New York-based Keryx Biopharmaceuticals Inc. reported positive Phase II study data for perifosine (KRX-0401) in patients with advanced metastatic colon cancer and advanced kidney cancer, causing shares in the company to rocket 74 percent Monday.
Perifosine was shown to be effective as a single agent therapy in patients with advanced kidney cancer (renal cell carcinoma) and as a combination therapy with chemotherapy in patients with advanced colon cancer.
The study data were presented over the weekend at the annual meeting of the American College of Clinical Oncology (ASCO).
Perifosine showed activity in advanced kidney cancer in patients who had failed to improve on VEGF receptor inhibitors (sunitinib or sorafenib) or both a VEGF receptor inhibitor and an mTOR inhibitor inhibitor (either everolimus or temsirolimus).
The response rate for perifosine was 11 percent and three to four months of progression-free survival.
In the colon cancer study, perifosine combined with the chemotherapy medication capecitabine (sold as Xeloda by Roche Laboratories Inc.) more than doubled the time to disease progression compared to capecitabine plus placebo. In addition, the perifosine-capecitabine combo more than doubled the overall response rate and nearly doubled the clinical benefit rate vs. capecitabine plus placebo.
It was studied in patients with second- or third-line metastatic colon cancer. Third-line treatment for colon cancer is an area where Keryx CEO Ron Bentsur said there is an unmet medical need.
Currently, there are no third-line drugs approved for advanced colon cancer. Though, physicians may try chemotherapy at that point to fight the cancer, he said.
"As it turns out, we did well compared to the active control, Xeloda," Bentsur told BioWorld Today. "It's not easy to beat an active control in any study," he said, adding that that point resonated well with investors.
The expected progression-free survival (PFS) for third-line metastatic colon cancer, he said, is usually around three months. "Anything that can exceed that is obviously a blessing."
In the study group treated with perifosine plus Xeloda, PFS lasted roughly seven months (around 28 weeks), "well in excess of what you would typically expect a patient to achieve in this setting," Bentsur said. With Xeloda alone, PFS was just under 12 weeks.
The treatment regimen for first- and second-line care of advanced colon cancer are typically chemotherapy regimens such as Folfox and Folfiri (either with or without bevacizumab (Avastin).
There are seven approved drugs for patients with metastatic colorectal cancer: 5-FU, capecitabine (Xeloda), irinotecan (Camptosar), oxaliplatin (Eloxatin), bevacizumab, cetuximab (Erbitux) and panitumumab (Vectibix). Depending on the stage of the cancer, two or more of those types of treatment may be combined at the same time or used after one another.
Few companies are working on treatments for third-line colon cancer, and Keryx has one of the more advanced drug candidates.
In advanced kidney cancer, the mTOR inhibitor Rad 001 (Afinitor) was approved for advanced mestastatic renal cell carcinoma based on a response rate of 2 percent and four months PFS in a study that was much larger than Keryx's.
In the perifosine study, the response rate was 11 percent and three to four months PFS in a sicker patient population, Bentsur said. Those data, he said, "stacks up to the data that got that drug (Afinitor) approved."
Of all kidney tumors, 85 percent are classified as renal cell carcinoma (RCC), and of all patients with RCC, 25 percent present with advanced disease. Advanced RCC is resistant to such standard treatments as radiation therapy and chemotherapy, and the initial treatment for most patients is surgical removal of the kidney.
If the cancer is confined to the kidney, the five-year survival rate is 60 to 70 percent; but the survival rate is considerably lower after the cancer has metastasized to other parts of the body.
Perifosine is licensed to Keryx in the U.S., Canada and Mexico, while Aeterna Zentaris Inc. owns rest of the world rights. Shares in Quebec City-based Aeterna (NASDAQ:AEZS) also soared on the positive study results, rising 51 cents, or 34 percent, to close at $2.20.
As for the company's next steps, Bentsur said that the company would bring in scientific advisors to help make that decision and finalize details with the FDA for its various programs. At this point, he said, the company is not in a rush to raise money.
He said Keryx has enough cash to complete a Phase III study, though he said he is not yet sure whether that will be for colon cancer, kidney cancer or multiple myeloma or its phosphate binder for dialysis patients.
Keryx is developing Zerenex (ferric citrate) an oral, iron-based compound that has the capacity to bind to phosphate and form non-absorbable complexes. Zerenex has recently completed a Phase II program as a treatment for hyperphosphatemia (elevated phosphate levels) in patients with end-stage renal disease.
Rodman & Renshaw analyst Reni Benjamin said in a research note that "we believe the upcoming results from ongoing Phase II trial of perifosine and radiation in non-small-cell lung cancer could stimulate investor interest if positive."
Shares in Keryx (NASDAQ:KERX) shot up 52 cents or 74 percent, closing at $1.22.
In other news reported at ASCO:
A.P. Pharma Inc., of Redwood City, Calif., said data from its Phase III trial with APF530, sustained-release formulation of granisetron for the prevention of chemotherapy-induced nausea and vomiting, showed complete response rates for APF530 10 mg dose were noninferior to Aloxi (palonosetron, Eisai Co. Ltd.) during acute CINV (0 to 24 hours) following moderate or highly emetogenic chemotherapy and also during delayed CINV (24 to 120 hours), following moderately emetogenic chemo. The CR rate observed for APF530 in delayed CINV following highly emetogenic chemo also was comparable to palonosetron, and was generally well tolerated. Preliminary results were disclosed in September 2008. (See BioWorld Today, Oct. 1, 2008.)
Abraxis BioScience Inc., of Los Angeles, said results from two ongoing studies evaluating the chemotherapy agent Abraxane (paclitaxel as albumin-bound particles) for metastatic melanoma proved positive. One study that evaluated Abraxane (150 mg/m2) given in combination with the targeted agent Avastin (bevacizumab, Genentech Inc., 10 mg/kg), and 74 percent of patients were alive without their disease progressing four months after treatment, with a median progression-free survival of 5.8 months. In addition, 91 percent of patients were alive six months after treatment with the Abraxane/bevacizumab combination, and the one-year survival rate was 68 percent. In a second study, previously untreated patients who received combination treatment with Abraxane (100 mg/m2) and the standard chemo carboplatin (AUC 2) achieved a median overall survival of 11.1 months. Patients who received the same combination treatment with Abraxane but had received prior chemo had an overall survival rate of 10.9 months. Shares of Abraxis (NASDAQ:ABII) dropped $8.07, or 16 percent, to close at $43.25.
Alder Biopharmaceuticals Inc., of Bothell, Wash., said a Phase 1 study with the firm's lead monoclonal antibody, ALD518, for treatment of advanced cancer, showed the drug to be safe, well-tolerated and to reduce fatigue in patients with advanced cancer. ALD518 is a humanized anti-IL-6 antibody being developed for the treatment of cancer cachexia - unplanned weight loss, weakness, muscle atrophy - as well as fatigue. The trial enrolled nine patients with advanced cancer.
Allos Therapeutics Inc., of Westminster, Colo., reported updated data from the pivotal Phase II PROPEL study of pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma. The overall response rate for pralatrexate as evaluated by central independent oncology review using International Workshop Criteria was 28 percent (30 of 109 evaluable patients) with a median duration of response of 9.4 months, or 287 days. Of the 30 patients who responded to pralatraxate, 21 patients (70 percent) did so after cycle one of therapy. Median overall survival was 14.7 months, with 57 percent of responders surviving 12 months or more. The most common Grade 3/4 adverse events were thrombocytopenia, mucositis, neutropenia, and anemia, which were manageable.
Antisoma plc, of Cambridge, UK, said a Phase I trial with its antibody-cytokine fusion drug, AS1409 identified a well-tolerated dose of AS1409 at which biomarker activation, clinical improvement and objective radiological evidence of anticancer activity were seen. Two patients with malignant melanoma showed substantial tumor shrinkage.
ArQule Inc., of Woburn, Mass., disclosed data from a Phase I trial with ARQ 197, a selective inhibitor of the c-Met receptor tyrosine kinase, demonstrating that treatment with ARQ 197 was very well tolerated over extended dosing periods, with more than 60 percent of patients experiencing partial responses, minor responses or stable disease. Findings resulted in a recommended Phase II dose of 240 mg daily.
Ascenta Therapeutics Inc., of Malvern, Pa., offered promising results from ongoing clinical studies in prostate (Phase I/II), brain (Phase II) and lung cancers (Phase II) with AT-101, an oral, pan-Bcl-2 inhibitor.
AstraZeneca plc, of London, said data from the Phase III ZODIAC study in advanced non-small-cell lung cancer patients with the investigational drug vandetanib (branded Zactima) showed that the study met its primary endpoint, demonstrating that the addition of vandetanib to docetaxel resulted in a statistically significant improvement in progression-free survival. Vandetanib is the first oral targeted therapy to show evidence of clinical benefits when added to chemotherapy in a Phase III study in second-line advanced NSCLC.
Bayer AG, of Leverkusen, Germany, disclosed results from Phase I and II trials of BAY 73-4506, an oral multi-kinase inhibitor being studied in multiple tumor types. Preliminary data from the Phase II, open-label study in renal cell carcinoma demonstrated a 27 percent partial response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST) and a disease control rate of 79 percent. The most common drug-related adverse events were hand-foot skin reaction, fatigue, hypertension, mucositis, dysphonia, rash, diarrhea and anorexia. The Phase II study enrolled 49 previously untreated patients. A Phase I study of patients with advanced refractory colorectal carcinoma showed BAY 73-4506, dosed at 160 mg daily, using a treatment schedule of 21 days on/seven days off, was feasible in patients with advanced refractory CRC. Disease control rate was 74 percent in evaluable patients.
Calistoga Pharmaceuticals Inc., of Seattle, said Phase I data demonstrated that CAL-101, an oral, p110 delta selective PI3 kinase inhibitor, showed antitumor activity in six of 12 patients with hematologic malignancies. CAL-101 was well tolerated, with no dose-limiting toxicity in any patient.
Celtic Pharmaceutical Holdings LP, of New York, said results from two Phase III studies showed that Xerecept (corticorelin acetate) was well tolerated and enabled clinically significant reductions compared to dexamethasone in corticosteroid use in patients with cerebral edema associated with both primary and metastatic brain tumors. On the primary endpoint, the study demonstrated a strong trend in favor of Xerecept, though it did not reach statistical significance. Preclinical studies of Xerecept demonstrated the drug's potential antitumor and angiogenesis-inhibiting effects. Celtic gained rights to Xerecept from Emeryville, Calif.-based Neurobiological Technologies Inc.
ChemGenex Pharmaceuticals Ltd., of Melbourne, Australia, reported the latest data from its Phase II/III pivotal study of omacetaxine in patients with T315I-positive chronic myeloid leukemia, showing a complete hematologic response rate of 85 percent, with a median response duration of 8.9 months, in the 66 evaluable patients. Data also showed a major cytogenetic response rate of 15 percent, with a median response duration of 6.1 months.
Cytokinetics Inc., of South San Francisco, reported interim data from the Phase I portion of a Phase I/II trial of SB-743921, a kinesin spindle protein inhibitor, in patients with non-Hodgkin's and Hodgkin's lymphoma, which showed that greater dose-density was achieved with a dosing schedule of days one and 15 of a 28-day cycle. In addition, a potential amplified efficacy signal was observed without any significant increase in side effects.
EntreMed Inc., of Rockville, Md., presented Phase I data from 25 patients showing that ENMD-2076, a small-molecule Aurora A/angiogenic kinase inhibitor, is associated with clinical benefit as determined by reductions in tumor volume, reductions in tumor markers and improvement in cancer-related symptoms. In addition, plasma soluble KDR (VEGFR2), a marker of effect against the VEGF receptor, was reduced in all patients when compared to baseline.
Enzon Pharmaceuticals Inc., of Bridgewater, N.J., said Phase I data showed that EZN-2968, which targets the HIF-1 alpha transcription factor, was well tolerated and that early signs of clinical benefit, prolonged stable disease, were observed in several patients. Durable stable disease was seen in two patients with soft-tissue sarcoma (angiosarcoma, leiomyosarcoma), in one patient with renal cancer and in one patient with ovarian cancer.
Exelixis Inc., of South San Francisco, and partner Bristol-Myers Squibb Co., of New York, reported data from an ongoing Phase II trial of XL184, a small-molecule tyrosine kinase inhibitor, in previously treated glioblastoma multiforme patients showing that seven of 35 (20 percent) of the antiangiogenic-naïve patients had a confirmed partial response. The overall rate of response in all patients, including the refractory population of previously treated patients with an antiangiogenic therapy, was 15 percent. In an exploratory analysis, among 35 patients with at least one post-baseline MRI scan, 12 (34 percent) had tumor shrinkage of equal or greater than 50 percent. In a separate presentation, Exelixis reported data from an ongoing Phase I trial of XL228 in advanced malignancies, showing that of 40 evaluable patients, one patient with non-small-cell lung cancer had a confirmed partial response and was on study for 48 weeks. XL228 is a small-molecule inhibitor of insulin-like growth factor-1, SRC, Aurora kinases and fibroblast growth factor types 1, 2 and 3.
Gemin X Pharmaceuticals Inc., of Malvern, Pa., said results from a Phase Ib trial of obatoclax (GX15-070), as small-molecule Bcl-2 inhibitor, in first-line patients with extensive-stage small-cell lung cancer showed that a three-hour infusion schedule of the drug can enhance the effects of standard chemotherapy. After six cycles of therapy, researchers observed a significant response rate in 100 percent of patients, including two complete responses. No patients progressed during the planned six cycles of combination chemotherapy with obatoclax.
Genentech Inc., of South San Francisco, said results from a Phase III study of Avastin (bevacizumab) plus six months of chemotherapy following surgery in patients with early-stage colon cancer showed that the additional of one year of Avastin treatment did not result in a statistically significant improvement in overall disease-free survival (DFS). In the first year of the study, while patients received Avastin in addition to a standard six months of adjuvant chemotherapy, DFS improved by 67 percent vs. chemotherapy alone, though that early improvement began to diminish after the first year. Overall DFS was not improved. Top-line results from the trial were reported in April. (See BioWorld Today, April 23, 2009.)
Genta Inc., of Berkeley Heights, N.J., said preliminary results from an ongoing study of tesetaxel, an oral taxane, showed a favorable safety profile with a low incidence of serious adverse events, as well as objective responses that have been observed at less than the maximally tolerated dose. Three objective and ongoing responses have been seen in the first nine evaluable patients who received at least two doses, including one patient each with nasopharyngeal cancer, gastrointestinal stromal tumor and uterine cancer.
GenVec Inc., of Gaithersburg, Md., presented an interim analysis of a Phase III trial of TNFerade, an adenovector containing tumor necrosis factor-alpha, in locally advanced pancreatic cancer patients showing a 25 percent reduction in the risk of death compared to the standard-of-care-alone arm, with a hazard ratio of 0.75. The study is enrolling 330 patients, and the next interim analysis is scheduled to occur after two-thirds of events, or 184 deaths.
ImmunoGen Inc., of Waltham, Mass., reported updated data from the first trastuzumab-DM1 (T-DM1) Phase II trial in patients with HER2-positive metastatic breast cancer that had progressed on a regimen containing trastuzumab (Herceptin). In the study, 25 percent of patients had a confirmed objective response as assessed by an independent review facility, the primary endpoint of the study. The antitumor activity seen in patients who had received lapatinib (Tykerb) as well as trastuzumab was similar to that seen in the overall study population. Among the 75 efficacy-evaluable patients who were verified to be HER2-positive by a central laboratory, 32 percent had a confirmed objective response
Isis Pharmaceuticals Inc., of Carlsbad, Calif., reported new data from a Phase I study of LY2181308, being developed by partner Eli Lilly and Co., of Indianapolis. The new data confirmed that LY2181308 penetrates tumor tissue and reduces Survivin mRNA and protein levels in tumor cells. In addition, the company reported results from a pharmacokinetic study of LY2181308 in patients with cancer, showing that it penetrated tumor tissues. LY2181308 currently is being evaluated in two separate Phase II studies in patients with relapsed or refractory acute myeloid leukemia, and as a combination therapy in patients with hormone refractory prostate cancer.
Medarex Inc., of Princeton, N.J., reported efficacy data for MDX-1106 (also known as ONO-4538), a fully human anti-PD-1 antibody that Medarex is co-developing with Ono Pharmaceutical Co. Ltd., of Osaka, Japan, for the treatment of recurrent or treatment-refractory cancers, including malignant melanoma, renal cell carcinoma, colorectal carcinoma, non-small cell lung cancer, and castrate resistant prostate carcinoma. Phase I single-dose and Phase Ib multi-dose data were presented at the meeting. Also, Medarex and Bristol-Myers Squibb Co., of New York, reported updated survival results from follow-up extensions of three Phase II ipilimumab studies in patients with advanced metastatic melanoma (Stage III or IV). The two-year survival rate ranged from 29.8 to 41.8 percent in patients who received ipilimumab (10 mg/kg). Results from the first biomarker analysis of Phase II ipilimumab studies also were presented.
Merck KGaA, of Darmstadt, Germany, reported that cilengitide increased overall survival in patients with glioblastoma multiforme (GBM) in an independent Phase II study. Cilengitide is the first in a new class of investigational anticancer therapies called integrin inhibitors having reached Phase III development. It also presented data confirming KRAS and first-cycle rash as markers of Erbitux efficacy. The drug also is being studied in ongoing research involving numerous other biomarkers such as BRAF.
Mersana Therapeutics Inc., of Cambridge, Mass., presented preliminary results of a Phase 1 trial for its lead development candidate, XMT-1001. Ten of 37 evaluable patients dosed to date demonstrated evidence of stable disease, and seven patients had prolonged stable disease for at least 12 weeks. The study also demonstrated that XMT-1001 can be safely given to patients.
Micromet Inc., of Orlando, Fla., presented updated data from a Phase Ib combination study of adecatumumab (MT201) in combination with the chemotherapeutic docetaxel in patients with metastatic breast cancer. The overall response rate was 38 percent in patients with high expression of EpCAM (n = 8), the target of adecatumumab, compared to 9 percent in patients with low EpCAM expression (n = 11). Patients treated with higher doses of adecatumumab also appeared to have a longer time to progression when compared to patients treated at lower doses (167 days vs. 83 days).
Millennium Pharmaceutical Inc., of Cambridge, Mass., said that in a Phase I trial in patients with advanced solid tumors, MLN4924 was shown to induce pharmacodynamic changes in blood and skin. In a Phase I study of MLN8237, a pharmacodynamic response consistent with Aurora A inhibition was observed in tumor and skin. When combined with rituximab, it induces anti-tumor activity in preclinical B-cell non-Hodgkin's lymphoma models. Millennium also reported data from two trials evaluating Velcade-based combinations for patients with non-Hodgkin's lymphoma (NHL). The VERTICAL Phase I/II trial of a three-drug combination of Velcade, rituximab and bendamustine reported an 80 percent overall response rate (ORR) and 53 percent complete response (CR) rate in patients with relapsed or refractory follicular lymphoma. The second Phase I/II trial of Velcade plus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone with modified vincristine dosing for patients with previously untreated indolent NHL showed that adding Velcade produced an ORR of 100 percent and a CR rate of 73 percent.
Oncolytics Biotech Inc., of Calgary, Alberta, said interim Phase II results demonstrated that treatment with intravenous Reolysin in sarcomas metastatic to the lung was well tolerated, with 15 of 36, or 42 percent, of evaluable patients experiencing stable disease for more than 16 weeks, including five patients who have had stable disease for more than 24 weeks, with one patient having stable disease for more than 80 weeks.
Oncothyreon Inc., of Seattle, presented preliminary data from an ongoing Phase I trial of the phosphoinositide-3 (PI-3) kinase inhibitor PX-866 in advanced cancer, showing that six of 24 patients had stable disease, and the maximally tolerated dose had not been reached. Oncothyreon also presented final results from two Phase Ib trials of the thioredoxin inhibitor PX-12 in advanced cancer, showing three of 32 patients achieved stable disease and the drug was well tolerated.
OSI Pharmaceuticals Inc., of Melville, N.Y., lauded favorable results disclosed by U.S. Tarceva (erlotinib) partner Genentech Inc., of South San Francisco (now part of the Basel, Switzerland-based Roche Group). Data from the Phase III ATLAS study showed Tarceva met its primary endpoint by demonstrating that patients with advanced non-small cell lung cancer (NSCLC) who received Tarceva in combination with Avastin (bevacizumab, also from Genentech) as first-line maintenance treatment had a 39 percent improvement in the time they lived without the disease worsening (progression-free survival), compared with those who received Avastin plus placebo as an active control (hazard ratio = 0.72; p = 0.0012). Adverse events were consistent with previous Avastin or Tarceva NSCLC studies, or trials evaluating the two medicines together. OSI's shares (NASDAQ:OSIP) closed Monday at $30.31, down $3.49, or 10.3 percent.
Peregrine Pharmaceuticals Inc., of Tustin, Calif., said initial results from a Phase II trial of bavituximab, an antiphosphatidylserine antibody, in combination with docetaxel in patients with advanced breast cancer indicated that 10 of 14 evaluable patients in the first cohort of the trial achieved an objective tumor response by the end of the treatment period. Recent analysis showed the median progression free survival of the patients enrolled in the first part of the study was 7.4 months. Shares of Peregrine (NASDAQ:PPHM) lost 2 cents to close at 80 cents.
Pfizer Inc., of New York, said study results demonstrated a 60 percent response rate in 56 patients with squamous cell carcinoma non-small-cell lung (NSCLC) cancer treated with chemotherapy and figitumumab (CP-751,871), the firm's investigational anti-insulin growth factor-type 1 receptor (IGF-1R) antibody. In addition, the company said results from an expansion cohort of a Phase I study showed that 10 of 19 patients with NSCLC carrying the anaplastic lymphoma kinases fusion gene had a partial response, with three unconfirmed, with the duration of response ranging from more than two weeks to more than 23 weeks. Additionally, five patients had stable disease, with the duration of response ranging from more than eight weeks to 40 weeks.
Plexxikon Inc., of Berkeley, Calif., said preliminary data from a Phase I study showed that patients whose cancer harbors the BRAFV600E mutation who were treated with therapeutic doses of PLX4032 (R7204) experienced tumor shrinkage and extended progression-free survival.
Proteolix Inc., of South San Francisco, said data from the Phase II trial of carfilzomib in relapsed and refractory multiple myeloma patients showed anticancer activity and progression-free survival. Of 39 evaluable patients who received a dose of 20 mg/m(2), 18 percent achieved an overall response and 26 percent achieved a clinical benefit response. An additional 41 percent achieved stable disease. Patients achieving partial or minor responses stayed on therapy for a median treatment duration of 240 days, and the median duration of response was 7.4 months. Ten percent of patients completed 12 cycles of treatment and an extension study has been initiated for patients who have stayed on drug for one year. Proteolix also said data from a Phase Ib study and an ongoing Phase II trial of carfilzomib in relapsed patients with advanced solid tumors demonstrated promising single-agent anticancer activity.
Provectus Pharmaceuticals Inc., of Knoxville, Tenn., said interim data from the first 40 subjects in its Phase II trial of PV-10 for the treatment of metastatic melanoma showed it was well tolerated and caused selective tumor destruction in the majority of subjects. Objective response of treated lesions was observed in 60 percent of subjects and locoregional disease control of treated lesions was observed in 75 percent of subjects. Response of untreated bystander lesions was consistent with observations from Phase I testing. Interim safety data were comparable to Phase I, with transient mild to moderate locoregional pain, vesicles, edema or swelling most common.
Seattle Genetics Inc., of Seattle, said data from an ongoing Phase I weekly-dosing trial of SGN-35 included multiple complete and partial responses in patients with relapsed or refractory Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Of 27 patients who were evaluable for response, 13 achieved objective responses, including 10 complete responses and three partial responses. Eleven patients had stable disease and three had progressive disease. The median duration of response is at least 16 weeks, with 12 responses still ongoing. Among 20 evaluable patients treated at doses of 0.8 mg/kg and higher, 60 percent achieved an objective response, including 50 percent with complete responses.
Semafore Pharmaceuticals Inc., of Indianapolis, said data from a Phase I trial of its vascular targeted pan-PI3K/mTORC1/2 inhibitor, SF1126, in advanced solid tumor patients showed 16 of 36 patients achieved disease stabilization with a median duration of 12 weeks. Of note, a GIST, endometrial, and prostate cancer patient each achieved durable stable disease for 20 weeks. These specific tumor types are associated with aberrations of the PI3K pathway that commonly lead to resistance and poor prognostic outcomes.
Sunesis Pharmaceuticals Inc., of South San Francisco, presented data from three ongoing trials of voreloxin, an anticancer quinolone derivative that induces apoptosis. In a Phase II single-agent acute myeloid leukemia study, 28 of 83 evaluable patients achieved a complete response, while interim data from an ongoing Phase Ib/II trial AML trial combining voreloxin with cytarabine showed complete responses in seven of 16 patients. In a Phase II, single-agent, 137-patient ovarian cancer study, voreloxin induced an 11 percent response rate and 52 percent disease control rate.
Synta Pharmaceuticals Corp., of Lexington, presented preliminary data from its Phase III trial of oxidative stress inducer elesclomol in metastatic melanoma, which was halted earlier this year due to a higher-than-expected death rate. The initial data showed a trend toward improvement in progression-free survival (3.4 months for drug vs. 1.9 months for control), but statistical significance was seen only in a subset of patients with normal lactate dehydrogenase levels (3.7 months for drug vs. 2.1 months for control). Shares of Synta (NASDAQ:SNTA) fell $1.14 cents, or 27.4 percent, to close at $3.02 on Monday. (See BioWorld Today, March 2, 2009.)
Telik Inc., of Palo Alto, Calif., presented data from its Assist-5 Phase III trial of Telcyta (canfosfamide) plus pegylated liposomal doxorubicin in ovarian cancer. Telik said last fall it would stop investing in Telcyta after Assist-5 became the third trial to fail, but new data from a pre-specified subset analysis in patients with platinum refractory or primary platinum resistant disease showed median progression-free survival of 5.6 months for drug vs. 2.9 months for control (p = 0.0425). Shares of Telik (NASDAQ:TELK) soared 41 cents, or 61 percent, to close at $1.08 on Monday. (See BioWorld Today, Oct. 31, 2008.)
TransMolecular Inc., of Cambridge, Mass., presented data showing that antiangiogenic peptide TM601 reduced cerebral blood flow and/or volume in two of six patients with glioblastoma. A separate study of radiolabeled TM601 showed specific tumor uptake in several tumor types.
Trubion Pharmaceuticals Inc., of Seattle, reported encouraging interim Phase I safety and efficacy results following administration of low doses of TRU-016 in heavily pre-treated patients with high-risk genomic factors and relapsed or refractory chronic lymphocytic leukemia. Evidence of biologic activity was observed beginning with the 0.1 mg/kg dose. The median reduction in peripheral lymphocytes was 67 percent and was as high as 98 percent. Two patients with leukemia cutis had complete or partial clearance of skin lesions. One patient had a 36 percent reduction in lymph node size, a 28 percent decrease in spleen size and a 44 percent decrease in hemoglobin. Mild grade 1 or 2 infusion toxicity was observed and there were three dose-limiting toxicities reported that all occurred in different dose cohorts. A maximum tolerated dose has not yet been reached.
Vion Pharmaceuticals Inc., of New Haven, Conn., said an analysis of clinical data of Onrigin (laromustine) Injection in patients older than 60 with acute myeloid leukemia showed that patients with a hematopoetic cell transplantation-specific co-morbidity index score of 3 or greater had an overall response rate of 34 percent, an induction death rate (death within 30 days of first induction) of 14 percent, and a Kaplan-Meier estimate of survival at 12 months of 21 percent.
Ziopharm Oncology Inc., of New York, presented positive data from both Phase II intravenous and Phase I oral studies of darinaparsin (Zinapar or ZIO-101), the organic arsenic molecule. Of 19 evaluable patients, initial findings are seven objective responses, for an overall response rate of 37 percent, with three complete responses (CRs) and four partial responses (PRs). Four additional patients had prolonged stable disease. There are five peripheral T-cell lymphoma patients included in the 19 patients, and in that group, there were three objective responses, for an overall response rate of 60 percent, of which two were CRs and one PR. Darinaparsin was well tolerated with neutropenic fever as a severe adverse event in one patient.
ZymoGenetics Inc., of Seattle, announced positive final results from a Phase II trial in patients receiving second- or third-line therapy for advanced renal cell carcinoma with the combination of recombinant Interleukin 21 (IL-21) and Nexavar (sorafenib) tablets. The combination demonstrated considerable clinical benefit, with an overall response rate (as assessed by an independent review) of 21 percent, a disease control rate of 82 percent and progression-free survival of 5.7 months in this heavily pretreated population.