Randomized Phase II Study of Bevacizumab in Combination With Carboplatin Plus Paclitaxel in Patients With Previously Untreated Advanced Mucosal Melanoma

2021 ◽  
pp. JCO.20.00902 ◽  
Author(s):  
Xieqiao Yan ◽  
Xinan Sheng ◽  
Zhihong Chi ◽  
Lu Si ◽  
Chuanliang Cui ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Mucosal Melanoma ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Open Label ◽  
Open Label Phase

PURPOSE Mucosal melanoma (MM) is a highly vascularized tumor with an extremely poor prognosis. In this randomized, open-label, phase II study, we characterized the efficacy and safety of bevacizumab in combination with carboplatin plus paclitaxel (CPB) in patients with previously untreated advanced MM. PATIENTS AND METHODS Patients were randomly assigned in a 2:1 ratio to receive carboplatin (area under the curve, 5) plus paclitaxel (175 mg/m2) once every 4 weeks in combination with (CPB arm, 5 mg/kg) or without (CP arm) bevacizumab once every 2 weeks. Progression-free survival (PFS) was the primary end point. Secondary end points included overall survival (OS), objective response rate, and adverse events. RESULTS We recruited 114 patients to our study. The median PFS was significantly longer in the CPB arm (4.8 months; 95% CI, 3.6 to 6.0 months) than in the CP arm (3.0 months; 95% CI, 1.7 to 4.3 months) (hazard ratio, 0.461; 95% CI, 0.306 to 0.695; P < .001). Objective response rates were 19.7% and 13.2%, respectively ( P = .384). The median OS was also significantly longer in the CPB arm than in the CP arm (13.6 v 9.0 months; hazard ratio, 0.611; 95% CI, 0.407 to 0.917; P = .017). No new safety signals were observed. CONCLUSION PFS and OS were significantly better in patients with metastatic MM who received bevacizumab in addition to CPB than in those who received CPB alone. A phase III study should be performed to confirm these benefits (ClinicalTrials.gov identifier: NCT02023710 ).

scholarly journals Phase II Study of Vorinostat for Treatment of Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma

2011 ◽  
Vol 29 (9) ◽  
pp. 1198-1203 ◽  
Author(s):  
Mark Kirschbaum ◽  
Paul Frankel ◽  
Leslie Popplewell ◽  
Jasmine Zain ◽  
Maria Delioukina ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Open Label ◽  
Mantle Cell ◽  
Open Label Phase

Purpose We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma. Patients and Methods In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability. Results All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue. Conclusion Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted.

Overall survival results from the randomized phase II study of palbociclib (P) in combination with letrozole (L) vs letrozole alone for frontline treatment of ER+/HER2– advanced breast cancer (PALOMA-1; TRIO-18).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1001-1001 ◽  
Author(s):  
Richard S. Finn ◽  
John Crown ◽  
Istvan Lang ◽  
Katalin Boer ◽  
Igor Bondarenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Survival Data ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Frontline Treatment ◽  
Open Label Phase

1001 Background: Preclinical data identified a synergistic role for P and hormone blockade in blocking growth of ER+ breast cancer (BC) cell lines. PALOMA-1 was an open-label phase II trial comparing progression-free survival (PFS) in patients (pts) with advanced ER+/HER2– BC treated with P+L or L alone. Median PFS increased with addition of P to L to 20.2 mos (vs 10.2 mos with L alone; HR = 0.488), with an acceptable safety profile, leading to accelerated approval by the US FDA. These results were confirmed in the phase 3 PALOMA-2 trial. At the time of the final PFS analysis, overall survival (OS) data were immature with only 61 events in both arms and a median follow-up of < 30 mos with a trend in favor of P+L vs L (37.5 vs 33.3 mos; HR = 0.813; P= 0.211). Here we present final OS results. Methods: PALOMA-1 was a 2-part study evaluating P+L in ER+/HER2– advanced BC. Part 1 enrolled postmenopausal pts with this subtype using only ER+/HER2– while Part 2 enrolled pts of this subtype additionally screened for CCND1 amplification and/or loss of p16. The primary endpoint was investigator-assessed PFS. Secondary endpoints included objective response rate, OS, safety, and correlative biomarker studies. A total of 165 pts were randomized; 66 in Part 1 and 99 in Part 2. Baseline characteristics were balanced between treatment arms. In both parts, pts were randomized 1:1 to receive P+L or L alone. OS data were collected as well as post-study therapy. Results: As of Dec 2016, there were 116 OS events. Median OS was 37.5 mos (95% CI: 31.4, 47.8) with P+L vs 34.5 mos (95% CI: 27.4, 42.6) for L (HR = 0.897 [95% CI: 0.623, 1.294]; P= 0.281). Median OS was 37.5 vs 33.3 mos (HR = 0.837; P= 0.280) for Part 1 and 35.1 vs 35.7 mos (HR = 0.935; P= 0.388) for Part 2. 78.6% of pts in the P+L arm received post-study systemic therapy vs 86.4% in the L arm. More pts in the L arm received ≥3 lines of therapy (37% vs 18%). Further subgroup analyses and details on post-study therapies will be presented. Conclusions: In PALOMA-1, P+L provided a statistically non-significant trend towards an improvement in OS. Survival data from the phase III, PALOMA-2 study is awaited. Sponsor: Pfizer; Clinical trial information: NCT00721409.

A randomized phase II study comparing mFOLFOX-6 combined with axitinib or bevacizumab or both in patients with metastatic colorectal cancer (mCRC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 485-485 ◽  
Author(s):  
J. R. Infante ◽  
A. L. Cohn ◽  
T. R. Reid ◽  
W. J. Edenfield ◽  
T. Cescon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Antiangiogenic Agents ◽  
Open Label ◽  
Open Label Phase ◽  
C 32 ◽  
Ecog Ps

485 Background: Vascular endothelial growth factor receptor inhibitors, including axitinib (AG-013736), may be useful in treating patients with mCRC. The goals of this study were to estimate the objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety in patients with mCRC treated with mFOLFOX-6 combined with axitinib or bevacizumab or both. Methods: Patients with mCRC untreated with any systemic chemotherapy >12 months prior to enrollment, ECOG PS 0/1, adequate organ function, and controlled hypertension were eligible for this randomized, open-label, phase II study. Patients receiving prior treatment with antiangiogenic agents or those who were pregnant were ineligible. All patients received standard mFOLFOX-6 treatment and were randomized to receive either axitinib 5 mg (Arm A), or bevacizumab 5 mg/kg (Arm B), or axitinib 5 mg + bevacizumab 2 mg/kg (Arm C). Axitinib was administered orally twice daily. Efficacy was determined by RECIST criteria. Results: A total of 42, 43, and 41 patients were enrolled in Arms A, B, and C, respectively. The ORR was 29%, 49%, and 39% for Arms A, B, and C, respectively. Median PFS was 315 days, 350 days, and 377 days, with 1-year survival of 72%, 79%, and 80% for Arms A, B, and C, respectively. Discontinuations due to adverse events (AEs) were more common in Arm A (36%), than in Arms B (19%) or C (32%). More patients withdrew from Arm A (18%) than from Arms B (5%) or C 12%). The rates of grade 3 AEs were similar across arms, except for hypertension and fatigue which were more common in Arms A (15% and 12%) and C (21% and 29%) compared with Arm B (2% and 12%). Serious AEs were reported by 41%, 40%, and 56% of patients in Arms A, B, and C, respectively; the most common were gastrointestinal disorders (21%, 16%, 15%, respectively). Conclusions: In combination with mFOLFOX-6 chemotherapy, treatment with axitinib resulted in a lower ORR but comparable survival to bevacizumab and this did not appear to improve significantly in the presence of both agents. This result may have been affected by the higher numbers of discontinuations and withdrawals in Arm A compared with the other 2 arms. [Table: see text]

Phase II study of S-1 plus oxaliplatin (OX) at dose of 130 mg/m2 (SOX130) in Japanese patients (pts) with advanced gastric cancer (AGC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 112-112
Author(s):  
Yosuke Kito ◽  
Nozomu Machida ◽  
Satoshi Hamauchi ◽  
Takahiro Tsushima ◽  
Akiko Todaka ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Completion Rate ◽  
Phase Iii ◽  
Open Label ◽  
Α Level ◽  
Ecog Ps

112 Background: The phase III G-SOX trial had adopted SOX100 due to high incidence of thrombocytopenia in the previous phase I/II study, and failed to demonstrate the non-inferiority of SOX100 to S-1 plus cisplatin in chemotherapy-naïve Japanese pts with AGC. However, OX 130 mg/m2 has been approved for AGC in Japan since Sep 2014 on the evidence of the REAL-2 trial. Therefore, we conducted a study to evaluate the feasibility of SOX130 in Japanese AGC pts. Methods: This is a single-arm, open-label, multicenter, phase II study. Pts with unresectable or recurrent adenocarcinoma of stomach, no prior chemotherapy and ECOG PS 0 or 1 were treated with SOX130 (S-1 80-120 mg/day according to BSA for 2 weeks, OX 130 mg/m2 on day 1, every 3 weeks). The primary endpoint was the 3-cycle completion rate, defined as the proportion of pts who receive at least 80% of the planned OX dose for the first 3-cycle. We set the threshold 3-cycle completion rate at 50% and the expected rate at 75%. A sample size of 23 pts was needed with 80% power at a 5% α-level (one-sided). Results: From April 2015 to June 2016, 25 pts were enrolled. Pts’ characteristics were as follows: median age 64.5 years (range, 32-76), male/female 21/4, PS 0/1 15/10, unresectable/recurrent 21/4, and intestinal/diffuse 7/18. The 3-cycle completion rate was 72.0% (90% CI 53.8-86.1%). Among the 12 pts with measurable lesions, objective response rate and disease control rate were 58.3% and 83.3%, respectively. With a median follow-up period of 5.2 months, median progression-free survival was 7.5 months. Grade 3 adverse events were anorexia (n = 5), anemia (n = 3), thrombocytopenia (n = 2), neutropenia (n = 1) and nausea (n = 1). No treatment-related death was observed. Conclusions: SOX130 could be a first-line treatment option even in Japanese AGC pts. Clinical trial information: UMIN000016973.

Silmitasertib (CX-4945) in combination with gemcitabine and cisplatin as first-line treatment for patients with locally advanced or metastatic cholangiocarcinoma: A phase Ib/II study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 312-312
Author(s):  
Mitesh J. Borad ◽  
Li-Yuan Bai ◽  
Ming-Huang Chen ◽  
Joleen M. Hubbard ◽  
Kabir Mody ◽  
...  
Keyword(s):  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Preliminary Evidence ◽  
Phase Iii ◽  
Response To Treatment ◽  
Open Label ◽  
Phase Ib ◽  
Open Label Phase ◽  
Almost All

312 Background: Silmitasertib (CX-4945), an oral small molecule inhibitor of casein kinase 2 (CK2), has exhibited preclinical antitumor activity and strong synergism with gemcitabine + cisplatin. We investigated the safety and efficacy of silmitasertib in combination with gemcitabine + cisplatin in patients with unresectable cholangiocarcinoma (CCA). Methods: S4-13-001 is a multicenter, open-label, phase Ib/II study of silmitasertib in combination with gemcitabine + cisplatin in patients with locally advanced or metastatic CCA. The phase Ib portion included dose-escalation, expansion, and exploratory cohorts of silmitasertib with doses ranging from 200 to 1000 mg bid (6 days for the escalation/expansion cohorts and 10 and 21 days’ continuous dosing for the exploratory cohorts). In the phase II portion patients received silmitasertib 1000 mg bid for 10 days in combination with gemcitabine + cisplatin on days 1 & 8 over a 21-day cycle. In this interim analysis, we present findings from the combined population of patients from the phase Ib and II portions of the study. Response to treatment was assessed by RECIST v1.1 every 6 weeks. Primary efficacy outcome measure was progression-free survival (PFS). ClinicalTrials.gov (NCT02128282). Results: A total of 87 patients were enrolled and received silmitasertib in the phase Ib (n=50) and phase II (n=37) portions of the study. Of these, 55 patients were evaluable for efficacy with details as follows: median PFS 11.1 (95% CI 7.6–14.7) months; median overall survival (OS) 17.4 (95% CI 13.4–25.7) months; overall response rate (ORR) 32.1%; and disease control rate (DCR) 79.3%. Almost all patients (79/87; 90.8%) evaluable for safety reported ≥1 treatment-related adverse event (TEAE). The most common TEAEs (all grades) with silmitasertib were diarrhea (65.5%), nausea (50.6%), vomiting (33.3%), fatigue (31.0%), and anemia (21.8%). The most common grade ≥3 TEAEs were diarrhea (13.8%), neutropenia (11.5%), nausea (9.2%), anemia (8.0%), and thrombocytopenia (8.0%). Eleven patients (12.6%) discontinued treatment due to TEAEs. Conclusions: Silmitasertib in combination with gemcitabine + cisplatin yields promising preliminary evidence of efficacy in patients with locally advanced or metastatic CCA. Based on these data a randomized phase III trial is planned. Clinical trial information: NCT02128282.

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

REACT: A phase II study of rindopepimut (CDX-110) plus bevacizumab (BV) in relapsed glioblastoma (GB).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS2103-TPS2103 ◽  
Author(s):  
David A. Reardon ◽  
James J. Vredenburgh ◽  
Annick Desjardins ◽  
Ronald G. Steis ◽  
Erin M. Dunbar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Peptide Sequence ◽  
Phase Iii ◽  
Open Label ◽  
Term Survival ◽  
Gm Csf ◽  
Phase Ii Studies

TPS2103 Background: EGFRvIII is a constitutively active tumorigenic deletion mutation of EGFR. It is expressed in ~30% of primary GB where it is linked to poor long-term survival (Pelloski 2007). The investigational vaccine rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally (500ug with 150ug GM-CSF as an adjuvant). Remarkably consistent and promising results across 3 phase II studies in newly diagnosed, resected EGFRvIII+ GB (Lai 2011) represent a statistically significant improvement over a historical control cohort matched for major eligibility criteria (median overall survival [OS] = 24.4 - 24.6 vs. 15.2 months from diagnosis [m] and median progression-free survival [PFS] = 12.3 - 15.3 vs. 6.4 m). ACT IV, a phase III trial in this population, is ongoing. The immunosuppressive influence of residual/advanced GB presents a challenge to activation of efficacious antitumor immune responses. Anecdotal evidence (compassionate use cases, Sampson 2008) suggests that rindopepimut may induce specific immune responses and regression in multifocal and bulky residual tumors. Rindopepimut with BV, which inhibits VEGF and its immunosuppressive properties (including impaired maturation of dendritic cells and disruption of tumoral T cell infiltration [Johnson 2007, Shrimali 2010]) may further optimize EGFRvIII-specific immune response and antitumor activity. Methods: ReACT is a Phase II study of rindopepimut plus BV in patients (pts) with 1st or 2nd relapse of EGFRvIII+ GB. BV-naïve pts will be enrolled to Group 1 (n=70: randomized 1:1 to BV plus either rindopepimut/GM-CSF or control injection [low-dose KLH]) while BV-refractory patients will enter Group 2 (n=25: to receive BV plus open-label rindopepimut/GM-CSF). Concurrent with BV (10 mg/kg, q 2 wks), blinded treatment or open-label vaccine is given in priming phase (days 1, 15 and 29), then monthly until PD. Tumor response is assessed every 8 weeks, and patients are followed for survival after PD. Objectives are PFS at 6 months (primary), objective response rate, PFS, OS, safety, immunogenicity and elimination of EGFRvIII. ReACT opened to accrual in December 2011 (NCT01498328).

Final report of an open-label phase II trial of bevacizumab plus docetaxel and gemcitabine in metastatic, previously untreated nonsquamous non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18046-e18046
Author(s):  
Nathan A. Pennell ◽  
Sujith R. Kalmadi ◽  
Marc A. Shapiro ◽  
Hamed Daw ◽  
Cristina P. Rodriguez ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Final Report ◽  
Hematologic Toxicity ◽  
Open Label ◽  
Open Label Phase

e18046 Background: Platinum and non-platinum doublet chemotherapy has similar efficacy in advanced NSCLC patients (pts). Bevacizumab (B) improves outcomes when added to platinum doublets, but its safety and efficacy in combination with non-platinum doublets is unknown. This study was designed to test the combination of B, docetaxel (D), and gemcitabine (G) in first-line treatment of advanced NSCLC. Methods: Pts with metastatic, non-squamous NSCLC, PS 0-1, and measurable disease by RECIST were enrolled in this open-label, single arm phase II trial. Pts received D (75 mg/m2) on d1, G (900 mg/m2) on d1 & 8, and B (15 mg/kg) on d1 every 21d for up to 6 cycles, followed by B maintenance until progression or 12 mos total. Pts received growth factor d9. CT scans were performed every 6 wks. The primary endpoint was 1-yr progression-free survival (PFS), with secondary endpoints of safety, objective response rate (ORR), overall PFS, and overall survival (OS). Pts with tumor cavitation, untreated brain metastases, and hemoptysis were excluded. Planned enrollment was 46. Results: 13 pts were enrolled from 12/2009 to 4/2011. Pt characteristics: Median age 63 (35-69), 85% male, PS 0 (38%), PS 1 (62%). The median # of cycles of chemotherapy was 6 (1-6), median # cycles of B was 4 (1-15), with 2 pts coming off study prior to the first evaluation (1 grade 5 encephalopathy, 1 grade 4 febrile neutropenia). 5 pts (38%) had chemo dose reduction and 4 (31%) discontinued treatment for toxicity. 3 pts (23%) discontinued B prior to progression, 2 for tumor cavitation and 1 for grade 1 hemoptysis. The grade 3-5 non-hematologic toxicity rate was 69%, with 6 pts (46%) hospitalized with pneumonitis/pneumonia felt possibly related to study drugs. At this point enrollment was halted for safety concerns. The 1-yr PFS was 8%, and the median PFS was 6.9 mos (95% CI 2.0-NYR). 11 pts were evaluable for response, and 6 pts had partial responses for an ORR of 55%. The median OS was NYR with median follow up of 10.9 mos. Conclusions: The combination of B, D, and G was not tolerable at the doses and schedule used in this study. A formal phase I trial is needed if this combination is to be investigated further.

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.

SPIRITT (study 20060141): A randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 454-454 ◽  
Author(s):  
J. Randolph Hecht ◽  
Allen Lee Cohn ◽  
Shaker R. Dakhil ◽  
Mansoor N. Saleh ◽  
Bilal Piperdi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Grade 5 ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Previously Treated

454 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 2nd-line tx in a phase III trial comparing pmab + FOLFIRI vs FOLFIRI alone. Here, we describe the results of SPIRITT, a multicenter, randomized phase II study evaluating pmab + FOLFIRI and bev + FOLFIRI in pts with WT KRAS mCRC previously treated with a 1st-line bev + oxaliplatin (Ox)-based chemotherapy regimen. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + FOLFIRI Q2W or to bev 5.0 or 10.0 mg/kg + FOLFIRI Q2W. Eligibility criteria included: WT KRAS mCRC, ECOG ≤ 1, no prior irinotecan or anti-EGFR tx, and tx failure of prior 1st-line bev + Ox-based therapy (≥ 4 cycles). The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 182 pts with WT KRAS mCRC were randomized. All pts received tx. Efficacy results are shown (table). Worst grade of 3/4 adverse events (AE) occurred in 78% of pts in the pmab + FOLFIRI arm and 65% in the bev + FOLFIRI arm. Grade 5 AEs occurred in 7% of pts in the pmab + FOLFIRI arm and 7% in the bev + FOLFIRI arm. Tx discontinuation due to any AE was 29% in the pmab + FOLFIRI arm and 25% in the bev + FOLFIRI arm. Conclusions: In this estimation study of pts with WT KRAS mCRC that previously received bev + Ox-based tx, the PFS hazard ratio (HR) was 1.01 (95% CI: 0.68 - 1.50). The OS HR was 1.06 (95% CI: 0.75 - 1.49). The observed ORR was higher in the pmab + FOLFIRI arm. 54% of bev + FOLFIRI pts received subsequent anti-EGFR tx. The safety profile for both arms was similar to previously reported studies. Tx discontinuation rates due to AEs were similar between the arms. Clinical trial information: NCT00418938. [Table: see text]

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