Press Release:
Millennium Announces Findings from Novel Antibody-Chemotherapeutic
Press Release
News Article February 2005
ORLANDO, Fla., Feb. 20 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals, Inc. today announced final results from a phase I clinical trial of MLN2704 in patients with advanced hormone-refractory prostate cancer. These results were presented at the 2005 Prostate Cancer Symposium taking place this week in Orlando, Fl.
The findings from this first in human MLN2704 single ascending dose trial indicated the molecule was well tolerated and produced sustained anti-tumor activity, including one patient who achieved a durable partial response in measurable disease for 11 months, as well as a sustained prostate specific antigen (PSA) decline of more than 50 percent. This patient received 14 doses prior to measurable disease progression at 47 weeks. MLN2704 is composed of a deimmunized monoclonal antibody (MLN591) directed at prostate specific membrane antigen (PSMA) conjugated to the chemotherapeutic agent DM1.
"We are encouraged by these findings with MLN2704 in prostate cancer, and we are continuing to assess the dose and schedule," said David Schenkein, M.D., senior vice president, clinical research, Millennium. "These results allow us to continue to pursue this important area of unmet medical need, and we are hopeful that further development can lead to new therapeutic options for patients with hormone-refractory prostate cancer."
Interim data from the Company's ongoing multiple ascending dose trial evaluating MLN2704 in patients with prostate cancer has been accepted for presentation at the 41st Annual Meeting of the American Society of Clinical Oncology (ASCO) scheduled for May 13-17 in Orlando, Fl.
Also presented at the meeting were results from two VELCADE studies in patients with progressive hormone-refractory prostate cancer: a phase I/II clinical trial of VELCADE in combination with docetaxel and a phase II study of VELCADE with and without steroids. The findings from the study evaluating VELCADE(R) (bortezomib) for Injection and 40mg docetaxel in combination weekly indicated the combination was well tolerated and showed promising activity. Specifically, in the higher VELCADE dose cohort, there were two partial responses in 18 patients with measurable disease and there were confirmed PSA declines of at least 50 percent in 36 percent of the 28 evaluable patients.
VELCADE is being co-developed by Millennium and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Millennium is responsible for commercialization of VELCADE in the U.S.; Ortho Biotech and Janssen-Cilag are responsible for commercialization in Europe and the rest of the world. Janssen Pharmaceutical K.K. is responsible for Japan.
"We are continuing to evaluate the data from the VELCADE trials in the prostate cancer population to better assess and understand the activity we have seen in these and past trials," said Dr. Schenkein. "We anticipate finalizing our evaluation and determining next steps in prostate cancer with VELCADE later this year in collaboration with our partner, Johnson & Johnson Pharmaceutical Research & Development, L.L.C."
MLN2704 in patients with advanced androgen independent metastatic prostate cancer; updated results
A single ascending dose phase I study of MLN2704, led by Howard I. Scher, M.D. at Memorial Sloan-Kettering, New York and Mario Eisenberger, M.D. at Johns Hopkins Oncology Center, Maryland enrolled 23 patients and examined the maximum tolerated dose, dose-limiting toxicity, pharmacokinetics and immunogenicity of MLN2704. Patients received MLN2704 at doses ranging from 18 to 343mg/m2. Responses in patients with measurable disease were evaluated based on the RECIST (Response Evaluation Criteria In Solid Tumors) criteria and confirmed four to six weeks after the first documentation of a complete or partial response. In addition, anti-tumor activity was evaluated based on a sustained PSA decline of at least 50 percent confirmed by two separate measurements at least four weeks apart. Dose escalation continued if no dose- limiting toxicity was observed. Investigators reported the following results:
* Of 11 patients with measurable disease, one patient treated with a
264mg/m2 dose, achieved a durable partial response, including a PSA
decline of more than 50 percent . This patient received 14 doses prior
to measurable disease progression at 47 weeks;
* One additional patient, treated with a 343mg/m2 dose, achieved a PSA
decline of more than 50 percent that persisted for 24 weeks;
* Four patients achieved stable disease;
* Toxicities greater than grade three occurred in three patients
including an episode of uncomplicated febrile neutropenia with
lymphopenia and leukopenia, lymphopenia, and a transient grade three
elevation in hepatic transaminases. No grade four toxicities were
observed; and
* No immunogenicity was observed despite repeat dosing.
VELCADE(R) (bortezomib) for Injection in combination with docetaxel in patients with advanced androgen independent prostate cancer
A phase I/II study of VELCADE in combination with docetaxel, being led by Robert Dreicer, M.D., at the Cleveland Clinic Foundation, Cleveland, OH, examined the dose-limiting toxicities, maximum tolerated dose, and the effects on PSA levels of VELCADE and docetaxel, both given weekly for two out of three weeks, in patients with advanced androgen-independent prostate cancer. Two dose levels were expanded into phase II cohorts, one with VELCADE 1.3mg/m2 and docetaxel 40 mg/m2, the second with VELCADE 1.6mg/m2 and docetaxel 40 mg/m2. Anti-tumor responses in patients with measurable disease were evaluated based on the RECIST criteria and confirmed four to six weeks after the first documentation of a complete or partial response. In addition, anti-tumor activity was evaluated based on a sustained PSA decline of more than 50 percent confirmed by two separate measurements at least four weeks apart. Investigators reported the following results:
* In the cohort in which patients were treated with VELCADE 1.3mg/m2 and
docetaxel 40 mg/m2:
-- Of 25 evaluable patients, six patients (24 percent) achieved a
confirmed PSA decline of more than 50 percent of which four patients
achieved a confirmed PSA decline of at least 90 percent; and
-- 100 percent of the 13 patients with measurable disease achieved
either partial remission or stable disease, specifically three
achieved partial remission.
* In the cohort in which patients were treated with VELCADE 1.6mg/m2 and
docetaxel 40 mg/m2:
-- Of 28 evaluable patients, 10 (36 percent) had a PSA decline of more
than 50 percent;
-- 78 percent of 18 patients with measurable disease achieved partial
remission or stable disease, specifically two patients achieved
partial remission.
* Adverse events observed included fatigue, gastrointestinal events,
neuropathy, and hematologic toxicities.
VELCADE in combination with prednisone in patients with advanced androgen independent prostate cancer
A phase II study of VELCADE, led by Michael Morris M.D. and Howard I. Scher, M.D. at Memorial Sloan-Kettering, New York, NY enrolled 30 patients and examined the efficacy of VELCADE in patients with progressive androgen independent metastatic prostate cancer. Patients were treated in two groups, the first 12 patients receiving VELCADE 1.5mg/m2 twice weekly for two out of three weeks at induction with daily prednisone 10mg, and the next 18 patients receiving VELCADE 1.3mg/m2 on the same schedule at induction with prednisone 10mg upon progression. All patients received VELCADE 1.6 mg/m2 weekly as maintenance. Antitumor activity was evaluated based on imaging and measurement of PSA decline at six and twelve weeks. Investigators reported the following results from pooled cohorts:
* Of nine patients with measurable disease, two patients achieved stable
PSA and stable scans at 12 weeks;
* Two patients had a stable PSA at 12 weeks but progressed
radiographically;
* One patient in the higher dose group demonstrated a partial response on
scans but PSA continued to rise; and
* Side effects included hematologic, metabolic and hepatic side effects,
neuropathy, syncope, diarrhea and fatigue.
About Prostate Cancer
According to the American Cancer Society, this year approximately 230,110 new cases of prostate cancer will be diagnosed in the United States and approximately 29,900 men will die of this disease. The five-year survival rate of men with prostate cancer is 98 percent with this percentage jumping to 100 percent if the cancer is found before it metastasizes (spreads to another area of the body). Once the tumor spreads beyond the primary tumor, the five-year survival rate drops to 34 percent. Today there is a tremendous unmet medical need for treating the disease, particularly for end-stage or androgen-independent prostate cancer for which therapeutic options are limited. The exact cause of prostate cancer is not yet known; however, scientists have identified certain risk factors, including family history of the disease, age, diet and race.
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