Phase 2, two-group, two-stage study of avelumab in patients (pts) with microsatellite stable (MSS), microsatellite instable (MSI), and polymerase epsilon (POLE) mutated recurrent/persistent endometrial cancer (EC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5502-5502 ◽  
Author(s):  
Panagiotis A. Konstantinopoulos ◽  
Joyce F. Liu ◽  
Weixiu Luo ◽  
Carolyn N. Krasner ◽  
Jeffrey Joseph Ishizuka ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Eligibility Criteria ◽  
Prior Therapy ◽  
Primary Endpoints ◽  
Phase 2 Study ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Mmr Proteins

5502 Background: This non-randomized phase 2 study evaluated the PD-L1 inhibitor avelumab in two cohorts of EC: i) MSI/ POLE cohort including ECs with immunohistochemical (IHC) loss of expression of at least one of the mismatch repair (MMR) proteins and/or documented mutation in the exonuclease domain of POLE and ii) MSS cohort including ECs with normal IHC expression of all MMR proteins. Methods: Eligibility criteria included measurable disease, unlimited prior therapies, and any EC histology. Co-primary endpoints were confirmed objective response (OR) and progression-free survival rate at 6 months (PFS6). Avelumab 10 mg/kg IV was given every 2 weeks until progression or unacceptable toxicity. In the 1st stage, 16 pts were enrolled in each cohort; if there were ≥2 ORs or ≥2 PFS6 responses, accrual would continue to the 2nd stage with enrollment of 19 additional pts. Overall, if there are ≥4 ORs or ≥8 PFS6 responses, avelumab would be considered worthy of further study in each cohort. Results: As of 12/2018, 33 pts were enrolled. The MSS cohort was closed at the 1st stage due to futility; of 16 pts in the MSS cohort, only 1 pt exhibited an OR and PFS6 response [ORR and PFS6 rate 6.25% (95% CI 0.16%-30.2%)]. Conversely, the MSI/POLE cohort reached the primary endpoint of 4 ORs after accrual of only 17 pts. Two pts in the MSI/POLE cohort did not initiate protocol therapy and were excluded from all analyses. Of 15 pts in the MSI/POLE cohort, 4 pts exhibited OR [1CR+3PRs, OR rate (ORR) 26.7% (95% CI 7.8%-55.1%)] and 6 pts (including the 4 pts with OR) exhibited PFS6 responses [PFS6 rate 40.0% (95% CI 16.3%-66.7%)], 4 ongoing and 3 approaching 2 yrs. Twenty-two pts (71%) reported treatment related toxicities, 6 patients (19%) G3 toxicities; there were no treatment-related G4 and G5 toxicities. In the MSI/POLE cohort, 5 of 6 PFS6 responses were observed in pts with ≥3 lines of prior therapy (p = 0.011) and in tumors who were PD-L1 negative by IHC. Further correlative work will be reported at the meeting. Conclusions: In EC pts stratified by MSI/POLE status, MSI vs MSS status appears to be correlated with avelumab response even in PD-L1 negative tumors. Responses in the MSI/POLE cohort were more frequent in more heavily pretreated patients, a finding that warrants further investigation. Clinical trial information: NCT02912572.

Final results of the McCAVE trial: A double-blind, randomized phase 2 study of vanucizumab (VAN) plus FOLFOX vs. bevacizumab (BEV) plus FOLFOX in patients (pts) with previously untreated metastatic colorectal carcinoma (mCRC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3539-3539 ◽  
Author(s):  
Johanna C. Bendell ◽  
Tamara Sauri ◽  
Antonio Cubillo ◽  
Carlos López-López ◽  
Pilar Garcia Alfonso ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Prior Therapy ◽  
Phase 2 Study ◽  
History Of ◽  
Dual Blockade ◽  
Grade 3

3539 Background: VEGF-A and ANG-2 have complementary roles in regulation of tumor angiogenesis. Targeting VEGF-A with BEV in combination chemotherapy (CT) in mCRC has proven to increase PFS and OS. ANG-2 is overexpressed and associated with poor outcome of mCRC pts receiving BEVcontaining treatment. Hence, dual blockade of VEGF-A and ANG-2 by the bispecific mAb VAN with standard CT may improve clinical activity in mCRC. Methods: All pts received mFOLFOX-6 and were randomized 1:1 to also receive intravenous VAN 2000 mg every other week (Q2W) (Arm A) or BEV 5 mg/kg Q2W (Arm B). The primary end point was investigator assessed progression-free survival (PFS). Key eligibility criteria included pts with non-resectable mCRC, no prior therapy for advanced disease, PS 0-1, adequate organ functions, and no history of GI fistula/perforation or intraabdominal abscess within the last 6 months. Results: 192 pts were randomized (Arms A/B, n = 95/97) by 39 sites in 7 countries, between Oct 2014 and May 2016. Median follow-up was 17.6 months (range 2.8 – 20.7). In the ITT population (n = 189; Arms A/B, n = 94/95), median PFS in Arms A and B was 11.3 and 11.0 months (stratified hazard ratio (HR) 1.00 (95%CI 0.64-1.58; p = 0.985)), respectively. Objective response rate was 52.1% vs 57.9%. Relevant prognostic factors incl. RAS/BRAF status and tumor sidedness were balanced between arms and did not significantly influence outcome. Baseline plasma ANG-2 levels were prognostic in both arms but not predictive for response to VAN. The overall incidence of adverse events (AEs) grade ≥ 3 was similar (Arms A/B, 83.9%/82.1%); AEs grade ≥ 3 attributed to the mode of action of VAN/BEV included hypertension (37.6%/18.9%), hemorrhage (2.2%/1.1%), thromboembolic events (venous 6.5%/2.1%; arterial 1.1%/3.2%) and GI perforations incl. GI fistula & abdominal abscess (10.6%/8.4%). Conclusions: The combination of VAN and FOLFOX did not improve PFS and was associated with a marked increase in hypertension compared with BEV plus FOLFOX. Our results strongly suggest that ANG-2 is not a relevant therapeutic target in the setting of first line mCRC. Clinical trial information: NCT02141295.

SHERLOC: A phase 2 study of MM-121 plus with docetaxel versus docetaxel alone in patients with heregulin (HRG) positive advanced non-small cell lung cancer (NSCLC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9036-9036 ◽  
Author(s):  
Lecia V. Sequist ◽  
Pasi A. Janne ◽  
Rudolf M. Huber ◽  
Jhanelle Elaine Gray ◽  
Enriqueta Felip ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase 2 ◽  
Multiple Cancer ◽  
Open Label ◽  
Eligibility Criteria ◽  
Phase 2 Study

9036 Background: Seribantumab (MM-121) is a human monoclonal IgG2 antibody that blocks the HRG domain of HER3. Preclinical data suggest that seribantumab reverses HRG mediated drug resistance across multiple cancer models. In prior retrospective analyses, addition of seribantumab to standard of care (SOC) appeared to improve outcomes in pts with HRG+ tumors. Here we tested if seribantumab plus SOC improved progression-free survival (PFS) in pts with HRG+ lung adenocarcinoma who had received prior platinum-based therapy. Methods: SHERLOC was a randomized, open-label, multicenter, Phase 2 study in pts with advanced HRG+ adenocarcinoma of the lung. Archival or pre-treatment tumor samples were assessed for HRG+ by RNA in situ hybridization. Eligibility criteria included prior platinum-based therapy for advanced disease with ≤ 2 total prior lines of therapy (prior IO was allowed) and no EGFR or ALK mutations. Pts were randomized 2:1 to receive seribantumab 3000 mg/docetaxel 75 mg IV q3w (experimental; exp) or docetaxel 75 mg IV q3w alone (control). Primary endpoint was PFS. Key secondary endpoints were overall survival (OS), objective response rate (ORR), and adverse event (AEs) profile. Results: At a pre-specified interim analysis of 75% of total PFS events, 108 pts were enrolled (exp n = 71, control n = 37). Median age was 62y (range 34-83y); female 34%; one prior treatment only 39%. Median PFS was 3.0m for exp and 4.0m for control, HR = 1.66m (p = 0.084). Median OS was 7.9m for exp and 8.4m for control, HR = 1.50 (p = 0.235). ORR was 19.7% for exp and 5.6% for control (p = 0.052). Serious AEs were more frequent in the exp arm (40.8%) vs control (24.3%). Most common treatment emergent AEs (TEAEs) in the exp arm were diarrhea (47%), fatigue (37%), and neutropenia (27%). Based on a determination of futility at interim analysis, the study was terminated early. Conclusions: Seribantumab failed to improve PFS when added to docetaxel among previously treated advanced HRG+ NSCLC pts. A higher response rate and a higher incidence of TEAEs were observed in the exp arm. No further study of seribantumab is planned in NSCLC. Clinical trial information: NCT02387216.

Phase II randomized, open-label study of YM155 (sepantronium bromide) plus docetaxel versus docetaxel alone as first-line treatment for HER2 negative metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 548-548
Author(s):  
Michael R. Clemens ◽  
Anne Therese Keating ◽  
Oleg Gladkov ◽  
Fei Jie ◽  
Joyce Steinberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Randomized Study ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Open Label ◽  
Eligibility Criteria ◽  
Prior Therapy

548 Background: YM155 (YM) is a small molecule survivin suppressant. In a phase I/II study of YM plus docetaxel (D) in solid tumors evidence of anti-tumor activity was observed in women with human epidermal growth factor 2 non-overexpressing (HER2 negative) metastatic breast cancer (mBC). Methods: This was a randomized study of YM plus D versus D as 1st line treatment in subjects with HER2 negative mBC. Eligibility criteria were: ECOG < 1, no prior chemotherapy for mBC, and at least one measurable lesion. Primary endpoint was progression free survival (PFS); secondary endpoints were: objective response rate (ORR), overall survival (OS), duration of response (DOR), clinical benefit rate (CBR), time to response (TTR) and safety. YM was administered at 5 mg/m2/day as a 168 hr continuous infusion followed by 14 Day (d) observation and D was administered at 75 mg/m2over 1 hr on d1 every 21d. In the control arm, D was dosed per investigator choice q 21d. Results: 101 subjects were randomized (50 YM + D; 51 D). Median (m) age 55 (range: 25 – 79), 25% had triple negative disease, > 60% had bone and lymph mets, 86% had prior therapy for BC. mPFS (days) was 251 (95%CI: 176 – 333) YM + D vs 252 (95%CI: 202-433) D (p=0.34). ORR, CBR and TTR (YM+D; D): 26% vs. 25.5%; 82% vs. 84.3% and 45 vs 59 d. OS data are immature but showed no difference (p=0.911). Adverse events [AEs (> 25%)] [YM + D% vs D %]: neutropenia 83 vs 84, alopecia 62.5 vs 53, fatigue 50 vs 41.2, nausea 35.4 vs 41.2, leucopenia 27 vs 33 and dyspnoea 33 vs 14. Common (>10%) serious AEs [YM + D% vs D%]: febrile neutropenia 21 vs 8 and neutropenia 10 vs 8. Conclusions: Preclinical and clinical evidence suggested the combination of YM + D may offer additional benefit to D alone in subjects with mBC. This study showed no difference in efficacy, but the combination appeared to be well tolerated. Clinical trial information: NCT01038804.

Phase 2 study of the CDK4 inhibitor abemaciclib in dedifferentiated liposarcoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11004-11004 ◽  
Author(s):  
Mark Andrew Dickson ◽  
Andrew Koff ◽  
Sandra P. D'Angelo ◽  
Mrinal M. Gounder ◽  
Mary Louise Keohan ◽  
...  
Keyword(s):  
Partial Response ◽  
Primary Endpoint ◽  
Study Drug ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Cancer Center ◽  
Phase 2 ◽  
Prior Therapy ◽  
Phase 2 Study ◽  
Cdk4 Inhibitor

11004 Background: The oncogene cyclin-dependent kinase 4 (CDK4) is amplified in > 90% of de-differentiated liposarcomas (DDLS). We previously demonstrated that treatment with the CDK4 inhibitor palbociclib results in favorable progression-free survival (PFS) in DDLS. Abemaciclib is a newer and more potent CDK4 inhibitor. This single-arm phase 2 study was designed to test the activity of abemaciclib in DDLS. Methods: Participants were adults with advanced DDLS, measurable disease by RECIST 1.1, any (or no) priory therapy, and progression by RECIST in the 6 months prior to study entry. The primary endpoint was PFS at 12 weeks. Based on historical data, promising drugs have 12-week PFS of ≥ 40% and not promising ≤ 20%. This study would be positive if 12-week PFS was ≥ 60%. The study was approved by the Institutional Review Board of Memorial Sloan-Kettering Cancer Center and all patients provided written informed consent. The study was registered at Clinicaltrials.gov (NCT02846987) and study drug was provided by Eli-Lilly. Results: Treatment was abemaciclib 200 mg by mouth twice daily continuously. 30 patients were treated and 29 were evaluable for the primary endpoint. Patient characteristics: Median age 62 (range 39-88), 60% male. Lines of prior therapy: 0 (50%); 1 (33%); ≥ 2 (17%). The observed PFS at 12 weeks was 76% (95% CI 57-90%). Median PFS was 30.4 weeks (95% CI 28.9-NE). There was one partial response. A further 3 patients had > 10% decrease in tumor size by RECIST but did not meet the criterion for partial response. Grade 3-4 toxicity included anemia (37%), neutropenia (20%), thrombocytopenia (17%) and diarrhea (7%). Conclusions: This study met its primary endpoint. In patients with advanced progressive DDLS, abemaciclib treatment results in favorable PFS and objective tumor response with manageable toxicity. Updated response data and results of paired tumor biopsies will be presented. Clinical trial information: NCT02846987.

A phase 2 trial of lenvatinib 18 mg versus 14 mg once daily (QD) in combination with everolimus (5 mg QD) in renal cell carcinoma (RCC) after 1 prior VEGF-targeted treatment.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS707-TPS707
Author(s):  
Hilary Glen ◽  
Javier Puente ◽  
Daniel Yick Chin Heng ◽  
Sun Young Rha ◽  
Di Li ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
The United States ◽  
Similar Efficacy ◽  
P Value ◽  
Phase 2 ◽  
Double Blind ◽  
Phase 2 Study ◽  
Grade 3

TPS707 Background: Based on findings from a randomized phase 2 study (Study 205), lenvatinib (LEN) + everolimus (EVE) was approved in the United States and European Union for patients (pts) with advanced RCC following 1 prior anti-angiogenic therapy. In that study, LEN 18 mg QD + EVE 5 mg QD significantly prolonged progression-free survival (PFS) compared with either monotherapy. In the LEN+EVE cohort, grades 3 and 4 treatment-emergent adverse events (TEAEs) occurred in 71% of pts. We report the design of an ongoing, multicenter, randomized, double-blind, phase 2 study (Study 218) to evaluate if a lower LEN starting dosage regimen provides similar efficacy with a better safety profile than LEN 18 mg + EVE 5 mg (NCT03173560). Methods: Eligible pts are aged ≥ 18 years with advanced clear cell RCC, 1 prior anti-VEGF therapy, ≥ 1 measurable target lesion per RECIST 1.1, a KPS score of ≥ 70, and prior nivolumab is allowed. Pts will receive LEN 18 mg or 14 mg QD + EVE 5 mg QD in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The LEN 14-mg dose will be escalated to 18 mg if no intolerable grade 2, or any grade ≥ 3 TEAEs requiring dose reduction occur in cycle 1. The primary endpoints are objective response rate (ORR) at week 24 (ORR24W) and the proportion of pts with intolerable grade 2 and any grade ≥ 3 TEAEs within 24 wks after randomization. Secondary endpoints include PFS and ORR. An estimated 306 pts will be randomized. Sample size is based on detecting noninferiority (NI) of ORR24W and superiority of the primary safety endpoint. Two interim analyses (IA) will be performed when 150 and 200 pts have completed 24 wks of follow-up or discontinue earlier. Each analysis will test NI and futility of the LEN 14-mg arm ORR24W vs the 18-mg arm ORR24W. An O’Brien-Fleming boundary will be used for NI. If the 1-sided P-value is ≤ 0.005 at the first IA, ≤ 0.014 at the second IA, or ≤ 0.045 at the final analysis, then NI in ORR24W will be claimed. If the futility boundary is crossed (ie, 1-sided P-value is ≥ 0.776 at the first IA or ≥ 0.207 at the second IA), then futility will be claimed. Clinical trial information: NCT03173560.

scholarly journals The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lars Ny ◽  
Henrik Jespersen ◽  
Joakim Karlsson ◽  
Samuel Alsén ◽  
Stefan Filges ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Median Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
Epigenetic Therapy ◽  
Phase 2 ◽  
Free Survival ◽  
Phase 2 Study ◽  
Phase 2 Clinical Trial ◽  
Registration Number

AbstractPreclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results of the PEMDAC phase 2 clinical trial (n = 29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic uveal melanoma (UM). The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Objective responses and/or prolonged survival were seen in patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.Trial registration ClinicalTrials.gov registration number: NCT02697630 (registered 3 March 2016). EudraCT registration number: 2016–002114-50.

scholarly journals Real-world effectiveness of eribulin in heavily pretreated patients with metastatic breast cancer in China: a multicenter retrospective study

2021 ◽  
Vol 13 ◽  
pp. 175883592110302
Author(s):  
Yannan Zhao ◽  
Ning Xie ◽  
Wei Li ◽  
Wenyan Chen ◽  
Zheng Lv ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Chinese Women ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Microtubule Inhibitor ◽  
Heavily Pretreated ◽  
Pretreated Patients

Background: Eribulin is a nontaxane microtubule inhibitor approved in China for patients with advanced breast cancer who show progression after ⩾2 lines of chemotherapy. The aim of this study was to determine the efficacy and safety profile of eribulin and explore potential predictive factors for the efficacy of eribulin among Chinese women with metastatic breast cancer (MBC) in real-world practice. Patients and Methods: A total of 272 consecutive MBC patients who were treated with eribulin between November 2019 and October 2020 in 9 institutions nationwide were included in this study. Eribulin was administered intravenously at a dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. Results: Eribulin showed a median PFS of 4.1 months (95% confidence interval [CI] 3.6–4.6); however, the OS data were immature. The ORR was 17.6% and the CBR was 24.6%. A total of 51.8% of patients received eribulin monotherapy, while 48.2% of patients were treated with eribulin plus targeted therapy or other chemotherapy. The number of metastatic sites, duration of previous taxane treatment for MBC, and combination with bevacizumab were significant in Cox multivariate analysis ( p = 0.023, p = 0.048, and p = 0.046, respectively) and were significantly associated with PFS of eribulin. The most common AEs with eribulin treatment were hematological toxicities, including neutropenia, leukopenia, and anemia. Conclusion: Eribulin was effective with a manageable toxicity profile in clinical practice. Furthermore, when prescribed in combination with other agents, eribulin did not increase the toxic effects of each agent. Eribulin monotherapy or plus other agents is an alternative for the heavily pretreated patients with MBC.

Phase 2 Study of Carfilzomib (CFZ) with or without Filanesib (FIL) in Patients with Advanced Multiple Myeloma (MM)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 728-728 ◽  
Author(s):  
Jeffrey A Zonder ◽  
Saad Usmani ◽  
Emma C. Scott ◽  
Craig C. Hofmeister ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Partial Response ◽  
Board Of Directors ◽  
Research Funding ◽  
Single Agent ◽  
Objective Response ◽  
Phase 2 ◽  
Advisory Committees ◽  
Phase 2 Study ◽  
Heavily Pretreated ◽  
Grade 3

Abstract Background: FIL (ARRY-520), a specific kinesin spindle protein (KSP) inhibitor, represents a novel class of agent under investigation for the treatment of patients (pts) with MM. Prognosis of pts refractory to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) is poor. These pts have a median survival of 9 months underscoring the importance of novel therapeutic strategies incorporating new mechanisms of action. FIL has shown interesting preliminary activity as a single agent as well as in Phase 1 studies in combination with bortezomib (BTZ) and with CFZ, all with a manageable safety profile. Methods: This trial is an ongoing, randomized, multicenter, open-label Phase 2 study for pts with relapsed and refractory MM who received at least 2 prior regimens, including BTZ and an IMiD, and with disease refractory to the last regimen as per IMWG criteria. No prior treatment with CFZ is allowed. Approximately 75 pts will be randomized 2:1 to receive CFZ (20/27 mg/m2 intravenous [IV] on Days 1, 2, 8, 9, 15 and 16) plus FIL (1.25 mg/m2 IV on Days 1, 2, 15 and 16) or single-agent CFZ, at the same dose as in the combination, in a 28-day cycle. Prophylactic filgrastim is administered in the CFZ + FIL arm. The primary endpoint is progression-free survival (PFS). Patients with progressive disease (PD) on CFZ are allowed cross-over to the CFZ + FIL arm if they continue to meet eligibility criteria. Results: As of 15 June 2015, 72 pts have been randomized (23 CFZ, 49 CFZ + FIL) with a median age of 65 years. Pts who could have potentially received ≥ 2 cycles of treatment (20 CFZ, 30 CFZ + FIL) were evaluable for efficacy. These pts were heavily pretreated with a median of 4 and 5 prior regimens in the CFZ and CFZ + FIL arm, respectively. A total of 25% and 30 % of pts, respectively, received prior pomalidomide. The objective response rate (ORR) was 10% in the CFZ arm and 30% in the CFZ + FIL arm. In the CFZ arm, 2 pts achieved a partial response (PR) and 2 pts (10%) achieved an MR. In the CFZ + FIL arm, 3 pts achieved a very good partial response and 6 pts achieved a PR, with 2 additional pts (7%) achieving an MR. In the population of pts who were refractory to both prior BTZ and prior IMiDs, the ORR was 14% and 35%, respectively. Grade 3-4 hematological laboratory abnormalities (≥ 5% of pts) were leukopenia (9% CFZ vs. 21% CFZ + FIL), neutropenia (14% vs. 24%), thrombocytopenia (14% vs. 24%), and anemia (9% vs. 26%). Neutropenia and thrombocytopenia were reversible. No adverse events (AEs) of febrile neutropenia were reported. The only Grade 3-4 non-hematological AE occurring in ≥ 5% of pts was dyspnea (5% vs.11%). The most common reason for treatment discontinuation was confirmed PD (39% vs. 28%) or Investigator discretion in case of unconfirmed PD or clinical PD (17% vs. 12%). Conclusions: The combination of FIL and CFZ was well-tolerated and noticeably increased the ORR compared to CFZ alone in heavily pretreated pts with advanced MM. The preliminary efficacy in pts who are double refractory to IMiDs and BTZ who were randomized to CFZ + FIL appears higher than in pts treated with CFZ alone (in the CFZ arm of this trial and in previously published reports involving such pts). Updated safety and efficacy data, including PFS, will be presented at the meeting. Table. Efficacy evaluable pts (potential to have received ≥ 2 cycles of treatment) CFZ (N = 20) CFZ + FIL (N = 30) Prior regimens, median (range) 4 (2,11) 5 (2,11) N cycles on study, median (range) 4 (1 - 16) 4 (1 - 15+) % ORR (≥ PR) 10 30 % CBR (≥ MR) 20 37 N (%) IMiD & BTZ Refractory 14 (70) 20 (67) % ORR (≥ PR) 14 35 % CBR (≥ MR) 21 40 CBR = clinical benefit rate Disclosures Zonder: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Prothena: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: research support. Off Label Use: carfilzomib; treatment of myeloma, but not in combination with filanesib. Usmani:Celgene Corporation: Consultancy, Honoraria; Onyx: Consultancy, Honoraria, Research Funding; Janssen: Research Funding. Berdeja:Onyx: Research Funding; Array: Research Funding; Takeda: Research Funding; Acetylon: Research Funding; Janssen: Research Funding; BMS: Research Funding; MEI: Research Funding; Celgene: Research Funding; Novartis: Research Funding; Abbvie: Research Funding; Curis: Research Funding. Anderson:Onyx: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Speakers Bureau. Hari:BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Onyx: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Honoraria, Research Funding. Singhal:Celgene: Speakers Bureau. Valent:Takeda/Millennium: Speakers Bureau; Celgene: Speakers Bureau. Faber:Celgene: Consultancy. Schiller:Sunesis: Honoraria, Research Funding. Schreiber:Array BioPharma: Employment. Oliver:Array BioPharma: Employment. Rush:Array BioPharma: Employment. Tunquist:Array BioPharma: Employment. Ptaszynski:Array BioPharma: Employment. Raje:Eli Lilly: Research Funding; Millenium: Consultancy; Takeda: Consultancy; Onyx: Consultancy; Acetylon: Research Funding; BMS: Consultancy; AstraZeneca: Research Funding; Novartis: Consultancy; Amgen: Consultancy; Celgene Corporation: Consultancy; Acetylon: Research Funding.

PEAK (study 20070509): A randomized phase II study of mFOLFOX6 with either panitumumab (pmab) or bevacizumab (bev) as first-line treatment (tx) in patients (pts) with unresectable wild‑type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 446-446 ◽  
Author(s):  
Lee Steven Schwartzberg ◽  
Fernando Rivera ◽  
Meinolf Karthaus ◽  
Gianpiero Fasola ◽  
Jean-Luc Canon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Prior Therapy ◽  
Randomized Phase Ii

446 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 1st-line tx in a phase III trial comparing pmab + FOLFOX4 vs FOLFOX4 alone. Here, we describe the results of PEAK, a multicenter, randomized phase II study evaluating pmab + mFOLFOX6 and bev + mFOLFOX6 in pts with previously untreated WT KRASmCRC. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + mFOLFOX6 Q2W or bev 5.0 mg/kg + mFOLFOX6 Q2W. Pt eligibility criteria included: WT KRASmCRC, ECOG performance status ≤ 1, and no prior chemotherapy, anti-VEGF tx, or anti-EGFR tx for mCRC. The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 285 pts with WT KRASmCRC were randomized and 278 pts received tx. Demographics were balanced between arms. Intent-to-treat efficacy results are shown (Table). Worst grade 3/4 adverse events (AE) occurred in 86% of pts in the pmab + mFOLFOX6 arm vs 76% of pts in the bev + mFOLFOX6 arm. Grade 5 AEs occurred in 5% of pts in the pmab + mFOLFOX6 arm and 6% of pts in the bev + mFOLFOX6 arm. Tx discontinuation due to any AE was 24% in the pmab + mFOLFOX6 arm and 27% in the bev + mFOLFOX6 arm. Conclusions: In this estimation study of pts with WT KRASmCRC without any prior therapy for mCRC, PFS and ORR were similar between arms. The median OS was not reached in the pmab + mFOLFOX6 arm. The safety profile for both arms was consistent with previously reported studies of either combination. Tx discontinuation rates due to AEs were similar between arms. Clinical trial information: NCT00819780. [Table: see text]

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