Hoping to file a biologics license application next year, Medarex Inc. and partner Bristol-Myers Squibb Co. started the second trial in the pivotal program to evaluate MDX-010 as a second-line treatment against metastatic melanoma.
Based upon an FDA-reviewed special protocol assessment, the open-label, single-arm study is expected to involve about 150 patients with unresectable Stage III or Stage IV metastatic melanoma who experience disease progression following at least one prior treatment with another melanoma therapy, most likely chemotherapy.
Patients will receive "an induction regimen" of 10 mg/kg of MDX-010 (ipilimumab) once every three weeks for up to four doses, followed by "a maintenance schedule once every 12 weeks until disease progression," Medarex President and CEO Don Drakeman said in a conference call.
The trial's primary endpoint will be best objective response rate based on both complete and partial responses. Secondary endpoints will include response duration, disease control rate, disease progression and survival.
"This is a very strong addition to our ipilimumab registration program," Drakeman said. "It's designed to provide another BLA filing opportunity, in addition to the ongoing combination trial of MDX-010 and our MDX-1379 peptide vaccine."
In September 2004, Medarex and BMS launched a Phase III study involving 750 patients with previously treated Stage III or Stage IV metastatic melanoma. Patients are being randomized to receive one of three treatment regimens: 3 mg/kg of MDX-010 plus MDX-1379 or one of those therapies alone. (See BioWorld Today, Aug. 24, 2004.)
"We're also starting a randomized, multi-arm, dose-ranging Phase II supportive study," Drakeman said.
That study is expected to enroll about 210 previously treated patients randomized to receive MDX-010 as a monotherapy at one of three dose levels: 0.3 mg/kg, 3 mg/kg or 10 mg/kg. Enrollment could be completed at the end of this year.
On top of those studies, Medarex and BMS are planning a front-line registrational study to start this year to evaluate MDX-010 plus chemotherapy vs. chemotherapy alone. About 500 patients, none of whom have received prior treatment, will be enrolled, with a primary endpoint of overall progression-free survival.
FDA approval "ultimately will depend on the totality of the clinical and safety data" incorporating results "of all the studies we've been pursuing," Drakeman said. "This will give us multiple shots on the FDA approval goal beginning next year."
MDX-010, a fully human antibody, is designed to enable the immune system to block tumor growth. The antibody targets the CTLA-4 receptor, a molecule found on T cells that is believed to suppress the immune response.
Beyond melanoma, the product is in early clinical testing against ovarian, prostate, breast, pancreatic and lymphoma cancer types, with additional trials expected this year and next year.
Drakeman said development plans include evaluating MDX-010 in other "combination opportunities."
Medarex and New York-based BMS agreed in 2004 to collaborate on development and commercialization of MDX-010. The deal also includes development of MDX-1379 for use in combination with MDX-010 in melanoma.
Under the terms, the companies will share costs of developing the antibody products in the U.S. and Europe, with BMS handling all development outside those territories. Medarex received an initial $50 million payment and could receive up to $480 million in regulatory and sales milestones.
The Princeton, N.J.-based company retains an option to co-promote MDX-010 in the U.S., and would be entitled to royalties for any sales outside the U.S. (See BioWorld Today, Nov. 9, 2004.)
Shares of Medarex (NASDAQ:MEDX) closed at $13.22 Friday, up 38 cents.