REGOMA: A randomized, multicenter, controlled open-label phase II clinical trial evaluating regorafenib (REG) activity in relapsed glioblastoma (GBM) patients (PTS).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS2085-TPS2085 ◽  
Author(s):  
Giuseppe Lombardi ◽  
Gian Luca De Salvo ◽  
Marica Eoli ◽  
Alba Ariela Brandes ◽  
Roberta Ruda ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Brain Mri ◽  
Objective Response ◽  
Progression Free Survival ◽  
High Recurrence Rate ◽  
Open Label ◽  
Multikinase Inhibitor ◽  
Rano Criteria

TPS2085 Background: GBM is the most common and malignant form of primary brain tumor with a high recurrence rate after surgery, radiation therapy and temozolomide. Currently, there is no established regimen for the treatment of recurrent GBM. GBMs are highly vascularized tumors with high expression of pro-angiogenic factors and activation of multiple signaling pathways in the tumor microenvironment, including the receptor tyrosine kinases, VEGFR, FGFR, and PDGFR, which control the tumor vasculature. REG, an oral multikinase inhibitor, inhibits these angiogenic kinases and the mutant oncogenic kinases KIT, RET and B-RAF. REG was demonstrated to be safe and effective in metastatic colon-rectal cancer, hepatocellular carcinoma and GIST PTS. It was shown that REG inhibits tumor angiogenesis and tumor cell proliferation in rat GBM tumor xenografts (Wilhelm S.M, et al. Regorafenib: a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int. J. Cancer:129,245-255.2011). Methods: Primary aim of the study is to assess the role of REG activity in prolonging the overall survival in relapsed GBM PTS after surgery and Stupp regimen; secondary aims are to analyze progression free survival, objective response rate, disease control rate and quality of life. Eligible PTS with ECOG PS 0-1, documented progression of disease (after Stupp treatment) as defined by RANO criteria, adequate bone marrow, liver and renal function are randomized in a 1:1 ratio to REG 160 mg/die (3 weeks on, 1 week off) or lomustine 110 mg/m2 (every 6 weeks). A total of 112 PTS will be randomized (α = 0.20, β = 0.20) and stratified based on surgery at recurrence. Disease evaluation is performed with gadolinium brain MRI every 8 weeks according to RANO criteria. Additional exploratory objectives include analysis of specific angiogenic and metabolic biomarkers in tissue as possible predictors of response to REG. The trial started in Nov 2015; as of Jan 2017, 105 PTS have been enrolled. Final analysis is planned in Dec 2017. Clinical trial information: NCT02926222.

An open-label phase II study of lenvatinib plus pembrolizumab in patients with advanced gastric cancer (EPOC1706).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 374-374 ◽  
Author(s):  
Akihito Kawazoe ◽  
Shota Fukuoka ◽  
Yoshiaki Nakamura ◽  
Yasutoshi Kuboki ◽  
Yuichi Mikamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Tyrosine Kinases ◽  
Objective Response ◽  
Progression Free Survival ◽  
In Vivo Model ◽  
Open Label ◽  
Multikinase Inhibitor ◽  
Open Label Phase

374 Background: Pembrolizumab, anti–PD-1 antibody, provides response rates of around 15% in patients (pts) with PD-L1-positive advanced gastric cancer (AGC). Lenvatinib, a multikinase inhibitor of VEGF receptors and other receptor tyrosine kinases, substantially decreased the tumor-associated macrophages and increased infiltration of CD8-positive T cells and enhanced anti-tumor activity of PD-1 inhibitors in vivo model. This phase 2 study has been conducted to evaluate efficacy and safety of the combination of lenvatinib plus pembrolizumab in pts with AGC. Methods: Eligible pts were with AGC having measurable lesions according to RECIST ver. 1.1. Pts could be enrolled regardless of PD-L1 status. Pts received 20 mg oral lenvatinib daily plus 200 mg intravenous pembrolizumab every 3 weeks. Primary endpoint was objective response rate (ORR). Planned sample size was 29 pts based on Simon’s optimal two-stage design with one-sided ɑ = 5% and power = 80%. The threshold and expected ORRs were 10% and 30%. PD-L1 combined positive score (CPS) was assessed using the anti–PD-L1 22C3 antibody. Results: From October 2018 to March 2019, 29 pts (27 MSS and 2 MSI-H) were enrolled and assessed for anti-tumor response. Fourteen pts received the study treatment as first-line and 15 pts as second-line. ORR was 69% (95% CI 49 to 85). The disease control rate was 100%. ORR in MSS pts was 70%. ORR was numerically higher in pts with CPS≥1 (n=19, ORR 84%) than that of pts with CPS<1 (n = 10, ORR 40%). Median progression-free survival was 6.9 months (95% CI, 4.4-9.4 months) with 14 pts with ongoing treatment at the data cut off in August 2019. Grade ≥ 3 treatment related adverse events occurred in 13 pts (45%) including hypertension (34%), proteinuria (17%), and platelet count decreased (7%). Conclusions: Lenvatinib with pembrolizumab showed a promising antitumor activity with acceptable safety profiles for pts with AGC, which warrants further investigations in a larger cohort. Clinical trial information: NCT03609359 .

Phase Ib/II open-label, randomized evaluation of atezolizumab (atezo) + Imprime PGG (Imprime) + bevacizumab (bev) vs regorafenib (rego) in MORPHEUS: Microsatellite-stable (MSS) metastatic colorectal cancer (mCRC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3559-3559
Author(s):  
Marwan Fakih ◽  
James M. Cleary ◽  
Yong Sang Hong ◽  
Tae-You Kim ◽  
Rachael A Safyan ◽  
...  
Keyword(s):  
Stable Disease ◽  
Checkpoint Inhibitors ◽  
Macrophage Polarization ◽  
Objective Response ◽  
Systemic Exposure ◽  
Progression Free Survival ◽  
Open Label ◽  
Multikinase Inhibitor ◽  
Phase Ib ◽  
M1 Macrophage

3559 Background: The MORPHEUS platform consists of multiple, global, open-label, randomized Phase Ib/II trials designed to identify early efficacy and safety signals of treatment (tx) combinations across cancers. Here, atezo (anti-PD-L1) was tested with Imprime and bev (anti-VEGF) for MSS mCRC, a poorly immunogenic cancer generally resistant to checkpoint inhibitors. Imprime acts as a pathogen-associated molecular pattern that, when bound to anti-β glucan antibodies (ABA), activates the innate immune system with the potential to 1) promote priming and expansion of tumor-specific T cells, 2) promote M2-M1 macrophage polarization and 3) enhance the immunomodulatory effects of atezo and bev. Therefore, we hypothesized that atezo + Imprime + bev would induce an antitumor response beyond that of rego, a standard-of-care multikinase inhibitor, in patients (pts) with MSS mCRC. Methods: Pts with MSS mCRC unselected for the Imprime-specific biomarker (ABA) and refractory to 1-2 prior lines of standard therapy received atezo (1200 mg IV every 3 weeks [q3w]) + Imprime (4 mg/kg IV on Days 1, 8, 15) + bev (7.5 mg/kg IV q3w) or control tx with rego (160 mg orally days 1-21; dose escalation to 160 mg during Cycle 1 allowed per institutional guidelines). The primary endpoint was objective response rate (ORR; investigator-assessed RECIST 1.1); secondary endpoints included disease control rate (DCR; response or stable disease ≥ 12 weeks), progression-free survival (PFS), overall survival (OS) and safety. Results: Pts were followed-up for ≥18 wk. 15 pts received atezo + Imprime + bev and 13 received rego. Grade (Gr) 3/4 tx-related adverse events (TRAEs) were seen in 13% of atezo + Imprime + bev and 62% of rego pts. No Gr 5 AEs occurred in atezo + Imprime + bev pts and 1 (8%) was reported in a rego pt. One pt in each arm (7% vs 8%, respectively) withdrew from tx due to a TRAE. No radiological responses were seen in either arm. Five pts (33%) receiving atezo + Imprime + bev and 8 (62%) receiving rego had stable disease as best response. DCR was 13% with atezo + Imprime + bev and 23% with rego. Median PFS was 1.5 mo (95% CI: 1.4, 2.8) and 2.8 mo (95% CI: 1.6, 3.1), and median OS was 5.7 mo (95% CI: 4.4, 10.5) and 10.2 mo (95% CI: 4.8, NE) with atezo + Imprime + bev and rego, respectively. There was no apparent correlation between baseline PD-L1 expression or CD8+ lymphocyte tumor infiltration and clinical benefit. Further, the systemic exposure of atezo, Imprime and bev and immunogenicity of atezo and bev are in line with previous clinical experience. Additional biomarker, pharmacokinetics and anti-drug antibody data will be shown. Conclusions: Atezo + Imprime + bev was well tolerated; toxicities were consistent with the safety profiles of the individual agents. No efficacy signal was identified with atezo + Imprime + bev in pts with MSS refractory mCRC. Clinical trial information: NCT03555149.

scholarly journals Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma

2020 ◽  
Vol 38 (26) ◽  
pp. 2960-2970 ◽  
Author(s):  
Richard S. Finn ◽  
Masafumi Ikeda ◽  
Andrew X. Zhu ◽  
Max W. Sung ◽  
Ari D. Baron ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antitumor Activity ◽  
Objective Response ◽  
Death Receptor ◽  
Progression Free Survival ◽  
Open Label ◽  
Multikinase Inhibitor ◽  
Expansion Phase ◽  
Phase Ib ◽  
Safety Signals

PURPOSE The immunomodulatory effect of lenvatinib (a multikinase inhibitor) on tumor microenvironments may contribute to antitumor activity when combined with programmed death receptor-1 (PD-1) signaling inhibitors in hepatocellular carcinoma (HCC). We report results from a phase Ib study of lenvatinib plus pembrolizumab (an anti–PD-1 antibody) in unresectable HCC (uHCC). PATIENTS AND METHODS In this open-label multicenter study, patients with uHCC received lenvatinib (bodyweight ≥ 60 kg, 12 mg; < 60 kg, 8 mg) orally daily and pembrolizumab 200 mg intravenously on day 1 of a 21-day cycle. The study included a dose-limiting toxicity (DLT) phase and an expansion phase (first-line patients). Primary objectives were safety/tolerability (DLT phase), and objective response rate (ORR) and duration of response (DOR) by modified RECIST (mRECIST) and RECIST version 1.1 (v1.1) per independent imaging review (IIR; expansion phase). RESULTS A total of 104 patients were enrolled. No DLTs were reported (n = 6) in the DLT phase; 100 patients (expansion phase; included n = 2 from DLT phase) had received no prior systemic therapy and had Barcelona Clinic Liver Cancer stage B (n = 29) or C disease (n = 71). At data cutoff, 37% of patients remained on treatment. Median duration of follow-up was 10.6 months (95% CI, 9.2 to 11.5 months). Confirmed ORRs by IIR were 46.0% (95% CI, 36.0% to 56.3%) per mRECIST and 36.0% (95% CI, 26.6% to 46.2%) per RECIST v1.1. Median DORs by IIR were 8.6 months (95% CI, 6.9 months to not estimable [NE]) per mRECIST and 12.6 months (95% CI, 6.9 months to NE) per RECIST v1.1. Median progression-free survival by IIR was 9.3 months per mRECIST and 8.6 months per RECIST v1.1. Median overall survival was 22 months. Grade ≥ 3 treatment-related adverse events occurred in 67% (grade 5, 3%) of patients. No new safety signals were identified. CONCLUSION Lenvatinib plus pembrolizumab has promising antitumor activity in uHCC. Toxicities were manageable, with no unexpected safety signals.

ABT-869 in non-small cell lung cancer (NSCLC): Interim results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8074-8074
Author(s):  
E. Tan ◽  
R. Salgia ◽  
B. Besse ◽  
G. Goss ◽  
D. R. Gandara ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Objective Response ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Specific Inhibitor ◽  
Progression Free Survival ◽  
Open Label ◽  
Eligibility Criteria ◽  
Phase 2 Trial

8074 Background: ABT-869 is a novel orally active, potent and specific inhibitor of vascular endothelial growth factor and platelet derived growth factor receptor tyrosine kinases. Methods: This ongoing, open-label, randomized, multicenter phase 2 trial of ABT-869 at 0.10 mg/kg daily (Arm A) and 0.25 mg/kg daily (Arm B) until progressive disease (PD) or intolerable toxicity, was initiated to assess antitumor activity and toxicity of ABT-869 in patients (pts) with NSCLC. Eligibility criteria included locally advanced or metastatic NSCLC; ≥ 1 prior systemic treatment, and ≥1 measurable lesion by RECIST criteria. The primary endpoint was the progression free (PF) rate at 16 wks. Secondary endpoints were objective response rate (ORR), time to progression (TTP), progression free survival (PFS) and overall survival (OS). CT scans were assessed by the investigator and centrally; central assessment results are provided. Results: 138 patients (pts) were enrolled from 08/07–10/08 from 27 centers with interim data available for 94 pts (Arm A, n=43; Arm B; n=51). Median age was 64 years and 62 years in Arm A and B respectively. For the interim analysis population (Arm A, n=24; Arm B, n=24), 16 (33.3%) pts were PF at 16 wks: 7 (29.2%) in Arm A and 9 (37.5%) in Arm B. The ORR in Arm A (n=30) was 0% and 7.3% in Arm B (n=41). The median TTP and median PFS were 110 and 109 days, and 112 days and 108 days in Arm A and B, respectively. The most common adverse events (AEs) in Arm A were fatigue (35%), nausea (21%), and anorexia (21%), and in Arm B were hypertension (51%), fatigue (51%), diarrhea (43%), anorexia (41%), nausea (31%), proteinuria (31%) and vomiting (26%). The most common grade 3/4 toxicities in the Arm A were fatigue (7%), ascites (5%), dehydration (5%), pleural effusion (5%), and in the Arm B were hypertension (23%), fatigue (8%), PPE syndrome (8%), dyspnoea (6%) and stomatitis (6%). Most AE's were mild/moderate and reversible with interruptions/dose reduction/or discontinuation of ABT-869. Conclusions: ABT-869 demonstrates an acceptable safety profile and appears to be active in NSCLC patients. [Table: see text]

Nimotuzumab combined with cisplatin plus fluorouracil chemotherapy in patients with metastatic nasopharyngeal carcinoma after radical radiotherapy: A multicentre, open-label, phase II clinical trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6028-6028 ◽  
Author(s):  
Chong Zhao ◽  
Jingjing Miao ◽  
Guanzhu Shen ◽  
Jin-Gao Li ◽  
Ning Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Nasopharyngeal Carcinoma ◽  
Median Time ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Radical Radiotherapy ◽  
Open Label ◽  
Randomised Study ◽  
Metastatic Nasopharyngeal Carcinoma

6028 Background: Cisplatin plus fluorouracil (PF) is main therapy for metastatic nasopharyngeal carcinoma (NPC). However, the efficacy is not satisfactory, especially in patients with metastasis after radical radiotherapy. The purpose of this study was to investigate the efficacy and toxicity of Nimotuzumab combined with PF in patients with metastatic NPC after radical radiotherapy. Methods: Patients with untreated metastatic NPC after radical radiotherapy were recruited from 9 hospitals in China with Simon’s two-stage design. All patients received Nimotuzumab (200mg/w) and cisplatin (100mg/m2, day 1) plus fluorouracil (4g/m², day 1-4) every 3 weeks until progressive disease (PD) or unacceptable toxicity or a maximum of 6 cycles. If patients had still not progressed at this stage, Nimotuzumab (200mg/w) as monotherapy would be delivered until PD. This study was registered in ClinicalTrials.gov, Number NCT01616849. Results: Between Jun, 2012 and April, 2015, 35 patients were enrolled (Table). The objective response rate (ORR) and disease control rate (DCR) were 71.4% and 85.7%, and the median time of progression free survival (PFS) and overall survival (OS) were 6.97 and 11.01 months. The most common toxicities were leukopenia (94.1%), vomiting (97.1%) and nausea (97.1%); the grade 3/4 toxicities were leukopenia (62.9%) and mucositis (20.0%). There was only 1 patient have mild hypotension which related to Nimotuzumab. The ORR, DCR, median time of PFS and OS were 88.9%, 100.0%, 7.29 and 11.47 months in patients who received a total dose of Nimotuzumab ≥ 2400mg, respectively. Conclusions: Nimotuzumab combined with PF has achieved encouraging efficacy with an acceptable safety profile in metastatic NPC after radical radiotherapy. A phase III randomised study is needed. Clinical trial information: NCT01616849. [Table: see text]

Phase Ib/II trial of lenvatinib plus pembrolizumab in advanced melanoma.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 15-15
Author(s):  
Matthew H. Taylor ◽  
Nicholas J. Vogelzang ◽  
Allen Lee Cohn ◽  
Daniel E. Stepan ◽  
Robert Charles Shumaker ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Clinical Activity ◽  
Open Label ◽  
Multikinase Inhibitor ◽  
T Cell Infiltration ◽  
Rational Combination ◽  
Macrophage Populations ◽  
Ecog Ps

15 Background: Lenvatinib (LEN) is a multikinase inhibitor of VEGFR 1−3, FGFR 1−4, PDGFRα, RET, and KIT. Pembrolizumab (PEM), an anti-PD-1 antibody, is approved for first-line treatment of advanced melanoma (objective response rates [ORR], 21–34%). In preclinical studies, LEN decreased tumor-associated macrophage populations, increased CD8+ T cell infiltration, and augmented PD-1 inhibitor activity; thus, LEN is a rational combination partner for PEM. We report interim results of an ongoing phase 1b/2 trial of LEN + PEM in solid tumors, focusing on advanced melanoma. Methods: In this multicenter, open-label study, patients (pts) with measurable, confirmed, metastatic melanoma and ECOG PS ≤1 received oral LEN (20 mg/day) + PEM (200 mg Q3W, IV). Pts were not preselected for PD-L1 status. Tumor assessments were by investigator per immune-related RECIST (irRECIST). Phase 2 primary end point was ORR at 24 weeks (ORRWK24). Secondary end points included ORR, progression-free survival (PFS) and duration of response (DOR). Results: At data cutoff (March 1, 2018), 21 pts were enrolled: 14 (67%) were PD-L1+, 4 (19%) were PD-L1-; 3 (14%) not tested. 38% had ≥1 prior anticancer therapy. ORRWK24 was 47.6% (95% CI, 25.7–70.2). All pts had ≥1 treatment-related adverse event (TRAE). Grade 3 and 4 TRAEs occurred in 13 (62%) and 1 (5%; adrenal insufficiency) pts respectively. There were no fatal TRAEs. Most common any-grade TRAEs were fatigue (52%), decreased appetite (48%), diarrhea (48%), hypertension (48%), dysphonia (43%), and nausea (43%). Dose reduction and interruption due to TRAEs occurred in 13 (62%) and 10 (48%) pts, respectively. Conclusions: LEN + PEM was well-tolerated and had encouraging clinical activity. The combination may potentially improve on the antitumor activity of anti-PD-1 monotherapies, supporting further evaluation in advanced melanoma. Clinical trial information: NCT02501096. [Table: see text]

A phase II study of ABT-869 in hepatocellular carcinoma (HCC): Interim analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4581-4581 ◽  
Author(s):  
H. Toh ◽  
P. Chen ◽  
B. I. Carr ◽  
J. J. Knox ◽  
S. Gill ◽  
...  
Keyword(s):  
Growth Factor ◽  
Ct Scan ◽  
Phase Ii ◽  
Tyrosine Kinases ◽  
Interim Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Eligibility Criteria ◽  
Phase 2 Trial

4581 Background: ABT-869 is a novel orally active, potent and selective inhibitor of the vascular endothelial growth factor and platelet derived growth factor families of receptor tyrosine kinases. Results of an interim analysis of a phase 2 trial of ABT-869 in HCC are presented. Methods: An open-label, multicenter phase II trial (M06–879) of oral ABT-869 at 0.25 mg/kg daily in Child-Pugh A (C-PA) or QOD in Child-Pugh B (C-PB) patients (pts) until progressive disease (PD) or intolerable toxicity, is ongoing. Key eligibility criteria included unresectable or metastatic HCC; up to one prior line of systemic treatment; and at least one measurable lesion by computed tomography (CT) scan. The primary endpoint was the progression free (PF) rate at 16 weeks. Secondary endpoints included objective response rate (ORR), time to progression (TTP), progression free survival (PFS) and overall survival (OS). CT scans were assessed centrally and by the investigators; presented results are from central assessment. Results: 44 pts were enrolled from 09/07 to 08/08 at 6 centers internationally, with interim data available for 34 pts. There were 28 C-PA pts (median age, 63.5 y [range, 20- 81]) and 6 C-PB pts (median age, 64.5 y [range, 36–69]) and 73.5% received no prior systemic therapy. For the 19 evaluable C-PA pts included in the per-protocol interim analysis, 8 (42.1%) were progression free at 16 weeks [95% CI 20.3, 66.5]. The estimated ORR was 8.7% [95% CI, 1.1, 28] for the 23 C-PA pts and 0% for the 2 C-PB pts who had at least one post-baseline CT scan reviewed by central imaging. For all 34 pts, median TTP was 112 d [95% CI, 110, -], median PFS was 112 d [95% CI, 61, 168] and median OS was 295 d [95% CI, 182, 333]. The most common adverse events (AEs) for all pts were hypertension (41%), fatigue (47%), diarrhea (38%), rash (35%), proteinuria (24%), vomiting (24%), cough (24%) and oedema peripheral (24%). The most common grade 3/4 AEs for all pts were hypertension (20.6%) and fatigue (11.8%). Most AEs were mild/moderate and reversible with interruption/dose reductions/or discontinuation of ABT-869. Conclusions: ABT-869 appears to benefit HCC patients, with an estimated TTP of 112 days and an acceptable safety profile. Updated results from this ongoing study will be presented. [Table: see text]

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

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

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

A randomized phase III study of mFOLFOX6/bevacizumab combination chemotherapy with or without atezolizumab or atezolizumab monotherapy in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) metastatic colorectal cancer (mCRC): Colorectal Cancer Metastatic dMMR Immuno-Therapy (COMMIT) study (NRG-GI004/SWOG-S1610).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS260-TPS260
Author(s):  
Caio Max Sao Pedro Rocha Lima ◽  
Greg Yothers ◽  
Samuel A. Jacobs ◽  
Hanna Kelly Sanoff ◽  
Deirdre Jill Cohen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Mismatch Repair ◽  
Tumor Tissue ◽  
Dna Mismatch Repair ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Dna Mismatch

TPS260 Background: Deficient DNA mismatch repair (dMMR) colorectal cancer (CRC) is highly immunogenic. Preclinical data showed synergistic interactions among FOLFOX, anti-VEGF, and programmed cell death-1 (PD-1) pathway blockade. Prior phase I study of mFOLFOX6/ bevacizumab (bev) + atezolizumab (atezo) was well tolerated and enhanced intratumoral infiltration of CD8+ T cells. We hypothesize that the dMMR subset of CRC may be effectively targeted with combination of PD-1 pathway blockade and mFOLFOX6/bev. Methods: This is a prospective randomized phase III open-label trial. Pts (N=347) with mCRC dMMR will be randomized to three trial arms (1:1:1): mFOLFOX6/bev; atezo monotherapy; or mFOLFOX6/bev + atezo. Stratification factors include BRAFV600E status, metastatic site, and prior adjuvant CRC therapy. Primary endpoint is progression-free survival (PFS) assessed by study investigator of mFOLFOX6/bev/atezo and atezo monotherapy compared to mFOLFOX6/bev. Secondary endpoints include OS, objective response rate, safety profile, disease control rate, duration of response, and PFS by retrospective central review. Health-related quality of life is an exploratory objective. Archived tumor tissue and blood samples will be collected for correlative studies. Key inclusion criteria are: mCRC without prior chemotherapy for advanced disease; dMMR tumor determined by local CLIA-certified IHC assay (MLH1/MSH2/MSH6/PMS2); availability of archived tumor tissue for central confirmation of dMMR status; and measurable disease per RECIST. Activated 11-7-17. As of 9-11-19, enrollment continues with 44/347 pts enrolled. Clinical trial: NCT02997228. Support:U10CA180868, -180822, -180888, -180819, UG1CA189867, U24CA196067; Genentech, Inc. Clinical trial information: NCT02997228.

Phase II trial of ABT-869 in advanced renal cell cancer (RCC) after sunitinib failure: Efficacy and safety results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5036-5036
Author(s):  
N. Tannir ◽  
Y. Wong ◽  
C. Kollmannsberger ◽  
M. S. Ernstoff ◽  
D. J. Perry ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tyrosine Kinases ◽  
Phase Ii Trial ◽  
Cell Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Open Label ◽  
Eligibility Criteria ◽  
Best Response

5036 Background: ABT-869 is a novel, orally active and potent inhibitor of all VEGF and PDGF receptor tyrosine kinases. Results from a phase I study suggested antitumor activity in advanced solid tumors including RCC. The recommended dose for phase II investigation was 0.25 mg/kg (maximum 25 mg) daily. Methods: We conducted an open-label, multicenter phase II trial of oral ABT-869 in advanced RCC. Eligibility criteria included progressive disease (PD) within 100 days of enrollment after at least 2 cycles of sunitinib, prior nephrectomy, and adequate organ function. The primary endpoint was objective response rate (ORR) per RECIST by central imaging. Secondary endpoints were best response, time to progression (TTP), progression free survival (PFS), and overall survival (OS). Safety was assessed by NCI-CTCAE, v3.0. Results: 53 patients (pts, median age, 61 y [range, 40–80]; clear-cell histology [41 pts]; median number of prior therapies, 2 [range, 1–4]) were enrolled from 8/07 to 10/08. All pts were previously treated with sunitinib, and additional prior treatments included cytokine (19%), sorafenib (15%), temsirolimus (4%), and bevacizumab (4%). Preliminary efficacy data are shown in the Table below. Median TTP was 4.9 mos [95% CI: 3.5–6.8] per central imaging. Median OS is not estimable. The most common adverse events (AEs) were diarrhea (78%), fatigue (67%), hypertension (53%), nausea (51%) and vomiting (39%). AEs ≥ grade 3 included hypertension (24%), fatigue (18%), diarrhea (14%) and hand-foot syndrome (14%). 39 pts required dose reductions. Of the 20 pts who have discontinued therapy at the time of this analysis, 16 were due to PD, 3 due to AEs (1 hemoptysis, 1 fatigue, 1 fatigue/hypertension) and 1 withdrew consent. The remaining 33 pts continue protocol treatment, and updated results will be presented. Conclusions: ABT-869 has activity in RCC after sunitinib failure. The dose will be optimized for future studies. [Table: see text] [Table: see text]

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