Study evaluating metastatic castrate resistant prostate cancer (mCRPC) treatment using 177Lu-PNT2002 PSMA therapy after second-line hormonal treatment (SPLASH).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5087-TPS5087
Author(s):  
Kim N. Chi ◽  
Ur Metser ◽  
Johannes Czernin ◽  
Jeremie Calais ◽  
Vikas Prasad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Alternative Hypothesis ◽  
Treatment Options ◽  
Objective Response ◽  
Hormonal Treatment ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Psma Pet ◽  
To Receive

TPS5087 Background: Treatment options with minimal toxicity and novel mechanisms of action are urgently needed to improve clinical outcomes from mCRPC. Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) represents a new treatment for patients with PSMA-avid mCRPC. 177Lu-PNT2002 (also known as [Lu-177]-PSMA-I&T) is a PSMA-targeting agent and studies have shown demonstrable promising initial data. This trial seeks to prospectively evaluate the efficacy of 177Lu-PNT2002 for men with progressive mCRPC after androgen receptor axis-targeted (ARAT) therapy. Methods: This is a multi-center, open-label, phase III study. All patients must be at least 18 years of age, have documented progressive mCRPC at time of screening, high PSMA expression by PSMA PET/CT per blinded independent central review (BICR), chemotherapy naïve for CRPC and unfit or unwilling to receive chemotherapy. The study will commence with a 25-patient dosimetry lead-in. In the dosimetry phase, patients will receive up to four cycles of 177Lu-PNT2002 at 6.8 GBq every 8 weeks. In the randomization phase, approximately 390 patients will be randomized in a 2:1 ratio to receive 177Lu-PNT2002 (Arm A) versus enzalutamide or abiraterone (with prednisone or dexamethasone) (Arm B). Patients randomized to Arm B have an option to crossover to 177Lu-PNT2002 treatment after BICR-assessed radiologic progression. The primary endpoint is Radiological progression-free survival (rPFS) assessed by BICR using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG3) (bone) criteria. Key secondary endpoints include objective response rate, duration of response, PSA response, and overall survival. The study is powered at 90% to test the alternative hypothesis of a hazard ratio (HR) ≤ 0.66 at an α of 0.025. ClinicalTrials.gov identifier: NCT04647526. Clinical trial information: NCT04647526.

An open label, randomized phase III trial evaluating the treatment (tx) effects of panitumumab (pmab) + best supportive care (BSC) versus BSC in chemorefractory wild-type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC) and in WT RAS mCRC.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 642-642 ◽  
Author(s):  
Tae Won Kim ◽  
Anneli Elme ◽  
Zvonko Kusic ◽  
Joon Oh Park ◽  
Anghel Adrian Udrea ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Open Label ◽  
Exon 2 ◽  
Ras Mutation ◽  
Secondary Endpoints ◽  
To Receive ◽  
Kras Exon

642 Background: An overall survival (OS) benefit in WT KRAS exon 2 mCRC was not seen with pmab monotherapy in study 20020408 possibly due to crossover of patients (pts) in the BSC arm. Retrospective analyses have indicated that other KRAS and NRAS mutations beyond KRAS exon 2 are predictive of anti-EGFR tx effects. Study 20100007 assesses the OS benefit of pmab in chemorefractory WT KRAS exon 2 mCRC and is the first phase 3 trial to prospectively evaluate pmab tx effects in WT RAS (exons 2, 3, and 4 of KRAS and NRAS) mCRC. Methods: Anti-EGFR naive pts were randomized 1:1 to receive pmab (6 mg/kg Q2W) + BSC or BSC. KRAS exon 2 and RAS mutation status of tumors were determined centrally. The primary endpoint was OS in WT KRAS exon 2 mCRC. Secondary endpoints were OS in WT RAS mCRC and progression-free survival (PFS), objective response rate (ORR), and safety in both WT KRAS exon 2 and WT RAS groups. Crossover was not permitted. Results: 377 pts with WT KRAS exon 2 mCRC were enrolled. RAS ascertainment rate was 86%. OS was significantly improved with pmab + BSC vs BSC in both WT KRAS exon 2 (HR=0.73, 95% CI=0.57-0.93, P=0.0096) and WT RAS (HR=0.70, 95% CI=0.53-0.93, P=0.0135) mCRC (results in table). Pts with mutant RAS mCRC did not benefit from pmab tx (OS HR=0.99, 95% CI=0.49-2.00). No new safety signals were seen. Conclusions: Pmabsignificantly improved OS in chemorefractory WT KRAS exon 2 mCRC. The tx effects in OS and PFS were more pronounced in those with WT RAS mCRC, further substantiating the importance of RAS testing at diagnosis to best inform the use of pmab to treat mCRC. Clinical trial information: NCT01412957. [Table: see text]

A phase III, randomized, open-label, study (CONTACT-02) of cabozantinib plus atezolizumab versus second novel hormone therapy (NHT) in patients (pts) with metastatic, castration-resistant prostate cancer (mCRPC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS190-TPS190
Author(s):  
Neeraj Agarwal ◽  
Arun Azad ◽  
Joan Carles ◽  
Simon Chowdhury ◽  
Bradley Alexander McGregor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Soft Tissue ◽  
Objective Response ◽  
Specific Antigen ◽  
Phase Iii ◽  
Disease Stage ◽  
Open Label ◽  
Phase 3 ◽  
Recist 1.1 ◽  
Cancer Aggressiveness

TPS190 Background: Cabozantinib inhibits multiple tyrosine kinases, including MET, VEGFR, RET, and TAM kinases (Tyro3, AXL, MER), involved in tumor growth and angiogenesis, and whose mutations and expression are associated with prostate cancer aggressiveness and poor prognosis. Targeting these kinases with cabozantinib may promote an immune permissive tumor environment and may enhance response to immune checkpoint inhibitors. In the ongoing phase 1b COSMIC-021 study of pts with solid tumors, cabozantinib plus the PD-L1 inhibitor atezolizumab, showed preliminary meaningful clinical activity in soft tissue disease and a tolerable safety profile for 44 pts with mCRPC (Agarwal et al., ASCO 2020; abstract 5564). We present the study design of a phase 3 trial of cabozantinib plus atezolizumab versus second NHT in pts with mCRPC. Methods: This randomized, open-label, controlled phase 3 study (NCT04446117) evaluates the efficacy and safety of cabozantinib plus atezolizumab versus second NHT (abiraterone or enzalutamide) in pts with mCRPC who previously received one NHT to treat metastatic castration-sensitive PC (mCSPC), non-metastatic CRPC (M0 CRPC), or mCRPC. Additional eligibility criteria include histologically or cytologically confirmed adenocarcinoma of the prostate, measurable visceral disease or measurable extrapelvic adenopathy per RECIST 1.1 by investigator, prostate specific antigen progression and/or soft-tissue disease progression, ECOG 0 or 1, and age ≥18 years. Key exclusion criteria include prior nonhormonal therapy for mCRPC and uncontrolled significant illness. Eligible pts (N = 580) are randomized 1:1 to receive cabozantinib (40 mg PO QD) + atezolizumab (1200 mg IV Q3W) vs abiraterone (1000 mg PO QD) + prednisone (5 mg PO BID) or enzalutamide (160 mg PO QD). Designated NHT will differ from previous NHT taken. Randomization is stratified by: liver metastasis (yes, no), prior docetaxel treatment for mCSPC (yes, no), and disease stage for which the first NHT was given (mCSPC, M0 CRPC, mCRPC). Treatment will continue until there is no longer clinical benefit as determined by the treating investigator, unacceptable toxicity, or consent withdrawal. The multiple primary endpoints are progression-free survival per RECIST 1.1 by blinded independent radiology committee (BIRC) and overall survival. Additional endpoints include objective response rate per RECIST 1.1 by BIRC, safety, correlation of biomarkers with outcomes, quality of life and pharmacokinetics. Patient enrollment is ongoing. Clinical trial information: NCT04446117.

Efficacy of avelumab plus axitinib (A + Ax) versus sunitinib (S) by number of IMDC risk factors and tumor sites at baseline in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 302-302
Author(s):  
Yoshihiko Tomita ◽  
Robert J. Motzer ◽  
Toni K. Choueiri ◽  
Brian I. Rini ◽  
Hideaki Miyake ◽  
...  
Keyword(s):  
Risk Factors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Risk Groups ◽  
Phase Iii ◽  
Once Daily ◽  
Free Survival ◽  
To Receive

302 Background: In the phase III JAVELIN Renal 101 trial (NCT02684006), A + Ax demonstrated progression-free survival (PFS) and objective response rate (ORR) benefit across IMDC risk groups (favorable, intermediate, and poor) vs S in patients with previously untreated aRCC. Here we report efficacy of A + Ax vs S by number of IMDC risk factors (0, 1, 2, 3, and 4-6) and target tumor sites (1, 2, 3, and ≥4) at baseline from the second interim analysis of overall survival (OS). Methods: Patients were randomized 1:1 to receive A 10 mg/kg intravenously every 2 wk + Ax 5 mg orally twice daily or S 50 mg orally once daily for 4 wk (6-wk cycle). PFS and ORR per independent central review (RECIST 1.1) and OS were assessed. Results: At data cut-off (Jan 2019), median (m) follow-up for OS and PFS was 19.3 vs 19.2 mo and 16.8 vs 15.2 mo for the A + Ax vs S arm, respectively. The table shows OS, PFS, and ORR by number of IMDC risk factors and target tumor sites at baseline. A + Ax generally demonstrated efficacy benefit vs S across subgroups. Conclusions: With extended follow-up, A + Ax generally demonstrated efficacy benefit vs S across the number of IMDC risk factors and tumor sites at baseline in aRCC. OS was still immature; follow-up for the final analysis is ongoing. Clinical trial information: NCT02684006 . [Table: see text]

Vandetanib versus erlotinib in patients with advanced non-small cell lung cancer (NSCLC) after failure of at least one prior cytotoxic chemotherapy: A randomized, double-blind phase III trial (ZEST)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8009-8009
Author(s):  
R. B. Natale ◽  
S. Thongprasert ◽  
F. A. Greco ◽  
M. Thomas ◽  
C. M. Tsai ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Double Blind ◽  
Equivalent Efficacy ◽  
Secondary Endpoints ◽  
Previously Treated ◽  
Grade 3 ◽  
To Receive

8009 Background: Vandetanib is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. This phase III study compared the efficacy of vandetanib vs erlotinib in patients (pts) with advanced, previously treated NSCLC. Methods: Eligible pts (stage IIIB/IV NSCLC, PS 0–2, 1–2 prior chemotherapies; all histologies permitted) were randomized 1:1 to receive vandetanib 300 mg/day or erlotinib 150 mg/day until progression/toxicity. The primary objective was to show superiority in progression-free survival (PFS) for vandetanib vs erlotinib. Secondary endpoints included overall survival (OS), objective response rate (ORR), time to deterioration of symptoms (TDS; EORTC QoL Questionnaire) and safety. Results: Between Oct 06-Nov 07, 1240 pts (mean age 61 yrs; 38% female; 22% squamous) were randomized to receive vandetanib (n=623) or erlotinib (n=617). Baseline characteristics were similar in both arms. Median duration of follow-up was 14 months, with 88% pts progressed and 67% dead. There was no difference in PFS for pts treated with vandetanib vs erlotinib (hazard ratio [HR] 0.98, 95.22% CI 0.87–1.10; P=0.721), and no difference in the secondary endpoints of OS (HR 1.01, 95.08% CI 0.89–1.16; P=0.830), ORR (both 12%) and TDS (pain: HR 0.92, P=0.289; dyspnea: HR 1.07, P=0.407; cough: HR 0.94, P=0.455). A preplanned non-inferiority analysis for PFS and OS demonstrated equivalent efficacy for vandetanib and erlotinib. The adverse events (AEs) observed for vandetanib were generally consistent with previous NSCLC studies with vandetanib 300 mg. There was a higher incidence of some AEs (any grade) with vandetanib vs erlotinib, including diarrhea (50% vs 38%) and hypertension (16% vs 2%); rash was more frequent with erlotinib (38% vs 28%). The overall incidence of CTCAE grade ≥3 AEs was also higher with vandetanib (50% vs 40%). The incidence of protocol-defined QTc prolongation in the vandetanib arm was 5%. Conclusions: The study did not meet its primary objective of demonstrating PFS prolongation with vandetanib vs erlotinib in pts with previously treated advanced NSCLC. However, vandetanib and erlotinib showed equivalent efficacy for PFS and OS in a preplanned non-inferiority analysis. [Table: see text]

SELECT: Randomized phase III study of docetaxel (D) or pemetrexed (P) with or without cetuximab (C) in recurrent or progressive non-small cell lung cancer (NSCLC) after platinum-based therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7502-7502 ◽  
Author(s):  
Edward S. Kim ◽  
Marcus A. Neubauer ◽  
Allen Lee Cohn ◽  
Lee Steven Schwartzberg ◽  
Lawrence E. Garbo ◽  
...  
Keyword(s):  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Staining Intensity ◽  
Primary Objective ◽  
Phase Iii ◽  
Open Label ◽  
Duration Of Response ◽  
Independent Review ◽  
Secondary Endpoints

7502 Background: SELECT investigated whether the addition of C to standard chemotherapy improved progression-free survival (PFS) in patients (pts) with recurrent or progressive NSCLC after failure of platinum-based therapy. Methods: SELECT was a multicenter, open label, randomized phase III trial. Per investigator choice, pts received either P (500 mg/m2) or D (75 mg/m2) on day 1 and then were randomized within each group to chemotherapy plus C (400/250 mg/m2) (initial/weekly) or chemotherapy alone. Therapy was given for up to six 3-week cycles; pts randomized to C continued weekly monotherapy until disease progression or unacceptable toxicity. The primary objective was PFS for PC vs. P as determined by an Independent Review Committee (IRC). Secondary endpoints included overall survival (OS), objective response rate (ORR) and duration of response (DOR) by IRC, and safety. Preplanned subgroup analyses for epidermal growth factor receptor (EGFR) staining intensity by immunohistochemistry and histology were performed. Results for PC vs. P only are presented. Results: Between Jan 2005 and Feb 2010, 938 total pts were randomized. Baseline demographics were comparable between PC (n=301) and P (n=304): median age 64 years; male 60%; Caucasian 88%; KPS 80-100/60-70 84%/16%; squamous/non-squamous 24%/76%. Median PFS (months) PC: 2.89 and P: 2.76 (hazard ratio [HR] =1.03 [95% confidence interval (CI)=0.87-1.21]; p=0.76). Median OS (months) PC: 6.93 and P: 7.79 (HR=1.01 [95% CI=0.86-1.20]; p=0.86). ORR PC: 6.6% and P: 4.3% (odds ratio =1.59 [95% CI=0.78-3.26]; p=0.20). Median DOR (months) PC: 4.17 and P: 6.93 (HR=1.58 [95% CI=0.74-3.36]; p=0.24). There were no statistical differences in efficacy based on histology or EGFR staining intensity. More drug-related AEs/SAEs were observed in the PC arm, with differences mainly attributable to skin toxicities, GI (diarrhea/stomatitis), and hypomagnesemia. Conclusions: The addition of C to P did not improve efficacy in this pt population. Further biomarker analyses are planned. The safety profiles for C and P were consistent with existing data and no new safety signals were observed.

ELOQUENT-2: A phase III, randomized, open-label trial of lenalidomide/dexamethasone (Len/Dex) with or without elotuzumab (Elo) in relapsed or refractory multiple myeloma (RR MM) (CA204-004).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS8112-TPS8112
Author(s):  
Sagar Lonial ◽  
Paul Gerard Guy Richardson ◽  
Philippe Moreau ◽  
Robert Z. Orlowski ◽  
Jesùs F. San-Miguel ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Response Duration ◽  
Surface Glycoprotein ◽  
Phase Iii ◽  
Open Label ◽  
Cell Surface Glycoprotein ◽  
Open Label Phase ◽  
Related Quality ◽  
Duration Of Response

TPS8112 Background: MM remains incurable and patients (pts) typically relapse or become refractory to current treatments. Novel regimens are needed to improve pt outcomes. Elo is a humanized monoclonal IgG1 antibody targeting the cell surface glycoprotein CS1, which is highly expressed on >95% of MM cells. Len/Dex is approved for treatment of relapsed MM and an objective response rate (ORR) of ~60% was reported in phase III trials of this combination in RR MM. In a phase II study (N=73) of Elo (10 or 20 mg/kg) in combination with Len/Dex in pts with RR MM, the 10 mg/kg group (n=36) demonstrated an ORR of 92% and median progression-free survival (PFS) that was not reached after a median follow-up of 14.1 months. Encouraging activity was seen in patients with high-risk cytogenetics and/or stage 2-3 disease. Based on these data, a randomized, open-label phase III trial has been initiated to determine if the addition of Elo to Len/Dex will improve PFS in patients with RR MM compared with Len/Dex alone. Methods: Pts (N=640) with RR MM and 1-3 prior therapies are eligible, including pts with mild or moderate renal impairment. Pts are randomized in a 1:1 ratio to receive 28-day cycles of Len 25 mg PO (days 1-21) and Dex 40 mg PO (days 1, 8, 15 and 22) with or without Elo. Elo dose and schedule is 10 mg/kg IV on days 1, 8, 15, 22 in the first 2 cycles and on days 1 and 15 in subsequent cycles. Dex 8 mg IV + 28 mg PO is used during the weeks with Elo. Treatment will continue until disease progression, death, or withdrawal of consent. Patients will be followed for tumor response every 4 weeks until progressive disease and then survival every 12 weeks. The primary endpoint is PFS (90% power for a hazard ratio [experimental to control arm] of 0.74) and the secondary endpoints are ORR and overall survival. Exploratory endpoints are safety, time to response, duration of response, time to subsequent therapy, health-related quality of life, and pharmacokinetics and immunogenicity of Elo. Potential biomarkers will also be assessed. As of January 10th, 2012, 107 pts were enrolled and 68 pts were treated. NCT01239797.

Comparison of two doses of cabazitaxel plus prednisone in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with a docetaxel (D)-containing regimen.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4692-TPS4692 ◽  
Author(s):  
Mario A. Eisenberger ◽  
Anne-Claire Hardy-Bessard ◽  
Loic Mourey ◽  
Paul N. Mainwaring ◽  
Daniel Ford ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Measurable Disease ◽  
Previously Treated ◽  
Grade 3 ◽  
Ecog Ps

TPS4692^ Background: The phase III TROPIC study (NCT00417079) reported a significant improvement in overall survival (OS) for cabazitaxel (Cbz) + prednisone (P;CbzP) (25 mg/m2 IV Q3W/10 mg PO QD) vs mitoxantrone (M) + P (MP) (median OS 15.1 vs 12.7 mos; HR 0.70; P < 0.0001) in pts with mCRPC (also known as hormone-refractory prostate cancer) previously treated with a D-containing regimen. CbzP is approved by the FDA, EMA and other health authorities for the treatment of pts with mCRPC that has progressed after a D-containing regimen. Cbz toxicity is consistent with other taxanes; compared with M, more hematologic toxicities are reported (primarily Grade 3–4 neutropenia). Phase I/II studies identified 20 and 25 mg/m2 as recommended doses; 25 mg/m2 was selected for the phase III TROPIC study. As pooled data show Grade 3–4 neutropenia incidence is lower with Cbz < 25 mg/m2 (61%) vs ≥ 25 mg/m2 (74%), it is of interest to assess if reducing the Cbz approved dose in mCRPC lessens hematologic toxicity and is non-inferior in terms of efficacy. Methods: PROSELICA (NCT01308580) is a randomized, open-label, multinational, phase III study comparing 20 mg/m2 and 25 mg/m2 Cbz for efficacy and tolerability. Pts with a life expectancy > 6 mos, ECOG PS ≤ 2, histologically/cytologically confirmed metastatic prostate adenocarcinoma resistant to hormone therapy and previously treated with a D-containing regimen are eligible. Pts are randomized 1:1 to receive Cbz 20 mg/m² or 25 mg/m² IV Q3W + P 10 mg PO QD, treated until disease progression, unacceptable toxicity or withdrawal of consent (max 10 cycles), and stratified according to ECOG PS, measurable disease (yes/no) and region. The primary endpoint is OS (non-inferiority design). Secondary endpoints include safety, progression-free survival (PCWG2 criteria), PSA and pain progression and response, tumor response in pts with measurable disease and health-related quality of life. Cbz PK and pharmacogenomics will be assessed in pt subgroups. Planned enrollment is 1,200 pts. Study start was in May 2011; as of Jan 2012, 270 pts had been enrolled. The first DMC meeting recommended continuing the study without change.

IMPALA, a randomized phase III study in patients with metastatic colorectal carcinoma: Immunomodulatory maintenance therapy with TLR-9 agonist MGN1703.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. TPS791-TPS791 ◽  
Author(s):  
David Cunningham ◽  
Alfredo Zurlo ◽  
Ramon Salazar ◽  
Michel Ducreux ◽  
Tom Samuel Waddell ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Immune Cell ◽  
Cox Regression ◽  
Objective Response ◽  
Phase Iii ◽  
Induction Treatment ◽  
Self Administration ◽  
Open Label ◽  
Response To Chemotherapy ◽  
To Receive

TPS791 Background: The potent TLR-9 agonist MGN1703, a synthetic DNA-based immunomodulator, was compared to placebo in metastatic colorectal cancer (mCRC) patients with disease control after standard induction chemotherapy +/- bevacizumab in the phase II IMPACT trial and showed a superior effect with a hazard ratio for the primary endpoint PFS on maintenance of 0.55 (p=0.041) by local investigator assessment and 0.56 (p=0.070) by independent radiological review. In the MGN1703 arm 3 objective responses were observed, two of them appearing as late as 9 months after the start of treatment. At time of study closure 4 MGN1703 patients were still without progressive disease and continued treatment by self-administration in a compassionate use setting. Exploratory Cox regression and ROC analyses suggested a potential predictive role at baseline for normal CEA, objective response to prior chemotherapy and presence of activated NKT-cells. Methods: The pivotal IMPALA study has been designed to confirm these data and started to enroll patients with smaller tumor burden after a good response to chemotherapy, as best candidates to receive a maintenance treatment with immunotherapy. IMPALA is a randomized, international, multicenter, open-label phase III trial that will include 540 patients from 120 centers with the collaboration of the AIO, TTD, and GERCOR cooperative groups and is currently recruiting patients. In this study mCRC patients with an objective tumor response following any first line induction therapy will be randomized to MGN1703 monotherapy maintenance or local standard of care. At time of relapse, patients will reintroduce the induction treatment whenever feasible, with those in the experimental arm continuing to receive MGN1703 in the weeks without chemotherapy. Patients will also be stratified by CEA level and activated NKT at baseline. The primary endpoint of the study will be overall survival. Secondary endpoints include PFS, response rates, safety, and QoL in selected centers. All patients will be evaluated for cytokines and chemokines in serum and the activation status of various immune cell populations. Clinical trial information: NCT02077868.

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

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

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

OlympiAD: Phase III trial of olaparib monotherapy versus chemotherapy for patients (pts) with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm).

2017 ◽  
Vol 35 (18_suppl) ◽  
pp. LBA4-LBA4 ◽  
Author(s):  
Mark E. Robson ◽  
Seock-Ah Im ◽  
Elżbieta Senkus ◽  
Binghe Xu ◽  
Susan M. Domchek ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Parp Inhibitor ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Hormone Receptor Positive ◽  
Eortc Qlq

LBA4 Background: Olaparib is an oral PARP inhibitor with anti-tumor activity in HER2-negative mBC with a g BRCAm (NCT00494234). OlympiAD (NCT02000622) was a randomized, open-label, phase III study that assessed efficacy and safety of olaparib vs standard single agent chemotherapy treatment of physician’s choice (TPC) in pts with HER2-negative mBC and a g BRCAm. Methods: Pts aged ≥18 y with HER2-negative mBC (hormone receptor positive or triple negative [TN]) and a g BRCAm, who had received ≤2 chemotherapy lines for mBC, were randomized (2:1) to olaparib tablets (300 mg po bid) or TPC (21-day cycles of either capecitabine [2500 mg/m2 po days 1–14], vinorelbine [30 mg/m2 IV days 1 and 8] or eribulin [1.4 mg/m2IV days 1 and 8]). Treatment was continued until objective disease progression (RECIST v1.1) or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR). Results: 302 pts were randomized (median age 44 y; 50% TN; 71% prior chemotherapy for mBC; 28% prior platinum) of whom 205 received olaparib and 91 received TPC (6 TPC pts were not treated). At 77% data maturity, PFS by BICR was significantly longer in pts treated with olaparib vs TPC (HR 0.58; 95% CI 0.43, 0.80; P=0.0009; 7.0 vs 4.2 months, respectively). Time to second progression (investigator-assessed) was also longer in the olaparib arm (HR 0.57; 95% CI 0.40, 0.83). Objective response rate was 59.9 and 28.8% in olaparib and TPC arms, respectively. Grade ≥3 adverse events (AE) occurred in 36.6 and 50.5% of olaparib and TPC pts, with AEs leading to discontinuation in 4.9 and 7.7% of pts, respectively. Mean change from baseline in global health-related quality of life (HRQoL, EORTC-QLQ-C30) across all timepoints favored olaparib (difference vs TPC 7.5; 95% CI 2.48, 12.44; P=0.0035). Conclusions: Olaparib tablet monotherapy provided a statistically significant and clinically meaningful PFS benefit to HER2-negative mBC pts with a g BRCAm, compared to standard TPC. The safety profile of olaparib was consistent with prior studies. The efficacy benefit was seen beyond the first progression and HRQoL also improved. Clinical trial information: NCT02000622.

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