Efficacy and safety of PF-00299804 (PF299) in patients (pt) with advanced NSCLC after failure of at least one prior chemotherapy regimen and prior treatment with erlotinib (E): A two-arm, phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8063-8063 ◽  
Author(s):  
P. A. Janne ◽  
K. Reckamp ◽  
M. Koczywas ◽  
J. A. Engelman ◽  
D. R. Camidge ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Median Duration ◽  
Tyrosine Kinases ◽  
Progressive Disease ◽  
Chemotherapy Regimen ◽  
Objective Response ◽  
Progression Free Survival ◽  
Prior Chemotherapy ◽  
Prior Chemotherapy Regimen

8063 Background: Options are limited for pts with NSCLC following chemotherapy and E. PF299 is an oral irreversible small molecule inhibitor of the HER-1,-2, and -4 tyrosine kinases. Based on non-clinical and phase I NSCLC data, this ongoing phase II U.S. trial evaluates PF299 in pts with NSCLC (KRAS wild-type) who have progressive disease after at least 1 prior chemotherapy regimen and after E. Methods: Pts were enrolled by histology: adenocarcinoma (Arm A) and non-adenocarcinoma (Arm B), and received PF299 45 mg QD. Endpoints include objective response rate, duration of response, progression-free survival, survival, safety/tolerability, and pharmacokinetics. Pharmacodynamic endpoints include assessment of serum levels of HER2 and EGFR extracellular domains. Tissue and blood KRAS assays, and EGFR studies on available tissue, are also being performed. Forty-four and 22 response-evaluable pts were planned to be enrolled into Arms A and B respectively. Results: Thirty-four pts with progressive NSCLC (25 female, 14 smoker) have enrolled to date (Arm A: 30; Arm B: 4): median duration of prior E: 11.5 months; median time since E: 2.5 months. Among 20 response-evaluable pts, stable disease (SD) was observed in 9/18 pts in Arm A, and 1/2 pts in Arm B: median duration of SD: 11.5 weeks [range 6+, 32+ weeks]. Observation of disease control included pts who had recently (≤8 weeks) discontinued E; and also pts whose tumor had known EGFR T790M mutations. At time of data cutoff, confirmation per RECIST of 2 partial responses is pending. The most common treatment-related AEs were skin and gastrointestinal disorders, with grade 3 AEs in 19% and 13% of pts, respectively. Two pts experienced grade 4 pulmonary embolus/dyspnea deemed possibly treatment-related, both in the setting of progressive disease. Conclusions: PF299 shows encouraging activity in NSCLC pts after failure of prior chemotherapy and E. The AE profile was predictable and consistent with the prior phase I trial. At submission, enrollment in the adenocarcinoma arm is complete and enrollment in the non-adenocarcinoma arm continues; updated efficacy data and tumor characterization will be presented. [Table: see text]

A phase II study of GW786034 (pazopanib) in patients with recurrent or metastatic invasive breast carcinoma: Results after completion of stage I: A trial of the Princess Margaret Hospital Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1133-1133 ◽  
Author(s):  
S. K. Taylor ◽  
S. Chia ◽  
S. Dent ◽  
M. Clemons ◽  
P. Grenci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Progressive Disease ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Lesion Size ◽  
Grade 3

1133 Background: Pazopanib, an oral small molecule inhibitor of VEGFR, PDGFR, and KIT, has demonstrated activity in phase I, with a recommended phase II dose of 800 mg/d (Hurwitz H et al, J Clin Oncol. 2005;23[16 suppl]:3012.1). We evaluated the activity of single agent pazopanib in recurrent or metastatic breast cancer (MBC). Methods: In this 2-stage design, patients with recurrent or MBC received pazopanib 800 mg/d. The primary endpoint was objective response rate (ORR) of 20%. Response in 3 out of 18 patients was required to go to stage 2. Treatment was continued until progression. Results: 21 patients entered stage 1; 67% were ER positive and all were HER-2-negative. Prior lines of chemotherapy were 1 in 76% and 2 in 14%. Of the 19 evaluable patients, 2 patients remain on treatment. 14 (74%) stopped due to progressive disease, 2 (10%) due to adverse events, and 1 (5%) due to patient request. Best response was partial response (PR) in 1 (5%), stable disease (SD) in 11 (58%), and progressive disease in 7 (37%). Clinical benefit rate (CR, PR, or SD for ≥ 6 months) was 26%. Median time to progression (TTP) was 3.7 months (95% C.I. 1.7 months - not reached). 9 out of 18 patients (50%) with measurable target lesions had some decrease in target lesion size. Estimated progression-free survival at 3 months was 55%, and 28% at 6 months. Adverse events were grade 3/4 elevations in AST (14%) and ALT (10%), and grade 3 hypertension and neutropenia (14% each). Other common events were grade 1/2 lymphopenia, neutropenia, diarrhea, fatigue, skin hypopigmentation, hypertension, nausea, vomiting, anorexia, and headache. Conclusions: Pazopanib is well tolerated and demonstrates activity in pretreated breast cancer. While the target ORR of 20% has not been met, rates of SD and TTP are comparable to other active agents in this setting, and therefore pazopanib may be an interesting agent for future studies in breast cancer. [Table: see text]

A single-arm, open-label, multicenter phase I/II study of the combination of panobinostat (pan) and carfilzomib (cfz) in patients (pts) with relapsed/refractory multiple myeloma (RR MM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS8115-TPS8115
Author(s):  
Jesus G. Berdeja ◽  
Joseph Mace ◽  
Ruth E. Lamar ◽  
Victor Gian ◽  
Patrick Brian Murphy ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Histone Deacetylase Inhibitors ◽  
Standard Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Current Status ◽  
Open Label ◽  
Starting Dose

TPS8115 Background: Despite novel therapies, MM remains an incurable disease. Changes in histone modification are commonly found in human cancers including MM. Preclinical studies demonstrate synergistic anti-MM activity with histone deacetylase inhibitors (HDACi) and proteasome inhibitors (PI) through the dual inhibition of the proteasome and aggresome pathways. Pan is an oral pan-HDACi which has shown synergy with bortezomib in clinical studies. Cfz is a 2nd generation PI which has shown marked anti-MM activity with an improved safety profile. In this trial we evaluate the safety and efficacy of the combination of pan and cfz in pts with RR MM. Methods: This multi-center US study plans to enroll up to 52 adults with RR MM. The phase I study will determine the MTD of the combination of cfz and pan and follow a standard dose escalation design. Pan will be administered orally three times weekly during weeks 1 and 3 of each 28-day cycle (Days 1, 3, 5, 15, 17, 19) at a starting dose of 20 mg. Cfz will be administered intravenously on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Cfz starting dose will be 20mg on days 1,2 of cycle 1 with escalation to the corresponding dose level beginning at 27 mg , if well tolerated. Dose modifications will not be permitted during cycle 1 unless a pt experiences a DLT. A maximum of four dose levels will be evaluated. Approximately 24 pts will be enrolled during the phase I portion to establish the MTD. In the phase II portion of this study, pts with RR MM will receive treatment with the optimal dose of pan and cfz established during phase I. Pts will be assessed for response to treatment after each cycle (4 weeks). Pts with objective response or stable disease will continue treatment until disease progression or unacceptable toxicity occurs. The primary endpoint is to establish the optimal doses of cfz and pan that can be administered to pts with RR MM (phase I) and to evaluate the overall response rate (phase II). Secondary endpoints include time-to-progression, progression-free survival, overall survival and safety. Approximately 25 pts are planned for the phase II portion. Current status: As of 1/27/12 3 patients have been enrolled.

scholarly journals Nivolumab for the Treatment of Classical Hodgkin Lymphoma

2017 ◽  
Vol 33 (6) ◽  
pp. 237-244
Author(s):  
Maryann R. Cooper ◽  
Bassem Almalki ◽  
Kristine C. Willett
Keyword(s):  
Overall Survival ◽  
Phase I ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Objective Response ◽  
Immune Surveillance ◽  
Progression Free Survival ◽  
Classical Hodgkin Lymphoma ◽  
Durable Response

Objective: To review nivolumab for the treatment of classical Hodgkin lymphoma (cHL). Data Sources: Literature searches were conducted in Medline (1946 to May week 3 2017), EMBASE (1974 to 2017 week 22), and Google Scholar using the terms Hodgkin lymphoma AND nivolumab. Study Selection and Data Extraction: Two clinical trials (phase I and phase II) were identified. Data Synthesis: Nivolumab inhibits programmed death receptor-1 allowing for increased T-cell mediated immune surveillance of tumors. Nivolumab was evaluated in cHL patients after failure of autologous stem cell transplantation and brentuximab vedotin consolidation. Patients received nivolumab 3 mg/kg every 2 weeks. In the phase I trial, the objective response rate was 87% (95% confidence interval [CI] = 66-97) and the rate of progression-free survival (PFS) at 24 weeks was 86% (95% CI = 62-95). The most common adverse events (AE) included rash (22%) and decreased platelet count (17%). Following extended follow-up at a median of 86 weeks, 50% of the initial responders maintained a durable response. In the phase II clinical trial, 53 patients (66.3%, 95% CI = 54.8-76.4) achieved an objective response and PFS at 6 months was 76.9% (95% CI = 64.9-85.3). The common AE were fatigue (25%), infusion-related reactions (20%), and rash (16%). After further follow-up at a median of 15.4 months, 12-month overall survival was 94.9% (median overall survival not reached). Conclusions: Nivolumab is an effective option in treating patients with relapsed/refractory cHL with an acceptable safety profile. Further studies are needed to investigate the role of nivolumab for the treatment of cHL.

scholarly journals Daily Oral Everolimus Activity in Patients With Metastatic Pancreatic Neuroendocrine Tumors After Failure of Cytotoxic Chemotherapy: A Phase II Trial

2010 ◽  
Vol 28 (1) ◽  
pp. 69-76 ◽  
Author(s):  
James C. Yao ◽  
Catherine Lombard-Bohas ◽  
Eric Baudin ◽  
Larry K. Kvols ◽  
Philippe Rougier ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Phase Ii ◽  
Progressive Disease ◽  
Objective Response ◽  
Neuron Specific Enolase ◽  
Progression Free Survival ◽  
Pancreatic Neuroendocrine Tumor ◽  
Clinical Activity ◽  
Open Label ◽  
Octreotide Lar

PurposeNo established treatment exists for pancreatic neuroendocrine tumor (NET) progression after failure of chemotherapy. Everolimus (RAD001), an oral inhibitor of mammalian target of rapamycin, in combination with octreotide has demonstrated encouraging antitumor activity in patients with NETs.Patients and MethodsThis open-label, phase II study assessed the clinical activity of everolimus in patients with metastatic pancreatic NETs who experienced progression on or after chemotherapy. Patients were stratified by prior octreotide therapy (stratum 1: everolimus 10 mg/d, n = 115; stratum 2: everolimus 10 mg/d plus octreotide long-acting release [LAR], n = 45). Tumor assessments (using Response Evaluation Criteria in Solid Tumors) were performed every 3 months. Chromogranin A (CgA) and neuron-specific enolase (NSE) were assessed monthly if elevated at baseline. Trough concentrations of everolimus and octreotide were assessed.ResultsBy central radiology review, in stratum 1, there were 11 partial responses (9.6%), 78 patients (67.8%) with stable disease (SD), and 16 patients (13.9%) with progressive disease; median progression-free survival (PFS) was 9.7 months. In stratum 2, there were two partial responses (4.4%), 36 patients (80%) with SD, and no patients with progressive disease; median PFS was 16.7 months. Patients with an early CgA or NSE response had a longer PFS compared with patients without an early response. Coadministration of octreotide LAR and everolimus did not impact exposure to either drug. Most adverse events were mild to moderate and were consistent with those previously seen with everolimus.ConclusionDaily everolimus, with or without concomitant octreotide LAR, demonstrates antitumor activity as measured by objective response rate and PFS and is well tolerated in patients with advanced pancreatic NETs after failure of prior systemic chemotherapy.

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]

IMMUNOSARC: a collaborative Spanish (GEIS) and Italian (ISG) sarcoma groups phase I/II trial of sunitinib and nivolumab in advanced soft tissue and bone sarcoma: Results from the phase II part, bone sarcoma cohort.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11522-11522 ◽  
Author(s):  
Emanuela Palmerini ◽  
Antonio Lopez-Pousa ◽  
Giovanni Grignani ◽  
Andres Redondo ◽  
Nadia Hindi ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Bone Sarcoma ◽  
Dedifferentiated Chondrosarcoma ◽  
Free Survival ◽  
Multicentre Phase ◽  
Pleomorphic Sarcoma

11522 Background: Herein, we present the results of the cohort on advanced bone sarcoma patients of the phase II part of the IMMUNOSARC study (NCT03277924), a European multicentre phase I-II trial aimed at investigating the activity of the combination of sunitinib (SU) and nivolumab (NI) in selected advanced sarcoma subtypes. Methods: Adult, pre-treated, progressing patients, ECOG 0-1, with a diagnosis of osteosarcoma, high-grade bone sarcoma, Ewing sarcoma, chondrosarcoma or dedifferentiated chondrosarcoma were eligible. SU 37.5 mg/day as induction was given days 1-14 and then reduced to 25mg/day continuously. NI was administered at 3 mg/Kg every 2 weeks from week 3. SU-NI was maintained up to progression or intolerance. Primary end-point was progression-free survival rate (PFSR) at 6 months (H1: PFSR 6-months: 15%). Secondary end-points: overall survival (OS), objective response rate (ORR) by RECIST v 1.1 and toxicity. Results: From Nov 2017 to Dec 2018, 40 eligible patients were included: (M/F = 27/13), median age 47 years (range 21-74), ECOG 0 in 11 (27%) cases, 36 (90%) were metastatic, 4 (10%) locally advanced. Histology: 17 osteosarcomas (43%), 14 chondrosarcomas (35%) (4 dedifferentiated), 8 Ewing sarcomas (20%), 1 bone undifferentiated pleomorphic sarcoma (2%). PFSR at 6 months based on local evaluation was 32%. At a median FU of 12.5 months (2-26), median PFS was 3.7 months (95% IC 3.4-4) while median OS was 14.2 months (95%CI: 7.1-21.3). OS rate at 3 and 6 months were 87% and 73%, respectively. ORR by RECIST: 1 CR (2.5%) (1 patient with dedifferentiated chondrosarcoma, lasting 22 months and on going), 1 PR (2.5%) (1 patient with osteosarcoma, lasting 5.7 months), 22 SD (55%, lasting > 6 months in 45% of the cases) and 16 PD (40%). G3/5 toxicities are detailed in Table. Conclusions: The trial met its primary endpoint in the cohort of patients with advanced bone sarcoma, with > 30% of patients free from progression at 6 months. Pre-planned tumor microenvironment genomic, exploratory analysis on pre and post-treatment tumor samples is on going. Clinical trial information: NCT03277924 . [Table: see text]

scholarly journals CTNI-53. SINGLE ARM, OPEN-LABEL, MULTICENTER PHASE II STUDY OF THE RADIONUCLIDE 177LU-DOTATATE (LUTATHERA) IN ADULTS WITH ADVANCED INTRACRANIAL MENINGIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii54-ii55
Author(s):  
Sylvia Kurz ◽  
Elcin Zan ◽  
Jasone Gurewitz ◽  
Christine Cordova ◽  
Andrea B Troxel ◽  
...  
Keyword(s):  
Treatment Response ◽  
Phase Ii ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Somatostatin Receptor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Intracranial Meningiomas ◽  
Promising Treatment

Abstract BACKGROUND Meningiomas are the most common primary intracranial neoplasm. Once surgical and radiotherapeutic options are exhausted, there are no effective medical treatments available. A majority of meningiomas express somatostatin receptor 2 (SSTR2), representing a promising treatment target. 177Lu-DOTATATE is a SSTR2-targeting radionuclide that has been successful in SSTR2-expressing neuroendocrine tumors. Here we hypothesize that 177Lu-DOTATATE is effective in treating progressive intracranial meningiomas. METHODS In this ongoing phase II study (NCT03971461), adults with advanced intracranial meningiomas received 177Lu-DOTATATE 7.4 GBq (200 mCi) every 8 weeks for 4 doses. 68Ga-DOTATATE PET-MRI was obtained before and at the end of treatment (EOT). The primary endpoint was progression-free survival at 6 months (PFS-6). Correlative studies evaluated the association of PFS-6, objective response rate, progression-free survival, overall survival with radiographic tumor measurements, 68Ga-DOTATATE uptake on PET-MRI, SSTR2 expression in tumor, and meningioma methylation subclass. RESULTS Nine patients (F = 7, M = 2) with progressive meningiomas (WHO I = 2, II = 6, III = 1) have been enrolled. Median age was 63 (range 49–78) years. All patients previously underwent tumor resection and at least one course of radiation. Treatment with 177Lu-DOTATATE was well tolerated, although CTCAE grade 3/4 electrolyte derangements and cytopenias were observed. Six patients reached PFS-6, three patients experienced progressive disease. Four patients had EOT 68Ga-DOTATATE PET-MRI evaluations in which anatomic measurements and 68Ga-DOTATATE standardized uptake values (SUV) pre- and post-treatment were assessed: one patient had reduced SUV measurements in all target lesions indicating altered SSTR2 expression and functional treatment response, one patient had stable disease, one patient had a mixed treatment response, and one patient experienced progressive disease. CONCLUSIONS SSTR2-targeting 177Lu-DOTATATE represents a promising treatment option for patients with progressive intracranial meningiomas. Treatment is well tolerated and can lead to functional alteration of tumoral SSTR2 expression by 68Ga-DOTATATE PET-MR imaging.

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