Cabozantinib (CABO) plus durvalumab (DURVA) in patients with advanced and chemotherapy-treated bladder carcinoma of urothelial and non-urothelial histology: An open-label, single-arm, phase 2 trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS536-TPS536 ◽  
Author(s):  
Andrea Necchi ◽  
Patrizia Giannatempo ◽  
Daniele Raggi ◽  
Andrea Anichini ◽  
Giuseppina Calareso ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Immune Cell ◽  
Single Agent ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Effective Combination ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps

TPS536 Background: DURVA and CABO have shown single-agent activity in patients (pts) with urothelial carcinoma (UC). Their combination may result in prolonging overall survival (OS) in pts who have failed prior platinum-based chemotherapy (CT). Additionally, DURVA+CABO may be an effective combination for treating subgroup of pts like those with bone metastases only (not having RECIST-measurable disease) or with non-UC histology. Methods: In an open-label, single-arm, multicenter, phase 2 trial, pts will assume CABO 40 mg daily, orally, and will be administered DURVA 1500 mg, intravenously, q28 days, until disease progression (PD, RECIST 1.1) or onset of unacceptable toxicity. Treatment beyond PD is not allowed. Key inclusion criteria: ECOG-PS 0-1, bladder or upper tract primary tumor, UC and non-UC histology, failure of 1 or 2 platinum-based CT for metastatic disease (2nd-to-3rd line only). Neoadjuvant/adjuvant CT is counted if relapse occurred ≤6 months (m) of the last CT cycle. Response is evaluated by RECIST criteria v.1.1 q2 cycles. The primary endpoint of the study is OS. The target is to detect an improvement in median OS from ≤6m (H0) to ≥9m(H1). To achieve 90% power with a one-sided non-parametric test at 5% significance, 122 pts must will be accrued over 36m and follow-up may be closed 12m after the end of accrual. PD-L1 expression will be assessed using with the Ventana SP142 assay, and categorized as high (≥25% of tumor cells [TC] or immune cells [IC]) or low/negative ( < 25% TC or IC). The decision on whether or not to undertake PD-L1+ cohort expansion will be based on predictive power (PP) calculation: a PP ≥30% will be regarded as promising and necessary to continue. An interim analysis is planned after 24m (50% expected events). This analysis will be based on PP. The criterion for stopping the trial because of futility will be a PP < 20%. Analyses on tissue/blood samples will include immune-cell profiling, cytokine assessment, gene expression analyses and next-generation sequencing (FoundationOne). FDG-PET response in bone metastases will represent another translational endpoint (EudraCT number 2017-000580-32). Clinical trial information: 2017-000580-32.

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.

scholarly journals RBTT-01. A PHASE 2 TRIAL WITH ABI-009 (NAB-SIROLIMUS) AS SINGLE-AGENT AND COMBINATIONS IN RECURRENT HIGH-GRADE GLIOMA (rHGG) AND IN NEWLY DIAGNOSED GLIOBLASTOMA (ndGBM)

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi218-vi219 ◽  
Author(s):  
Santosh Kesari ◽  
Tiffany Juarez ◽  
Jose Carrillo ◽  
Judy Truong ◽  
Minhdan Nguyen ◽  
...  
Keyword(s):  
Single Agent ◽  
Mtor Inhibitors ◽  
High Grade Glioma ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Promising Target ◽  
Open Label Phase ◽  
Newly Diagnosed Glioblastoma ◽  
Cns Penetration

Abstract BACKGROUND The mTOR pathway is frequently activated in patients with GBM and is associated with reduced survival, making this pathway a promising target. However, mTOR inhibitors, including everolimus and temsirolimus, have poor brain penetration, limiting their potential use for GBM. ABI-009 is a novel albumin-bound mTOR inhibitor that has a distinct PK profile and biodistribution, including CNS penetration. The goal of this prospective, multi-cohort open-label phase 2 study is to evaluate the efficacy and safety of ABI-009 monotherapy and combination therapy in rHGG and ndGBM. METHODS Eligible patients are ≥18 years old, KPS score ≥70, and have histologically confirmed rHGG or ndGBM. Arm A has 5 cohorts in patients with rHGG, naïve to mTOR inhibitors: 1) ABI-009 single agent IV 100 mg/m2; 2–5) ABI-009 60mg/m2 plus TMZ 50mg/m2 or BEV 5mg/kg or marizomib 0.8mg/m2 or CCNU 90mg/m2. In Arm B for patients with ndGBM, ABI-009 100mg/m2 is given weekly for 4 weeks (Induction) after surgery, followed by ABI-009 at 60mg/m2 plus RT/TMZ. Up to 19 patients per cohort will be enrolled: initial 9 patients with a stopping rule that only if there are ≥2 responses will the study proceed to further enrollment of the next 10 patients (Simon’s 2-stage design). Treatment will continue until disease progression or unacceptable toxicity. The primary endpoint for all cohorts is overall response rate per RANO criteria; secondary endpoints are median PFS and OS, 6-month and 12-month PFS, 12-month OS, and safety. This study is open and actively enrolling patients. The anticipated enrollment period is 24 months. NCT03463265

Analysis of efficacy and safety of POM as a replacement therapy for lenalidomide for relapsed/refractory multiple myeloma pts refractory to a lenalidomide-containing combination regimen.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19528-e19528
Author(s):  
James R. Berenson ◽  
Alexa Cohen ◽  
Tanya M. Spektor ◽  
Ashkan Lashkari ◽  
Roy Mackintosh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Replacement Therapy ◽  
Randomized Study ◽  
Combination Regimen ◽  
Phase 2 ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Phase 2 Trial ◽  
Previous Regimen

e19528 Background: Pomalidomide (POM) is a third –generation immunomodulatory drug shown to be safe and effective for the treatment of relapsed/refractory multiple myeloma (RRMM) for patients (pts) previously treated with bortezomib and lenalidomide (LEN) and in combination with dexamethasone it has been shown to overcome resistance in RRMM. In this phase 2 trial, we are evaluating the efficacy, safety and tolerability of POM as a replacement therapy for LEN for pts who have progressed receiving a LEN combination regimen. Methods: This is a phase 2, multicenter, open-label and non-randomized study. Pts who have failed a combination regimen containing LEN were treated with POM along with all of the other drugs previously used in the regimen. POM administered orally (dose is determined based on the previous regimen) on days 1-21 of a 28-day cycle, whereas other drugs are administered using the same schedule(s), dose(s) and drug combination as the last LEN-containing regimen that the patient received and failed. The planned enrollment on the study will be 45 pts. Results: To date, a total of 29 pts have been enrolled, 25 pts are evaluable and 12 pts have discontinued treatment. Of the evaluable pts, 9 (36%) and 16 (64%) received 3mg and 4mg of POM, respectively. The median age of all pts was 72 years (range, 52-81), and 17 (68%) were males. Pts have received a median of 3 prior treatments (range, 1-7). The median follow-up time for all pts is 3.1 months (range, 0.2-8.1). Amongst evaluable pts, 5 (23.8%) pts achieved at least a minimal response, 10 (47.6%) pts showed stable disease while 6 (28.6%) pts exhibited disease progression. At the time of data cutoff, only 17 pts have completed more than 1 full cycle of treatment; and, thus, the overall response and clinical benefit rates are fairly low (14.3% and 23.8%, respectively) but expected to improve with further follow up. The median PFS for the cohort was 7.6 months. Common ≥ Gr3 adverse events were neutropenia (8%), hypomania (4%) and leukopenia (4%). Conclusions: We show thatPOM appears to be promising replacement therapy for LEN in RRMM pts who have progressed within receiving a LEN combination regimen.

TROPHY-u-01: A phase II open-label study of sacituzumab govitecan (IMMU-132) in patients with advanced urothelial cancer after progression on platinum-based chemotherapy and/or anti-PD-1/PD-L1 checkpoint inhibitor therapy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS495-TPS495 ◽  
Author(s):  
Scott T. Tagawa ◽  
Daniel Peter Petrylak ◽  
Petros Grivas ◽  
Neeraj Agarwal ◽  
Cora N. Sternberg ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Checkpoint Inhibitor ◽  
Objective Response ◽  
Locally Advanced ◽  
Low Grade ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy

TPS495 Background: Patients (pts) with unresectable locally advanced or metastatic urothelial cancer (mUC) who progress after platinum-based chemotherapy and checkpoint inhibitor (CPI) therapy and pts ineligible for platinum-based chemotherapy who progress after CPI have limited treatment options and poor outcomes. Trop-2 is an epithelial cell surface antigen that is overexpressed in UC. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate that targets Trop-2 and delivers the active metabolite (SN38) of the topoisomerase I inhibitor irinotecan to tumor cells. In a phase 1/2 single-arm trial, pts with advanced cancers received SG 10 mg/kg intravenously on days 1 and 8 of a 21-day cycle; preliminary results in the cohort of 41 evaluable pts with mUC and a median of 3 (range 1–6) prior therapies showed an objective response rate (ORR) of 34%. Adverse events (AE) were mostly low grade, including diarrhea (63%), nausea (56%), and fatigue (49%). Neutropenia (all grades) occurred in 49% of pts (≥ grade 3/4, 39%; treatment-related serious AE of febrile neutropenia, 5%). Median overall survival was 16.1 months, and median progression-free survival was 7.1 months. These results warrant further investigation in a dedicated phase 2 trial. Methods: TROPHY-U-01 is a single-arm, open-label, global phase 2 trial evaluating the antitumor activity and safety of SG in 140 pts with advanced UC. The primary cohort (progression after platinum chemotherapy and CPI) will enroll 100 pts in a Simon 2-stage design with > 90% power accounting for dropouts to exclude the null hypothesis or ORR < 12%, while a second cohort (40 pts) will comprise cisplatin-ineligible pts who received prior CPI. The primary objective is ORR per RECIST 1.1, assessed by central review. Secondary objectives include response duration, PFS, OS, and safety/tolerability. Enrollment began in August 2018. Clinical trial information: NCT03547973.

Phase 2 trial of tisotumab vedotin in platinum-resistant ovarian cancer (innovaTV 208).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5602-TPS5602 ◽  
Author(s):  
Haider Mahdi ◽  
Steven Robert Schuster ◽  
David M. O'Malley ◽  
Donna M. McNamara ◽  
Reshma A. Rangwala ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Primary Endpoint ◽  
Human Monoclonal Antibody ◽  
Single Agent ◽  
Ca 125 ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy ◽  
Increased Risk

TPS5602 Background: Ovarian cancer (OC) is the most lethal gynecologic cancer, accounting for ≈185,000 deaths worldwide in 2018. Most patients (pts) initially respond to platinum-based chemotherapy (chemo), but more than 50% of pts recur. Pts who recur in ≤6 months have platinum-resistant OC (PROC), which is associated with poor prognosis. Standard therapy for PROC includes chemo ± bevacizumab (bev). However, many pts receive single-agent chemo, which demonstrates limited response and survival (≈12% ORR, 3-4 mo PFS, ≈12 mo OS). Therefore, there is an urgent need for novel therapeutic strategies. Tissue factor (TF) is a novel oncogenic target expressed in OC. Tisotumab vedotin (TV) is a first-in-class antibody drug conjugate comprising a TF-targeted fully human monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. TV has shown encouraging antitumor activity and a manageable safety profile in PROC in the multicohort phase 1/2 innovaTV 201 study. innovaTV 208 is a multicenter, open-label, phase 2 trial with a safety run-in phase for a dose-dense regimen (DDR) evaluating the efficacy and safety of TV in pts with PROC. Methods: innovaTV 208 will enroll ≈142 adult pts with platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer; measurable disease by RECIST v1.1; and ECOG score 0-1. Eligible pts must have received bev-containing treatment for OC. Pts with platinum-refractory disease, increased risk of bleeding, active ocular surface disease, or grade > 1 peripheral neuropathy will be excluded. A safety run-in phase for the DDR will be performed in up to 12 pts who received ≤5 prior treatment regimens for PROC. In the DDR, TV will be given at previously decided lower doses IV 3Q4W for the same dose intensity as the standard 1Q3W dose; the primary endpoint is incidence of DLTs. In phase 2, pts who received ≤1 prior cytotoxic chemo regimen for PROC will be randomized to receive TV administered as IV 1Q3W or as IV 3Q4W, if shown to be tolerable. The primary endpoint for phase 2 is confirmed ORR by RECIST v1.1. Secondary endpoints include DOR, time to response, DCR, CA-125 response rate by GCIG criteria, PFS, OS, pharmacokinetics, and safety. Clinical trial information: NCT03657043.

Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 999-1004 ◽  
Author(s):  
Bertrand Godeau ◽  
Raphael Porcher ◽  
Olivier Fain ◽  
François Lefrère ◽  
Pierre Fenaux ◽  
...  
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Phase 2 ◽  
Open Label ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Chronic Immune Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Phase 2 Trial ◽  
Phase 2 Study

Abstract Whether rituximab could effectively and safely avoid splenectomy for adults with chronic immune thrombocytopenic purpura (ITP) remains unresolved. A multicenter, prospective, open-label, single-arm, phase 2 trial was conducted to assess rituximab safety and efficacy in adult splenectomy candidates with chronic ITP. Sixty patients with chronic (≥ 6 months) ITP and platelet counts less than 30 × 109/L received a weekly intravenous infusion of rituximab (375 mg/m2) for 4 weeks. All other ITP treatments were stopped. A good response was defined as a platelet count 50 × 109/L or more, with at least a doubling of the initial value at 1 and 2 years after the first rituximab infusion. Patients who required another treatment during follow up were considered nonresponders. Sixteen patients experienced transient side effects that necessitated treatment discontinuation for only 1. Good 1-year responses were obtained in 40% of the patients (24/60 [95% confidence interval: 28%-52%]). At 2 years, 33.3% (20/60 patients) had good responses and 6.7% (4/60) had sustained platelet counts of 30 × 109/L or more without treatment. Thirty-six (60%) patients failed to respond; 25 underwent splenectomy. Based on these results, rituximab was an apparently safe and effective splenectomy-avoiding option in some adults with chronic ITP. This trial is registered at http://clinicaltrials.gov as NCT00225875.

Results of a randomized phase II trial of amrubicin (AMR) versus topotecan (Topo) in patients with extensive-disease small cell lung cancer (ED-SCLC) sensitive to first-line platinum-based chemotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8028-8028
Author(s):  
R. Jotte ◽  
P. Conkling ◽  
C. Reynolds ◽  
L. Klein ◽  
J. F. Fitzgibbons ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Open Label ◽  
Ecog Performance Status ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps

8028 Background: SCLC presents as ED-SCLC in 60%-70% of patients (pts). AMR, a synthetic anthracycline, is approved for these pts in Japan. We compare the efficacy and safety of single-agent AMR vs topotecan in non-Japanese pts with 2nd-line ED-SCLC sensitive to 1st-line platinum-based chemotherapy. Methods: This phase II, open-label, multicenter study enrolled pts with ED-SCLC sensitive to 1st-line platinum-based chemotherapy (recurrence or progression ≥90 days from 1st-line treatment). Pts aged ≥18 years with ECOG performance status (PS) ≤2 and only 1 prior therapy were eligible. Pts were randomized (2:1) to receive IV AMR 40 mg/m2/d (d, 1–3) or IV topotecan 1.5 mg/m2/d (d 1–5) and treated every 21 days until progression, unacceptable toxicity, or withdrawal. The primary endpoint, overall response rate (ORR, complete + partial response), used RECIST criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: In all, 76 pts were randomized to AMR (n=50) or topotecan (n=26) with AMR given for a median of 6 cycles (range 1–16) and topotecan 3 cycles (1–16). AMR significantly improved ORR rates vs topotecan (p<0.012; Table ). Median PFS/OS was 4.3 months (95% CI 2.0, 6.1)/9.3 months (95% CI 5.7, 12.0) with AMR vs 3.5 months (95% CI 2.1, 6.3)/8.9 months (95% CI 4.8, 13.8) with topotecan. There was a higher proportion of ECOG PS 2 pts in the AMR group (n=6) vs the topotecan group (n=2). A trend towards improved OS was observed in the ECOG 0–1 subgroup of 68 pts: median OS was 10.5 months with AMR vs 9.7 months with topotecan. The most common grade ≥3 adverse events with AMR vs topotecan were neutropenia (53% vs 74%), thrombocytopenia (31% vs 52%) and leukopenia (27% vs 30%). Three AMR pts (6%) and 1 topotecan pt (4%) died of neutropenic infection. Conclusions: AMR significantly improves ORR and has acceptable tolerability as 2nd-line treatment in pts with sensitive ED-SCLC. [Table: see text] [Table: see text]

Updated 5-y landmark analyses of phase 2 (BREAK-2) and phase 3 (BREAK-3) studies evaluating dabrafenib monotherapy in patients with BRAF V600–mutant melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9526-9526 ◽  
Author(s):  
Paul B. Chapman ◽  
Paolo Antonio Ascierto ◽  
Dirk Schadendorf ◽  
Jean Jacques Grob ◽  
Antoni Ribas ◽  
...  
Keyword(s):  
Single Agent ◽  
Braf Inhibitor ◽  
Stage Iv ◽  
Braf V600e ◽  
Phase 2 ◽  
Open Label ◽  
Phase 3 ◽  
Study Results ◽  
Landmark Analyses

9526 Background: Prior analyses of phase 2 (BREAK-2; NCT01153763) and phase 3 (BREAK-3; NCT01227889) trials showed that durable clinical benefit and tolerability lasting ≥ 3 y are achievable with the BRAF inhibitor dabrafenib in some patients (pts) with BRAFV600–mutant metastatic melanoma. Here, we report 5-y landmark analyses for BREAK-2 and BREAK-3. Methods: BREAK-2, a single-arm, phase 2 study, evaluated dabrafenib 150 mg twice daily in pts with stage IV BRAF V600E/K–mutant MM. BREAK-3, an open-label, randomized (3:1), phase 3 study, assessed dabrafenib 150 mg twice daily vs dacarbazine 1000 mg/m2 every 3 weeks in pts with previously untreated BRAFV600E–mutant unresectable stage III or stage IV MM. Updated analyses were performed to describe ≥ 5-y outcomes in each study. Results: BREAK-2 enrolled 92 pts (V600E, n = 76; V600K, n = 16), of whom most (90%) had prior systemic anticancer therapy. At data cutoff (17 Jun 2016), all pts had discontinued, mostly due to progression (84%). In V600E pts, 5-y progression-free survival (PFS) was 11%, and 5-y overall survival (OS) was 20%. Postprogression immunotherapy was received by 22% of enrolled pts. In BREAK-3 (data cutoff, 16 Sep 2016), median follow-up was 18.6 mo for the dabrafenib arm (n = 187) and 12.8 mo for the dacarbazine arm (n = 63). Follow-up for the 37 dacarbazine-arm pts (59%) who crossed over to receive dabrafenib was based on the initial assignment of dacarbazine. The 5-y PFS was 12% vs 3% and 5-y OS was 24% vs 22% for the dabrafenib and dacarbazine arms, respectively. A subset of pts in each respective arm received postprogression anti–CTLA-4 (24% vs 24%) and/or anti–PD-1 (8% vs 2%) therapy, whereas 31% vs 17% did not receive any further therapy following study treatment. No new safety signals were observed in either study with long-term follow-up. Additional characterization of pts using cfDNA analysis will be presented. Conclusions: These data provide the longest reported PFS and OS follow-up for BRAF inhibitor monotherapy in BRAF V600–mutant MM. Both BREAK-2 and BREAK-3 showed that 11%-12% of pts initially treated with single-agent dabrafenib remained progression free at 5 y. Clinical trial information: NCT01153763; NCT01227889.

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