Ribi ImmunoChem Research Inc. got approval to start a Phase IIItrial of its Melacine melanoma theraccine in combination withinterferon alpha-2b in patients with Stage IV, or disseminated,melanoma.

The controlled, randomized, stratified 300-patient trial will compareMelacine and interferon alpha against interferon alpha (IFN-alpha)alone. Enrollment is expected to start in 1995, perhaps in as few asfour months.

The primary endpoint is survival. Other endpoints are disease-freesurvival, quality of life, tumor regression, duration of response, safetyand toxicity. Each arm of the study will include 150 patients.

The pivotal trial is based on an 18-patient pilot study conducted byMalcolm Mitchell and others at the University of SouthernCalifornia. Mitchell now is at the University of California at SanDiego. Results of that study were published in the February 1994issue of the Journal of Clinical Oncology. (See BioWorld Today,March 10, 1994, p. 1.)

The 18 patients in Mitchell's study had been designated non-responders to an earlier Phase II study of Melacine. Eight of the 18responded to the follow-up INF-alpha therapy. The 44 percentresponse rate, which included partial and complete responses, isbetter than that achieved with Melacine (20 percent) or IFN (17percent) alone.

Median duration of the response rate was 11 months. Median survivalhad exceeded 32 months at the time study results were published.Updated analysis showed median survival of the eight patients was36 months, said Jeffrey McDowell, Ribi's corporate informationmanager. Historic median survival of those with disseminatedmelanoma is six to 10 months, Ribi said.

Ribi, of Hamilton, Mont., has a separate, ongoing Phase III trial ofMelacine in Stage II melanoma patients. That study is testing itsability to prevent recurrence of melanoma in those who have lesionssurgically removed. That trial is being run by the SouthwestOncology Group and sponsored by the National Cancer Institute.Patient accrual is expected to be completed this year.

The new trial will involve a slightly different treatment regimen thanthe Mitchell study. Patients in the combination treatment group willget 10 Melacine immunizations over 12 weeks. INF-alpha (Madison,N.J.-based Schering-Plough Corp.'s Intron A) will be given topatients at the fourth week, rather than four weeks after the Melacinetreatment. The regimen was modified to optimize the synergies of thetwo therapies, said Ken Von Eschen, Ribi's vice president of clinicaland regulatory affairs.

Melacine contains tumor cells from two cell lines plus Ribi's Detoxadjuvant to enhance the immune response. The tumor cells, which arekilled and lysed, act as antigens that stimulate an immune response inpatients against their tumors. Detox combines monophosphoryl lipidA, a non-toxic derivative of gram-negative endotoxin, withmycobacterial cell wall skeleton, another immunostimulant. n

-- Jim Shrine

(c) 1997 American Health Consultants. All rights reserved.

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