Immunotherapy Continues to Advance in Head and Neck Cancer

Source: www.onclive.comAuthor: Megan Garlapow, PhD   Concomitant administration of motolimod with cetuximab (Erbitux) increases the innate and adaptive immune response in the blood and the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC), overcoming negative prognostic biomarkers of cetuximab therapy alone, according to the biomarker data from a recent phase Ib clinical trial that was presented at the 2016 Head and Neck Cancer Symposium. The trial was recently amended to add nivolumab to the combination of cetuximab and motolimod. Dr. Robert Ferris, MD PhD   “We know that PD-1 and PD-L1 are overexpressed in head and neck cancer, and so it was somewhat irresistible to combine our baseline treatment of cetuximab and motolimod with the PD-L1 inhibition pathway. EGFR itself drives PD-L1, so combining cetuximab with anti-PD-1 inhibitor makes sense. So, we’ve amended this trial. We’re now accruing to treatment with cetuximab, motolimod, and the anti–PD-L1 nivolumab in this trial,” said lead author Robert Ferris, MD, PhD, professor, Departments of Otolaryngology, Radiation Oncology, and Immunology, Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. According to the authors of the phase Ib data presented at the symposium, the rationale for combining cetuximab with motolimod (VTX2337) as neoadjuvant therapy was that cetuximab induces cellular immunity that correlates with neoadjuvant clinical response. The phase I dose-escalation and safety of the combination had been established (NCT 01334177). This study of neoadjuvant cetuximab and motolimod had accrued 14 patients with HNSCC that was stage II-IV, resectable, and located in the oropharynx, [...]

2016-02-29T10:49:56-07:00February, 2016|Oral Cancer News|

Excitement at new cancer treatment

Source: www.news.doximity.comAuthor: James Gallagher A therapy that retrains the body's immune system to fight cancer has provoked excitement after more than 90% of terminally ill patients reportedly went into remission.   White blood cells were taken from patients with leukaemia, modified in the lab and then put back. But the data has not been published or reviewed and two patients are said to have died from an extreme immune response. Experts said the trial was exciting, but still only "a baby step." The news bubbled out of the American Association for the Advancement of Science's annual meeting in Washington DC. The lead scientist, Prof Stanley Riddell from the Fred Hutchinson Cancer Research Centre in Seattle, said all other treatments had failed in these patients and they had only two-to-five months to live. He told the conference that: "The early data is unprecedented." Re-training In the trial, cells from the immune system called killer t-cells were taken out of dozens of patients. The cells normally act like bombs destroying infected tissue. The researchers genetically modified the t-cells to engineer a new targeting mechanism - with the technical name of chimeric antigen receptors - to target acute lymphoblastic leukaemia. Prof Riddell told the BBC: "Essentially what this process does is, it genetically reprograms the T-cell to seek out and recognise and destroy the patient's tumour cells. "[The patients] were really at the end of the line in terms of treatment options and yet a single dose of this therapy put more than [...]

2016-02-22T12:19:53-07:00February, 2016|Oral Cancer News|

Research Leader Discusses FDA-Funded Immunotherapy for Head and Neck Cancer

 Source: www.onclive.comAuthor: Gina Columbus  Brett Miles, MD, DDS   The investigational immunotherapy axalimogene filolisbac (ADXS11-001) has emerged as a potentially practice-changing agent in the treatment of HPV-related oropharyngeal cancer. Shown to generate T cells directed against a cancer antigen and neutralize suppressor regulatory T cells and myeloid-derived suppressor cells that protect the tumor microenvironment from an immunologic attack and contribute to tumor growth, ADXS11-001 is the first of its kind—a therapeutic vaccine for the disease. The agent is being examined in an ongoing phase II trial, which was reported as one of 18 recipients of research grants recently awarded by the FDA’s Office of Orphan Product Development. The grants, given to sites for product development in rare diseases, total more than $19 million. The ADXS11-001 grant provides collaborating researchers from Baylor College of Medicine and the Icahn School of Medicine at Mount Sinai with more than $1.1 million over 3 years. Eligible patients for the phase II study are newly diagnosed with stage II to IV HPV16-positive oropharynx squamous cell carcinoma who are scheduled to receive ablative transoral robotic surgery. In an interview with OncLive, the study’s surgical principal investigator, Brett Miles, MD, DDS, associate professor of Otolaryngology Head and Neck Surgery, co-chief, Division of Head and Neck Oncology, Icahn School of Medicine at Mount Sinai, discusses the potential of ADXS11-001 in HPV-associated head and neck cancer and other emerging therapies and treatment strategies. OncLive: Congratulations on your study being awarded a research grant from the FDA. How does it [...]

2015-09-29T11:26:02-07:00September, 2015|Oral Cancer News|

FDA Grant Forwards Listeria-Based Throat Cancer Vaccine

Source: www.targetedonc.comAuthor: Sandra Kear An experimental immunotherapy for human papillomavirus-, or HPV-, related throat cancers, which is driven by the Listeria bacteria (that wreaks havoc when ingested), may now move forward due to a $1.1 million dollar grant from the FDA to researchers at Baylor College of Medicine.   “Immunotherapy, such as axalimogene filolisbac, which targets HPV proteins expressed in cancer cells is a great example of using a cancer’s own unique biology against it.” said principal investigator Andrew Sikora, MD, PhD, leader of the head and neck cancer program in the NCI Comprehensive Designated Dan L. Duncan Cancer Center and an associate professor of otolaryngology at Baylor College, in an interview with Targeted Oncology.   "This is hopefully the first step toward development of more targeted treatment approaches that reduce side effects and cancer treatment-related morbidity by uniquely targeting only virus-infected cells.” 
The Listeria-based HPV immunotherapy, axalimogene filolisbac (ADXS11-001), is developed by Advaxis, and functions by stimulating an immune response against HPV proteins, thus killing infected cells.   The drug is currently being evaluated in phase I-II study3 alone or in combination with MedImmune’s durvalumab, in patients with cervical or HPV-positive head and neck cancer. The study has three arms: axalimogene filolisbac alone, durvalumab alone, and the two drugs combined. Primary outcomes established for the study are: number of subjects with adverse events (AEs) in each dose level, number of subjects with AEs in the combination dose, and progression-free survival.   Patients must have measurable disease by RECIST criteria, as well [...]

2015-09-17T09:22:55-07:00September, 2015|Oral Cancer News|

An HPV-E6/E7 immunotherapy plus PD-1 checkpoint inhibition results in tumor regression and reduction in PD-L1 expression

Source: www.nature.comAuthor: A E Rice, Y E Latchman, J P Balint, J H Lee, E S Gabitzsch and F R Jones We have investigated if immunotherapy against human papilloma virus (HPV) using a viral gene delivery platform to immunize against HPV 16 genes E6 and E7 (Ad5 [E1-, E2b-]-E6/E7) combined with programmed death-ligand 1 (PD-1) blockade could increase therapeutic effect as compared to the vaccine alone. Ad5 [E1-, E2b-]-E6/E7 as a single agent induced HPV-E6/E7 cell-mediated immunity. Immunotherapy using Ad5 [E1-, E2b-]-E6/E7 resulted in clearance of small tumors and an overall survival benefit in mice with larger established tumors. When immunotherapy was combined with immune checkpoint blockade, an increased level of anti-tumor activity against large tumors was observed. Analysis of the tumor microenvironment in Ad5 [E1-, E2b-]-E6/E7 treated mice revealed elevated CD8+ tumor infiltrating lymphocytes (TILs); however, we observed induction of suppressive mechanisms such as programmed death-ligand 1 (PD-L1) expression on tumor cells and an increase in PD-1+ TILs. When Ad5 [E1-, E2b-]-E6/E7 immunotherapy was combined with anti-PD-1 antibody, we observed CD8+ TILs at the same level but a reduction in tumor PD-L1 expression on tumor cells and reduced PD-1+ TILs providing a mechanism by which combination therapy favors a tumor clearance state and a rationale for pairing antigen-specific vaccines with checkpoint inhibitors in future clinical trials. *This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

2015-09-08T09:28:07-07:00September, 2015|Oral Cancer News|

AstraZeneca joins the world of immunotherapy against cancer

Source: www.youthhealthmag.com Author: staff Cancer drug companies have been fighting lately in a completely different and interesting arena: immunotherapy. The competition is indeed heating up that firms such as AstraZeneca are willing to pay millions of dollars for promising treatments. AstraZeneca, through its research company called MedImmune, has just recently announced its decision to purchase a novel drug INO-3112 from Inovio, based in Pennsylvania, for a staggering price tag of $727 million. INO-3112 is a drug for immunotherapy, a new way of combating cancer by boosting the body's immune system. This then allows the antibodies and specific cells to fight off the tumor. The treatment may also provide synthetic proteins to boost the body's fighting chance. MedImmune believes that with the proper immunotherapy protocol for the patient, conventional methods such as chemotherapy and radiotherapy, which have plenty of serious risks, can now be significantly reduced, if not eliminated. In fact, patients may no longer have to go through surgery, which is a common first-line treatment. While AstraZeneca already has immunotherapy products in the market, the acquisition of INO-3112 will make it an instrument for combination therapies. As for Inovio, the drug, which is still not approved, is currently in the advanced stages of the clinical trials. It will be intended for treating head and neck cancers, as well as cervical cancer. While there are already cervical cancer vaccines, they cite the rather poor record of them. Their drug, on the other hand, will work on modifying DNA sequencing that will [...]

HPV16 Antibodies Signal Even Better Oral Cancer Outcomes

Source: www.medscape.comAuthor: Neil Osterweil Another prognostic tool may be in the offing for clinicians to use in evaluating patients with oropharyngeal cancers, new research suggests. The presence in serum of three antibodies to human papillomavirus type 16 (HPV16) was predictive of better progression-free and overall survival in these patients, according to Kristina R. Dahlstrom, PhD, from the University of Texas MD Anderson Cancer Center, in Houston, and colleagues. Patients whose serum was positive for the presence of three specific antibodies to "early" (E) proteins involved in replication and growth of HPV16 had dramatically better rates of overall survival (OS) and progression-free survival (PFS) compared with patients whose serum was negative for the antibodies, they reported online June 15 in Clinical Cancer Research. Specifically, for those patients whose serum was positive for any E antibodies, 5-year estimated OS was 87.4%, compared with 42.2% for patients whose sereum was negative for all E antibodies (P < .001). The respective 5-year PFS rates were 82.9% and 46.1% (P < .001). "These results hint at a prognostic stratification of patients with HPV-related oropharynx cancer reflecting humoral immune response to HPV type 16 E proteins and thus may help in choosing immunotherapy approaches for such patients in future," said senior author Erich M. Sturgis, MD, MPH, a surgeon at MD Anderson, in comments to Medscape Medical News. Currently, the serology results are not strong enough to be used as clinical decision tools for choosing current therapies, she added. Their findings also suggest that vaccine-based immunotherapy targeted [...]

Keytruda doubles efficacy of only targeted therapy for head and neck cancer

Source: www.curetoday.com Author: Lauren M. Green The immunotherapy Keytruda (pembrolizumab), in a recent study, proved twice as effective for the treatment of head and neck cancer as Erbitux (cetuximab), the only targeted therapy indicated as a therapy for the disease. The multisite study offers the largest experience to date of how immunotherapy can be deployed in patients with head and neck cancer, and could change the way the disease is treated. The findings were announced May 29 during the annual meeting of the American Society of Clinical Oncology, a gathering of nearly 30,000 oncology professionals taking place in Chicago. Keytruda is an antibody designed to disable the protein PD-1 so it cannot do its job of keeping the immune system in check; this allows T cells to become more active in recognizing and fighting cancer cells. In the study, investigators found that the drug produced broad and durable responses in patients with advanced head and neck cancer. Fifty-six percent of patients in the study experienced some tumor shrinkage with Keytruda, and 86 percent of those patients continued to respond to treatment at data cutoff on March 23, 2015. Keytruda produced an overall response rate (ORR) of 25 percent, and it proved active in both HPV (human papillomavirus)-positive and HPV-negative patients. “The efficacy was remarkable — pembrolizumab seems to be roughly twice as effective, when measured by response, as our only targeted therapy, cetuximab,” said Tanguy Seiwart, an assistant professor of medicine and associate leader of the head and neck cancer [...]

Pembrolizumab immunotherapy effective in recurrent, metastatic head and neck cancer

Source: www.cancertherapyadvisor.com Author: Debra Hughes, MS Pembrolizumab immunotherapy is effective for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), results of the KEYNOTE-012 trial presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting have shown. At a fixed dose of 200 mg intravenously every 3 weeks, pembrolizumab “was well tolerated and demonstrated a clinically meaningful overall response rate of 24.8% in patients with recurrent/metastatic SCCHN,” reported Tanguy Y. Seiwert, MD, an assistant professor of medicine, and associate HNC program leader at The University of Chicago in Chicago, IL. However, “it is important to note that response rate may underestimate the rate of benefit in patients, and ultimately we need to assess survival,” said Dr. Seiwert in an ASCO press release. “We know from other diseases where the experience with immunotherapy is larger, that patients who have disease stabilization or even initially experience disease progression upon receiving immunotherapy ultimately may derive significant benefit that can translate into longer survival.” Pembrolizumab (MK-3475), a humanized monoclonal antibody that blocks interaction of PD-1 with its ligands, PD-L1 and PD-L2, promotes activity of tumor-specific effector T cells. Previously, the KEYNOTE 012 study had demonstrated clinical activity of pembrolizumab 10 mg/kg every 2 weeks in patients with recurrent/metastatic SCCHN enriched for PD-L1–positive tumors. Response rate was 20%. Dr. Seiwert reported on the study's larger SCCHN expansion cohort, irrespective of PD-L1 expression or HPV status, using a 3-weekly fixed dose. The primary end point was overall response rate [...]

Merck immunotherapy appears effective in head and neck cancer – study | Reuters

Source: www.firstpress.comAuthor: Bill Berkrot  A Merck & Co drug that helps the immune system fight cancer was about twice as effective as the current standard therapy for patients with recurrent or advanced head and neck cancers, according to study data released on Friday. A quarter of the 132 patients who received the drug, Keytruda (pembrolizumab), saw their tumors shrink by at least 30 percent. Fifty-six percent of patients experienced at least some tumor shrinkage in the ongoing single drug Phase I study dubbed Keynote-012, researchers reported. "This is remarkable because we don't usually see this level of activity with new agents. We have a track record of failure," said Dr. Tanguy Seiwert, lead investigator of the study from the University of Chicago. Advanced head and neck cancer is currently treated with Eli Lilly's Erbitux, known chemically as cetuximab, which typically has a response rate of 10 percent to 13 percent. "The only thing that works is cetuximab and this looks at least twice as good," said Seiwert, who was presenting the Keytruda data at the American Society of Clinical Oncology meeting in Chicago. ADVERTISING Merck shares rose more than 1 percent to $60.43 on the New York Stock Exchange. Keytruda and Opdivo from Bristol-Myers Squibb Co are at the forefront of a promising new class of drugs called PD-1 inhibitors that block a mechanism tumors use to evade the immune system. Keytruda is approved to treat advanced melanoma and awaits a decision for use in lung cancer. It is being [...]

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