotide appears to be an effective antiproliferative agent in the treatment of advanced NETs, the high incidence of hyperglycemia raises concerns regarding its suitability as a first-line systemic agent in unselected patients. SSTR5expression is a potentially predictive biomarker for response.

scholarly journals Phase I study of pasireotide (SOM 230) and everolimus (RAD001) in advanced neuroendocrine tumors

2012 ◽  
Vol 19 (5) ◽  
pp. 615-623 ◽  
Author(s):  
Jennifer A Chan ◽  
David P Ryan ◽  
Andrew X Zhu ◽  
Thomas A Abrams ◽  
Brian M Wolpin ◽  
...  
Keyword(s):  
Phase I ◽  
Neuroendocrine Tumors ◽  
Phase I Study ◽  
Tumor Regression ◽  
Somatostatin Receptor ◽  
Preliminary Evidence ◽  
Response To Therapy ◽  
Receptor Subtypes ◽  
Somatostatin Receptor Subtypes ◽  
Grade 3

Octreotide and everolimus have demonstrated efficacy in neuroendocrine tumors. Pasireotide is a somatostatin analog with binding affinity to a broader range of somatostatin receptor subtypes than octreotide. We performed a phase I study to evaluate the safety and feasibility of combining pasireotide with everolimus in patients with advanced neuroendocrine tumors. Cohorts of patients with advanced neuroendocrine tumors were treated with escalating doses of pasireotide (600–1200 μg s.c. b.i.d., followed by pasireotide LAR 40–60 mg i.m. monthly) and everolimus (5–10 mg daily). Twenty-one patients were treated. Dose-limiting toxicities consisting of grade 3 rash and grade 3 diarrhea were observed. Twelve patients were safely treated at the maximum protocol-defined dose level of pasireotide LAR 60 mg i.m. monthly and everolimus 10 mg daily. Hyperglycemia was common; other observed toxicities were consistent with the known toxicities of either agent alone. Partial tumor response was observed in one patient; 17 (81%) patients experienced at least some tumor regression as their best response to therapy. In conclusion, pasireotide LAR 60 mg i.m. monthly in combination with everolimus 10 mg daily is feasible and associated with preliminary evidence of antitumor activity in patients with advanced neuroendocrine tumors. Further studies evaluating this combination are warranted.

A phase II study of aflibercept (VEGF trap) in recurrent or metastatic gynecologic soft-tissue sarcomas: A study of the Princess Margaret Hospital Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5591-5591
Author(s):  
C. Townsley ◽  
H. Hirte ◽  
P. Hoskins ◽  
R. Buckanovich ◽  
H. Mackay ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Adverse Events ◽  
Phase Ii ◽  
Stable Disease ◽  
Soft Tissue Sarcomas ◽  
Vascular Tumors ◽  
Open Label ◽  
Grade 3 ◽  
Long Acting ◽  
Vegf Trap

5591 Background: Targeting angiogenesis and vascular endothelial growth factor (VEGF) represents a promising approach to treat highly vascular tumors, like gynecologic sarcomas. Aflibercept, a long-acting inhibitor of VEGF signaling, potently binds and inactivates VEGF, thus blocking tumor angiogenesis and growth. Methods: This is a single-arm, open-label, two-stage phase II clinical trial designed to evaluate the efficacy and toxicity of aflibercept as treatment for patients (pts) with recurrent, or metastatic gynecologic soft tissue sarcoma. Aflibercept was administered at 4 mg/kg IV every 2 weeks and pts had radiologic imaging performed every 8 weeks. The primary endpoints were response rate and prolonged stable disease. Results: Twenty-five pts with leiomyosarcoma of the uterus and 13 pts with carcinosarcoma of the uterus were enrolled in 2 cohorts. In the leiomyosarcoma group, 24/25 pts had an ECOG of <1, most pts (22/25) had <1 previous lines of treatment and 7/25 pts had prior radiotherapy. A total of 149 cycles were administered for this group, with a median of 4 (range 2–28). In the carcinosarcoma group, 10/13 pts had an ECOG of <1, most pts (12/13) had <1 previous lines of treatment and 5/13 pts had prior radiotherapy. A total of 31 cycles were administered with a median of 3 (range 1–4). The most frequent adverse events experienced by all pts, of any grade, were fatigue 71% pts, constipation 53% and hypertension 39% . The most frequent grade 3 or higher, adverse events were hypertension 18%, fatigue 13% and lymphopenia 8%. Eight pts with leiomyosarcoma had stable disease (4pts > 6 mo). No reponses were seen in either cohort and no stable disease was seen in the carcinosarcoma group. Median overall survival was 15.1 mo (95% CI: 8.5 - not reached) for the leiomyosarcoma cohort and 3.1 mo for the carcinosarcoma cohort (95% CI: 1.9 - not reached). The requirements to proceed to stage 2, in leiomyosarcoma, were met after more than 2/21 patients had > 6 mo PFS. Carcinosarcoma cohort has not finished stage 1 and both cohorts continue accrual. Conclusions: VEGF-trap was well tolerated in this pt population with acceptable side effects. Initial efficacy data suggests modest activity, particularly in patients with leiomyosarcoma. [Table: see text]

An open-label, randomized, phase II study of nivolumab (anti-PD-1; BMS-936558; ONO-4538) given sequentially with ipilimumab in patients (pts) with advanced or metastatic melanoma (MEL).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS9107-TPS9107
Author(s):  
F. Stephen Hodi ◽  
Christine Baudelet ◽  
Allen C. Chen ◽  
Jeffrey S. Weber
Keyword(s):  
Monoclonal Antibody ◽  
Induction Period ◽  
Clinical Response ◽  
Phase Ii ◽  
Time Course ◽  
Phase Ii Study ◽  
Braf Inhibitor ◽  
Clinical Activity ◽  
Open Label ◽  
Grade 3

TPS9107^ Background: Programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) are immune checkpoint receptors that attenuate T-cell responses and contribute to immune evasion by tumor cells. Nivolumab is a PD-1 receptor blocking monoclonal antibody that has shown clinical activity in phase 1 trials with various tumor types including MEL. Ipilimumab is an anti-CTLA-4 monoclonal antibody approved for advanced or metastatic MEL. Preclinical data suggest that combined PD-1 and CTLA-4 receptor blockade may improve antitumor activity in MEL, with PD-1 blockade upregulating CTLA-4 expression and CTLA-4 blockade upregulating PD-1 expression on tumor-infiltrating T cells. We describe a phase II study evaluating nivolumab administered sequentially with ipilimumab in pts with advanced (unresectable stage III) or metastatic (stage IV) MEL. Methods: This open-label, phase II study will enroll approximately 80 pts. During the induction period, pts will be randomized 1:1 to either nivolumab (3 mg/kg, q2w) from Weeks (Wk) 1-13 followed by ipilimumab (3 mg/kg, q3w) from Wks 14-25, or ipilimumab followed by nivolumab at the same doses and schedules. All pts will then receive nivolumab (3 mg/kg, q2wk) during the continuation period until disease progression or unacceptable toxicity, for ≤2 years from initial study treatment. Pts may be treatment-naive or have disease recurrence or progression after one prior systemic therapy, excluding prior anti-PD-1, anti-CTLA-4, or a BRAF inhibitor. The primary endpoint is the incidence of treatment-related Grade 3–5 adverse events (AEs) during the induction period. Secondary endpoints are response rate at Wk 25 and progression rates at Wks 13 and 25. Exploratory endpoints include safety and tolerability; overall survival; pt-level time course of treatment-related grade 3–5 AEs, response, progression, treatment discontinuation, and death; the association of changes in pharmacodynamic immune markers from baseline to Wk 13 and Wk 25 and clinical response; the association between baseline immunological parameters and clinical response; and immune-related single nucleotide polymorphisms. Clinical trial information: NCT01783938.

Phase II trial of nab-paclitaxel (ABI) and ipilimumab (ipi) in patients with treatment naïve metastatic melanoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9554-9554
Author(s):  
Kaysia Ludford ◽  
Daniel H. Johnson ◽  
Tarin Hennegan ◽  
Stephen K. Gruschkus ◽  
Cara L. Haymaker ◽  
...  
Keyword(s):  
T Cells ◽  
Adverse Events ◽  
Metastatic Melanoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Clinical Activity ◽  
Braf Mutations ◽  
Open Label ◽  
Treatment Naïve ◽  
Grade 3

9554 Background: Conventional chemotherapies possess intrinsic immune-regulatory properties. Some taxanes for instance, stimulate antigen presentation and impair regulatory T-cells while leaving effector T cells intact. Combining chemotherapies with immune checkpoint inhibitor at carefully designed dosing regimens may increase tumor cell susceptibility to immune-mediated death and thus enhance therapeutic efficacy. We describe the safety and updated efficacy of ABI and ipi in patients with metastatic melanoma. Methods: In this open-label, single center, phase II trial, ABI was administered to treatment naïve metastatic patients at 150mg/m2 on days 1,8 and 15 every 4 weeks and ipi at 3mg/kg on day 1 every 3 weeks limited to 4 cycles until disease progression or unacceptable toxicity. Endpoints included ORR, OS and safety. Results: 18 of 21 enrollees between 6/2013 and 6/2015 with Stage IV melanoma (M1c: 56%, M1b: 33%, M1a: 11%) were included in the analysis. The median age was 57 years old (33-69) and 67% were men. 44% harbored BRAF mutations. Median duration of treatment was 9 weeks (5 to 17). Median follow-up time for OS analysis was 22.5 months (2 to 52 months). 12 and 24 month OS were 77.8% and 60.6% respectively with median not yet reached. The ORR by by irRECIST was 27.8%. Grade 3 adverse events were reported in 50% of patients, the most common being neutropenia. 17% of patients had grade 3 immune-related adverse events, the most common being hypophysitis and colitis. Immune analysis showed absolute lymphocyte count was significantly elevated post treatment compared with pre-treatment (p = 0.024). In addition, deep immune analysis of peripheral blood samples and tumor tissue including nanostring, gene expression and TCR sequencing will be assessed and reported. Conclusions: The combination of ipi and ABI in this small study demonstrates acceptable safety, tolerability and clinical activity. ABI may contribute to tumor cytoreduction and enhance antitumor clinical response of ipi without impactful immunosuppression. This data together with further immune analysis may provide rationale to design prospective chemo-immunotherapy regimens and treatments for metastatic melanoma and other solid tumors. Clinical trial information: NCT01827111.

scholarly journals A phase II study of axitinib in advanced neuroendocrine tumors

2016 ◽  
Vol 23 (5) ◽  
pp. 411-418 ◽  
Author(s):  
J R Strosberg ◽  
M Cives ◽  
J Hwang ◽  
T Weber ◽  
M Nickerson ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Response Rate ◽  
Progression Free Survival ◽  
Carcinoid Tumors ◽  
High Rate ◽  
Open Label ◽  
End Points ◽  
Radiographic Response ◽  
Grade 3

Neuroendocrine tumors (NETs) are highly vascular neoplasms overexpressing vascular endothelial growth factor (VEGF) as well as VEGF receptors (VEGFR). Axitinib is a potent, selective inhibitor of VEGFR-1, -2 and -3, currently approved for the treatment of advanced renal cell carcinoma. We performed an open-label, two-stage design, phase II trial of axitinib 5mg twice daily in patients with progressive unresectable/metastatic low-to-intermediate grade carcinoid tumors. The primary end points were progression-free survival (PFS) and 12-month PFS rate. The secondary end points included time to treatment failure (TTF), overall survival (OS), overall radiographic response rate (ORR), biochemical response rate and safety. A total of 30 patients were enrolled and assessable for toxicity; 22 patients were assessable for response. After a median follow-up of 29months, we observed a median PFS of 26.7months (95% CI, 11.4–35.1), with a 12-month PFS rate of 74.5% (±10.2). The median OS was 45.3 months (95% CI, 24.4–45.3), and the median TTF was 9.6months (95% CI, 5.5–12). The best radiographic response was partial response (PR) in 1/30 (3%) and stable disease (SD) in 21/30 patients (70%); 8/30 patients (27%) were unevaluable due to early withdrawal due to toxicity. Hypertension was the most common toxicity that developed in 27 patients (90%). Grade 3/4 hypertension was recorded in 19 patients (63%), leading to treatment discontinuation in six patients (20%). Although axitinib appears to have an inhibitory effect on tumor growth in patients with advanced, progressive carcinoid tumors, the high rate of grade 3/4 hypertension may represent a potential impediment to its use in unselected patients.

Safety and efficacy of pasireotide (SOM230) in patients with metastatic carcinoid tumors refractory or resistant to octreotide LAR: Results of a phase II study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4082-4082 ◽  
Author(s):  
L. Kvols ◽  
B. Wiedenmann ◽  
K. Oberg ◽  
J. E. Glusman ◽  
T. M. O’dorisio ◽  
...  
Keyword(s):  
Phase Ii ◽  
Somatostatin Receptor ◽  
Safety Data ◽  
Carcinoid Tumors ◽  
Fixed Dose ◽  
Somatostatin Analogue ◽  
Receptor Subtypes ◽  
Metastatic Carcinoid ◽  
Octreotide Lar ◽  
Somatostatin Receptor Subtypes

4082 Background: Pasireotide is a novel multiligand somatostatin analogue that exhibits high binding affinity to 4 of 5 somatostatin receptor subtypes: sst1,2,3 and sst5. Compared with octreotide, pasireotide has 30, 5 and 40 times greater affinity for sst1,3 and sst5 receptors respectively and a comparable affinity for sst2. Methods: This was a Phase II, open-label, multicenter study in patients with metastatic carcinoid tumors whose symptoms (diarrhea and flushing) were inadequately controlled by octreotide LAR. Patients had histopathologically confirmed disease, elevated 5-HIAA and/or CgA levels and at least one measurable lesion (excluding bone). Patients initially received pasireotide 300 μg sc bid and escalated to a maximum dose of 1200 μg sc bid every 3 days until clinical response was achieved. Partial response (PR) was defined as a mean of <4 bowel movements (BM)/day with no more than 6 BM on any given day, and a mean of <2 flushing episodes/day for 15 consecutive days on a fixed dose of pasireotide. Complete response (CR) was defined as a mean of ≤3 BM/day, with no more than 3 BM on any given day, and no flushing episodes. Results: Safety data are reported from 45 patients as of September 2005; 44 patients (mean age 61 years) qualified for efficacy assessment. Carcinoid tumors were predominantly of midgut origin. Preliminary efficacy data in controlling symptoms of carcinoid syndrome showed PR in 9 patients (20%) at 600–1200 μg sc bid doses and CR in 2 patients (5%) at the 600 and 900 μg sc bid doses. Objective tumor response in 11 patients showed 9 with stable disease and 2 with progressive disease at 6 months. Adverse events (AEs) were primarily gastrointestinal (GI): abdominal pain (31%) and nausea (27%). Weight loss (22%) and fatigue (22%) were also reported. Most AEs were mild or moderate. Glucose-related AEs (predominantly CTC grade 1–2) were observed in 24% of patients. Most discontinuations were due to GI AEs (n = 6) or lack of therapeutic response. Conclusions: Pasireotide 600–1200 μg sc bid was effective in controlling symptoms of diarrhea and flushing in 25% of patients with metastatic carcinoid tumors inadequately controlled by octreotide LAR. The safety profile of pasireotide is similar to octreotide LAR. [Table: see text]

Phase II clinical trial of pasireotide LAR in patients with metastatic neuroendocrine tumors.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 241-241
Author(s):  
Jonathan R. Strosberg ◽  
Helen Jump ◽  
Tiffany Valone ◽  
Jill Weber ◽  
Vilay H. Khandelwal ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Somatostatin Receptor ◽  
High Rate ◽  
Receptor Subtypes ◽  
Low Grade ◽  
Intermediate Grade ◽  
Somatostatin Receptor Subtypes ◽  
Treatment Naïve ◽  
Prior Systemic Therapy

241 Background: Pasireotide LAR is a novel somatostatin analog (SSA) with avid binding to somatostatin receptor subtypes (SSTR) 1, 2, 3 and 5. It has been studied in patients who are refractory to SSAs, but has not yet been investigated in treatment naïve patients. Methods: We performed a phase II trial of first-line pasireotide LAR 60mg q4 weeks in patients with metastatic low and intermediate grade NETs. Prior systemic therapy, including octreotide and lanreotide, was not permitted. The primary endpoint was PFS. Immunohistochemical SSTR subtype analysis was performed on archival tissue. Results: 29 patients were enrolled of whom 28 patients were assessable for response. Primary sites included small intestine (14 pts), pancreas (6), rectal (2), unknown (4) and other sites (3). 13 patients had low-grade and 16 patients had intermediate-grade tumors. Best radiographic response was stable disease in 17 patients (60%), progressive disease in 10 patients (36%) and partial response in 1 patient (4%). Median PFS was 12.2 months (95% CI 7.7-17.5). The 1 year OS rate was 92% (CI 72%-98%). Although generally well tolerated, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia. 4 patients (14%) developed grade 3 hyperglycemia. 6 patients were started on insulin during the trial period, and at least 2 have remained on long-term insulin therapy despite discontinuation of pasireotide. Conclusions: Although the median PFS of 12.2 months in a heterogeneous population of NET patients is encouraging, the high rate of hyperglycemia requiring intervention represents a significant concern. Future studies of pasireotide should explore specific populations such as octreotide refractory patients. Clinical trial information: NCT01253161.

scholarly journals Abiraterone in patients with recurrent epithelial ovarian cancer: principal results of the phase II Cancer of the Ovary Abiraterone (CORAL) trial (CRUK – A16037)

2020 ◽  
Vol 12 ◽  
pp. 175883592097535
Author(s):  
Susana Banerjee ◽  
Holly Tovey ◽  
Rebecca Bowen ◽  
Elizabeth Folkerd ◽  
Lucy Kilburn ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Clinical Activity ◽  
Low Grade ◽  
Open Label ◽  
Grade 3

Background: Recurrent epithelial ovarian cancer (EOC) remains difficult to treat, with an urgent need for more therapy options. Androgens bind to the androgen receptor (AR), commonly expressed in EOC. CYP17 inhibitor abiraterone irreversibly inhibits androgen biosynthesis. The Cancer of the Ovary Abiraterone (CORAL) trial was designed to evaluate the clinical activity of abiraterone in EOC. Patients & Methods: CORAL was a multi-centre, open-label, non-randomised, 2-stage phase II clinical trial. Eligible patients had progression within 12 months of last systemic therapy and no prior hormonal anti-cancer agents. Patients received abiraterone 1000 mg daily plus 5 mg prednisone until progression. The primary endpoint was objective response rate (ORR) according to combined Response Evaluation Criteria in Solid Tumours/Gynaecological Cancer Intergroup (RECIST/GCIG) criteria at 12 weeks. Secondary endpoints included clinical benefit rate (CBR) at 12 weeks. Results: A total of 42 patients were recruited; median age 65 (range 34–85) years; 37 (88.1%) had high-grade serous tumours; 20 (48%) had at least three prior lines of therapy; 29/40 (72.5%) were AR+. In stage 1, 1/26 response was observed (in an AR+, low-grade serous EOC); response lasted 47 weeks. Overall, 12 week ORR was 1/42 (2%), CBR was 11/42 (26%) (8/29 (28%) in AR+ patients). Disease control was ⩾6 months for 4/29 (14%). One patient (AR+, low-grade serous) had a RECIST response at 82 weeks. Four (10%) had grade ⩾3 hypokalaemia; 11 (26%) had dose delays. Conclusions: CORAL represents the first trial of an AR targeted agent in ovarian cancer. While responses were rare, a subset of patients achieved sustained clinical benefit. Targeting AR in EOC including low-grade serous cancer warrants further investigation. Trial registration: CORAL is registered on the ISRCTN registry: ISRCTN63407050; http://www.isrctn.com/ISRCTN63407050

Phase I/II study of durvalumab and tremelimumab in patients with unresectable hepatocellular carcinoma (HCC): Phase I safety and efficacy analyses.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4073-4073 ◽  
Author(s):  
Robin Kate Kelley ◽  
Ghassan K. Abou-Alfa ◽  
Johanna C. Bendell ◽  
Tae-You Kim ◽  
Mitesh J. Borad ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Progressive Disease ◽  
Hospice Care ◽  
Randomized Study ◽  
Immune Checkpoints ◽  
Clinical Activity ◽  
Open Label ◽  
Study Results ◽  
Grade 3

4073 Background: Durvalumab and tremelimumab, investigational monoclonal antibodies against PD-L1 and CTLA-4 immune checkpoints, respectively, have shown efficacy in monotherapy and offer promise in combination for patients (pts) with HCC. This is a phase I/II, open-label, randomized study of durvalumab combined with tremelimumab in unresectable HCC. Methods: Phase I part of this study is a safety run-in cohort treated at the recommended phase II doses of the durvalumab/tremelimumab combination (20 and 1 mg/kg IV Q4W respectively for 4 doses followed by 20 mg/kg Q4W durvalumab alone) in pts with unresectable HCC with or without concomitant HBV or HCV infection who progress on, are intolerant to, or have refused sorafenib therapy. Secondary objectives include evaluation of antitumor activity. Here we present results of a preplanned analysis from the completed phase I part of the study. Results: As of 10 January 2017, 40 pts have been enrolled (11 HBV+, 9 HCV+, 20 uninfected). 30% had no prior systemic therapy; 93% were Child Pugh Class A. 24 (60%) had ≥1 treatment-related AE; 20% had ≥1 grade ≥3 related AE. Most common (≥15%) treatment-related AEs: fatigue (20%), increased ALT (18%), pruritus (18%), and increased AST (15%). Most common grade ≥3 related AE was asymptomatic increased AST (10%). 24 pts have discontinued treatment: 3 due to treatment-related AEs (grade 3 pneumonitis, grade 3 colitis/diarrhea, asymptomatic grade 4 elevated AST and ALT), 16 due to progressive disease, 4 due to death unrelated to treatment (cardiac arrest, variceal bleed, progressive disease, probable HCC rupture), and 1 other (pt entered hospice care). 40 pts were evaluable for response at ≥16 weeks follow-up. Conclusions: No unexpected safety signals with durvalumab and tremelimumab were seen in this unresectable HCC population. Clinical activity observed predominantly in uninfected pts though interpretation limited by small subsets. Enrollment to the phase II portion of the study is ongoing. Clinical trial information: NCT02519348. [Table: see text]

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