Antigenics Presents Phase 3 Data from Trial of Oncophage in
Combined Population of Stage IV M1a and M1b Melanoma Patients Who Received at Least 10 Vaccinations Experienced Increased Survival of 143 Percent
Antigenics Inc. (NASDAQ: AGEN) today announced in an oralpresentation at the 42nd annual meeting of the American Society ofClinical Oncology (ASCO) updated findings from a Phase 3 clinicaltrial of the company's investigational cancer vaccine Oncophage(R)(vitespen; formerly HSPPC-96) in metastatic melanoma (abstract #8002).In the study, patients who received at least 10 doses of vaccineexperienced an extension in median survival of 29 percent comparedwith those who received physician's choice (hazard ratio = 0.749;nominal, one-sided P value = 0.130). In a subset analysis, Oncophagewas associated with a potentially clinically relevant benefit (hazardratio = 0.427; nominal, one-sided P value = 0.017) compared withphysician's choice for patients with stages IV M1a and M1b melanoma,if at least 10 doses of vaccine were administered.
"This is the first time a cancer vaccine has shown evidence of apotential survival benefit in this patient population," Jon Richards,MD, PhD, of the Oncology-Hematology department at Lutheran GeneralCancer Care Center, Park Ridge, IL, and lead investigator of thestudy. "These findings are consistent with preclinical and earlyclinical research conducted to date and lay a solid foundation for thecontinued exploration of Oncophage vaccine in better-prognosis stageIV melanoma patients."
Study Findings
The Phase 3, international, multicenter, open-label trial(protocol C-100-21) randomized 322 patients with stage IV melanoma toone of two treatment arms: Oncophage or physician's choice, in a 2:1ratio favoring Oncophage, and prospectively stratified based on AJCCmetastatic stage (M1a, M1b, M1c). Physician's choice includedinterleukin 2 (IL-2) and/or dacarbazine-/temozolomide-based therapyand/or complete tumor resection, and could also include any otherlicensed treatments for cancer. The primary endpoint of the trial wasoverall survival, and comparison of survival data was made using theKaplan-Meier method (an estimate of the cumulative probability ofsurvival for a set of data) and a one-sided log-rank test. Overall, inthe intent-to-treat analysis, patients in the Oncophage arm (M1a, -band -c combined) fared similarly to those in the physician's choicearm in terms of survival (9.4 months vs. 10.7 months, respectively;hazard ratio = 1.157; nominal, one-sided P value = 0.157).
Researchers also found that patients who received at least 10doses of vaccine (44 patients) experienced an extension in mediansurvival of 29 percent compared with those who received physician'schoice (72 patients; 16.5 months vs. 12.8 months, respectively; hazardratio = 0.749; nominal, one-sided P value = 0.130). A more pronouncedeffect was observed in M1a and M1b patients who received at least 10vaccines (25 patients) compared with those who received physician'schoice (33 patients), with an improved survival of 31.2 months vs.12.8 months, respectively (hazard ratio = 0.452; nominal, one-sided Pvalue= 0.017).
Adverse events reported during the trial were generally mild andexpected. The more frequently reported adverse events were mainlyconstitutional in nature and included, but were not limited to nausea,pyrexia (fever), fatigue, constipation, dyspnea (difficultybreathing), arthralgia (pain in the joints), headache, back pain andabdominal pain. Approximately 50 percent of patients receivingOncophage reported a serious adverse event (SAE), but only two SAEswere considered by the investigators to be related and unexpected.These events included one report of a thyroid disorder and anotherreport of cellulitis (inflammation of connective tissue).
Oncophage, Antigenics' lead product in development, is aninvestigational personalized cancer vaccine based on the company'sproprietary heat shock protein technology. Derived from each patient'scancerous tissue or cells, the vaccine is designed to capture the'antigenic fingerprint' of the patient's particular cancer. This isdesigned to reprogram the body's immune system to target and destroyonly cells bearing this fingerprint, leaving healthy tissue unaffectedand minimizing debilitating side effects associated with traditional,broader-acting cancer treatments. Oncophage has been granted fasttrack and orphan drug designations from the US Food and DrugAdministration (FDA) in both metastatic melanoma and renal cellcarcinoma.
"These clinical data add to the growing set of observations inother clinical research with Oncophage that the potential benefit ofour vaccine may be most apparent when more doses are administered tobetter-prognosis patients," said Garo H. Armen, PhD, chairman and CEOof Antigenics Inc. "We will soon have results from the in-depthanalysis of our Phase 3 kidney cancer trial, the largest studyconducted in the adjuvant setting, which we expect to show a similarpattern of effect in a much larger patient population. We are alsoexploring our next steps from a clinical development perspective,including potential combination treatments in melanoma as well asother indications."
About Melanoma
Melanoma is the most serious form of skin cancer. According to theAmerican Cancer Society, melanoma accounts for only about 4 percent ofskin cancer cases, but causes most skin cancer deaths. It is estimatedthat in 2006 there will be 62,190 new cases of melanoma in the UnitedStates and that about 7,910 people will die of the disease.
Oncologists treat advanced or metastatic melanoma, also known asstage III or IV melanoma, with surgery, radiation therapy,immunotherapy or chemotherapy, depending on the case. Approximately 15percent of all melanoma patients at the time of first diagnosis havestage III or stage IV disease. Existing treatments have notsignificantly improved overall survival of patients with melanoma.According to published literature, the median survival of patientswith late-stage III melanoma is about 24 months, and patients withstage IV melanoma have a median survival of about seven months.Although oncologists use various treatments, the only FDA-approvedtherapies for patients with metastatic melanoma are high-doseintravenous interleukin 2 and alpha interferon, another humancytokine.
About Antigenics
Antigenics is working to develop treatments for cancers,infectious diseases and autoimmune disorders. The company'sinvestigational product portfolio includes Oncophage(R) (vitespen;formerly HSPPC-96), a patient-specific therapeutic cancer vaccinebeing evaluated in several indications; Aroplatin(TM), a liposomal,third-generation platinum chemotherapeutic; ATRA-IV, a liposomalretinoic acid; AG-707, a therapeutic vaccine for the treatment ofgenital herpes; AU-801, a preclinical program targeting autoimmunedisorders; and QS-21, an adjuvant being evaluated by Antigenics'corporate partners in several late-stage clinical trials. For moreinformation, please visit www.antigenics.com.
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