August 8, 2016
Seattle Genetics and Takeda Pharmaceutical reported phase III results of ADCETRIS (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL). The ALCANZA trial is a randomized, open-label study designed to evaluate single-agent ADCETRIS versus a control arm of investigator’s choice of standard therapies, methotrexate or bexarotene, in patients with CD30-expressing CTCL, including those with primary cutaneous anaplastic large cell lymphoma (pcALCL) or mycosis fungoides (MF). The primary endpoint is ORR4 as assessed by Global Response Score in the ADCETRIS arm compared to the control arm. Key secondary endpoints are complete response rate, progression-free survival and reduction in the burden of symptoms during treatment. The clinical trial enrolled 131 patients at 50 sites globally. The results of the ALCANZA trial demonstrated that treatment with ADCETRIS resulted in a highly statistically significant improvement in the ORR4 versus the control arm as assessed by an independent review committee (p<0.0001). The ORR4 was 56.3% in the ADCETRIS arm compared to 12.5% in the control arm. The key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment, were all highly statistically significant in favor of the ADCETRIS arm. The safety profile associated with ADCETRIS from the ALCANZA trial was generally consistent with the existing prescribing information. ADCETRIS received Orphan Drug designation from the FDA for the treatment of mycosis fungoides, which is the most common type of CTCL. ADCETRIS also received Orphan Drug designation from the European Commission for CTCL, including subtypes primary cutaneous anaplastic large cell lymphoma and mycosis fungoides.
December 21, 2015
Spectrum Pharmaceuticals has reported results of a phase I combination trial of belinostat (Beleodaq) with the CHOP (cyclophosphamide, hydroxyl-doxorubicin, Oncovin and Prednisone) chemotherapy regimen as first-line treatment for newly diagnosed peripheral T-cell lymphoma (PTCL). Oncovin is a brand name for vincristine. The open-label, two-part trial enrolled a total of 23 patients. Eleven were enrolled in part A, the dose-escalation phase, to determine the study’s primary endpoint, the maximum tolerated dose (MTD). Part B of the study, the expansion phase, enrolled 12 additional patients at that dose level. The MTD of belinostat was established at 1,000mg/m2 IV infusion on days one through five (the recommended single agent dose) when combined with the CHOP regimen, with each component given at its full recommended dose. Secondary endpoints included safety, tolerability, Objective Response Rate (ORR: complete response + partial response) and pharmacokinetics. Results showed an ORR of 86% with the belinostat and CHOP combination, based on 21 evaluable patients (18/21), with the vast majority, 67%, achieving a complete response (14/21), and 19% achieving a partial response (4/21). In addition, the belinostat and CHOP combination was shown to have an acceptable safety profile with no new or unexpected toxicities. The most common (>10%) grade three/four hematologic adverse events (AEs) reported with Bel-CHOP were as expected: neutrophil count decreased (30%), anemia (22%), neutropenia (22%), white blood cell (WBC) count decreased (22%), febrile neutropenia (17%) and lymphocyte count decreased (17%). No grade three/four non-hematologic AEs >10% were reported. No patient discontinued therapy due to AEs. One patient died as a result of disease progression during the study. Beleodaq is a histone deacetylase (HDAC) inhibitor that received accelerated approval by the FDA for the treatment of relapsed or refractory PTCL in July 2014.
June 16, 2008
Bayer Schering reported positive results from a phase II trial of Leukine for the treatment of melanoma. This 24-month, single-arm, open-label study enrolled 45 subjects who had undergone potentially curative surgery. In the first year of treatment, Leukine was administered subcutaneously at 125mcg/m2/day for 14 consecutive days, followed by Interleukin-2 (IL-2) subcutaneously at nine million IU/m2/day for four days. The subjects then received no treatment for ten days. In the second year of treatment, Leukine was administered alone two times per week. In the subjects who experienced resected recurrence, the same adjuvant therapy was re-administered. At the end of the study, 32 of the original 45 subjects were alive. The survival data, expressed by Kaplan- Meier, showed disease-free survival of 60% and overall survival of 64% at 21 months. There was no statistical difference in survival by Log Rank between those who received only Leukine versus those treated by Leukine and IL-2 (p=.8). In addition, there was no increase in the number of dendritic cells during or after Leukine administration in 11 subjects who donated blood for dendritic cell counts. Leukine was generally well-tolerated, with toxicities mild to moderate in nature. Based on the results Bayer plans to move forward with the development of Leukine for this indication.
Epeius reported positive results from an ongoing phase I/II trial of Rexin-G for the treatment of breast cancer. This US, open-label, dose-comparison enrolled 24 subjects with rapidly progressive chemotherapy resistant breast cancer. The subjects received dose-escalations of Rexin-G given intravenously two to three times a week for four weeks, with doses ranging from 2 x 10e11 cfu to 6 x 10e11 cfu per week. The goal of the adaptive trial design was to confirm the over-all safety of Rexin-G and to determine the optimal dosing regimen. Rexin-G demonstrated significant biological activity without toxicity. Escalating doses of Rexin-G were associated with stabilization of disease, significant reductions in CA 15.3 levels, a median progression-free survival of six months and a median over-all survival of greater than seven months, with all subjects surviving at the 8-month follow-up period. Rexin-G was safe and well-tolerated up to the highest tested dose. Based on the results Epeius plans to continue with the trial as planned.
Gloucester released positive results from a phase IIb trial of romidepsin for the treatment of cutaneous T-cell lymphoma (CTCL). This non-randomized, open-label, single-arm international study, dubbed GPI-04-0001, enrolled 96 subjects. The subjects received romidepsin at a dose of 14 mg/m(2) intravenously on days 1, 8 and 15 of each 28-day cycle, for 6 cycles. Data is from 72 evaluable subjects. The primary endpoint, overall response rate, was achieved. In subjects who had failed previous therapy, 40.3% reached this goal. Partial response was observed in 33.3% and 6.9% of subjects achieved a complete response. The overall response rate in subjects with advanced stage disease was 47.9%, with 37.5% experiencing a partial response and 10.4% experiencing a complete response. Additionally, 92.3% of subjects with pruritus at the outset of the trial had some relief. Gloucester plans to file an NDA with the FDA later in 2008.
January 7, 2008
Cephalon reported positive results from a phase III trial of Treanda for the treatment of chronic lymphocytic leukemia (CLL). This randomized, international, multicenter, open-label study enrolled three-hundred and five subjects. It was designed to compare Treanda to chlorambucil. The subjects received Treanda (100 mg /M2 on days one and two) or chlorambucil (0.8 mg/kg on days one and fifteen) for up to six treatment cycles. The co-primary endpoints, overall response rate and progression-free survival, were both achieved. Overall response rate was significantly higher with Treanda than with chlorambucil (68% versus 39%; p<0.0001) with a strong complete response rate of 30% compared to 2%, a nodular partial response of 10% compared to 3%, and a partial response of 28% compared to 34%, respectively. Treanda significantly improved progression-free survival compared to chlorambucil (median 21.7 months versus 9.3 months, respectively; p<.0001). The median duration of response in the Treanda arm was 18.9 months compared to 6.1 months in the chlorambucil arm. An NDA is currently under review by the FDA.
Gloucester reported positive preliminary results from a phase II trial of romidepsin for the treatment of cutaneous t-cell lymphoma (CTCL) at the American Society of Hematology (ASH) Annual Meeting. Subjects enrolled in this non-randomized, open-label, single-arm international study received romidepsin at a dose of 14 mg/m(2), intravenously over four hours, on days one, eight and fifteen of a twenty-eight day cycle. The duration was six cycles, although those subjects who had an objective response or stable disease were eligible to continue therapy until disease progression. Of seventy- three evaluable subjects, an overall response rate of 37% was reported, with four complete responses, twenty-three partial responses and forty reports of stable disease. Six subjects had progressive disease. Of the subjects with severe pruritus at baseline, 37% reported significant relief. In addition, 38% of the subjects who exhibited any pruritus at baseline reported significant relief from symptoms. Treatment was determined to be safe and well tolerated. Based on the results, this phase II trial continues as planned.
Medarex and Bristol-Myers Squibb announced mixed top-line results from three phase III registrational trials (008, 022, 007) evaluating ipilimumab monotherapy for the treatment of metastatic melanoma. These international trials included an open-label, single arm trial (008) evaluating overall response rate in one hundred and fifty-five subjects who progressed on or following standard treatment; a randomized, double-blind trial (022) evaluating the efficacy of three dose levels of ipilimumab in two hundred and sixteen subjects who were previously treated, relapsed or failed to respond to experimental treatment or were unable to tolerate currently approved therapies; and a randomized, double-blind, placebo-controlled trial (007) in one-hundred and sixteen subjects comparing the safety of ipilimumab, with or without prophylactic oral budesonide (primarily evaluating the rate of grade 2+ diarrhea). The results from study 008, conducted under a SPA, did not meet the primary endpoint, which was to rule out a best objective response rate of less than ten percent. However, the totality of data from the trials included a clear dose response effect observed in study 022 and best objective response rates across the three studies ranging from mid-single digits to mid-teens as determined by independent radiology review. The objective responses included complete and partial responses. Medarex and BMS were planning to meet with the regulatory authorities and file for US approval by the first half of 2008.
December 15, 2003
Aton Pharma reported positive results from a phase II trial investigating SAHA, a suberoylanilide hydroxamic acid for the treatment of T-cell lymphomas (TCL). Results showed that out of thirteen subjects with refractory or relapsed TCL unresponsive to conventional therapies treated with SAHA, five achieved partial remissions as measured by Physician Global Assessment, five had stable disease and three progressed on therapy. The most commonly reported side effects were dry mouth, change in taste, decreased appetite, nausea, diarrhea and fatigue. Results were presented at the American Society of Hematology 45th Annual Meeting in San Diego.
SuperGen reported results from two multicenter clinical studies with Nipent (pentostatin for injection), for the treatment of non-hodgkin's lymphoma (NHL). The first was a phase II trial that enrolled 60 subjects with previously treated and untreated NHL at 25 sites across the U.S. Results showed that the objective response rate at day 60 was 59.6%, with 12 complete responses and 19 partial responses. In addition, the objective response rate at day 115 was 50.9% with 17 complete responses and 9 partial responses. Subjects received a combination of Nipent and rituximab. The second study was a multi-center pilot trial that enrolled 26 subjects with previously untreated, Stage III or Stage IV low-grade NHL. Results showed there were nine complete responses (37.5%), eight partial responses (33.3%) and four subjects with stable disease (16.7%) for an overall response rate of 83.3%. Subjects received a combination consisting of Nipent, mitoxantrone, and rituximab. Results were presented at the 45th Annual Meeting of the American Society of Hematology (ASH) in San Diego.