1stOncology™: Cancer Intelligence Service – Page 15624 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Advaxis Announces that Phase 2 Head and Neck Cancer Study with AXAL Advances to Second Stage

On August 11, 2016 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported that its Phase 2 "window of opportunity" clinical study of its lead immunotherapy candidate, axalimogene filolisbac (AXAL), in patients with late-stage HPV-associated oropharyngeal cancer (HPVOPC) met its stage 1 primary objective and is advancing into the second stage of the clinical study (Press release, Advaxis, AUG 11, 2016, View Source [SID:1234514508]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

This is an investigator-initiated prospective clinical study of patients with stage I-IV HPVOPC who are to undergo ablative trans-oral robotic surgery (TORS) as a preoperative treatment. The clinical study leverages the five- to six-week period between diagnosis and TORS, making it possible to analyze and compare the tumor microenvironment as well as peripheral blood samples collected before and after AXAL treatments.

The clinical study is designed to show that AXAL is highly immunogenic and worth further investigation if the overall rate of vaccine-induced T-cell responses is 75 percent or more. By looking at both IFN-γ and TNFα expressing T cells in the peripheral blood, it was found that systemic HPV-reactive T-cell responses were increased in enough patients treated with AXAL to meet the stage 1 immune response target. This evidence of systemic response is consistent with a recent abstract presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) describing increased cytotoxic T-cell infiltration into the tumor microenvironment in HPVOPC patients treated with AXAL.

"The assessment of the TNFα and IFN-γ response based on data from eight of the anticipated nine patients to be enrolled in stage 1 confirmed that the clinical study has already met the target for the overall rate of vaccine-induced T-cell response, paving the way for us to progress to stage 2," said the study’s lead investigator Andrew G. Sikora, MD, PhD, of the Bobby R. Alford Department of Otolaryngology-Head and Neck Surgery at Baylor College of Medicine. "Together with our prior published data showing increased intratumoral T-cell infiltration in a significant number of AXAL treated patients, these data provide the confidence needed to move forward with the definitive evaluation of its immunogenicity."

Stage 2 of the clinical study will enroll up to 13 patients with late-stage HPVOPC. This stage of the clinical study will be conducted at the Icahn School of Medicine at Mount Sinai and a second investigative site anticipated to be the Baylor College of Medicine. The study received a three-year $1.1 million grant from the U.S. Food and Drug Administration’s Office of Orphan Products Development, which funds research for the development of products for rare diseases.

HPV-Associated Head and Neck Cancers

More than 90 percent of head and neck squamous cell oropharyngeal cancers originate from the mucosal linings of the oral cavity, pharynx or larynx. Currently, 60 to 80 percent of these cancers are caused by HPV. Head and neck cancers are treated by surgical removal of the cancer and lymph nodes, often followed by radiation and chemotherapy based on the extent of the disease. While patients may achieve good long-term survival, standard treatments can change their physical appearance and are associated with significant short and long-term toxicities which may interfere with salivary gland function, taste, smell, and the ability to swallow.

The incidence of HPV-associated head and neck cancers has been increasing at an epidemic rate, while head and neck cancers from other causes have been decreasing. According to the World Health Organization, approximately 15 to 20 percent of the 400,000 new cases of head and neck cancer are HPV-related. In the US, there are about 12,000 new cases of HPV-associated head and neck cancer per year and it affects men about 3 times more frequently than women. HPV-associated head and neck cancer is growing fastest in developed countries like the U.S.

About Axalimogene Filolisbac

AXAL is Advaxis’ lead Lm Technology immunotherapy candidate for the treatment of HPV-associated cancers and is in clinical trials for three potential indications: invasive cervical cancer, head and neck cancer, and anal cancer. AXAL has Orphan Drug Designation in the U.S. for the treatment of these three indications. In a completed randomized Phase 2 study in recurrent/refractory cervical cancer, AXAL showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the company’s Lm Technology.

Epizyme Doses First Patient in Global Phase 2 Study Evaluating Tazemetostat in Mesothelioma

On August 11, 2016 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported that the first patient has been dosed in the Company’s global phase 2 study evaluating tazemetostat, a first-in-class EZH2 inhibitor, for the treatment of adults with mesothelioma characterized by BAP1 loss-of-function (Press release, Epizyme, AUG 11, 2016, View Source [SID:1234514505]).

"Mesothelioma remains a cancer that is very difficult to treat and has an extremely poor prognosis," said Marjorie Zauderer, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center. "The overwhelming majority of patients are refractory to or relapse following first-line treatment with chemotherapy leaving them with no approved treatment options. The preclinical data demonstrating that EZH2 inhibition may play a role in the treatment of mesothelioma is promising, and I look forward to exploring the potential for tazemetostat as a targeted agent for patients with this devastating disease."

Mesothelioma affects nearly 12,000 people each year in major markets, of which 40 to 60% have tumors characterized by BAP1 loss-of-function. The median overall survival for all patients with mesothelioma generally ranges from eight to 14 months from the time of diagnosis. The most commonly used first-line treatment consists of cisplatin or carboplatin combined with pemetrexed, which is the only drug approved (2004) for the treatment of mesothelioma1.

"Patient dosing in this phase 2 study marks another milestone for Epizyme and the expansion of our clinical development program into a new cancer indication for which there is a significant medical need," said Peter Ho, M.D., Ph.D., Executive Vice President and Chief Medical Officer, Epizyme. "With this study, Epizyme now has four registration-supporting monotherapy trials underway with tazemetostat, and plans for two combination trials to be initiated later this year."

Phase 2 Study Design
The international, open-label, phase 2 study will evaluate tazemetostat as a monotherapy in a total of 67 patients at multiple sites in the United States, United Kingdom and France. Tazemetostat is orally administered at a dose of 800 mg twice-daily. The safety and pharmacokinetic profile of tazemetostat will first be evaluated in 12 patients with relapsed or refractory mesothelioma regardless of BAP1 status. Subsequently, a total of 55 patients with relapsed or refractory mesothelioma characterized by BAP1 loss-of-function will be treated using a two-stage study design. The primary endpoint of the study is disease control rate (complete response, partial response or stable disease) at 12 weeks. Secondary endpoints include overall response rate, progression-free survival, duration of response and overall survival.

EZH2 Inhibition in Mesothelioma
Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary drug development platform. Aberrant EZH2 activity results in misregulation of genes that control cell proliferation and has been associated with a diverse set of human cancers. Preclinical findings from published reports suggest that mesothelioma, and particularly mesothelioma characterized by BAP1 loss of function, may be sensitive to EZH2 inhibition2. Mesothelioma characterized by BAP1 loss of function accounts for 40 to 60 percent of the approximately 12,000 new mesothelioma cases each year in major markets3-6.

About the Tazemetostat Clinical Trial Program
Tazemetostat, a first-in-class EZH2 inhibitor, is currently being studied in ongoing phase 2 programs in non-Hodgkin lymphoma (NHL), certain genetically defined solid tumors, including INI1-negative and SMARCA4-negative tumors and synovial sarcoma, and mesothelioma.

The company plans to initiate additional clinical trials of tazemetostat in 2016, including a combination with R-CHOP in collaboration with the Lymphoma Study Association and a combination with Tecentriq (atezolizumab) in collaboration with Genentech, a member of the Roche Group, both in patients with diffuse large B-cell lymphoma.

CEL-SCI Corporation Reports Third Quarter Fiscal Year 2016 Financial Results

On August 10, 2016 CEL-SCI Corporation (NYSE MKT: CVM) reported financial results for the quarter ended June 30, 2016 and updates shareholders in regards to the upcoming date for the Company’s arbitration hearing against its former Clinical Research Organization (CRO) (Press release, Cel-Sci, AUG 10, 2016, View Source [SID:1234514501]).

Key corporate and clinical developments during the quarter include:

Enrolled an additional 92 patients in the global pivotal Phase 3 head and neck cancer trial during the third quarter of FY 2016 which is a 12% increase over the third quarter of FY 2015.
Enrolled another 29 patients in July 2016, following the end of the quarter.
A total of 877 patients have been enrolled in the study as of July 31, 2016.
Continued patient enrollment in the Phase 1 trial of Multikine* in HIV/HPV co-infected men and women with peri-anal warts at San Diego Naval Medical Center and University of California, San Francisco (UCSF).
Raised $5 million to finance the Phase 3 head and neck cancer trial.
CEL-SCI’s net loss for the quarter ended June 30, 2016 was ($3,849,324) or ($0.03) per basic and diluted share, versus ($4,429,137) or ($0.05) per basic share and ($0.06) per diluted share during the quarter ended June 30, 2015. The net loss for the nine months ended June 30, 2016 was ($10,352,366) or ($0.09) per basic and diluted share, versus ($24,830,691) or ($0.32) per basic and diluted share during the same nine months ended June 30, 2015.

CEL-SCI reported an operating loss of ($6,382,747) for the quarter ended June 30, 2016 versus an operating loss of ($8,201,475) for the quarter ended June 30, 2015. The operating loss for the nine months ended June 30, 2016 was ($18,439,482) versus ($25,956,559) during the nine months ended June 30, 2015.

Geert Kersten, CEL-SCI’s Chief Executive Officer said, "The current focus remains the completion of the Phase 3 clinical trial with Multikine and the upcoming arbitration hearing ("trial") against the Company’s former CRO scheduled for September 7, 2016."

About Multikine (Leukocyte Interleukin, Injection)

Multikine is an investigational immunotherapeutic agent that is being tested in an open-label, randomized, controlled, global pivotal Phase 3 clinical trial as a potential first-line treatment for advanced primary (not yet treated) squamous cell carcinoma of the head and neck. Multikine is designed to be a different type of therapy in the fight against cancer: one that appears to have the potential to work with the body’s natural immune system in the fight against tumors.

BIO-PATH HOLDINGS REPORTS SECOND QUARTER 2016 FINANCIAL RESULTS

On August 10, 2016 Bio-Path Holdings, Inc. (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer drugs, reported its financial results for the second quarter ended June 30, 2016 and also provided an update on recent corporate developments (Press release, Bio-Path Holdings, AUG 10, 2016, View Source [SID:1234514494]).

"We made significant progress advancing our clinical development programs during the second quarter. Specifically, we were pleased to announce a sponsored research agreement with Thomas Jefferson University to investigate our DNAbilize technology for the development of a brain cancer immunotherapy," said Peter Nielsen, President and CEO of Bio-Path Holdings. "In addition, we advanced preparations for the efficacy portion of our Phase II program of BP1001 for the treatment of acute myeloid leukemia (AML). We have seven leading cancer centers committed to conducting this trial and look forward to dosing patients in the near term."

Recent Corporate Highlights

· Entered Sponsored Research Agreement with Thomas Jefferson University. The Company entered into a sponsored research agreement with Thomas Jefferson University to investigate Bio-Path’s DNAbilize antisense DNA technology for the development of a brain cancer immunotherapy that works by activating the patient’s own immune system to fight the patient’s cancer.

· Completed Registered Direct Public Offering. On July 5, 2016, the Company completed the sale and issuance of 5,882,353 shares of common stock and warrants to purchase up to 2,941,177 shares of common stock in a registered direct offering with gross proceeds of approximately $10.0 million.

· Presented Data at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper). Dr. Maro Ohanian, Assistant Professor at The University of Texas MD Anderson Cancer Center, presented data at the 2016 ASCO (Free ASCO Whitepaper) Annual Meeting. Results from the Phase I study of BP1001 for the treatment of AML and CML as well as the safety segment of the Phase II combination therapy of BP1001 in combination with low-dose cytarabine (LDAC) as a treatment for advanced AML were presented in a poster titled, "Phase I Study of BP1001 (Liposomal Grb2 Antisense) in Patients with Hematologic Malignancies."

· Presented Data at the 18th Annual TIDES: Oligonucleotide and Peptides Therapeutics Conference. In May, Dr. Ana Tari Ashizawa delivered a presentation titled, "Clinical Studies of BP1001, a drug candidate utilizing DNAbilize Antisense DNA Technology, in Hematologic Malignancies" at the 18th Annual TIDES: Oligonucleotide and Peptides Therapeutics Conference.

Financial Results for the Second Quarter Ended June 30, 2016

The Company reported a net loss of $1.9 million, or $0.02 per share, for the three months ended June 30, 2016, compared to a net loss of $1.1 million, or $0.01 per share, for the same period last year. The increase was primarily due to preparations related to the Company’s Phase II clinical trial for BP1001 in AML.

Research and development expenses for the three months ended June 30, 2016 increased to $1.2 million, compared to $0.6 million for the same period last year. General and administrative expenses for the three months ended June 30, 2016 increased to $0.8 million, compared to $0.6 million for the same period last year.

As of June 30, 2016, the Company had cash of $4.2 million, compared to $8.9 million at December 31, 2015. Net cash used in operating activities for the six months ended June 30, 2016 was $4.6 million compared to $2.8 million for the comparable period in 2015.

Kura Oncology Reports Second Quarter 2016 Financial Results

On August 10, 2016 Kura Oncology, Inc., (NASDAQ:KURA) a clinical stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported second quarter 2016 financial results and recent business highlights (Press release, Kura Oncology, AUG 10, 2016, View Source;p=RssLanding&cat=news&id=2194722 [SID:1234514478]). In the company’s Phase 2 trial of tipifarnib in HRAS mutant solid tumors, positive clinical activity, including objective responses, has been observed in patients with head and neck squamous cell carcinomas and patients with salivary gland cancer. Based on these responses, enrollment will be expanded to an additional seven patients.

"We are encouraged by the promising activity observed in patients with HRAS mutant solid tumors that supports the potential use of tipifarnib as a single agent to inhibit HRAS-mediated activation of the MAPK pathway to produce therapeutic responses," said Troy Wilson, Ph.D., J.D., President and CEO of Kura Oncology. "There are currently no approved treatments that specifically target HRAS mutations, and the activity we have seen in patients with HRAS mutant head and neck squamous cell carcinomas is particularly exciting. I am pleased with Kura’s progress to date in 2016 and look forward to providing additional updates on our ongoing activities as the year continues to unfold."

Update on Phase 2 Clinical Trial in HRAS Mutant Solid Tumors

Kura Oncology’s Phase 2 trial of tipifarnib in HRAS mutant solid tumors was designed to initially enroll two cohorts of 11 patients each with HRAS mutations, with the first cohort comprising patients with thyroid cancers and the second comprising patients with non-hematologic malignancies other than thyroid cancer. The primary objective of the study is to investigate the antitumor activity of tipifarnib in terms of objective response rate. Secondary objectives include progression-free survival, duration of response and safety. Per the protocol, two objective responses are required from the first 11 evaluable patients in a cohort in order to proceed to the second stage and enroll an additional seven patients.

In the second cohort, 11 evaluable patients have been enrolled to date with the most common histologies comprising salivary gland tumors (5 patients) and head and neck squamous cell carcinomas (3 patients).

Among the three patients with HRAS mutant head and neck squamous cell cancer, two patients have had confirmed partial responses (PR), and disease stabilization has been observed in the third patient. The two patients with PR’s have been on study for more than 12 and 5 months, and responses were seen after 6 and 2 cycles of treatment, respectively. The third patient demonstrated disease stabilization for 7 months.

No objective responses have been observed in patients with salivary gland tumors; however, 3 of 5 salivary gland cancer patients experienced disease stabilization beyond 6 months (>6, 9 and >11 months).

The first cohort of the Phase 2 trial, which consists of patients with thyroid cancers with HRAS mutations, continues enrolling.
Upcoming Clinical and Preclinical Milestones for Kura Oncology Programs

Initiation of a Phase 2 clinical trial for tipifarnib in patients with CMML is planned in the second half of 2016.

IND submission for ERK inhibitor, KO-947, is anticipated in the second half of 2016.

Nomination of a development candidate for the menin-MLL program is anticipated in the second half of 2016.
Financial Results for the Second Quarter 2016

Cash, cash equivalents and short-term investments totaled $80.1 million as of June 30, 2016, compared with $85.7 million as of December 31, 2015. Management expects that current cash, cash equivalents and short-term investments will be sufficient to fund current operations into 2018.

Research and development expenses for the second quarter of 2016 were $4.9 million, compared to $4.4 million for the second quarter of 2015.

General and administrative expenses for the second quarter of 2016 were $1.9 million, compared to $1.5 million for the second quarter of 2015.

Net loss for the second quarter of 2016 was $6.7 million, or $0.36 per share, compared to a net loss of $5.6 million, or $0.54 per share, for the second quarter of 2015.

During the second quarter of 2016, as previously disclosed, Kura Oncology put in place a $20.0 million term loan facility, of which $7.5 million has been drawn to date.