scholarly journals CTIM-09. DOUBLE-BLINDED, PLACEBO CONTROLLED PHASE 2 STUDY OF ERC1671 IN RECURRENT GLIOBLASTOMA: VACCINE OVERALL SURVIVAL IN BEVACIZUMAB NAIVE AND BEVACIZUMAB RESISTANT PATIENTS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii34-ii34
Author(s):  
Daniela Bota ◽  
Thomas Taylor ◽  
Xiao-Tang Kong ◽  
Beverly Fu ◽  
Frank Hsu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Overall Survival ◽  
Therapeutic Vaccine ◽  
Clinical Results ◽  
Recurrent Glioblastoma ◽  
Phase 2 ◽  
Gm Csf ◽  
Phase 2 Study ◽  
Pre Treatment ◽  
Double Blinded

Abstract ERC1671 is an allogeneic/autologous therapeutic vaccine – composed of whole, inactivated tumor cells mixed with tumor- cell lysates. The hypothesized action of ERC1671 is to potentiate the patients’ immune system against the tumor. Goals of this ongoing, phase 2 study are to determine the safety and effectiveness (overall survival) of ERC1671 in combination with GM-CSF and cyclophosphamide as an add-on treatment to bevacizumab at the time of GBM recurrence. To date 22 recurrent bevacizumab-naïve rGBM patients have been randomized to ERC1671/GM-CSF/Cyclophosphamide + Bevacizumab or Placebo + Bevacizumab. Median age is 56.5 (33–74), 7 patients (32%) are female, and average KPS is 82.3 (70–100). Of the 22, two discontinued before completing one cycle of therapy and two remain on blinded treatment. Currently 18 patients are unblinded due to further progression: 8 were on vaccine and 10 on placebo. Five of those on placebo crossed to vaccine at progression. All but one of the 18 are now deceased. Median overall survival of unblinded patients randomized to ERC1671 + Bevacizumab (n = 8) is 264.5 days from the start of study treatment, compared to 182 days for those randomized to placebo + Bevacizumab who did not cross over (n = 5). Median overall survival of unblinded patients on vaccine at randomization or crossover is 328 days after first study treatment (n = 13). While sparse, the data to date suggest pre-treatment and maximal CD4+T lymphocyte count in the peripheral blood correlate with OS more strongly in the ERC1671 group than in the placebo group. First clinical results for toxicity show no difference in the distribution of AEs between the Vaccine and Placebo groups, with no Gr4/Gr5 AEs in either group. This phase 2 randomized, double-blinded study is ongoing, with the addition of one more site.

scholarly journals ATIM-42. DOUBLE-BLINDED, PLACEBO CONTROLLED PHASE 2 STUDY OF ERC1671 IN RECURRENT GLIOBLASTOMA: OS CORRELATIONS WITH INITIAL AND MAXIMUM CD4+T LYMPHOCYTE COUNT IN THE PERIPHERAL BLOOD

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi10-vi11
Author(s):  
Daniela Bota ◽  
Thomas Taylor ◽  
Kong Xiao-Tang ◽  
Beverly Fu ◽  
Mohamad Alsharif ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Peripheral Blood ◽  
Lymphocyte Count ◽  
Therapeutic Vaccine ◽  
Clinical Results ◽  
Recurrent Glioblastoma ◽  
Phase 2 ◽  
Gm Csf ◽  
Phase 2 Study ◽  
Double Blinded

Abstract Standard therapy for recurrent GBM is bevacizumab, a monoclonal VEGF inhibitor that targets tumor vascularization. The response to bevacizumab is transient and short-lived (4–6 months) after which patients typically develop progressive physical and mental debilitation culminating in death. ERC1671 is an allogeneic/autologous therapeutic vaccine – composed of whole, inactivated tumor cells mixed with tumor- cell lysates. The hypothesized action of ERC1671 is to potentiate the patients’ immune system against the tumor. Goals of this ongoing, phase 2 study are to to determine the safety and effectiveness (over-all survival) of ERC1671 in combination with GM-CSF and cyclophosphamide as an add-on treatment to bevacizumab at the time of GBM recurrence. To date 16 recurrent bevacizumab-naïve GBM patients have been randomized to ERC1671/GM-CSF/Cyclophosphamide + Bevacizumab or Placebo + Bevacizumab. Median age is 56.5 (39–74), 5 patients (31%) are female, and average KPS is 83 (70–100). Thirteen patients are deceased and were unblinded at the time of further progression: 5 received vaccine, 7 received placebo, and 1 is non-evaluable due to discontinuation before completing 1 cycle. Median overall survival of the deceased patients treated with ERC1671 + Bevacizumab was 328 days (10.9 months), compared to 245 days (8.2 months) for patients treated with Placebo + Bevacizumab. While sparse, the data to date suggest pre-treatment and maximal CD4+T lymphocyte count in the peripheral blood correlate with OS more strongly in the ERC1671 group than in the placebo group. First clinical results for toxicity show no difference in the distribution of AEs between the Vaccine and Placebo groups, with no Gr4/Gr5 AEs in either group. The phase 2 randomized, double-blinded study is ongoing with the addition of 2 subsites.

scholarly journals OR25-07 A Multi-Center, Open-Label, Pivotal Phase 2 Study of Azedra® (HSA I-131-MIBG) in Patients with Unresectable, Locally Advanced or Metastatic Pheochromocytoma or Paraganglioma: Updated Long-Term Survival and Safety

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Camilo Jimenez ◽  
Bennett B Chin ◽  
Richard B Noto ◽  
Joseph Stephen Dillon ◽  
Lilja B Solnes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Time ◽  
Median Survival ◽  
Median Survival Time ◽  
Locally Advanced ◽  
Phase 2 ◽  
Pivotal Phase ◽  
Term Survival ◽  
Phase 2 Study ◽  
Therapeutic Doses

Abstract Background: Pheochromocytoma/Paraganglioma (PPGL) are rare neuroendocrine tumors with a 5-yr survival rate as low as 12%. There is a high unmet medical need for effective treatment options for patients with advanced disease. AZEDRA®, a high-specific-activity iodine-131 meta-iodobenzylguanidine (HSA I-131-MIBG), is the first and only FDA-approved therapeutic radiopharmaceutical agent indicated for the treatment of adult and pediatric patients with iobenguane scan positive, unresectable, locally advanced or metastatic PPGL who require systemic anticancer therapy. Methods: Patients with advanced PPGL who were heavily pre-treated and were ineligible for curative surgery or chemotherapy received a dosimetric dose followed by up to two therapeutic doses (each at 296 MBq/kg to a max of 18.5 GBq). The primary endpoint, defined as the proportion of patients with at least 50% reduction of all antihypertensive medication(s) lasting ≥6 months, was met and previously reported. Updated secondary endpoints including overall survival (OS) and safety are reported. Results: A dosimetric dose of HSA I-131-MIBG was administered to 74 patients. Of those, 68 patients received one therapeutic dose and 50 received two doses of HSA I-131-MIBG. Clinical benefit rates (objective tumor responses defined by RECIST 1.0 and stable disease) were observed in 71.4% and 98.0% of patients receiving one and two therapeutic doses, respectively. As of October 10, 2019, median survival time for all patients was 43.2 months (95% CI 31.4, >60). Median survival time was 19.3 months (95% CI 4.5, 32.4) and 49.1 months (95% CI 36.9, >60) in patients receiving one and two doses, respectively. The overall survival was 73.8% at 2 yrs, 47.5% at 4 yrs and 41.5% at 5 yrs. The most common (≥50%) adverse events were nausea, fatigue, and myelosuppression. Myelosuppressive events resolved within 4-8 wks without requiring stem cell transplantation. Late radiation toxicity included 7 patients with secondary malignancies (myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), colon cancer, and lung carcinoma) of which MDS, ALL and AML were considered related to I-131 radiotherapy. Conclusions: Results from this pivotal phase 2 study suggest that HSA I-131-MIBG is an efficacious and safe treatment for advanced PPGL.

scholarly journals OS07.5 Interim analysis data from Phase 2 study on efficacy, safety & intratumoral pharmacokinetics of oral Selinexor (KPT-330) in patients with recurrent glioblastoma (GBM)

2017 ◽  
Vol 19 (suppl_3) ◽  
pp. iii14-iii14
Author(s):  
A. B. Lassman ◽  
M. J. V. D. Bent ◽  
P. Y. Wen ◽  
A. Walenkamp ◽  
S. Plotkin ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Analysis Data ◽  
Recurrent Glioblastoma ◽  
Phase 2 ◽  
Phase 2 Study

scholarly journals Overall Survival and Biomarker Results from a Phase 2 Study of Mek1/2 Inhibitor Binimetinib (Mek162) in Patients with Advanced Nras-Mutant Melanoma

2014 ◽  
Vol 25 ◽  
pp. v1 ◽  
Author(s):  
C. van Herpen ◽  
S.S. Agarwala ◽  
A. Hauschild ◽  
R. Dummer ◽  
C. Berking ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase 2 ◽  
Phase 2 Study

scholarly journals Performance of adjuvant treatment correlates with survival in reoperated glioblastomas

2016 ◽  
Vol 74 (11) ◽  
pp. 887-894 ◽  
Author(s):  
Willey Gonçalves Zanovello ◽  
Suzana M. F. Malheiros ◽  
João Norberto Stavale ◽  
Orestes P. Lanzoni ◽  
Miguel M. Canteras ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Treatment ◽  
Healthcare Service ◽  
Median Overall Survival ◽  
Therapeutic Option ◽  
Sao Paulo ◽  
Recurrent Glioblastoma ◽  
Public Healthcare ◽  
São Paulo ◽  
Single Factor

ABSTRACT Objective To analyze cases of recurrent glioblastoma subjected to reoperation at a Brazilian public healthcare service. Methods A total of 39 patients subjected to reoperation for recurrent glioblastoma at the Department of Neurosurgery, São Paulo Hospital, Federal University of São Paulo, from January 2000 to December 2013 were retrospectively analyzed. Results The median overall survival was 20 months (95% confidence interval – CI = 14.9–25.2), and the median survival after reoperation was 9.1 months (95%CI: 2.8–15.4). The performance of adjuvant treatment after the first operation was the single factor associated with overall survival on multivariate analysis (relative risk – RR = 0.3; 95%CI = 0.2–0.7); p = 0.005). Conclusion The length of survival of patients subjected to reoperation for glioblastoma at a Brazilian public healthcare service was similar to the length reported in the literature. Reoperation should be considered as a therapeutic option for selected patients.

scholarly journals ACTR-27. PHASE 2 STUDY OF DIANHYDROGALACTITOL (VAL-083) IN PATIENTS WITH MGMT-UNMETHYLATED, BEVACIZUMAB-NAÏVE RECURRENT GLIOBLASTOMA

2018 ◽  
Vol 20 (suppl_6) ◽  
pp. vi17-vi17
Author(s):  
Barbara O’Brien ◽  
John de Groot ◽  
Carlos Kamiya-Matsuoka ◽  
Shiao-Pei Weathers ◽  
Jeffrey Bacha ◽  
...  
Keyword(s):  
Recurrent Glioblastoma ◽  
Phase 2 ◽  
Phase 2 Study

Nilotinib in Chronic Myeloid Leukemia Patients in Accelerated Phase (CML-AP) with Imatinib Resistance or Intolerance: 2-Year Follow-up Results of a Phase 2 Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3229-3229 ◽  
Author(s):  
Philipp D. le Coutre ◽  
Francis Giles ◽  
Andreas Hochhaus ◽  
Jane F. Apperley ◽  
Gert Ossenkoppele ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Cytogenetic Response ◽  
Phase 2 ◽  
Time To Progression ◽  
Phase 2 Study ◽  
Grade 3

Abstract Background: Nilotinib is a rationally designed, potent and highly selective BCR-ABL kinase inhibitor, and binds to ABL with higher affinity and improved topological fit compared to imatinib. Nilotinib is approved for the treatment of patients (pts) with Philadelphia chromosome-positive chronic myeloid leukemia pts in chronic (CML-CP) or accelerated phase (CML-AP) resistant or intolerant to prior therapy including imatinib. Methods: This open-label, single-arm, phase 2 study was designed to evaluate the efficacy and safety of nilotinib in CML-AP pts who are resistant or intolerant to imatinib. Nilotinib was dosed at 400 mg twice daily with the option to dose escalate to 600 mg twice daily for lack of response. The primary endpoint was confirmed hematologic response (HR). Complete hematologic response (CHR) was defined as meeting all of the following criteria: myeloblast count <5% in bone marrow, no myeloblast in peripheral blood, neutrophil count ≥1.5 × 109/L, platelet count ≥100×109/L, basophils <5%, no evidence of extramedullary involvement. Secondary endpoints included major cytogenetic response (MCyR), time to progression, overall survival, and safety. Results: A total of 138 CML-AP pts (80% imatinib resistant; 20% imatinib intolerant) who received at least 1 dose of nilotinib were included in the analysis. Median age was 57 years (range, 22–82 years); median duration of prior imatinib treatment was 28 months. Seventy-nine percent of pts received prior imatinib doses ≥600 mg/day; overall, 45% received ≥800 mg/day imatinib. Median dose intensity of nilotinib was near planned dose at 775 mg/day with a median duration of exposure of 253 days (8.4 months). Of 134 pts with at least 6 months of follow-up included in the efficacy analysis, 56% had confirmed HR and 30% had CHR. Responses were rapid, with a median time to first HR of 1 month. Hematologic responses were durable at 1 year, with 78% of pts who achieved HR maintaining their response. MCyR and complete cytogenetic response (CCyR) occurred in 32% and 19% of pts, respectively. Cytogenetic responses were also durable, with 69% of pts maintaining MCyR at 18 months. Median time to progression was 16 months in this population of pts with advanced disease. Progression was defined as any of the following: investigator’s evaluation as progression, development of CML-AP or blast crisis, loss of CHR, loss of MCyR. Estimated overall survival at 1 year is 82%. Longer follow-up has not significantly changed the safety profile of nilotinib. The most frequently reported grade 3/4 laboratory abnormalities were thrombocytopenia (40%), neutropenia (40%), anemia (25%), elevated serum lipase (17%), and hypophosphatemia (12%). Grade 3/4 non-hematologic adverse events were uncommon (<1%) and included rash, nausea, fatigue, and diarrhea. Brief dose interruptions were sufficient to manage most adverse events. Conclusions: The long-term follow-up results of this phase 2 study confirm that nilotinib induces rapid and durable responses in pts with CML-AP who failed prior imatinib therapy due to intolerance or resistance, with a favorable toxicity profile.

Final Results of a Phase 2 Open-Label, Monotherapy Efficacy and Safety Study of Quizartinib (AC220) in Patients ≥ 60 Years of Age with FLT3 ITD Positive or Negative Relapsed/Refractory Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 48-48 ◽  
Author(s):  
Jorge E. Cortes ◽  
Alexander E Perl ◽  
Hervé Dombret ◽  
Sabine Kayser ◽  
Björn Steffen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Qt Interval ◽  
Median Overall Survival ◽  
Phase 1 ◽  
Phase 2 ◽  
Interval Prolongation ◽  
Hematopoietic Stem ◽  
Qt Interval Prolongation ◽  
Duration Of Response

Abstract Abstract 48 FMS-like tyrosine kinase 3 internal tandem duplications (FLT3-ITD) in acute myeloid leukemia (AML) are associated with early relapse after standard chemotherapy and poor survival. Quizartinib (AC220) is an oral FLT3 receptor tyrosine kinase inhibitor that is active against both ITD mutant and wild type FLT3, and has shown promising activity in a Phase 1 study of patients (pts) with AML. This Phase 2 study was conducted to assess the efficacy and safety of quizartinib monotherapy in FLT3-ITD positive (+) and FLT3-ITD negative (-) pts with a total of 333 pts included in two cohorts. Cohort 1 included pts aged ≥ 60 yrs with AML relapsed in <1 yr or refractory to 1st-line chemotherapy. A total of 134 pts were included in this cohort and constitute the basis for this analysis. Data through 31 January 2012 from 134 pts in this cohort were analyzed. These pts included 92 (69%) who were FLT3 ITD(+), 41 (31%) who were FLT3-ITD(-), and 1 (1%) whose FLT3-ITD status was unknown. Half the 92 FLT3-ITD(+) pts and 46% of the 41 FLT3-ITD(-) pts were male. The FLT3-ITD(+) pts had a median age of 70 yrs (range 54 to 85 yrs), and the FLT3-ITD(-) pts had a median age of 69 yrs (range 60 to 78 yrs). Pts received quizartinib at a starting dose of 90 mg/day (females) or 135 mg/day (males and 1 female), and were treated continuously during 28-day cycles. The composite complete remission (CRc) rate included complete remission (CR), complete remission with incomplete platelet recovery (CRp), and complete remission with incomplete hematologic recovery (CRi). For FLT3-ITD(+) pts the CRc rate was 54% (0 CR, 3% CRp, and 51% CRi), with a median duration of response of 12.7 weeks and median overall survival of 25.3 weeks. Of those refractory to their last AML therapy, 39% achieved a CRc with quizartinib. For FLT3-ITD(-) pts the CRc rate was 32% (2% CR, 2% CRp, and 27% CRi), with a median duration of response of 22.1 weeks and median overall survival of 19.0 weeks. Of those refractory to their last AML therapy, 44% achieved a CRc with quizartinib. Efficacy Results in Relapsed/Refractory AML Pts ≥ 60 Yrs FLT3-ITD(+) (N = 92) FLT3-ITD(−) (N = 41) Cumulative CRc, n (%) 50 (54) 13 (32) CRc + PR, n (%) 66 (72) 17 (41) Prior nonresponders achieving CRc to quizartinib, n (%) 12/31 (39) 8/18 (44) Subjects discontinuing quizartinib because of HSCT, n (%) 9 (10) 1 (2) Median CRc duration, weeks 12.7 22.1 Median overall survival, weeks 25.3 19.0 CRc = composite complete remission; HSCT = hematopoietic stem cell transplantation; PR = partial remission. The most common (≥20%) treatment-related adverse events (AEs) were nausea (40%), fatigue (31%), anemia (28%), QT interval prolongation (25%), diarrhea (23%), vomiting (23%), dysgeusia (22%), and febrile neutropenia (20%). The most common (≥10%) Grade 3 or 4 treatment-related AEs were anemia (25%), febrile neutropenia (20%), QT interval prolongation (13%), and thrombocytopenia (12%). An AE of QT interval prolongation occurred in 33/134 pts (25%) and was Grade 3 or 4 in 17 pts (13%). There was 1 occurrence of Grade 4 QT prolongation with torsade de pointes. QT interval prolongations were transient, and none were fatal. A total of 17 pts (13%) experienced a treatment-related AE resulting in discontinuation of quizartinib. The final data from this Phase 2 study for elderly relapsed/refractory AML pts with few other available therapy options confirm the high degree of activity of quizartinib monotherapy in FLT3-ITD(+) pts and also suggest activity in FLT3-ITD(-) pts. These data represent the highest level of single agent activity observed to date for FLT3-targeted therapy in elderly pts with relapsed/refractory FLT3-ITD(+) AML. Of clinical significance in this elderly population, a number of pts refractory to prior therapy responded to quizartinib, with some pts (8%) able to bridge to potentially curative hematopoietic stem cell transplantation. Safety findings were manageable, and were primarily myelosuppression and QT prolongation that was mitigated with dose modifications. Results from the total study population will be presented. Further Phase 1 and 2 studies investigating lower doses of quizartinib as monotherapy and in combination with other agents in FLT3-ITD(+) and FLT3-ITD(-) AML are being planned/ongoing. Disclosures: Cortes: Novartis: Consultancy. Perl:Ambit Biosciences: Consultancy. Dombret:Celgene: Consultancy. Steffen:Novartis: Travel/accommodations/meeting expenses Other. Rousselot:Ambit Biosciences: Consultancy. Martinelli:BMS, Novartis; Pfizer, Roche: Consultancy. Estey:Ambit Biosciences: Consultancy. Burnett:Ambit Biosciences: Consultancy. Gammon:Ambit Biosciences: Employment. Trone:Ambit Biosciences: Employment. Leo:Ambit Biosciences: Employment. Levis:Ambit Biosciences: Consultancy.

Sign in / Sign up

Export Citation Format

Share Document