Overall response rate (ORR) in STEAM, a randomized, open-label, phase 2 trial of sequential and concurrent FOLFOXIRI-bevacizumab (BEV) vs FOLFOX-BEV for the first-line (1L) treatment (tx) of patients (pts) with metastatic colorectal cancer (mCRC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 492-492 ◽  
Author(s):  
Johanna C. Bendell ◽  
Benjamin R. Tan ◽  
James Andrew Reeves ◽  
Henry Xiong ◽  
Bradley G. Somer ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Tumor Location ◽  
Induction Phase ◽  
Phase 2 ◽  
Open Label ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Disease Rates ◽  
Open Label Phase ◽  
The Impact

492 Background: 3-drug chemotherapy (CT) + BEV (cFOLFOXIRI-BEV) significantly improved efficacy vs FOLFIRI-BEV for 1L mCRC tx, but safety and the impact of subsequent fluoropyrimidine-BEV maintenance tx require further definition. The phase 2 STEAM (NCT01765582) trial assessed efficacy of 1L cFOLFOXIRI-BEV vs FOLFOX-BEV and safety of alternating 2-drug CT (FOLFOX and FOLFIRI) + BEV tx monthly in a sequential sFOLFOXIRI-BEV regimen. Methods: Pts with unresectable, previously untreated mCRC were randomized 1:1:1 to BEV-containing (5 mg/kg) arms (cFOLFOXIRI, sFOLFOXIRI [alternating FOLFOX and FOLFIRI every 4 weeks {q4w}], or FOLFOX q3w) in a 4–6 month induction phase, followed by BEV-containing maintenance tx. Stratification factors included extent of metastatic disease and tumor location. Primary objectives: 1L ORR, 1L progression-free survival (PFS), safety. Secondary objectives: resection and conversion to resectable disease rates, time to 2L PFS, overall survival. ORR was tested with a 1-sided alpha of 5%; tx arms were compared with a stratified 1-sided Cochran-Mantel-Haenszel test. PFS was analyzed descriptively. Results:Among 280 enrolled pts (median age, 57.5 yrs), 186 remainined in the study on July 1, 2015. Efficacy and safety are shown (see Table). Conclusion: While not statistically significant, there was a trend of increased ORR with cFOLFOXIRI-BEV vs FOLFOX-BEV in 1L mCRC tx. Analysis of PFS is ongoing. All 3 regimens were well tolerated. Clinical trial information: NCT01765582. [Table: see text]

scholarly journals Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial

2020 ◽  
Vol 8 (1) ◽  
pp. e000798
Author(s):  
Lu Xie ◽  
Jie Xu ◽  
Xin Sun ◽  
Wei Guo ◽  
Jin Gu ◽  
...  
Keyword(s):  
Pulmonary Metastases ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Open Label Phase ◽  
High Grade Osteosarcoma

BackgroundResults of our previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy.MethodsThis open-label, phase 2 trial was conducted at Peking University People’s Hospital. We enrolled patients with advanced osteosarcoma progressed after chemotherapy. Patients received 500 mg apatinib orally once daily plus 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) and clinical benefit rate at 6 months, which were based on RECIST V.1.1.Results43 patients were enrolled between January 25 and September 4, 2018. With median follow-up time of 48.3 (Q1, Q3, 30.6, 66.6) weeks, 13 (30.23%, 95% CI 17.2%, 40.1%) of 43 patients were progression free at 6 months and the 6-month PFS rate was 50.9% (95% CI 34.6%, 65.0%). Until final follow-up, the objective response rate was 20.9% (9/43) and two patients with durable disease control were observed. Patients with programmed cell death 1 ligand-1 (PD-L1) tumor proportion score ≥5% and pulmonary metastases tended to have a longer PFS in comparison to the others (p=0.004 and 0.017, respectively). Toxic effects led to dose reductions, or interruptions, or both in 24 (55.8%) of 43 patients and permanent discontinuation in 4 (9.3%) patients. There were no treatment-related deaths.ConclusionsAlthough the combination of apatinib and camrelizumab seemed to prolong PFS in comparison to single agent apatinib in treating advanced osteosarcoma, it did not reach the prespecified target of 6-month PFS of 60% or greater. Overexpression of PD-L1 and the presence of pulmonary metastases only were associated with longer PFS.Trial registration numberNCT03359018.

Impact of primary tumor side (TS) on outcomes of once-every-2-weeks (q2w) cetuximab + first-line (1L) FOLFOX or FOLFIRI in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC) in the phase 2 APEC trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 747-747
Author(s):  
Timothy Jay Price ◽  
Lin Shen ◽  
Brigette Ma ◽  
Regina Esser ◽  
Wen-Feng Chen ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Hepatic Flexure ◽  
Asia Pacific ◽  
Phase 2 ◽  
Exon 2 ◽  
Free Survival ◽  
Prognostic Effect ◽  
Phase 2 Trial ◽  
Colon And Rectum ◽  
The Impact

747 Background: In the RAS wt population of APEC, q2w cetuximab combined with 1L FOLFOX or FOLFIRI achieved a best confirmed overall response rate (BORR), median progression-free survival (PFS), and median overall survival (OS) similar to those reported in prior 1L pivotal studies involving weekly (qw) cetuximab. In this hypothesis-generating subgroup analysis, we evaluated the impact of TS in APEC study patients with RAS wt mCRC. Methods: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region, with BORR as the primary endpoint. Patients with KRAS exon 2 wt tumors received q2w cetuximab + investigator’s choice of FOLFOX or FOLFIRI; subsequent analyses considered patients who were RAS wt ( KRAS/ NRAS, exons 2-4). TS was categorized in evaluable patients with RAS wt tumors (left [L]-sided = splenic flexure, descending colon, sigmoid colon, and rectum; right [R]-sided = appendix, cecum, ascending colon, hepatic flexure, and transverse colon). Results: Among 167 patients with RAS wt mCRC, 159 were evaluable for TS; 130 (81.8%) had L-sided and 29 (18.2%) had R-sided mCRC. Baseline characteristics in the TS subgroups reflected the known differences between L- and R-sided mCRC. Efficacy data for the TS subgroups are summarized in the table. Conclusions: Consistent with prior 1L pivotal studies involving qw cetuximab, a prognostic effect of TS in patients receiving 1L q2w cetuximab was confirmed in APEC. BORR remained ≥50% in patients with R-sided mCRC, in line with prior evidence that use of cetuximab may be appropriate when tumor shrinkage/cytoreduction is the goal. These hypothesis-generating data also raise the possibility of synergy between cetuximab and, in particular, irinotecan for PFS and OS in patients with R-sided tumors, although numbers are small. Clinical trial information: NCT00778830. [Table: see text]

scholarly journals Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 trial (ORIENT-2)

2021 ◽  
Author(s):  
Jian Ming Xu ◽  
Yi Li ◽  
Qingxia Fan ◽  
Yongqian Shu ◽  
Lei Yang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Open Label Phase

Abstract This randomized, open-label, multi-center phase 2 study (ClinicalTrials.gov, number NCT03116152) assessed sintilimab, a PD-1 inhibitor, versus chemo in patients with advanced esophageal squamous cell carcinoma (ESCC) refractory to first-line (1L) chemotherapy. The primary endpoint was overall survival (OS), while exploratory endpoint was the association of biomarkers with treatment efficacy. The median OS in the sintilimab group was significantly prolonged compared with that of the chemotherapy group, (objective response rates 12.6% and 6.3 %, respectively). Incidence of treatment-related adverse events of grade 3–5 was lower with sintilimab than with chemotherapy (20.2 vs. 39.1 %). Patients with high TCR clonality and low mTBI showed the longest median OS (15.0 mo), while patients with low NLR at 6 wk post-treatment had a significantly prolonged median OS compared with those with high NLR. High expression of T-follicular helper cells or activated B-cell signature was significantly associated with longer progression-free survival in the sintilimab group.

scholarly journals Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial

2021 ◽  
Author(s):  
Kjetil Boye ◽  
Alessandra Longhi ◽  
Tormod Guren ◽  
Susanne Lorenz ◽  
Stine Næss ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Progression Free Survival ◽  
Complete Response ◽  
Positive Sample ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Combination Strategies ◽  
Open Label Phase ◽  
Stage 1

Abstract Aim To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma. Material and methods The study was a single-arm, open-label, phase 2 trial in patients with unresectable, relapsed osteosarcoma. The primary endpoint was clinical benefit rate (CBR) at 18 weeks of treatment, defined as complete response, partial response, or stable disease using RECIST v1.1. The trial had a Simon´s two-stage design, and ≥ 3 of 12 patients with clinical benefit in stage 1 were required to proceed to stage 2. The trial is registered with ClinicalTrials.gov, number NCT03013127. NanoString analysis was performed to explore tumor gene expression signatures and pathways. Results Twelve patients were enrolled and received study treatment. No patients had clinical benefit at 18 weeks of treatment, and patient enrollment was stopped after completion of stage 1. Estimated median progression-free survival was 1.7 months (95% CI 1.2–2.2). At time of data cut-off, 11 patients were deceased due to osteosarcoma. Median overall survival was 6.6 months (95% CI 3.8–9.3). No treatment-related deaths or drug-related grade 3 or 4 adverse events were observed. PD-L1 expression was positive in one of 11 evaluable tumor samples, and the positive sample was from a patient with a mixed treatment response. Conclusion In this phase 2 study in advanced osteosarcoma, pembrolizumab was well-tolerated but did not show clinically significant antitumor activity. Future trials with immunomodulatory agents in osteosarcoma should explore combination strategies in patients selected based on molecular profiles associated with response.

Updated efficacy, safety, and biomarker analyses of STEAM, a randomized, open-label, phase II trial of sequential (s) and concurrent (c) FOLFOXIRI-bevacizumab (BV) vs FOLFOX-BV for first-line (1L) treatment (tx) of patients with metastatic colorectal cancer (mCRC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 657-657 ◽  
Author(s):  
Herbert Hurwitz ◽  
Benjamin R. Tan ◽  
James Andrew Reeves ◽  
Henry Q. Xiong ◽  
Bradley G. Somer ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Induction Phase ◽  
Positive Trend ◽  
Wild Type ◽  
First Line ◽  
Open Label ◽  
Free Survival ◽  
Open Label Phase ◽  
Grade 3 ◽  
Clinical Trial Information

657 Background: STEAM (NCT01765582) assessed efficacy and safety of 1L cFOLFOXIRI-BV and sFOLFOXIRI-BV vs FOLFOX-BV. Updated efficacy, safety, and exploratory biomarker data are reported. Methods: 280 tx-naive pts with mCRC were randomized 1:1:1 to BV-containing (5 mg/kg q2w) arms (cFOLFOXIRI, sFOLFOXIRI [alternating FOLFOX and FOLFIRI every 4 weeks {q4w}], or FOLFOX) in a 4–6 month (mo) induction phase, followed by maintenance. Primary objectives include progression-free survival (PFS). Secondary objectives include overall survival (OS). Tumor-relevant biomarker evaluations were exploratory. Results: Median PFS significantly improved and median OS showed a positive trend with cFOLFOXIRI-BV vs FOLFOX-BV. PFS significantly improved with cFOLFOXFIRI-BV vs FOLFOX-BV in BRAF wild type (WT); there was a positive trend in RAS WT and mutant (MUT) pts; no tx difference observed in BRAF MUT pts. In the safety pop., (n = 271), 88% had Grade ≥ 3 tx emergent AEs: 91% cFOLFOXIRI-BV; 87% sFOLFOXIRI-BV; 86% FOLFOX-BV. Conclusions: Improved PFS and a positive trend in OS were observed for cFOLFOXIRI-BV vs FOLFOX-BV. A positive PFS trend was seen in RAS WT and MUT pts, with significantly improved PFS in BRAF WT. The small number of BRAF MUT pts precluded estimation of tx effects. AEs for all 3 txs were consistent with previous reports. Clinical trial information: NCT01765582. [Table: see text]

Eribulin and gemcitabine in previously treated patients with advanced liposarcoma or leiomyosarcoma: A multicenter, single-arm, phase 2-trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11516-11516
Author(s):  
Chang Gon Kim ◽  
Jin-Hee Ahn ◽  
Jeong Eun Kim ◽  
Jee Hung Kim ◽  
Min Kyung Jeon ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Alternative Hypothesis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Histologic Types

11516 Background: Eribulin and gemcitabine have shown encouraging efficacy in soft-tissue sarcoma (STS) as a monotherapy. Here, we evaluated the activity and safety of combined use of eribulin and gemcitabine in two most common histologic types of STS, liposarcoma and leiomyosarcoma. Methods: In this non-randomized, multi-center phase 2 study, patients were included if they had progressive disease after one or two prior chemotherapy including doxorubicin. Patient were given eribulin 1.4 mg/m2 and gemcitabine 1,000 mg/m2 on day1 and day 8 every 3 weeks. The primary endpoint was progression-free survival rate at 12 weeks (PFSR12wks) with null and alternative hypothesis of PFSR12wks≤20.0% and ≥40.0%, respectively. Results: Of 37 patients included, 22 had leiomyosarcoma, and 15 had liposarcoma. At 12-weeks after treatment, 16 and (72.7%) 11 (73.3%) patients in leiomyosarcoma and liposarcoma were progression-free. Overall PFSR12wks was 73.0%, satisfying the primary endpoint. Objective response rate, disease control rate, median progression-free survival, and median overall survival were 16.2%, 78.4%, 23.9 weeks, and 88.9 weeks, without any statistical differences according to histologic subtypes. No new safety signals and treatment-related death were observed. Conclusions: Eribulin and gemcitabine showed promising activity and manageable safety profile in patients with STS of liposarcoma and leiomyosarcoma histology. Updated outcomes for ongoing patients will be presented. Clinical trial information: NCT03810976.

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