Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing low (1–9%) or negative (<1%) levels of epidermal growth factor receptor (EGFr)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3547-3547 ◽  
Author(s):  
J. Hecht ◽  
E. Mitchell ◽  
J. Baranda ◽  
I. Malik ◽  
D. Richards ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Response Duration ◽  
Infusion Reaction ◽  
Prior Therapy ◽  
Epidermal Growth ◽  
Tumor Expression

3547 Background: Panitumumab is a fully human monoclonal antibody directed against EGFr. We investigated the antitumor activity of panitumumab in pts with mCRC who failed prior therapy and had low or negative EGFr tumor expression. Methods: In this multicenter, phase 2 study of 150 planned pts, pts had documentation of disease progression (PD) during or after adequate doses of fluoropyrimidine, irinotecan, and oxaliplatin (centrally confirmed refractory disease [CCRD]), 2–3 prior regimens, ECOG score 0–2, and low or negative EGFr staining (by IHC) in evaluable tumor cells. Pts received panitumumab at 6 mg/kg Q2W until PD or drug intolerability. Tumor assessments (modified WHO, blinded central review) were taken periodically from wk 8 until PD. Endpoints were objective response (OR) through wk 16 (+ ≥ 4 wk confirmation; primary) and OR throughout study, response duration, progression-free survival (PFS) time, survival time, and safety (secondary). Results: In this interim analysis (6/05), 88 pts were enrolled and had ≥ 1 dose of panitumumab (safety set); 23 pts had ≥ 20 wks before the cutoff and CCRD (efficacy set). The efficacy set consisted of 16M/7W, median age of 65 (range: 46, 85) yrs, 83% white, 100% with ECOG ≤ 1, 74% colon cancer and 26% rectal cancer; all received ≥ 2 prior regimens (equivalent characteristics for safety set). 2/11 (18%) pts with EGFr-negative tumors and 1/12 (8%) with low EGFr staining had a partial response. Duration was up to 16 wks. 7/23 (30%) of all pts had SD. Median (95% CI) PFS was 7.9 (7.0, 23.0) wks. In the safety set, all pts had a treatment-related adverse event; 19% grade (gr) 3; 2% gr 4. Integument and eye toxicities were: 92% skin, 17% eye, 28% nail, 8% hair, and 2% chelitis. 20 (23%) had diarrhea (1 gr 3); 7 (8%) had hypomagnesemia (2 gr 3/4). Three pts had an infusion reaction-1 gr 3 (led to panitumumab discontinuation) and 2 gr 1/2. In 65 pts with both a baseline and post-baseline sample, no human anti-human antibodies to panitumumab were detected. Updated data will be presented. Conclusions: Responses to panitumumab were seen in pts with mCRC with both low and negative EGFr levels. Efficacy appears similar to that in other studies with panitumumab in pts with higher EGFr tumor levels. [Table: see text]

Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing ≥ 10% epidermal growth factor receptor (EGFr)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3548-3548 ◽  
Author(s):  
J. Berlin ◽  
M. Neubauer ◽  
P. Swanson ◽  
W. G. Harker ◽  
H. Burris ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Interim Analysis ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Response Duration ◽  
Expression Levels ◽  
Prior Therapy ◽  
Tumor Expression

3548 Background: Panitumumab is a fully human monoclonal antibody directed against EGFr. We investigated panitumumab antitumor activity in pts who failed prior therapy and had EGFr tumor expression levels ≥ 10%. Methods: In this multicenter, phase 2 study of 300 planned pts, pts had documentation of disease progression (PD) during or following adequate doses of fluoropyrimidine, irinotecan, and oxaliplatin (centrally confirmed refractory disease [CCRD]), 2–3 prior regimens, ECOG score 0–2, and EGFr staining (by IHC) in ≥ 10% of evaluable tumor cells. Pts received panitumumab at 6 mg/kg Q2W until PD. Tumor assessments (modified WHO, blinded central review) were taken periodically from wk 8–48 until PD. Study endpoints were objective response rate (ORR) at wk 16 (+ ≥ 4 wk confirmation; primary) and ORR throughout study, response duration, progression-free survival (PFS) time, survival time, and safety (secondary). Results: In this interim analysis (5/05), 91 enrolled pts received ≥ 1 dose of panitumumab (safety set); 39 had ≥ 20 wks before the cutoff and CCRD (efficacy set). The efficacy set consisted of 23M/16W, mean (SD) age of 58.6 (10.1) years, 82% white, 95% ECOG ≤ 1, 74% colon cancer and 26% rectal cancer; all had ≥ 2 prior regimens (equivalent characteristics for safety set). At wk 16, 3 (8%) had a partial response, 8 (21%) had stable disease, and 19 (49%) had PD as best OR (9 not done/unevaluable). At the time of this interim analysis, response durations were 12.4, 13.2, and 14.0 wks. In the safety set, 96% had at least 1 treatment-related adverse event (24% grade [gr] 3, 1% gr 4, 1% gr 5). Integument and eye toxicities were: 96% skin, 30% nail, 8% eye, 5% hair, and 7% chelitis. 25 (27%) had diarrhea (3 gr 3); 11 (12%) had hypomagnesemia (3 gr 3/4). One pt had a gr 3 hypersensitivity reaction considered related to panitumumab, received medication, and the event resolved; this pt continued treatment with premedication; no further reactions occurred. In 66 pts with both a baseline and postdose sample, no human anti-human antibodies to panitumumab were detected.Additional data will be presented. Conclusions: Panitumumab has antitumor activity and is well tolerated in pts with EGFr tumor expression levels ≥ 10% who failed standard chemotherapy. [Table: see text]

Panitumumab activity in metastatic colorectal cancer (mCRC) patients (pts) with low or negative tumor epidermal growth factor receptor (EGFr) levels: An updated analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4082-4082 ◽  
Author(s):  
E. P. Mitchell ◽  
J. R. Hecht ◽  
J. Baranda ◽  
I. Malik ◽  
D. Richards ◽  
...  
Keyword(s):  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Response Duration ◽  
Infusion Reaction ◽  
Membrane Staining ◽  
Negative Tumor ◽  
Grade 3

4082 Background: Panitumumab, a fully human monoclonal antibody against EGFr, is approved for EGFr-expressing mCRC pts with disease progression (PD) on or after fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. However, the predictive value of EGFr tumor-membrane staining as measured by immunohistochemistry (IHC) is undetermined. Methods: This multicenter, single arm, phase 2 study enrolled pts with documented PD during or after fluoropyrimidine and adequate doses of irinotecan and oxaliplatin, and within 6 months after the most recent chemotherapy regimen (determined by an independent eligibility review committee [IERC]), 2–3 prior regimens, and low (1%-9%) or negative (<1%) EGFr tumor membrane staining (by IHC). Pts received panitumumab 6mg/kg Q2W until PD or intolerability. Tumor assessments (modified WHO, blinded central review) were performed every 8 weeks until PD or discontinuation. Endpoints were objective response rate (ORR) through wk 16 (+ =4 wk confirmation; primary), overall ORR, response duration, progression-free survival (PFS), and safety (secondary). Results: In this interim analysis, 91 pts had =20 wks of potential follow-up and comprised the IERC efficacy set; 118 pts comprised the evaluable safety set (=20 wks potential follow-up). In the IERC efficacy set, 57% were male, 86% were white, and median age (range) was 61 (26–85) years. ORR through week 16 is shown; overall ORR was the same ( Table ). The most common adverse events (all, grade 3/4) were dermatitis acneiform (72%, 6%), erythema (69%, 6%), pruritus (65%, 4%), and hypomagnesaemia by lab values (53%, 10%). Four pts (3%) had an infusion reaction per investigator (1 was grade 3). Conclusions: This analysis confirms earlier findings that panitumumab has anti-tumor activity in pts with low or undetectable EGFr tumor membrane levels as measured by IHC. This study has completed enrollment, and updated data will be presented. [Table: see text] No significant financial relationships to disclose.

Safety and pharmacokinetics (PK) of AMG 706, panitumumab, and carboplatin/paclitaxel (CP) for the treatment of patients (pts) with advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7119-7119 ◽  
Author(s):  
G. Blumenschein ◽  
A. Sandler ◽  
T. O’Rourke ◽  
M. Eschenberg ◽  
Y. Sun ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Preliminary Data ◽  
Drug Exposure ◽  
Advanced Nsclc ◽  
Kinase Inhibitor ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Dose Finding ◽  
Phase 1B

7119 Introduction: AMG 706 is an investigational, oral, multi-kinase inhibitor with both antiangiogenic and direct antitumor activity targeting VEGF, PDGF, and Kit receptors. Panitumumab, a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFr), has shown antitumor activity and acceptable safety in pts with solid tumors. Methods: This is an ongoing, multicenter, dose finding, phase 1b study of AMG 706 with panitumumab and CP in pts with advanced NSCLC. Primary objectives were to assess the safety and PK of AMG 706; secondary objectives included drug exposure and objective response rates. Pts had stage IIIB/IV NSCLC, ECOG score of 0–1, no symptomatic or untreated CNS metastases, and no prior chemotherapy for NSCLC (segments A&C) or ≤ 1 regimen for NSCLC (segment B). AMG 706 was given orally either QD (50 mg or 125 mg) or BID (75 mg) with CP Q3W (P:200 mg/m2; C: AUC = 6 mg/mL · min; Segment A), with panitumumab (9.0 mg/kg Q3W; Segment B), or with CP+ panitumumab (Segment C). AMG 706 was dosed continuously in 21-day cycles (days 3–21 in cycle 1; days 1–21 in cycle 2 and beyond); pts were sequentially enrolled into escalating AMG 706 dose cohorts. Results: As of 9/05, 22 pts were enrolled (10 in A, 12 in B) into AMG 706 dose cohorts of 50 mg and 125 mg QD. In A and B, respectively, 7 and 6 pts were men; median (range) age was 60.5 (60, 74) and 60.5 (55.7, 71.0). One pt in the 125 mg QD cohort in Segment B had grade (gr) 5 pneumonia. Treatment-related adverse events occurring in >5% of all patients are summarized ( table ). Preliminary data showed that AMG 706 PK profiles were similar when administered with CP either 30 min or 48 hrs apart. At 50 mg QD, there was no effect of AMG 706 on the PK of P. Conclusions: Preliminary data indicate that AMG 706 can be combined safely with CP or panitumumab in pts with advanced NSCLC and that there is no effect on the PK of AMG 706 or P. Updated data will be presented. [Table: see text] [Table: see text]

Mutant (MT) KRAS codon 12 and 13 alleles in patients (pts) with metastatic colorectal cancer (mCRC): Assessment as prognostic and predictive biomarkers of response to panitumumab (pmab).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3581-3581 ◽  
Author(s):  
Marc Peeters ◽  
Jean-Yves Douillard ◽  
Eric Van Cutsem ◽  
Salvatore Siena ◽  
Kathy Zhang ◽  
...  
Keyword(s):  
Human Monoclonal Antibody ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Allele Distribution ◽  
Three Phase ◽  
Epidermal Growth ◽  
Codon 12 And 13 ◽  
Kras Codon

3581 Background: Pmab is a fully human monoclonal antibody against the epidermal growth factor receptor (EGFR). Significant improvement in progression-free survival (PFS) was demonstrated in pts with wild-type (WT) KRAS mCRC treated with pmab+FOLFOX4 (1st-line; study 20050203), pmab+FOLFIRI (2nd-line; study 20050181), and pmab monotherapy (study 20020408). In mCRC, mutations in KRAS codons 12 and 13 are established biomarkers for lack of clinical benefit to anti-EGFR therapies. We retrospectively examined individual MT KRAS codon 12 and 13 alleles as prognostic and predictive biomarkers of response in three phase 3 studies. Methods: Pts were randomized to receive FOLFOX4, FOLFIRI, or best supportive care +/- pmab 6.0 mg/kg Q2W in trials 20050203, 20050181, and 20020408, respectively. The MT KRAS codon 12 and 13 alleles (G12A, G12C, G12D, G12R, G12S, G12V, G13D) were detected using the Therascreen K-RAS Mutation Kit (Qiagen). Results: MT KRAS codon 12 and 13 alleles were detected in 40% (440/1096), 45% (486/1083), and 43% (184/427) of pts in trials 20050203, 20050181, and 20020408, respectively. MT KRAS allele distribution was conserved across studies and balanced between treatment arms. Baseline demographic and clinical features were comparable between all MT KRAS allele subgroups. There was no consistent evidence that any individual MT KRAS allele, compared to the remaining MT KRAS alleles or the entire MT KRAS group, differentially impacted PFS or overall survival (OS) in control arm-treated or pmab-treated pts. Only in the pmab+FOLFOX4 arm of study 20050203 were G13D (unfavorably) and G12V (favorably) significantly associated with OS. Response rates were similar between MT KRAS allele groups in the 1st- and 2nd-line mCRC treatment setting. Finally, in analyses of pts pooled from all 3 trials, only the G12A KRAS allele emerged as a significant negative predictive factor for OS. Conclusions: The lack of consistent results across three lines of therapy indicates pts whose tumors harbor MT KRAS codon 12 or 13 alleles are unlikely to respond to pmab therapy. Currently, only pts with WT KRAS mCRC should be treated with EGFR antibodies.

An interim evaluation of efficacy and safety of the combination of panitumumab, gemcitabine, and irinotecan in patients with advanced or metastatic cholangiocarcinoma: A phase II study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 328-328
Author(s):  
Weijing Sun ◽  
Davendra Sohal ◽  
Kristine Mykulowycz ◽  
Ursina R. Teitelbaum ◽  
Nevena Damjanov ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Tumor Stage ◽  
Infusion Reaction ◽  
Primary Objective ◽  
Over Expression ◽  
Epidermal Growth ◽  
Efficacy Criteria ◽  
Tissue Specimens ◽  
Ecog Ps

328 Background: Cholangiocarcinoma is an aggressive neoplasm. Current chemotherapy approaches suggest that combinations may be superior to single agents in this disease. Over-expression of epidermal growth factor receptor (EGFR) is associated with tumor stage and prognosis. This study was designed to evaluate the efficacy and tolerability of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan in patients with advanced and metastatic cholangiocarcinoma. Methods: Pts with advanced unresectable or metastatic cholangiocarcinoma, ECOG PS 0-2, and adequate liver, kidney and bone marrow function were treated with panitumumab (9 mg/kg) on day 1, gemcitabine (1000 mg/m2/100 min) iv and irinotecan (100 mg/m2) iv on days 1 and 8 of a 21-day cycle. Tissue specimens were collected based on availability for future biomarker analyses. The primary objective was to evaluate the 5-month progression-free survival (PFS) rate. The secondary objectives include overall response rate (ORR), overall survival rate (OS) and toxicity of the combination. Results: There have been 24 (of planned 42) pts recruited to the study. Toxicity of the combination was assessed in all enrolled pts. There were no treatment related deaths. The most common gr 3 or higher toxicity was were neutropenia (10 pts [40%]), thrombocytopenia (6 pts, [25%]), skin rash (4 pts [17%]) and diarrhea (3 pts, [12%]). One pt developed a gr 2 infusion reaction, which was considered related to panitumumab. Efficacy was evaluated in 20 pts. Among them, there were 2 CR, 6 PR, and 10 SD (with disease control rate of 90%), and 2 PD (assessed by RECIST criteria). Two pts went on to have surgical resection. Eight pts had ≥ 10 cycles of the therapy, and dose modification/interruption were needed for some of these pts. Conclusions: The data of this on-going study showed encouraging results of the combination of panitumumab with gemcitabine and irinotecan in both tolerability and efficacy. The pre-specified efficacy criteria to continue enrollment were met. Further analysis by biomarker status (KRAS/BRAF/EGFR) is forthcoming.

scholarly journals Randomized Phase II Trial of Fulvestrant Plus Everolimus or Placebo in Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy: Results of PrE0102

2018 ◽  
Vol 36 (16) ◽  
pp. 1556-1563 ◽  
Author(s):  
Noah Kornblum ◽  
Fengmin Zhao ◽  
Judith Manola ◽  
Paula Klein ◽  
Bhuvaneswari Ramaswamy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Mammalian Target Of Rapamycin ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival ◽  
Er Positive ◽  
Epidermal Growth

Purpose The mammalian target of rapamycin inhibitor everolimus targets aberrant signaling through the PI3K/AKT/mammalian target of rapamycin pathway, a mechanism of resistance to anti-estrogen therapy in estrogen receptor (ER)–positive breast cancer. We hypothesized that everolimus plus the selective ER downregulator fulvestrant would be more efficacious than fulvestrant alone in ER-positive metastatic breast cancer resistant to aromatase inhibitor (AI) therapy. Patients and Methods This randomized, double-blind, placebo-controlled, phase II study included 131 postmenopausal women with ER-positive, human epidermal growth factor receptor 2–negative, AI-resistant metastatic breast cancer randomly assigned to fulvestrant (500 mg days 1 and 15 of cycle 1, then day 1 of cycles 2 and beyond) plus everolimus or placebo. The study was designed to have 90% power to detect a 70% improvement in median progression-free survival from 5.4 months to 9.2 months. Secondary end points included objective response and clinical benefit rate (response or stable disease for at least 24 weeks). Prophylactic corticosteroid mouth rinses were not used. Results The addition of everolimus to fulvestrant improved the median progression-free survival from 5.1 to 10.3 months (hazard ratio, 0.61 [95% CI, 0.40 to 0.92]; stratified log-rank P = .02), indicating that the primary trial end point was met. Objective response rates were similar (18.2% v 12.3%; P = .47), but the clinical benefit rate was significantly higher in the everolimus arm (63.6% v 41.5%; P = .01). Adverse events of all grades occurred more often in the everolimus arm, including oral mucositis (53% v 12%), fatigue (42% v 22%), rash (38% v 5%), anemia (31% v. 6%), diarrhea (23% v 8%), hyperglycemia (19% v 5%), hypertriglyceridemia (17% v 3%), and pneumonitis (17% v 0%), although grade 3 to 4 events were uncommon. Conclusion Everolimus enhances the efficacy of fulvestrant in AI-resistant, ER-positive metastatic breast cancer.

Cetuximab and irinotecan (CPT11) salvage treatment for colorectal cancer (CRC) in progression after two or more chemotherapy (CT) lines: The POLONORD Group experience

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14575-14575 ◽  
Author(s):  
D. Fagnani ◽  
A. Bertolini ◽  
E. Menatti ◽  
M. Duro ◽  
G. Luchena ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Cutaneous Toxicity ◽  
Free Survival ◽  
Epidermal Growth ◽  
Control Disease ◽  
Evaluating Methods ◽  
And Control

14575 Background: Cetuximab is a monoclonal antibody blocking the Epidermal Growth Factor Receptor (EGFR), that showed activity in advanced CRC. His safety and therapeutic profile in clinical practice is still carefully evaluating. Methods: 7 Italian Oncology Units (PoloNord Group) treated, from December 2004 to December 2006, 72 patients (pts) affected by metastatic (mts) CRC, in progression after two or more previous CT lines, with Cetuximab + CPT11 ± Fluorouracil (5FU). Cetuximab initial dose was 400 mg/m2, followed by 250 mg/m2 as weekly infusion; dose adjustments based on cutaneous toxicity. Median courses: 12 (range 2–59). CPT11 and 5FU was administered according centres favourite schedules. We evaluated pts for safety, objective response (RO), progression free survival (PFS) and overall survival (OS) Results: Pts characteristics: M/F 48/25; median age 64 years (range 39–74); previous chemotherapy lines: 2–6 (Oxaliplatin and CPT11± 5FU); EGFR positive: 72. Mts sites: liver 56%, lung 21%, peritoneum 10%; 13% of pts had two or more mts sites. Safety: 8/72 (11%) pts showed G3–4 toxicity (WHO): cutaneous 5 pts; vomiting 1 pts, and neutropenia 3 pts . No allergic reactions. 4/72 pts stopped therapy to unacceptable toxicity, while 53/72 pts to disease progression. RO in 68/72 pts were: 9 RP (13%), 14 SD (21%) and 45 PD (66%). 6/14 SD pts showed tumor markers (CEA/Ca19.9) reduction. No pts had surgery option after treatment. Median PFS from start of therapy in 58/72 pts was 4 months (range 1–15). Median OS from diagnosis of mts disease in 67/72 pts was 28 months (range 7–81). Conclusions: According to safety and control disease reporting by international trials, our experiences showed that, also in clinical practice, Cetuximab + CPT11 is a valid option for the treatment of advanced, pretreated CRC. No significant financial relationships to disclose.

Predictive value of skin toxicity severity for response to panitumumab in patients with metastatic colorectal cancer (mCRC): A pooled analysis of five clinical trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4134-4134 ◽  
Author(s):  
J. Berlin ◽  
E. Van Cutsem ◽  
M. Peeters ◽  
J. R. Hecht ◽  
R. Ruiz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Phase Ii Studies ◽  
Common Skin

4134 Background: Panitumumab, a fully human monoclonal antibody against the epidermal growth factor receptor (EGFr), is approved for EGFr-expressing mCRC patients (pts) with disease progression (PD) on or following fluoropyrimidine (5FU)-, oxaliplatin (Ox)-, and irinotecan (Ir)-containing chemotherapy. Skin toxicities are common with panitumumab; we examined the association between severity of skin toxicity and panitumumab efficacy. Methods: Data from 5 clinical trials were pooled (4 phase II studies and 1 phase III study). Pts with mCRC had documented PD on or after 5FU, Ox, and/or Ir. Pts received panitumumab 6 mg/kg every two weeks (Q2W) or 2.5 mg/kg weekly (QW) until PD or intolerability. Tumors were assessed using modified WHO or RECIST criteria (blinded central review in 4/5 studies). Endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). PFS and OS were measured from enrollment. Only pts with =2 infusions (exposure over 2 wks for QW dosing or over 4 weeks for Q2W dosing) were analyzed to help correct for lead-time bias. Results: 612 of 640 pts were included in the analysis set (62% were male, 92% were white, and median age [range] was 61 [21, 88] years). The median (95% CI) duration of PFS was 8.4 weeks (8.0 to 11.3), the median (95% CI) survival was 6.9 months (6.2 to 7.9), and the ORR (95% CI) was 9.0% (6.8 to 11.5). The most common skin toxicities (any grade, grade 3/4) were erythema (54%, 4%) pruritus (53%, 2%), dermatitis acneiform (52%, 5%), and rash (39%, 2%). ORR, PFS, and OS appeared to favor pts with grade 2–4 skin toxicity vs pts with grade 0- 1 skin toxicity ( table ). Conclusion: In this large combined analysis, severity of skin rash was correlated with increased efficacy of panitumumab in terms of ORR, PFS, and OS. [Table: see text] No significant financial relationships to disclose.

ELOQUENT-1: A phase III, randomized, open-label trial of lenalidomide/dexamethasone with or without elotuzumab in subjects with previously untreated multiple myeloma (CA204-006).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS8113-TPS8113 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Thierry Facon ◽  
Paul Gerard Guy Richardson ◽  
Robert Z. Orlowski ◽  
Jesùs F. San-Miguel ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Response Duration ◽  
Surface Glycoprotein ◽  
Phase Iii ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Open Label ◽  
Cell Surface Glycoprotein ◽  
Prior Therapy

TPS8113 Background: Elotuzumab (Elo) is a humanized monoclonal IgG1 antibody targeting the cell surface glycoprotein CS1, which is highly expressed on >95% of MM cells. In a MM xenograft mouse model, the combination of Elo + lenalidomide (Len) significantly reduced tumor volume in a synergistic manner compared with either agent alone. In a phase 2 study (N=73) of Elo (10 or 20 mg/kg) in combination with Len and low-dose-dexamethasone (Dex) in pts with RR MM, the 10 mg/kg dose group (n=36) demonstrated objective response rates (ORR) of 92% in all pts, and 100% in pts who had received only 1 prior therapy (n=16). The higher response rate in pts with fewer prior lines of therapy provides a rationale for investigating this combination earlier in the disease course. This randomized, open-label, phase 3 trial will determine if the addition of Elo to Len/Dex improves progression-free survival (PFS) in pts with newly diagnosed, untreated MM. Methods: Pts (N=750) with newly diagnosed symptomatic MM ineligible for stem cell transplant will be randomized in a 1:1 ratio to receive 28-day cycles of Len 25 mg PO (days1-21) 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 of cycles 3-18 followed by 20 mg/kg on day 1 of cycle 19 onward. 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. Pts will be followed up for response every 4 weeks until progressive disease and for survival every 16 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 1, 2012, 13 pts were enrolled and 9 pts were treated. NCT01335399.

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