Head and Neck Cancer

March 5, 2018

Intensity Therapeutics announced completion of the first safety cohort (A) of the Company’s Phase 1/2 international clinical study evaluating lead product, INT230-6. Following intratumoral drug injections into superficial lesions in six patients with either ovarian, thyroid, head and neck or skin cancers, there were no dose limiting toxicities. INT230-6 is a novel, anti-cancer drug for direct intratumoral injection. The product contains potent anti-cancer agents that disperse throughout tumors and diffuse into cancer cells. INT230-6 was identified from Intensity’s DfuseRx platform and is being evaluated in a clinical trial; IT-01. In preclinical studies INT230-6 administration eradicated tumors by a combination of direct tumor kill coupled with recruitment of dendritic cells to the tumor micro-environment that induced anti-cancer T-cell activation. The study will characterize the systemic pharmacokinetic profile of multiple doses of INT230-6’s drug substances after single and then multiple intratumoral injections. Exploratory analysis will characterize patient outcome, as well as evaluate various tumor and anti-tumor immune response biomarkers that may correlate with response.

April 15, 2013

Navidea Biopharmaceuticals issued interim results from a phase III trial of Lymphoseek (technetium 99m tilmanocept) for identifying sentinel lymph nodes (SLNs) in patients with head and neck squamous cell carcinoma. This open-label, multicenter, within-patient study, NEO3-06, enrolled 80 patients with head and neck squamous cell carcinoma. After receiving a Lymphoseek injection, 39 of the 80 patients were determined to have pathology-positive lymph nodes. Results demonstrated of these 39 patients, Lymphoseek accurately identified 38, for an overall False Negative Rate (FNR) of 2.56%, which was statistically significant (p=0.0205) and met the statistical threshold for success of the primary endpoint. Moreover, multiple-level nodal dissection of patients in the trial with cancer-positive lymph nodes led to an average removal of 38 lymph nodes per patient, whereas Lymphoseek on average led to the removal of approximately four lymph nodes, representing a substantial reduction in potential morbidity for patients with head and neck cancer undergoing sentinel lymph node biopsy. Based on these data, Navidea Biopharmaceuticals will evaluate the possibility of filing a Supplemental New Drug application (sNDA) later this year.

November 5, 2012

Alliance for Clinical Trials in Oncology released results from a phase III trial of doxepin for the treatment of head and neck cancer. This multi-institution, randomized, double-blind, placebo-controlled study enrolled 140 patients who were also receiving radiation therapy for their head and neck cancer (>50.0Gy), which involved more than one-third of the oral cavity. Subjects received a single, blinded dose of doxepin rinse (doxepin 25mg in 5ml of water) or placebo on day one, and then crossed over to the opposite study group on a subsequent day. Results indicated that the addition of doxepin significantly decreased pain, which was measured by the area under the curve (AUC) on the pain scale over time. Patients who received doxepin reported a reduction in pain to a -9.1 versus -4.7 for those who received the placebo. Analysis of the crossover data revealed similar findings, with an AUC score of -7.9 in the doxepin group versus -5.6 in the placebo group. Sixty-four percent of patients elected to continue doxepin after the study was completed. Doxepin was well tolerated. The most frequent adverse events were stinging/burning, unpleasant taste and greater drowsiness.

June 14, 2010

Genmab released positive results from a phase III trial of zalutumumab for the treatment of head and neck cancer. This randomized multicenter trial enrolled 286 subjects with squamous cell carcinoma of the head and neck who had failed at least one course of standard platinum-based chemotherapy. The subjects received zalutumumab in combination with best supportive care (BSC) or BSC alone. Zalutumumab was administered at an initial dose of 8 mg/kg, followed by weekly administrations of individually dose adjusted maintenance therapy of up to 16 mg/kg until disease progression. The subjects treated with BSC alone were also allowed to receive methotrexate at a maximum weekly dose of 50 mg/m2. Disease status was assessed every 8 weeks and response evaluated according to RECIST criteria. The primary endpoint was overall survival from randomization until death. While the results did not reach statistical significance, the median overall survival was improved with the addition of zalutumumab 6.7 months compared to 5.2 months for BSC alone. There was a 61% improvement in progression free survival (PFS) for the arm receiving zalutumumab plus BSC (p≡0.001). The six month PFS rate for the zalutumumab plus BSC arm was 20% compared to 7.3% for the BSC alone arm. The objective response and disease control rates for the subjects in the zalutumumab arm were 6.3% and 48% respectively, compared to 1.1% and 27% respectively for patients in the BSC alone arm.

February 27, 2006

CEL-SCI has announced positive results of a long-term follow-up to a phase II trial of Multikine, for the treatment of head and neck cancer. Trial data indicated that the drug extended overall survival and increased regional tumor localization at 2 years, compared to literature-established values for approved therapies. This open-label study enrolled patients with advances primary head and neck cancer, who received the drug for 3 weeks, prior to surgery or surgery plus radiation/chemotherapy (standard therapy for the disease). The company anticipated initiating phase III trials of the drug in the near future.

CuraGen issued results of a phase II trial of velafermin, for the prevention of oral mucositis (OM) due to chemotherapy/radiotherapy. Results from the study indicated that the drug failed to meet its primary efficacy endpoint, failing to establish a significant, dose-dependent trend in rates of severe OM (p>0.05). Secondary data did yield positive activity for the lowest dose of the drug, significantly reducing incidence (p=0.031) and duration (p=0.037) of severe Grade 3 or 4 adverse events, and reducing the use of antibiotics, analgesics, antiemetics and total parenteral nutrition (TPN), and reduced rates of febrile neutropenia compared, to placebo. This multi-center, dose-ranging, randomized, double-blind, placebo-controlled study enrolled 212 patients, who received one of three doses of the drug (0.03 mg/kg, n=50; 0.1 mg/kg, n=56; and 0.2 mg/kg, n=55) or placebo (n=51). Based on these results, the company announced plans to initiate a phase II study of the low dose of the drug in Q2 2006, with preliminary results expected in Q3 2007.

Introgen reported positive results of a phase I/II trial of INGN 225, for the treatment of advanced small cell lung cancer in the journal Clinical Cancer Research. Trial data yielded a 62% objective tumor response rate for subjects receiving the drug in combination with chemotherapy, compared to a literature-established baseline of 5-25%. Further, 75% of subjects who experienced a p53 immune response (the drug's targeted mechanism of action) experienced objective clinical responses and increased overall survival. This open-label study enrolled second-line patients at the H. Lee Moffitt Cancer Center.

April 4, 2005

Viventia Biotech reported positive preliminary results from a phase I investigating Proxinium, a monoclonal antibody conjugated to a cytotoxic protein payload for the monotherapy treatment of refractory head and neck cancer. Efficacy results showed that 25% of the 16 patients who expressed the therapeutic target for Proxinium had a complete response to therapy, which was defined as a complete disappearance of the tumor. Data showed that 63% of subjects had an objective response, defined as significant or partial shrinkage of the tumor; and 88% had tumor growth control, defined as an objective response or stabilization of disease. The drug was shown to have a good safety profile and was well tolerated. The study enrolled 20 subjects who had failed previous courses of surgery, chemotherapy and/or radiotherapy. The patients received the drug by direct intratumoral injection directly into a target tumor on a weekly basis for four weeks. The study was conducted in Brazil. The company plans to report full results at the American Society of Clinical Oncology (ASCO) Annual Meeting in May 2005.<

January 3, 2005

YM BioSciences reported preliminary results from a phase II trial with TheraCIM h-R3 (nimotuzumab), an EGF receptor monoclonal antibody being investigated for the treatment of nasopharyngeal carcinoma. The randomized, pivotal study was designed to assess the safety and efficacy of the drug combined with radiation compared to radiation alone in locally advanced, Stage 3-4, nasopharyngeal carcinoma, a subset of head-and-neck cancer. Results showed that subjects in the intent-to-treat analysis had a 90.6% Complete Response, defined as the elimination of tumor at the primary site, locoregional lymph nodes and distant metastases compared to 51.5% in the radiation-alone group. TheraCIM h-R3 was administered intravenously at a dose of 100 mg/person once a week for eight weeks beginning on the first day of radiotherapy. Safety data showed no evidence of the acneiform rash commonly associated with these types of agents. The study was conducted by CIMAB S.A. and Biotech Pharmaceuticals Limited. YM's European partner, Oncoscience AG, anticipates initiating a Phase III pivotal trial in adult glioma in Q1, 2005.

December 6, 2004

Genentech reported positive results of a phase III study of Avastin (bevacizumab), their monoclonal antibody approved for the treatment of non-small cell lung cancer, for the treatment of colorectal cancer. Interim results indicated that the addition of Avastin to a standard chemotherapy regimen produced a 26% reduction in the risk of death, compared to chemotherapy alone. Furthermore, the drug produced a 17% improvement in median survival time (12.5 vs. 10.7 months). This randomized, controlled, multicenter trial enrolled 829 patients with advanced refractory colorectal cancer, who received a standard FOLFOX4 chemotherapy regimen (oxaliplatin/5-FU/leucovorin) with or without Avastin. Genentech announced that they planned to discuss filing of an sBLA with the FDA based upon these results.

Genmab has announced positive preliminary results from a phase I/II trial of HuMax-EGFr, for the treatment of head and neck cancer. The trial used two neural imaging techniques to examine tumor size and function following 4 weekly doses of the drug. The first technique, which measured disease state by metabolic activity, found that of the 15 subjects evaluable by this method, 6 showed a partial metabolic response (PMR) and 3 patients out of the 15 showed a stable metabolic disease (SMD). All patients showing response were in one of the three highest dose cohorts, and all subjects in the two highest dose cohorts experienced either PMR or SMD. The second imaging technique, which measured tumor size, found that of the 16 patients evaluable by this method, 2 showed a partial response (PR) and 8 showed stable disease (SD). All responses occurring in one of the four highest dose groups, and six out of 7 patients in the two highest groups obtained a PR or SD. This open-label study enrolled a total of 17 subjects, who were randomized to receive a single-treatment of one of six doses of the drug (0.15, 0.5, 1, 2, 4 or 8 mg/kg), followed by a 28 day safety washout and subsequent treatment once weekly for 4 weeks at the same dose. The company announced that they expected additional data from the trial in 2005.

Point Therapeutics has announced positive interim results of a phase II trial of talabostat (PT-100), for the treatment of refractory non-small cell lung cancer (NSCLC). Data from the first 20 subjects met their interim efficacy requirements, with 2 subjects experiencing a reduction in tumor size of 50% or greater. Additional efficacy was observed in the secondary endpoint, with a median time to tumor progression of 24 weeks, compared to a historical baseline of 14. This open-label study plans to enroll a total of 41 patients with unresectable NSCLC, all of whom will receive daily oral talabostat for 2 weeks, following a standard dose of the chemotherapeutic taxotere. Achievement of this interim milestone allows the company to continue enrolling patients up to the full planned cohort size.

August 23, 2004

Cell Genesys has reported additional positive results from their phase I study of their GVAX modified-whole-cell pancreatic cancer vaccine. A previously reported phase I trial administered the vaccine to 14 subjects, of which 3 remain alive and disease free as of the most recent 6.5 year follow-up. The new data on these subjects has revealed a strong T-cell response to mesothelin, an immunogenic, tumor-associated molecule that is part of the GVAX vaccine. Furthermore, the data showed the specificity of mesothelin response to be unique in each patient. By contrast, only 1 of the 11 subjects who did not reach the 6.5 year survival mark had mounted any significant mesothelin response, and the level of response was markedly lower. These data were taken to support an ongoing phase II study of GVAX in the disease.<

Erimos Pharmaceuticals announced positive results of their phase I study of EM-1421, their small-molecule tumor-selective chemotherapeutic under investigation for the treatment of refractory head and neck cancer. Trail data showed the drug to be safe and well tolerated, without any observed systemic side effects after three treatments. Preliminary evidence of efficacy was also observed, with visible tumor necrosis noted in 5 of the 6 subjects on the completion of treatment. This open label dose escalation study treated 6 head and neck cancer patients with three intralesional injections of the drug, with a tumor-volume-dependant dosing regimen of 20 mg/cm3; the maximum cumulative administered dose was 1485 mg.

August 25, 2003

Antigenics reported positive results from a phase II trial investigating Oncophage (HSPPC-96), an individualized vaccine for the treatment of colorectal cancer. Results showed that more than half of the subjects who received Oncophage demonstrated a statistically significant immunological response. In addition, subjects who demonstrated an immune response to Oncophage treatment also experienced a significantly lower rate of recurrence (41%) compared with nonresponding subjects (92%). Subjects who responded demonstrated a two-year overall survival rate of 100%, compared with 50% for nonresponders. The study enrolled 29 subjects with stage IV colorectal cancer that had spread to the liver and who had undergone complete resection. Results were published in the August 15, 2003 issue of Clinical Cancer Research.

CEL-SCI reported positive results from a clinical study investigating Multikine, a mixture of human cytokines for the treatment of head and neck cancer. Results demonstrated that two subjects showed complete regression and two subjects showed partial regression of disease. Data also showed tumor fragmentation and the appearance of multinucleated macrophages. No serious adverse effects of treatment were reported. The study enrolled twelve previously untreated subjects with head and neck cancer who were treated by peritumoral injection of Multikine in addition to zinc sulfate, indomethacin and cyclopho-sphamide. Results were reported in Archives of Otolaryngology - Head & Neck Surgery, August 2003; Volume 129: 874-881.

April 29, 2002

Results from two phase II studies indicate that high-dose Advexin gene therapy produced increased survival compared to low-dose Advexin in head and neck cancer subjects. Both trials included subjects with recurrent head and neck cancer who were ineligible for surgery due to disease severity. Advexin was administered via intratumoral injection, and a median number of two treatment cycles was received in each study. Results demonstrated that high-dose Advexin produced a median survival advantage of 2.4 months (189 days vs. 114 days) compared to low-dose treatment. Advexin is being developed by Introgen.

December 10, 2001

Positive results were reported from a phase I trial of Inhale Therapeutic Systems' inhaleable leuprolide, a peptide analog used to treat prostate cancer and endometriosis. Data showed that a powdered formulation of leuprolide developed with Inhale's Inhance pulmonary delivery technology administered the drug with a bioavailability of 18% (inhaleable versus injectable systemic delivery). In the 12-subject trial, the powdered leuprolide dose was packaged in a single capsule, and subjects inhaled the drug using a small dry powder inhaler.

The final results from a phase IIb trial of Valentis' interleukin-2 (IL-2) GeneMedicine product did not confirm positive interim findings. The randomized trial was designed to compare the IL-2 GeneMedicine product plus standard chemotherapy to standard chemotherapy alone in subjects with advanced head and neck cancer. The trial data demonstrated that the positive trend in the IL-2 treatment group versus the chemotherapy alone group was not sustained throughout the trial. The trial was conducted in collaboration with Roche Holdings.