FOENIX-101: A phase II trial of TAS-120 in patients with intrahepatic cholangiocarcinoma harboring FGFR2 gene rearrangements.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS468-TPS468 ◽  
Author(s):  
Lipika Goyal ◽  
Rastilav Bahleda ◽  
Junji Furuse ◽  
Juan W. Valle ◽  
Markus Hermann Moehler ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Intrahepatic Cholangiocarcinoma ◽  
Oral Treatment ◽  
Objective Response ◽  
Gene Rearrangements ◽  
Tumor Type ◽  
Once Daily ◽  
Fgfr2 Gene ◽  
Platinum Based Chemotherapy

TPS468 Background: Intrahepatic cholangiocarcinoma (iCCA) is a cancer arising from the intrahepatic bile duct. Standard treatment of unresectable, recurrent, or metastatic iCCA is with cytotoxic chemotherapy. FGFR2 gene fusions have been identified as oncogenic drivers in 10–20% of iCCA tumors, but no targeted agents have been established to date. TAS-120 is an investigational irreversible FGFR1–4 inhibitor in development as a once-daily oral treatment for iCCA. Based on initial studies in multiple tumor types expressing FGFR abnormalities, iCCA was identified as a tumor type with potential susceptibility to FGFR inhibition and high unmet need. A phase I portion of the trial with an iCCA expansion cohort demonstrated tolerability and preliminary evidence of clinical efficacy with TAS-120 as a continuous, once-daily oral treatment in patients with iCCA. The most common AEs in the phase I portion of the trial were hyperphosphatemia, a mechanism-based on-target side effect, cutaneous AEs, and gastrointestinal AEs. The phase I portion of the study is continuing to enroll, and final results are anticipated in early 2019. Based on preliminary findings, a phase II portion of the study (FOENIX-101; clinicaltrials.gov registration NCT02052778) has been initiated. Methods: The phase II portion of the trial is a global, single-arm study of TAS-120 in patients with iCCA harboring FGFR2 gene rearrangements. The study will enroll approximately 100 adult patients with locally advanced or metastatic iCCA that progressed after ≥ 1 systemic therapies and with an ECOG PS of 0 or 1. Prior systemic therapy must include gemcitabine plus platinum-based chemotherapy. Screening for FGFR2 gene rearrangements will be performed at a central laboratory. The primary endpoint is objective response rate based on RECIST v1.1. Secondary endpoints include duration of response, disease control rate, overall survival, progression-free survival, safety, and health-related quality of life. Clinical trial information: NCT02052778.

FOENIX-CCA2: A phase II, open-label, multicenter study of futibatinib in patients (pts) with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 gene fusions or other rearrangements.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 108-108 ◽  
Author(s):  
Lipika Goyal ◽  
Funda Meric-Bernstam ◽  
Antoine Hollebecque ◽  
Juan W. Valle ◽  
Chigusa Morizane ◽  
...  
Keyword(s):  
Disease Progression ◽  
Intrahepatic Cholangiocarcinoma ◽  
Phase 1 ◽  
Objective Response ◽  
Locally Advanced ◽  
Gene Fusions ◽  
Phase 2 ◽  
Fgfr2 Gene ◽  
Platinum Based Chemotherapy ◽  
Grade 3

108 Background: Patients (pts) with intrahepatic cholangiocarcinoma (iCCA) have a 5-year survival rate of 24%. There is no standard treatment for advanced disease after first-line chemotherapy. Fibroblast growth factor receptor-2 ( FGFR2) gene fusions occur in 10% to 20% of pts with iCCA, offering a promising therapeutic avenue for this disease. Futibatinib is a highly selective irreversible FGFR1-4 inhibitor given as a continuous once-daily (QD) oral regimen. This phase 2 registrational trial was initiated because of results from a phase 1 dose escalation/expansion study showing tolerability and preliminary efficacy of futibatinib in pts with iCCA with FGFR2 fusions. Methods: FOENIX-CCA2 (NCT02052778), a single-arm multicenter phase 2 study, enrolled pts with locally advanced/metastatic unresectable iCCA harboring FGFR2 gene fusions or other rearrangements, disease progression after ≥1 line of systemic therapy (including gemcitabine plus platinum-based chemotherapy), no prior FGFR inhibitor treatment, and an ECOG performance status of 0 or 1. Pts received futibatinib 20 mg QD until disease progression/unacceptable toxicity. The primary endpoint is objective response rate (ORR) based on independent central radiology review. Secondary endpoints include disease control rate (DCR), duration of response (DOR), and safety. Results: A total of 103 pts were enrolled. For this interim analysis, data are reported for the 67 pts (65%) with ≥6 months of follow-up. Of these, 82.1% of pts had tumors harboring an FGFR2 fusion. One, 2, or ≥3 prior therapies were received by 44.8%, 28.4%, and 26.9% of pts, respectively. ORR was 34.3% (all partial response, n = 23), and DCR was 76.1%; assessment was pending for 8 pts. Median time to response was 1.6 months (range, 1.0-4.9), and median DOR was 6.2 months (range, 2.1-14.2). The most common treatment-related adverse events (AEs; all grade, grade ≥3) were hyperphosphatemia (79.1%, 25.4%), diarrhea (37.3%, 0%), and dry mouth (32.8%, 0%). Any-cause grade ≥3 AEs were reported in 73.1% of pts. Dose delay or dose reduction was required in 65.7% and 53.7% of pts, respectively; 6.0% of pts discontinued treatment because of AEs. Conclusions: Preliminary assessment of these phase 2 data indicate efficacy and tolerability of futibatinib for treatment of pts with iCCA harboring FGFR2 fusions or other rearrangements who have progressed after chemotherapy. Continued analysis of the study population is underway. Clinical trial information: NCT02052778.

A phase I/II study of the vascular disrupting agent BNC105P in combination with gemcitabine-carboplatin in partially platinum-sensitive ovarian cancer patients in first or second relapse: An international collaborative group trial of ANZGOG and HOG.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5612-TPS5612
Author(s):  
Danny Rischin ◽  
Daniela Matei ◽  
Jeffrey C. Goh ◽  
Michelle Margaret Vaughan ◽  
Philip James Beale ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Objective Response ◽  
Collaborative Group ◽  
Synergistic Activity ◽  
Vascular Disrupting Agent ◽  
Platinum Based Chemotherapy ◽  
Vascular Disrupting

TPS5612 Background: BNC105P is a tubulin polymerization inhibitor and a vascular disrupting agent (VDA). In vivo exposure to BNC105P leads to selective damage of tumor vasculature in both primary and metastatic lesions, causing disruption of blood flow to tumors, hypoxia, and associated tumor necrosis. BNC105P also has a direct anti-proliferative action on cancer cells, including ovarian cancer cell lines. Pre-clinical data has demonstrated synergistic activity of BNC105P when combined with platinum or with gemcitabine, supporting the proposed study design. This study will determine the safety and efficacy of BNC105P in ovarian cancer when used in combination with gemcitabine-carboplatin. The target population is women with ovarian or primary peritoneal cancers who progressed 4 to 9 months after first-line platinum based chemotherapy, or 4 to 12 months after second line platinum based chemotherapy. Methods: A single arm phase I will be used to determine the phase II dose for the triplet combination (3-6 subjects per dose level, maximum of 24 subjects). Four dose levels of BNC105P (12-16 mg/m2) and gemcitabine (800-1000 mg/m2) will be assessed. The dose of carboplatin will be set at AUC 4. Enrolment to cohort 2 started in January 2013. The phase II component will consist of a 2-arm, randomized (1:1) study of BNC105P, gemcitabine and carboplatin versus gemcitabine and carboplatin alone. The primary endpoint for the phase II trial is objective response rate (ORR, according to RECIST 1.1 and/or GCIG CA125 criteria. An ORR of 40% or more with the experimental regimen would be considered worthy of further investigation, assuming an ORR of 20% with the control regimen. 110 phase II participants are planned (N = 55/arm). Treatment allocation will be balanced using minimization for the study site, target lesions according to RECIST (present vs. absent), progression free interval from last platinum based chemotherapy regimen (<6 months vs 6 months or more), and first relapse vs. second relapse. Biomarker (tissue and blood-borne) sampling and PK analysis will also be undertaken. Clinical trial information: NCT01624493.

A phase I/II study of TQ-B2450, a PD-L1 mAb, plus anlotinib in EGFR+ advanced NSCLC patients failed to prior EGFR TKI therapies.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21062-e21062
Author(s):  
Meiqi Shi ◽  
Li Wang ◽  
Shaorong Yu ◽  
Fei Yan ◽  
Wei Peng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Phase I ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase 1 ◽  
Objective Response ◽  
Platinum Based Chemotherapy ◽  
Egfr Tki ◽  
Clinical Trial Information

e21062 Background: Platinum-based chemotherapy is the standard therapy for the patients(pts) with EGFR-mutation–positive advanced NSCLC failed to prior EGFR TKI therapies. However, the IMpower150 study subgroup analyses showed Atezolizumab (PD-L1) plus bevacizumab and chemotherapy improved overall survival in EGFR TKI treated NSCLC. This ongoing phase I/II study designed to assess the benefit of the chemo-free combination of TQ-B2450, a humanized PD-L1 mAb, plus anlotinib in EGFR+ advanced NSCLC pts failed to prior EGFR TKI therapies. Methods: Pts with EGFR+ advanced NSCLC who failed to prior EGFR TKI therapies were eligible. Pts with previous received platinum-based chemotherapy were excluded. Anlotinib was given orally at dose of 8mg to 12mg for 2 weeks of a 21-day cycle (days 1-14), with TQ-B2450 given at 1200mg every 3 weeks on day 1. Phase I determined RP2D. In the phase II part, pts were assessed for efficacy and tolerability. The primary endpoint for the phase II part is the progression free survival (PFS). Secondary endpoints were objective response rate (ORR) disease control rate (DCR), overall survival (OS), and safety. Assuming an expected the median PFS of 9 months (5 months in chemotherapy), and a loss to follow-up of 10%, a total of 54 pts were required to have 90% power at a two-tailed alpha of 0.05 at the phase II part. Results: As of 12 Jan 2021, 22 pts were enrolled (9 in phase 1, 14 in phase 2). 18 pts were included in efficacy and safety analysis. The median age was 64.5 years with 61% male. 50% pts harbored EGFR exon19 deletion, 44% pts had exon21 L858R mutation. While 39% pts had T790M mutation who progressed after osimertinib treatment. The dose escalation cohort included 9 pts, no dose limiting toxicity occurred. 13 pts in the phase II part were administered with dose of 12 mg for anolitinib and 1200mg for TQ-B2450. Of the evaluable pts(n = 18), ORR was 11.1%, DCR was 77.8%, median PFS was 8.0 months (95% CI 4.9 to 11.1). Most frequent TRAE included hypertension (27.8%), hand and foot skin reaction (22.2%) and proteinuria (16.7%). Grade 3 TRAE occurred in 16.7% pts(3/18 pts), all were hypertension, and no Grade 4/5 TRAE were observed. Dose delay due to TRAE occurred in 22.2% patients while no one discontinued treatment due to TRAE. Conclusions: The chemo-free combination of TQ-B2450, a PD-L1 mAb, plus anlotinib has shown a promising anti-tumor efficacy with a more favorable safety profile for pts with EGFR+ advanced NSCLC who failed to prior EGFR TKI therapies. Pts will be continuously monitored for safety and efficacy readouts (PFS, DOR and OS). Clinical trial information: ChiCTR1900026273. Clinical trial information: ChiCTR1900026273.

Romidepsin (HDACi) plus cisplatin and nivolumab triplet combination in patients with metastatic triple negative breast cancer (mTNBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1076-1076
Author(s):  
Priyanka Sharma ◽  
Vandana G Abramson ◽  
Anne O'Dea ◽  
Lauren Elizabeth Nye ◽  
Ingrid A. Mayer ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Phase I ◽  
Phase Ii ◽  
Histone Deacetylase Inhibitors ◽  
Objective Response ◽  
Common Grade ◽  
Group 2 ◽  
Grade 3 ◽  
Recognition And Response ◽  
Minimax Design

1076 Background: Histone deacetylase inhibitors (HDACi) upregulate genes involved in antigen presentation machinery and increase expression of natural killer group 2, member D ligands (NKG2DL), thus resulting in enhanced tumor cell recognition and response to PD-1/CTLA-4 blockade. Cisplatin and HDACi combination synergistically induces cytotoxicity, apoptosis, and DNA damage. This phase I-II trial investigated combination of romidepsin (HDACi) plus cisplatin and nivolumab (PD-1 inhibitor) in mTNBC. Patients and Methods: Eligible patients had mTNBC with any number of prior chemotherapies. Phase I was 3+3 dose-escalation design with three dose levels of romidepsin (8, 10, 12mg/m2, D2, 9) plus cisplatin 75mg/m2 D 1 every 21 days. Phase II treatment included romidepsin plus cisplatin plus nivolumab 360mg every 21 days and was designed according to Simon’s two stage minimax design. Primary endpoints were recommended phase 2 dose (RP2D) and objective response rate (ORR). Additional endpoints included safety, PFS, and pharmacokinetics. Results: 51 patients were enrolled (N=13 phase I, N=38 phase II) between 2015-2020. 69% had received ≥1 prior metastatic chemotherapy, 47% had prior platinum, 53% had liver metastasis, 12% had BRCA1/2 mutation, and 11% had PD-L1 positive disease. There were no dose limiting toxicities in phase I. The RP2D was romidepsin 12mg/m2 D2,9 + cisplatin 75mg/m2 D1 + nivolumab 360mg D1 every 21 days. Thrombocytopenia (G3:27%, G4:0%), neutropenia (G3:25%, G4:0%), anemia (G3:22%, G4:0%), nausea (G3:22%, G4:0%), and vomiting (G3:20%, G4:0%) were the most common grade 3/4 adverse events. 21% of patients had immune AEs (G3-4:8%). Among 34 evaluable phase II patients, ORR was 44% (Table), median PFS was 4.4 months, and 1-year PFS was 23%. Median OS was 10.3 months and 1-year OS was 43%. No pharmacokinetic interactions were detected with co-administration of romidepsin-cisplatin-nivolumab. Conclusions: The triplet combination of romidepsin plus cisplatin and nivolumab was well tolerated and shows encouraging efficacy in pretreated mTNBC, including in patients with PD-L1 negative disease and in those with liver metastasis. Correlative biomarker work is ongoing. This combination warrants further evaluation in larger studies. Clinical trial information: NCT02393794 .[Table: see text]

Results from a phase II study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in patients with PD-L1 unselected metastatic second-line squamous head and neck carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6028-6028
Author(s):  
Irene Brana ◽  
Martin Forster ◽  
Antonio Lopez-Pousa ◽  
Bernard Doger ◽  
Patricia Roxburgh ◽  
...  
Keyword(s):  
T Cell ◽  
Head And Neck ◽  
Phase Ii ◽  
T Cell Activation ◽  
Objective Response ◽  
Head And Neck Carcinoma ◽  
Upper Respiratory Tract ◽  
Part C ◽  
Neck Carcinoma ◽  
Platinum Based Chemotherapy

6028 Background: Eftilagimod alpha (efti) is a soluble LAG-3 protein that binds to a subset of MHC class II molecules to mediate antigen presenting cell (APC) activation and CD8 T-cell activation. The stimulation of the dendritic cell network and subsequent T cell recruitment with efti may lead to stronger anti-tumor responses in combination than observed with pembrolizumab alone. We hereby report results of the 2nd line metastatic squamous head and neck carcinoma (HNSCC) cohort (part C) of phase II trial (NCT03625323). Methods: Patients (pts) with HNSCC progressed on or after 1st line platinum-based therapy and unselected for PD-L1 expression were recruited into part C. The study used a Simon's 2-stage design (18 pts planned for stage 1 and 19 for stage 2), with objective response rate (ORR) by iRECIST as the primary endpoint (EP). Secondary EPs include tolerability, disease control rate (DCR), progression free survival (PFS), overall survival (OS), pharmacokinetics, pharmacodynamics and immunogenicity. Efti was administered as 30 mg subcutaneous injection every 2 wks for 8 cycles and then every 3 wks for 9 cycles with pembrolizumab (200 mg intravenous infusion every 3 wks for up to 2 yrs). Imaging was performed every 8 weeks. PD-L1 was assessed centrally (22C3 clone). The study was approved by ethics committees and institutional review boards. Results: In total 38 pts were enrolled. The median age was 62 yrs (range 37-84) and 89 % were male. The ECOG PS was 0 and 1 in 34% and 66%, respectively. Primary location at diagnosis was the oral cavity (29%), oropharynx (37%), hypopharynx (18%) and the larynx (16%). All PD-L1 subgroups (CPS < 1 %, ≥ 1 to ≤19; ≥20) were included. All pts were pre-treated with platinum-based chemotherapy. Pts received a median of 3.0 (range 1 – 21) pembrolizumab and 5.0 (range 1-31) efti administrations. Thirty-five (35) pts were evaluated for response (cut-off Jan 2021) with 4 (11 %) pts showing CR, 7 (20 %) pts PR, 3 (9 %) pts SD, 16 (46 %) pts PD with 5 (14 %) pts being not evaluable as per iRECIST. ORR was reported with 31.4 % (95 % CI 16.9 % - 49.3 %) and DCR 40 %Median PFS was 2.1 months and 35 % were progression free at 6 months. Median OS (46 % events) was 12.6 months. There were no adverse reactions leading to treatment discontinuation. The most common ( > 10 %) treatment emergent adverse events were cough (18 %), asthenia (16 %), dyspnea (11 %), fatigue (13 %), diarrhea (11 %), hypothyroidism (11%), upper respiratory tract infection (11%) and back pain (11%). Conclusions: Efti in combination with pembrolizumab is safe and shows encouraging antitumor activity in platinum pre-treated 2nd line HNSCC patients. Clinical trial information: NCT03625323.

scholarly journals Pyrotinib in HER2-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study

2020 ◽  
Vol 38 (24) ◽  
pp. 2753-2761 ◽  
Author(s):  
Caicun Zhou ◽  
Xingya Li ◽  
Qiming Wang ◽  
Guanghui Gao ◽  
Yiping Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Unmet Need ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Grade 3

PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of pyrotinib in patients with HER2-mutant advanced NSCLC in a prospective, multicenter, open-label, single-arm, phase II study. PATIENTS AND METHODS Patients with stage IIIB or IV HER2-mutant lung adenocarcinoma who were previously treated with platinum-based chemotherapy were enrolled to receive pyrotinib at a dose of 400 mg/d for 21-day cycles. The primary end point was objective response rate per independent review committee (IRC). RESULTS Between October 20, 2016, and December 10, 2018, 60 patients received pyrotinib monotherapy. At baseline, 58 (96.7%) were stage IV, and 25 (41.7%) received at least 2 lines of prior chemotherapy. As of data cutoff on June 20, 2019, IRC-assessed objective response rate was 30.0% (95% CI, 18.8% to 43.2%). All subgroups of patients with different HER2 mutation types showed a favorable objective response rate. The objective response rates were similar between patients with and without brain metastases (25.0% v 31.3%). The median duration of response was 6.9 months (95% CI, 4.9 to 11.1 months). The median progression-free survival was 6.9 months (95% CI, 5.5 to 8.3 months) per IRC. The median overall survival was 14.4 months (95% CI, 12.3 to 21.3 months). Treatment-related adverse events of grade 3 or 4 occurred in 28.3% of patients, with the most common being diarrhea (20.0%; all grade 3). No treatment-related deaths were reported. CONCLUSION Pyrotinib showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with HER2-mutant NSCLC.

Phase I-II Study of Gemcitabine and Carboplatin in Stage IIIB-IV Non–Small-Cell Lung Cancer

1999 ◽  
Vol 17 (3) ◽  
pp. 921-921 ◽  
Author(s):  
Rosario Vincenzo Iaffaioli ◽  
Anna Tortoriello ◽  
Gaetano Facchini ◽  
Francesco Caponigro ◽  
Maria Gentile ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iiib ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy ◽  
Duration Of Response

PURPOSE: Platinum-based chemotherapy currently represents standard treatment for advanced non–small-cell lung cancer. Gemcitabine is one of the most interesting agents currently in use in advanced non–small-cell lung cancer, and high response rates have been reported when it is administered in combination with cisplatin. The aim of the present study was to evaluate the combination of gemcitabine and carboplatin in a phase I-II study. PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB-IV non–small-cell lung cancer received carboplatin at area under the concentration-time curve (AUC) 5 mg/mL/min and gemcitabine at an initial dose of 800 mg/m2, subsequently escalated by 100 mg/m2 per step. Gemcitabine was administered on days 1 and 8 and carboplatin on day 8 of the 28-day cycle. Dose escalation proceeded up to dose-limiting toxicity (DLT), which was defined as grade 4 neutropenia or thrombocytopenia or grade 3 nonhematologic toxicity. RESULTS: Neutropenia was DLT, inasmuch as it occurred in three of five patients receiving gemcitabine 1,200 mg/m2. Nonhematologic toxicities were mild. Gemcitabine 1,100 mg/m2 plus carboplatin AUC 5 was recommended for phase II studies. An objective response was observed in 13 (50%) of 26 patients, including four complete responses (15%) and nine partial responses (35%). Median duration of response was 13 months (range, 3 to 23 months). Median overall survival was 16 months (range, 3 to 26 months). CONCLUSION: The combination of gemcitabine and carboplatin is well tolerated and active. Neutropenia was DLT. The observed activity matches that observable in cisplatin-gemcitabine studies, whereas duration of response and survival are even higher. A phase II trial is under way.

Phase II study of DMXAA combined with carboplatin and paclitaxel in recurrent ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5032-5032 ◽  
Author(s):  
H. Gabra
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Ovarian Cancer ◽  
Figo Stage ◽  
Vascular Disrupting Agent ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

5032 Background: DMXAA (AS1404) is a small-molecule vascular disrupting agent, which in animal models shows additive or supra-additive effects with cytotoxics, including taxanes and platinum agents. This phase II study evaluated DMXAA in combination with carboplatin and paclitaxel in recurrent platinum-sensitive ovarian cancer patients with a progression-free interval of more than 6 months after response to platinum-based chemotherapy. Methods: Patients had first diagnosed disease FIGO stage Ic-IV, with presence of recurrent disease confirmed by imaging. Patients were randomised 1:1 to receive up to 6 cycles of carboplatin (AUC 6 mg/ml × min) and paclitaxel (175 mg/m2) with or without DMXAA (1200 mg/m2). Safety assessments included EKG, adverse events, laboratory screens and ophthalmic exam. Efficacy endpoints are objective response rates, time to progression, duration of response and stable disease, and median and 1-year survival. Results: 55 patients have been enrolled to date from a planned total of ∼70. Initial safety findings in the two arms are comparable. Preliminary investigator-assessed RECIST response data show the following unconfirmed outcomes: of 17 patients in the DMXAA arm, there are 10 with partial responses (PRs), 7 with stable disease (SD) and 0 with progressive disease (PD); of 14 patients in the control arm, there are 8 PRs, 6 SDs and 0 PDs. Conclusions: Initial safety findings suggest that addition of DMXAA to standard doses of carboplatin and paclitaxel did not add significantly to toxicity. Efficacy assessments are ongoing to determine the value of the triple combination in recurrent ovarian cancer. No significant financial relationships to disclose.

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 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.

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