September 4, 2017
The Society of Urologic Oncology Clinical Trials Consortium and the Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC) published results from a phase II clinical study of Instiladrin (rAD-IFN/Syn3) in patients with high grade, BCG refractory or relapsed non-muscle invasive bladder cancer (NMIBC). The randomized, open label, parallel arm study reported durable responses in 35% of patients, which represents more than a three-fold improvement in recurrence-free survival compared to Valrubicin, the only agent currently approved for this indication. Instiladrin was well-tolerated and no patient discontinued treatment due to a treatment-related adverse event. The data are consistent with a previous phase I clinical trial. SUO-CTC has now launched a phase III registration trial of Instiladrin, sponsored by FKD Therapies, in patients with BCG-unresponsive NMIBC. The trial, which opened in 2016, is recruiting across the U.S. now and is expected to enroll approximately 135 patients at 35 centers.
May 22, 2017
Photocure released phase III study results of Blue Light Flexible Cystoscopy (BLFC) with Hexvix/Cysview for bladder cancer. The study was a prospective, open, comparative, within-patient controlled study, and included 304 patients with non-muscle invasive bladder cancer (NMIBC) enrolled at 17 academic institutions in the US. In the study, BLFC with Cysview was used with the Karl Storz D-Light C PDD Flexible Videoscope System. The study showed that BLFC with Cysview detected bladder cancer recurrence in 21.5% of the patients undergoing surveillance cystoscopy that otherwise would have been missed with white light (WL) alone, which is highly significant (p<0.0001). Of note, the study showed that nine out of 26 patients (34.6%) with flat, more aggressive high grade lesions (carcinoma in situ; CIS) were diagnosed using confirmatory Blue Light Cystoscopy with Cysview alone and not WL (p<0.0001). The study also showed that there was no increase in the rate of related adverse events after repeated administration of Cysview in bladder cancer patients undergoing cystoscopy examination. The company intends to submit the data to the FDA to seek approval of BLFC with Cysview in the surveillance setting in the U.S., and an expansion of the indication to include CIS.
February 27, 2017
OncoGenex Pharmaceuticals reported results of apatorsen in two randomized phase II clinical trials for bladder and prostate cancer. The Borealis-2 trial evaluated apatorsen in combination with docetaxel treatment in 200 patients with metastatic bladder cancer whose disease had progressed following first-line platinum-based chemotherapy. Patients who received apatorsen treatment experienced a 20% reduction in risk of death, compared to patients receiving docetaxel alone (overall survival hazard ratio (HR)=0.80; 80% CI: 0.65-0.98; p=0.078). Partial or complete responses occurred in 16.2% patients receiving apatorsen plus docetaxel compared to 10.9% patients receiving docetaxel alone with median response durations of 6.2 months versus 4.4 months, respectively. Higher baseline serum heat shock protein 27 (Hsp27) levels were significantly prognostic for indicating an almost two-fold higher risk of death (HR=1.96; p=0.0001). In an exploratory analysis on a subset of patients (20% of total) who completed at least two treatment cycles and had either a decrease in serum Hsp27 levels from baseline or had only a 20.5% increase in serum Hsp27 levels from baseline, the reduction in risk of death with apatorsen treatment was 71% (HR=0.29: 80% CI: 0.18-0.48; interaction p=0.0727). The Pacific trial evaluated the ability of apatorsen, when added to Zytiga (abiraterone acetate), to reverse or delay treatment resistance in 72 men who were experiencing a rising PSA on Zytiga alone. The primary endpoint evaluated the proportion of patients who were progression free (clinical and radiologic) at study day 60 with apatorsen added to Zytiga, compared to continuing Zytiga alone. In men receiving apatorsen, 33% were progression free at study day 60 compared to 17% for those men receiving Zytiga alone. For patients with five circulating tumor cells (CTCs) at baseline, 22% vs 11% of patients had a CTC reduction to less than five CTCs when apatorsen was added to Zytiga vs Zytiga alone, respectively. Clinical data from trials in bladder and prostate cancers demonstrated apatorsen was well-tolerated and improved patient outcomes when administered in combination with standard-of-care treatments.
January 12, 2015
OncoGenex Pharmaceuticals reported
results of a phase II study of apatorsen in
combination with gemcitabine/cisplatin chemotherapy
compared to chemotherapy alone
in the treatment of metastatic bladder cancer.
The trial, Borealis-1, enrolled approximately
180 patients with documented metastatic or
locally inoperable transitional cell carcinoma
(TCC) of the urinary tract who previously
had not received chemotherapy for metastatic
disease and were not candidates for
potentially curative surgery or radiotherapy.
Patients were randomized to receive standard
chemotherapy (gemcitabine/cisplatin) in
combination with apatorsen at two dose levels
(600mg and 1,000mg) or gemcitabine/cisplatin
plus placebo. Patients received up to six
cycles of weekly intravenous therapy. Overall
trial results indicated the addition of 600mg
apatorsen to standard of care chemotherapy
showed a 14% reduction in risk of death
(overall survival hazard ratio (HR) = 0.86) and
a 17% reduction in progressive disease and
death (progression-free survival HR = 0.83)
when compared to chemotherapy alone. Over
one-third of the patients in the trial had lower
performance status, as defined by a Karnofsky
score of 80% or less. These patients derived
the greatest benefit from 600mg apatorsen
in combination with chemotherapy, resulting
in a 50% reduction in risk of death (overall
survival HR = 0.50) compared to chemotherapy
alone. Less benefit was observed in
the 1000mg apatorsen arm due to increased
adverse events leading to a higher rate of discontinuation
of both apatorsen and chemotherapy.
Apatorsen 600mg was well tolerated
in combination with chemotherapy.
February 12, 2007
Adnexus released announced positive interim results from a phase I trial of Angiocept for the treatment of cancer. This open label, dose escalation trial was designed to assess the safety, tolerability and pharmacokinetics of the drug in cancer subjects as well as to evaluate preliminary anti-tumor and biological activity. Interim evidence revealed that within four hours of drug administration biological activity occurred, as evidenced by elevated plasma levels of biomarkers of VEGFR-2 pathway. These biomarkers remained significantly elevated above baseline throughout the multi-dose treatment duration. Pharmacokinetic data demonstrated a profile that could support an every other week dosing regimen. The maximum tolerated dose has not been reached. Based on the results, the development of Angiocept is to continue for this indication.
Celtic announced negative results from phase III trial, dubbed KSB311R/CIII/001, of TransMID for the treatment of glioblastoma multiforme. This randomized, open-label trial was to include tow sequential trials. The first planned to enroll 323 subjects with non-resectable, progressive or recurrent Glioblastoma Multiforme (GBM) who had failed conventional therapy, in North America, the EU and Isreal. It was designed to compare two intratumoral doses of TransMID to best standard of care in improving overall survival. The trial's primary efficacy endpoint was overall survival time; interim analysis was to occur when 50% of the required events were observed. The interim assessment revealed that the probability of the trial achieving the predefined overall survival rate by the trial end was unlikely to occur. Based on this data, Celtic decided to terminate the development of TRansMID for this or any other indication.
Spectrum released positive results from a pilot phase II trial of EOquin for the treatment of non-invasive bladder cancer. This single-arm, open-label study enrolled 20 subjects who received 4 mg of EOquin in 40 mL of diluent administered via an indwelling catheter that was then clamped for one hour. After an hour the bladder was drained and the catheter was removed. Subjects were assessed for adverse events during the one hour retention and at post-operative days eight and fifteen. Wound healing, assessed by cystoscopy performed at postoperative day 85, and systemic absorption were also evaluated. Treatment was well tolerated and no adverse events occurred on wound healing. In addition, EOquin was not systematically absorbed into the bloodstream when given immediately after surgery. A phase III protocol has been submitted to the FDA for a Special Protocol Assessment (SPA). Spectrum plans to start this trial in mid-2007.
May 29, 2006
Cell Genesys reported interim results of a phase I trial of CG0070, their investigational oncolytic virus under investigation for the treatment of bladder cancer, at the 2006 Annual Meeting of the American Urological Association in Atlanta. This open-label dose-escalation study had enrolled 9 patients to date who had failed previous therapy with BCG; subjects received single administrations of the drug. Results from the study indicated preliminary evidence of efficacy, with complete response noted on follow-up cystoscopy in 3 of 9 subjects (response lasted for 3+, 6 and 9 months). No serious adverse events or dose-limiting toxicities were reported to date; overall adverse events included local bladder toxicities.
November 15, 2004
Adherex Technologies reported updated results from a phase I safety and tolerability trial of Exherin, their investigational tumor-specific blood vessel destabilizing agent for the treatment of refractory, incurable solid tumors. Preliminary data indicate that the drug was safe and well tolerated across dose-ranging regimens of the drug, with mild fatigue, nausea, and transient dysgeusia noted most often. Maximum tolerated dose (MTD) has not been reached. In addition, preliminary evidence of efficacy was observed, with one partial response (>50% reduction in tumor size), one mixed response (<50% reduction in tumor size), and one secondary response (reduction in hormone hyper-secretion and evidence of necrosis in a patient with adrenal tumor). This open-label safety, tolerability, pharmacokinetic and MTD study has to date enrolled 29 subjects with incurable solid tumors, who received 45 treatment cycles of one of seven doses of the drug (50 mg/m2 to 840 mg/m2). Adherix announced that they have increased their patient enrollment rate with the inclusion of new investigative sites, and have additional plans to initiate an optimal-dose finding phase Ib/II trial before the end of 2004.
Spectrum Pharmaceuticals presented positive data from an ongoing phase II safety and efficacy trial of EOquin (apaziquone) for the treatment of bladder cancer at the Chemotherapy Foundation Symposium in New York. Interim data indicate that the drug demonstrated significant efficacy in treating recurrent refractory superficial bladder cancer, with 64% of the patients completing 6 weekly treatments (18 of 28) exhibiting complete disappearance of tumors. In addition, the drug has exhibited a positive safety profile, with low observed systemic absorption, no systemic toxicity, and only one case of localized toxicity (chemical cystitis). This ongoing, multi-center, open-label study is investigating the safety and efficacy of weekly intra-bladder administrations of EOquin for 6 weeks. It was designed to enroll up to 45 subjects with recurrent refractory superficial bladder cancer; 36 (28 evaluable) have been enrolled to date, and Spectrum announced that they expected enrollment to be completed by the end of 2004.
Vical Incorporated announced safety and efficacy results from a phase II trial of Allovectin-7, their gene therapy product under investigation for the treatment of metastatic melanoma, at the Annual Meeting of the International Society for Biological Therapy of Cancer. Trial data demonstrated that the drug produced clinical responses in 11.8% of subjects (n=15), including four complete responses and 11 partial responses. Furthermore, the company observed a median response duration of 12.7 months, and a median survival duration of 21.3 months. This open-label study enrolled a total of 133 patients, 127 of whom received the highest dose regimen of the drug (2 mg), and were evaluated for efficacy. Vical announced that it intended to use this data in support of a Special Protocol Assessment with the FDA, which would permit the initiation of an approval-enabling phase III trial, before the end of Q4 2004.
September 9, 2002
Results of a phase III European study indicated that Hexvix fluorescence cystoscopy (visual bladder inspection) may improve detection of bladder cancer compared to the standard white light cystoscopy method alone. In 211 subjects with high-risk bladder cancer, 97% of the flat cancer lesions (carcinoma in situ, CIS) were detected by Hexvix, compared to 59% that were detected with the standard approach. For Hexvix, the 97% tumor-detection rate was maintained regardless of tumor type, compared to 78% for white light. In addition, in more than 60% of the study subjects, Hexvix provided valuable information for diagnosis and treatment. Hexvix reportedly had an excellent safety profile. Hexvix is being developed by PhotoCure ASA.