A phase II, multicenter, randomized, open-label study to evaluate the safety and tolerability of proxalutamide (GT0918) in subjects with metastatic castrate-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 108-108
Author(s):  
Tie Zhou ◽  
Dingwei Ye ◽  
Zhongquan Sun ◽  
Qinggui Meng ◽  
Dalin He ◽  
...  
Keyword(s):  
Dose Level ◽  
Response Rate ◽  
Objective Response ◽  
Specific Antigen ◽  
Stage Iv ◽  
Study Drug ◽  
Progression Free Survival ◽  
Open Label ◽  
Significant Difference ◽  
Psa Progression

108 Background: GT0918 is a 2nd generation of AR antagonist and capability to down-regulate AR level. This study is an open-label, randomized, multicenter, Ph II study to evaluate the safety and efficacy in patients with mCRPC, and to determine the optimal dose for Ph III study. Methods: Patients with historically confirmed mCRPC who progressed after/intolerant to/reluctant to receive Docetaxel and previously treated with abiraterone or enzalutamide were excluded. All the patients received up to 6 cycles or, unacceptable toxicity, or loss of clinical benefit as recommended by PCWG3. Primary endpoint was prostate-specific antigen (PSA) reduction from baseline. Secondary endpoints included time to PSA progression (TTPP), objective response rate (ORR), progression free survival (PFS), disease control rate (DCR) and safety profiles. Results: As of June 30, 2019, 108 treated with GT0918 at three dose levels: 100 mg (n =37), 200 mg (n = 35) and 300 mg (n = 36), the median age of patients was 70.0 years (range 63-77), 88% of patients had stage IV disease at the initial diagnosis and 69.4% had Gleason score ≥ 8. The median duration of disease was 2.88 years. All received prior endocrine therapy, 35.2% received prior chemotherapy, 29.6% received Docetaxel. The median PSA at baseline was 35.285ng/ml, PSA response rate (≥50 % reduction from baseline) was 41.9%. The median time to PSA progression was not reached. There was no significant difference among three arms. Of 19 evaluable patients with target lesions at baseline, the ORR was 15.8% (all were PR) assessed by IRC with RECIST v 1.1, with 20.0% (1/5), 22.2% (2/9), 0 (0/5) at 100, 200, 300 dose level, respectively. The DCR assessed by IRC was 78.9% (CR 0+PR15.8%+SD 63.2%). Of 26 evaluable patients with target lesions at baseline, the ORR was 19.2% assessed by investigators (CR 3.8%+PR 15.4%), with 11.1% (1/9), 20.0% (2/10), 28.6% (2/7) at 100, 200, 300 dose level, respectively. Overall, AEs were experienced by most of patients (94.4 %, n=102). AEs leading to drug interruption were reported in 13 patients (12.0%), 9 (8.3%)of them were suspected to be drug related. AEs leading to discontinuation were reported in 6 patients (5.6%), 3(2.8%) were possibly related to GT0918. 14 patients (13.0%) experienced Grade 3 and 4 AEs. 17 patients (15.7%)experienced SAE, 5(4.6%) of them were suspected to be related to study drug. Most of AEs were mild or moderate. The common suspected AE (≥10%) were asthenia (17.6%, n=19), anemia (14.8%, n=16), AST increased (14.8%, n=16), ALT increased (13.0%, n=14), decreased appetite (13.0%, N=14), white blood cell count decreased (12.0%, n=13), proteinuria (12.0%, n=13). Conclusions: GT0918 showed a manageable safety profile. This study provided preliminary anti-tumor activity in patients with mCRPC. 200mg/day is recommended dose for Ph III trial. Clinical trial information: CTR20170177.

A phase II, multicenter, open-label study of YM155 plus docetaxel in subjects with stage III (unresectable) or stage IV melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8587-8587 ◽  
Author(s):  
Joyce Leta Steinberg ◽  
Agop Y. Bedikian ◽  
D. Scott Ernst ◽  
Bartosz Chmielowski ◽  
Bruce Redman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Continuous Infusion ◽  
Primary Endpoint ◽  
Clinical Benefit ◽  
Response Rate ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Open Label ◽  
Clinical Benefit Rate

8587 Background: Survivin is a microtubule-associated protein implicated in both preservation of cell viability and regulation of mitosis in tumor cells. It is over-expressed in melanoma, breast, and non-Hodgkin’s lymphoma. YM155 is a first in class survivin inhibitor. Methods: The study had 2 parts: Part 1 established the dose of docetaxel that was tolerable in combination withYM155 at 5 mg/m2/day continuous infusion over 168 hours q 3 weeks. Part 2 utilized the dose of docetaxel established in Part 1 to further evaluate the tolerability and activity of the combination. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints were overall response rate, 1-year overall survival (OS), time from first response to progression, clinical benefit rate, time to response, and safety. Results: 64 patients with metastatic melanoma were treated with docetaxel followed by continuous infusion YM155. 7 patients were treated with 100mg/m2 of docetaxel and 57 patients were treated with 75mg/m2 of docetaxel. Median age was 59, with 44 men and 20 women treated. 6-month PFS per Independent Review Committee (IRC) was 34.8% (95% CI 21.3 – 48.6%). Overall objective response rate per IRC was 12.5%, with no complete responses (CR) and 8 patients with partial responses (PR). The Stable disease (SD) rate was 51.6%, leading to a clinical benefit rate (CR + PR + SD) of 64.1%. Estimated 1-year overall survival is 50.5%. 87.5% of patients experienced a Grade 3 (G3) or Grade 4 (G4) event attributable to either YM155 or docetaxel. The clinically pertinent G3 or 4 toxicities occurring in greater than 5% of patients treated included neutropenia (59.4%), febrile neutropenia (12.5%), mucositis (9.4%), fatigue (7.8%), diarrhea (6.3%), and dehydration (6.3%). There were 3 deaths on study, all attributable to disease progression. Conclusions: YM155 is a novel agent that shows modest activity when combined with docetaxel in patients with melanoma. YM155 was generally well tolerated, but the pre-determined primary endpoint for efficacy was not achieved.

scholarly journals 357 Toripalimab plus chemoradiotherapy in patients with recurrent or metastatic cervical cancer: a multicenter, open-label, single-arm, phase II trial

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A384-A384
Author(s):  
Xiaoting Xu ◽  
Jian Huan ◽  
Hui Miao ◽  
Hao Wang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Treatment Options ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Nccn Guidelines ◽  
Significant Difference ◽  
Grade 3

BackgroundRecurrent or metastatic cervical cancer patients who progressed after standard therapy have limited treatment options and poor prognosis with a 1-year survival rate ranging between 15% and 20%. This study evaluates the efficacy and safety of toripalimab plus chemoradiotherapy in patients with recurrent or metastatic cervical cancer (Clinical trial ID: ChiCTR2000029068)MethodsIn this open-label, single-arm, phase 2 study conducted at four radiotherapy centers in East China, eligible patients were confirmed by pathology and/or imaging for recurrent or metastatic cervical cancer. According to the first-line therapies for cervical cancer recommended by NCCN guidelines, all patients were received paclitaxel plus cisplatin regimen, with or without bevacizumab, combined with radiotherapy. After seven fractions radiotherapy at the recurrent or metastatic regions, 240 mg toripalimab every three weeks for six cycles or more were given in combination.ResultsBetween Jan 14th, 2020, and May 1st, 2021, 24 patients were enrolled. All patients were staged at the first visit, as seven patients were with FIGO (2018) stage I, 10 with stage II, 2 with stage III, 1 with stage IV, and 2 with unclear stage. Of 24 included patients, 22 (91.67%) had squamous cervical cancer. The median age was 55 (range, 33–72) years. As of May 31, 2021, median follow-up time was 8.5 months [95% CI: 2.3–10.1]. 14 (58.3%) of 24 patients who achieved an objective response, including 10 (41.7%) complete response (CR) and 4 (16.7%) partial response (PR). The median duration of response was not reached and 7 (29.1%) patients continued toripalimab treatment after the previous 6-cycle immunotherapy. The disease control rate was 75% (18/24). Median progression-free survival (PFS) was 8.61 months (95% CI: 4.14–not reached). For subgroup analysis, the median PFS was significantly prolonged in the CR/PR group compared with that in the SD/PD group [not reached (95% CI: 6.21–not reached) versus 5.5 months (95% CI: 2.69–6.870), P = 0.023]. There was no significant difference in the median PFS between patients who previously received radiotherapy (8.61 months) and those who didn’t (6.87 months) (P = 0.641). 8 (33.3%) patients had grade 3–4 treatment-related adverse events (TRAEs). The most common grade 3-4 TRAEs were myelosuppression (29.2%), hypertriglyceridemia (8.3%), hypoalbuminemia (4.2%), pneumonia (4.2%), and hypercholesterolemia (4.2%).ConclusionsToripalimab plus chemoradiotherapy showed promising antitumor activity and tolerable toxicities in patients with recurrent or metastatic cervical cancer.

When will it be better? Lenvatinib combined with TACE for unresectable hepatocellular carcinoma: A retrospective analysis of real-world evidence in China.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 281-281
Author(s):  
Lan Zhang ◽  
Yanhong Wang ◽  
Ningling Ge ◽  
Yu-Hong Gan ◽  
ZhengGang Ren ◽  
...  
Keyword(s):  
Combination Treatment ◽  
Real World ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Combination Group ◽  
Optimal Timing ◽  
Real World Data ◽  
Combination Strategy ◽  
Significant Difference

281 Background: TACE and lenvatinib has each shown to prolong overall survival in patients with unresectable HCC, combination of which may also improve clinical outcomes and have been widely used in the real world accordingly. However, the optimal timing of adding on lenvatinb to TACE remains unclear. We are aiming to evaluate the efficacy and safety between two combination strategies. Methods: From Nov 2018 to Jun 2020, 79 consecutive patients had received a combination treatment of lenvatinib and TACE. Patients followed up for more than 2 months were included in this analysis. They were classified as early-combination group(add on lenvatinib before or after the first TACE ) and late-combination group(add on lenvatinib after at least two procedures of TACE ). Tumor response and progression-free survival (PFS,time from the first day of prescribing lenvatinib to progression or death) were assessed according to RECIST1.1 criteria. Liver function were also evaluated at baseline and every 2 months later. AEs were recorded during the combination treatment period according to CTCAE 5.0. Results: A total of 48 u-HCC patients was finally enrolled. Median follow-up in all patients was 9.3(5.3-14.3)months. Patients’ baseline characteristics were similar in two groups. For early-combination group(n=22)and late-combination group(n=26), the mean age was 65±9.7 and 61±11.6years(p=0.2);BCLC stage C HCC was 59% and 54%(p=0.89);and Child-Pugh A proportion was 81.8% and 77%(p=0.73) respectively. The objective response rate(ORR) was 22.9% in total 48 cases. There was no significant difference in response rate (18.2% vs 26.9%, P=0.51) or disease control rate (90.9% vs 92.3%, P=1.00). Median PFS was significantly longer in the early-combination group than that in late-combination group (14.5 vs 8.9 months; p=0.048). The safety profile was similar between two groups. Grade 3/4 adverse events were 3 (13.6%) and 2 cases(7.7%) respectively (P=0.65). Conclusions: This is to date the first real-world data of the combination timing of lenvatinib with TACE in u-HCC patients. Early-combination strategy may be a better option for the u-HCC patients with a longer mPFS.

Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

2019 ◽  
Vol 26 (6) ◽  
pp. 1331-1342
Author(s):  
Irena Ilic ◽  
Sandra Sipetic ◽  
Jovan Grujicic ◽  
Milena Ilic
Keyword(s):  
Overall Survival ◽  
Objective Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival

Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.

scholarly journals Phase Ib/II Study of Pembrolizumab and Pegylated-Interferon Alfa-2b in Advanced Melanoma

2018 ◽  
Vol 36 (35) ◽  
pp. 3450-3458 ◽  
Author(s):  
Diwakar Davar ◽  
Hong Wang ◽  
Joe-Marc Chauvin ◽  
Ornella Pagliano ◽  
Julien J. Fourcade ◽  
...  
Keyword(s):  
Overall Survival ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Pegylated Interferon ◽  
Gene Signature ◽  
Advanced Melanoma ◽  
Phase Ib

Purpose Objective responses are reported in 34% to 37% of patients with programmed death-1 (PD-1)–naïve advanced melanoma treated with PD-1 inhibitors. Pre-existing CD8+ T-cell infiltrate and interferon (IFN) gene signature correlate with response to PD-1 blockade. Here, we report a phase Ib/II study of pembrolizumab/pegylated (PEG)-IFN combination in PD-1–naïve advanced melanoma. Patients and Methods PEG-IFN (1, 2, and 3 μg/kg per week) was dose escalated using a modified toxicity probability interval design in three cohorts of four patients each, whereas pembrolizumab was dosed at 2 mg/kg every 3 weeks in the phase Ib portion. Thirty-one patients were enrolled in the phase II portion. Primary objectives were safety and incidence of dose-limiting toxicities. Secondary objectives included objective response rate, progression-free survival (PFS), and overall survival. Results Forty-three patients with stage IV melanoma were enrolled in the phase Ib and II portions of the study and included in the analysis. At the data cutoff date (December 31, 2017), median follow-up duration was 25 months (range, 1 to 38 months). All 43 patients experienced at least one adverse event; grade 3/4 treatment-related adverse events occurred in 21 of 43 patients (48.8%). Objective responses were seen at all three dose levels among 43 evaluable patients. The objective response rate was 60.5%, with 46.5% of patients exhibiting ongoing response. Median PFS was 11.0 months in all patients and unreached in responders, whereas median overall survival remained unreached in all patients. The 2-year PFS rate was 46%. Conclusion Pembrolizumab/PEG-IFN demonstrated an acceptable toxicity profile with promising evidence of clinical efficacy in PD-1–naïve metastatic melanoma. These results support the rationale to further investigate this pembrolizumab/PEG-IFN combination in this disease.

Phase II trial of BNC105P as second-line chemotherapy for advanced malignant pleural mesothelioma (MPM): Australasian Lung Cancer Trials Group and NHMRC Clinical Trials Centre Collaboration.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7079-7079
Author(s):  
Anna K. Nowak ◽  
Chris Brown ◽  
Michael Millward ◽  
Brett Gordon Maxwell Hughes ◽  
David C. Bibby ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Response Rate ◽  
Single Agent ◽  
Objective Response ◽  
Tumour Response ◽  
Dose Intensity ◽  
Study Drug ◽  
Progression Free Survival ◽  
Second Line ◽  
Vascular Disrupting Agent

7079^ Background: BNC105P is a tubulin polymerization inhibitor that acts as a Vascular Disrupting Agent (VDA), has direct cytotoxic effects, and had preclinical and phase I activity in MPM. This aim of this study was to determine activity and safety of BNC105P as second-line therapy after pemetrexed and a platin in MPM. Methods: Eligible patients had progressive MPM, prior pemetrexed and platinum, measurable disease by modified RECIST, ECOG 0-1, and adequate organ and cardiovascular function. Important exclusions included recent thromboembolic, cardiovascular or cerebrovascular disease, or therapeutic anticoagulation. Pts received BNC105P (16 mg/m2 IV) Day 1 + 8 q21d until progression or toxicity. The primary endpoint was centrally reviewed objective tumour response rate (RR); the Simon 2-stage design assumed a RR of interest of 20% and a RR of no interest of 5%, with α = β = 0.05. Continuation past first stage accrual required >1 objective response in 24 patients. Results: 30 subjects were accrued over 10 months (90% male; median age 65 (range 41-83); 77% ECOG PS 1; histology epithelioid (67%), biphasic (10%), sarcomatoid (7%), other/unspecified (17%)). All pts received at least one dose of study drug; pts received a median of 2 cycles and median dose intensity was 100%. No significant haematologic, biochemical, peripheral neurotoxic or cardiac adverse events (AEs) including hypertension were observed. Grade 3 or 4 AEs occurred in 10 pts (33%). There were 2 deaths on study: 1 due to stroke, the other due to pneumonia and respiratory failure. We observed 1 partial response (3%) and 13 pts with SD as their best response (43%). Median progression free survival was 1.5 mo (95% CI 1.4-2.4); median overall survival was 8.7 mo (95% CI 3.8-NR). Lung function and QOL data was collected. Biomarker analyses correlating to pharmacological changes induced by BNC105P are ongoing and will be presented. Conclusions: BNC105P was safe and tolerable but its single agent response rate failed to meet the pre-specified primary endpoint of interest.

Phase II study of pemetrexed (Pem) and cisplatin (Cis) plus cetuximab (Cet) followed by Pem and Cet maintenance therapy in patients (Pts) with advanced nonsquamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7554-7554
Author(s):  
Gerald Schmid-Bindert ◽  
Vittorio Gebbia ◽  
Frank Mayer ◽  
Edurne Arriola ◽  
Diego Marquez-Medina ◽  
...  
Keyword(s):  
Survival Rate ◽  
Performance Status ◽  
Objective Response ◽  
Stage Iv ◽  
Study Drug ◽  
Progression Free Survival ◽  
Free Survival ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
One Year

7554 Background: A prospective, nonrandomized, multicenter study was conducted to assess the effect of adding cet to pem and cis in pts with advanced nonsquamous NSCLC. Methods: 113 Caucasian performance status 0-1 pts received 1st line pem (500 mg/m2) and cis (75 mg/m2) on day 1 (21d cycle) for 4-6 cycles and cet (400 mg/m2 loading dose followed by 250 mg/m2) weekly. Non-progressive pts received pem 500 mg/m2 on day 1 (21d cycle) plus cet (250mg/m2 weekly) until progression. Pts received vitamin B12/folic acid and dexamethasone. Primary endpoint was objective response rate (ORR) (RECIST 1.0). Secondary endpoints were progression free survival (PFS), 1 year survival rate, translational research (TR) and safety. Results: Pts’ characteristics: median age 59.7 years, 64% male, 50% PS 0, 92% stage IV, and 78% adenocarcinoma. All pts completed ≥ 1 cycle of induction therapy and 45% and 43% completed ≥ 1 cycle of maintenance with pem and cet, respectively. ORR (n=109) was 38.5% (80% CI 32.2-45.1), all partial responses. Disease control rate (response/stable disease) was 59.6% (80% CI: 53.1-65.9). Median PFS was 5.82 months (80% CI: 4.40-6.70). One year survival rate was 0.45 (80% CI: 0.39-0.51). Significant associations were seen between high EGFR by IHC and increased PFS (cytoplasm: HR=0.46, p=0.035; membrane: HR=0.41, p=0.008), and between high nuclear TTF-1 and increased ORR (OR=7.73, p=0.021) / PFS (HR=0.21, p<0.001) / OS (HR=0.25, p=0.035). Of 113 pts evaluated for safety, 73 (64.6%) pts had drug related CTC Grade 3/4 adverse events (AE): most frequent were neutropenia (14.2%), rash (15%), and vomiting (8.8%). Drug related serious AEs were reported in 27.4% pts: most frequent were anemia (5.3%), neutropenia (5.3%), vomiting (3.5%), and rash, renal failure, diarrhea and fatigue (1.8% each). There were 2 potential on-study drug related deaths (sudden death and large intestinal perforation). Conclusions: Pem, cis and cet appeared efficacious and tolerable. These results support further evaluation in a randomized trial. The TR outcomes are hypothesis generating given the study’s size and nonrandomized nature.

Phase Ib trial of gemcitabine with yttrium-90 in patients with hepatic tumors of pancreatobiliary origin.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 460-460
Author(s):  
Hyun S Kim ◽  
Juan C. Camacho ◽  
Bassel F. El-Rayes
Keyword(s):  
Dose Level ◽  
Dose Escalation ◽  
Objective Response Rate ◽  
Response Rate ◽  
Liver Tumors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Hepatic Tumors ◽  
Free Survival ◽  
Yttrium 90

460 Background: The rationale for combining Gemcitabine (G) with Yttrium-90 (Y90) is based on G being a potent radio sensitizer and activity of Y90 against liver tumors of pancreatobiliary histology. Therefore, a safety and efficacy trial of adding G to Y90 is required. Methods: Eligibility: Chemo-naïve patients with histologic diagnosis of unresectable PC or CC with liver predominant disease. Design: Open label phase I design with 3+3 G dose escalation. Induction G on Day 1 followed by Y90 on Day 2 and subsequent pre-assigned dose levels of G until week 12. Primary objective: To determine the maximal tolerated dose of G that can be used in combination with Y90. Secondary objectives: To characterize the toxicity, evaluate hepatic progression free survival (HPFS); determine tumor response rate using RECIST and PERCIST criteria; determine the progression free survival (PFS) and overall survival (OS). Correlative Imaging: 18-FDG PET/CT with contrast at baseline and 12 weeks. Results: 14 patients were recruited and 8 met the inclusion criteria. Seven out of eight patients tolerated the dose escalation regime of G (dose level 1-400 and dose level 2-600mg/m2). All the patients developed grade 1 toxicities (Hepatobiliary 25%, Bone marrow 25%, Fatigue 100%). Three patients (37.5 %) had grade 2 hepatobiliary toxicity and one patient (12.5 %) had grade 3 hepatobiliary toxicity, which required short-term hospitalization. No radiation pneumonitis, gastrointestinal ulceration, or procedure-related mortality occurred. Six patients (75%) developed grade 1 toxicity (fatigue). All of the patients had SD in the liver by RECIST; the objective response rate was 62.5% by PERCIST (CR12.5%, PR50%, SD25% PD12.5%). Overall objective response rate was 0% by RECIST (SD62.5%, PD37.5%); and 50% for PERCIST (CR12.5%, PR37.5%, SD12.5%, PD37.5%). The median OS from diagnosis was 13.8 months (95% CI, 9.65 to 26.29 months) and from Y90 therapy 10.9 months (95% CI, 6.47 to 22.39 months). PFS was 6.92 months (95%CI, 4.37-16.5 months) and HPFS of 8.72 months (95%CI, 4.48-19.36 months). Conclusions: In patients with hepatic tumors of pancreatobiliary origin, Gemcitabine at 600mg/m2 with Y90 therapy appears to be a viable and safe therapy. Clinical trial information: NCT01434459.

Efficacy of vemurafenib in patients (pts) with non-small cell lung cancer (NSCLC) with BRAFV600 mutation.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9074-9074 ◽  
Author(s):  
Vivek Subbiah ◽  
Radj Gervais ◽  
Gregory J. Riely ◽  
Antoine Hollebecque ◽  
Jean-Yves Blay ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Braf Mutations ◽  
Open Label ◽  
Braf Inhibition ◽  
Duration Of Response ◽  
Secondary Endpoints ◽  
Prior Systemic Therapy ◽  
Grade 3

9074 Background: BRAFV600 mutations occur in 1–2% of pts with NSCLC. We previously reported the efficacy of vemurafenib, a selective BRAFV600 inhibitor, in BRAF mutation-positive non-melanoma tumors (VE-BASKET study). We now present final data for the expanded NSCLC cohort. Methods: This open-label, histology-independent, phase 2 study included 6 prespecified cohorts (including NSCLC) plus one ‘all-others’ cohort. Pts received vemurafenib (960 mg bid) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (RECIST v1.1). Secondary endpoints included best overall response rate, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Because the pre-specified clinical benefit endpoint was met in the initial NSCLC cohort, the cohort was expanded. ClinicalTrials.gov identifier NCT01524978. Results: Database lock was 12 Jan 2017. Of 208 pts enrolled at 25 centers worldwide, 62 pts had NSCLC: median age 65 years; 56% male; 13% had no prior systemic therapy; 50% had ≥2 prior therapies. Responses were seen in previously treated and untreated pts (Table). The most common all-grade adverse event (AE) was nausea (40%); grade 3–5 AEs included keratoacanthoma (15%) and squamous cell carcinoma of the skin (15%). Six pts discontinued vemurafenib due to AEs; two had non-treatment-related fatal AEs. Conclusions: Vemurafenib showed evidence of encouraging efficacy in pts with NSCLC with BRAFV600 mutation, with prolonged PFS in previously untreated pts; median OS was not estimable due to ongoing responses. The safety profile of vemurafenib was similar to that seen in melanoma studies. Our results suggest a role for BRAF inhibition in NSCLC with BRAF mutations. Clinical trial information: NCT01524978. [Table: see text]

Nimbus: A phase II study of nivolumab plus ipilimumab in metastatic hypermutated HER2-negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS1115-TPS1115 ◽  
Author(s):  
Romualdo Barroso-Sousa ◽  
Lorenzo Trippa ◽  
Paulina Lange ◽  
Chelsea Andrews ◽  
Heather L. McArthur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Breast Cancer Patients ◽  
Open Label ◽  
True Response ◽  
Tumor Mutational Burden

TPS1115 Background: A previous study from our group showed that approximately 9% of metastatic breast cancer (MBC) is hypermutated, defined as a tumor mutational burden (TMB) ≥10 Mutations/Megabase (Mut/Mb). The aim of this study is to evaluate if patients with hypermutated HER2-negative MBC benefit from the combination of nivolumab plus ipilimumab. Methods: This is an open-label, single-arm, multicenter, phase 2 study assessing the efficacy of nivolumab 3 mg/Kg intravenously (IV) every 14 days plus Ipilimumab 1 mg/Kg IV every 6 weeks in subjects with hypermutated metastatic HER2-negative breast cancer. Patients with measurable HER2-negative MBC, TMB ≥10 Mut/Mb assessed by a cancer-gene panel evaluating > 300 genes and performed in a CLIA-certified laboratory, and 0-3 prior lines of chemotherapy in the advanced setting are eligible. The primary objective is overall response rate according to RECIST 1.1. Secondary objectives include the safety and tolerability of the combination, progression-free survival, and overall survival. The study will follow a two-stage design. In the first stage 14 patients will be enrolled. If there is at least one patient with objective response, accrual will continue to the second stage where an additional 16 patients will be enrolled. If there are at least 4 patients with an objective response among the 30 patients, the regimen will be considered worthy of further study. If the true response rate is 5%, the chance the regimen is declared worthy of further study is less than 5%. If the true response rate is 25%, the chance that the regimen is declared worthy of further study is > 90%. Tumor biopsies, peripheral blood, and stool collection are mandatory and will be obtained at baseline, on treatment (end of cycle 1), and at disease progression and will be assessed for potential biomarkers of treatment response. The trial was activated in February 2019, and accrual should be completed in 18 months. Clinical trial information: NCT03789110.

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