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Adaptimmune Announces Initiation of Study to Evaluate SPEAR T-Cell Therapy Targeting AFP in Liver Cancer

On May 10, 2017 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported that it has initiated the first site for its AFP SPEAR T-cell study in patients with locally advanced or metastatic hepatocellular carcinoma, the sixth most common cancer worldwide (Press release, Adaptimmune, MAY 10, 2017, View Source [SID1234518986]). This study is now open for enrollment.

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This is Adaptimmune’s second wholly-owned therapeutic candidate to enter clinical trials. The Company already has ongoing studies to evaluate its T-cell therapy targeting the MAGE-A10 cancer antigen in patients with non-small cell lung cancer, urothelial cancer, melanoma, or head and neck cancers.

"We are excited to initiate this study to evaluate our AFP T-cell therapeutic candidate in patients with hepatocellular carcinoma," said Rafael Amado, Adaptimmune’s Chief Medical Officer. "HCC is one of the more common and deadly types of cancer worldwide and there is an urgent need for effective therapies for advanced disease."

This is a Phase I, open label, dose escalation study designed to evaluate the safety and anti-tumor activity of Adaptimmune’s alpha fetoprotein (AFP) therapeutic candidate in hepatocellular carcinoma (HCC). The study will enroll up to 30 patients with measurable, histologically confirmed HCC, not amenable to resection or loco-regional therapy, and with progressive disease. The primary objective of the study is to evaluate the safety and tolerability of this second-line therapy (post-sorafenib) in patients with AFP-positive HCC. Additional objectives include anti-tumor activity, persistence of genetically modified cells in the body, and evaluation of the phenotype and functionality of genetically modified cells isolated from peripheral blood or tumor post infusion.

Additional information about this study is available at www.clinicaltrials.gov by searching on NCT03132792.

About Hepatocellular (Liver) Cancer
A cancer that starts in the liver is called primary liver cancer. Hepatocellular carcinoma is the most common type of liver cancer in adults. Many patients who develop liver cancer have long-standing cirrhosis (scar tissue formation from liver cell damage), and early detection can be difficult because signs and symptoms often do not appear until later stages. It is estimated that approximately 40,710 new cases of primary liver cancer and intrahepatic bile duct cancer will be diagnosed (about 29,200 in men and 11,510 in women, and about 28,920 people will die from these cancers (about 19,610 men and 9,310 women) in the United States in 2017.

OncoSec Announces Clinical Collaboration with Merck to Evaluate Combination of ImmunoPulse® IL-12 and KEYTRUDA® (pembrolizumab) for Metastatic Melanoma

On May 10, 2017 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported it has entered a clinical trial collaboration and supply agreement with Merck (known as MSD outside the United States and Canada) to evaluate the combination of OncoSec’s ImmuoPulse IL-12 with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in a Phase II clinical trial, referred to as PISCES (Press release, OncoSec Medical, MAY 10, 2017, View Source [SID1234518980]). The planned clinical trial will evaluate the safety and efficacy of the combination in patients with metastatic melanoma following disease progression on previous treatment with an anti-PD-1 therapy.

"We are honored to collaborate with Merck – one of the world’s leading cancer immuno-oncology companies – to help bring innovative cancer treatments to patients with unmet medical needs," said Punit Dhillon, CEO and President of OncoSec. "This collaboration is supported by our recent clinical data demonstrating the potential ability of ImmunoPulse IL-12 to rescue patients who do not initially respond to anti-PD-1 therapy in melanoma. In addition to our recent Fast Track Designation for this population, OncoSec is uniquely positioned to meaningfully impact clinical outcomes for patients who do not currently have any other options. By working with innovative immuno-oncology leaders, this alliance underpins OncoSec’s strategy to combine our ImmunoPulse IL-12 program with checkpoint inhibitor therapies to advance the care of patients."

Eligible patients for this Phase II study will be those with Stage III/IV metastatic melanoma who are progressing, or have progressed, on previous treatment with an anti-PD-1 therapy. The collaboration agreement is between OncoSec Medical Incorporated and Merck, through a subsidiary. Under the agreement, OncoSec will sponsor and fund the study and Merck will provide KEYTRUDA. Additional details of the collaboration were not disclosed.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

ImmunoPulse is a registered trademark of OncoSec Medical Incorporated, San Diego, CA, USA.

About PISCES

PISCES (Anti-PD-1 IL-12 Stage III/IV Combination Electroporation Study) will be a Phase II multicenter study of ImmunoPulse IL-12 in combination with KEYTRUDA in patients with histological diagnosis of melanoma with progressive locally advanced or metastatic disease defined as Stage III or Stage IV. Eligible patients will be those with Stage III/IV metastatic melanoma who are progressing or have progressed on an approved anti-PD-1 therapy. The primary endpoint for this registration-directed trial will be best overall response rate (BORR).

Atossa Genetics Receives Second Positive Safety Committee Decision in Phase 1 Topical Endoxifen Dose Escalation Study

On May 10, 2017 Atossa Genetics Inc. (NASDAQ: ATOS), a clinical-stage pharmaceutical company, reported that it has received the second positive interim review on its Phase 1 study of endoxifen, which is an active metabolite of the FDA approved drug tamoxifen, which is indicated for breast cancer and breast cancer prevention in high risk patients (Press release, Atossa Genetics, MAY 10, 2017, View Source [SID1234518976]). The Independent Safety Committee reviewed the blinded data generated from the second cohort of the study (8 subjects) and concluded that the study may advance to the final topical dosing level.

"This is the second positive safety determination for our Phase 1 study," stated Steven Quay, CEO and President. "The first safety determination allowed us to proceed to the current dosing level and now this additional interim safety determination indicates that proceeding to the final dosing level with our proprietary topical Endoxifen is warranted."

The objectives of this double-blinded, placebo-controlled, repeat dose study of 48 healthy female subjects is to assess the pharmacokinetics of proprietary formulations of both oral and topical endoxifen dosage forms over 28 days, as well as to assess safety and tolerability. The study is being conducted in two parts based on route of administration.

The study is being conducted on behalf of Atossa by CPR Pharma Services Pty Ltd., Thebarton, SA, Australia.

Inovio Provides Update on MedImmune Launch of Combination Trial for HPV-associated Head & Neck Cancer

On May 10, 2017 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported MedImmune, AstraZeneca’s global biologics research and development arm, will start a new clinical trial investigating the combination of MEDI0457, an immunotherapy designed to generate antigen specific killer T cell responses targeting HPV-associated tumors, and durvalumab, an investigational PD-L1 checkpoint inhibitor (Press release, Inovio, MAY 10, 2017, View Source;Neck-Cancer/default.aspx [SID1234518975]). The combination trial will enroll patients with metastatic HPV-associated squamous cell carcinoma of the head & neck (SCCHN) with persistent or recurrent disease after chemotherapy treatment.

The open-label study is designed to evaluate the safety and efficacy of the combination therapy in approximately 50 subjects at multiple U.S. sites. Subjects will receive multiple doses of MEDI0457 (previously known as INO-3112) and durvalumab. The primary endpoints of the study are safety and objective response rate. The study will also evaluate immunological impact, progression-free survival and overall survival.

Dr. J. Joseph Kim, Inovio’s President and CEO, said, "This study marks a significant moment for Inovio as we transition into a late-stage biotechnology company. MedImmune is investigating the possibility of elevating the response rate of checkpoint inhibitors by using durvalumab in combination with a DNA plasmid vaccine originally from Inovio which has shown the ability to generate killer T cells. I’m a strong believer in this combination regimen strategy against cancer: utilize Inovio’s cancer vaccine to generate significant levels of antigen-specific killer T cells, have them infiltrate into tumors — or what is being referenced as turning a tumor from "cold" to "hot" — then suppress the cancer cells’ defensive mechanisms utilizing a checkpoint inhibitor. We think that powerful combination can be effective in treating multiple tumors going forward."

Increasing evidence suggests that response rates from checkpoint inhibitors such as MedImmune’s durvalumab can be enhanced when used in combination with cancer vaccines like MEDI0457 that generate tumor-specific T cells. Interim data from a MEDI0457 monotherapy study of head and neck cancer patients demonstrated that MEDI0457 generated robust HPV16/18 specific CD8+ T cell responses in peripheral blood and increased CD8+ T cell infiltration in resected tumor tissue samples.

In 2015, MedImmune acquired exclusive rights to Inovio’s INO-3112 immunotherapy for all HPV-associated cancers. MedImmune provided an upfront payment of $27.5 million to Inovio as well as potential future payments upon reaching development and commercial milestones totaling up to $700 million. MedImmune will fund all development costs. Inovio is entitled to receive up to double-digit tiered royalties on INO-3112 product sales.

About HPV-associated Head & Neck Cancer
Head and neck cancer is the sixth most common cancer worldwide. Human papillomavirus (HPV), the most common sexually transmitted disease in the US, is known to play a major role in the development of head and neck cancers, which include cancers of the oral cavity, oropharynx, nose/nasal passages and larynx. New cases of HPV-associated squamous cell carcinoma of the head & neck (SCCHN) are growing fastest in developed countries like the US. There are approximately 16,000 new cases of HPV-associated SCCHN per year in the US alone. In contrast, the rate of smoking and alcohol-related SCCHN has been steadily declining. Men are four times more likely than women to be diagnosed with this disease. Patients with HPV-associated SCCHN tend to be diagnosed at a younger age than those with smoking and alcohol related disease.

Head and neck cancers are currently 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 biology and natural history of oropharyngeal HPV infection and the best clinical management of patients with HPV-associated SCCHN are not well understood.

About MEDI0457 (INO-3112)
Inovio’s DNA-based immunotherapies help the immune system activate disease-specific killer T cells to fight a targeted disease. INO-3112 targets disease associated with the high-risk HPV types 16 and 18, which are responsible for over 70% of cervical pre-cancers and cancers and 60% of head and neck cancers. INO-3112 combines Inovio’s VGX-3100, its immunotherapy targeting HPV-associated diseases, with its DNA-based immune activator encoding IL-12.

About Durvalumab
Durvalumab, previously known as MEDI4736, a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour’s immune-evading tactics and inducing an immune response. Additional clinical trials are ongoing to investigate durvalumab as monotherapy or in combination with tremelimumab in non-small cell lung cancer, head and neck squamous cell carcinoma, bladder, hepatocellular carcinoma and blood cancers.

ENDOCYTE REPORTS FIRST QUARTER FINANCIAL RESULTS AND PROVIDES CLINICAL AND PIPELINE UPDATE

On May 10, 2017 Endocyte, Inc. (NASDAQ:ECYT), a leader in developing targeted small molecule drug conjugates (SMDCs) and companion imaging agents for personalized therapy, reported financial results for the first quarter ending March 31, 2017, and provided a clinical and pipeline update (Press release, Endocyte, MAY 10, 2017, View Source [SID1234518974]).

"We look forward to providing safety and efficacy updates for our clinical trials of both EC1169 and EC1456 at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) next month," said Mike Sherman, president and CEO at Endocyte. "In addition, we continue to discover compelling applications of the SMDC platform and are working to more rapidly bring assets toward clinical development in several exciting areas, to drive more value from our pipeline. These include our dual-targeted DNA crosslinker drug that can attack both tumor associated macrophages (TAMs) and cancer cells, EC2629, and our chimeric antigen receptor T-cell (CAR T-cell) SMDC adaptor platform."

"Enrollment in the expansion phase of the EC1169 trial in prostate cancer continues to progress well, and we recently completed our work with EC1456 exploring multiple dosing schedules," added Dr. Alison Armour, Endocyte’s chief medical officer. "We also enrolled the first patient in the study of EC1456 in ovarian cancer patients undergoing surgery to provide tissue-based characterization following drug administration."

Lead SMDC Programs

EC1169 (PSMA-targeted tubulysin): Enrolling patients in the expansion phase of the EC1169 trial in up to 50 taxane-exposed metastatic castration-resistant prostate cancer (mCRPC) patients and up to 50 taxane-naïve mCRPC patients at a maximum clinical dose of 6.5 mg/m2 once per week. The primary endpoint of this expansion phase is radiographic progression-free survival (rPFS), with a target of 5 months for taxane-naïve mCRPC patients and 3 months for taxane-exposed mCRPC patients. Secondary endpoints, which will provide earlier insight into drug activity, include overall response rates as measured by response evaluation criteria in solid tumors (RECIST) 1.1 and prostate-specific antigen (PSA). Enrollment is not limited based on the results of the scan with EC0652, but primary endpoints of the trial are to be assessed on PSMA positive patients.

EC1456 (folate receptor-targeted tubulysin): Enrolling expansion cohort of up to 40 folate receptor-positive (FR-positive) non-small cell lung cancer (NSCLC) patients, as determined by an etarfolatide scan, to receive the maximum clinical dose of 6.0 mg/m2 twice per week. Patients included in this expansion phase of the trial will have received first-line chemotherapy and may have also been treated with anti-programmed death-1 (anti-PD-1) therapy. Endocyte is also conducting an ovarian cancer surgical study to characterize EC1456 at the tumor level through a multifaceted analysis of collected tissue samples after administration of the drug.

Immuno-oncology Pipeline

EC2629: Pre-clinical development currently underway with a potential Investigational New Drug (IND) filing in mid-2017. EC2629 leverages a proprietary warhead with a dual mechanism of action: targeting both TAMs and FR-positive cancer cells.

CAR T-Cell Development Program: Continued progress with next-generation CAR T-cell therapeutic platform, in collaboration with leading experts in the field at Seattle Children’s Research Institute. Endocyte announced new research in a late-breaking poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2017, on the application of Endocyte’s SMDC technology. Data demonstrated that Endocyte’s bi-specific adaptor molecules can mitigate or eliminate cytokine storms in animal models and could meaningfully improve the safety and tolerability of CAR T-cell therapies. Pre-clinical evaluations for the CAR T-cell program by Dr. Michael Jensen are expected to be completed in the second half of 2017, in anticipation of a potential IND filing in 2018.

First Quarter 2017 Financial Results

Endocyte reported a net loss of $11.5 million, or $0.27 per basic and diluted share, for the first quarter of 2017, compared to a net loss of $10.2 million, or $0.24 per basic and diluted share for the same period in 2016.

Research and development expenses were $8.0 million for the first quarter of 2017, compared to $6.5 million for the same period in 2016. The increase was primarily attributable to increases in expenses related to the EC1169 phase 1 trial, including drug manufacturing expenses, expenses related to the development of EC2629 and other pre-clinical work and general research, and expenses related to the EC1456 phase 1 trial, which were partially offset by a decrease related to non-cash stock-based compensation expenses.

General and administrative expenses were $3.7 million for the first quarter of 2017, compared to $3.8 million for the same period in 2016. The slight decrease was primarily attributable to a decrease in compensation expense, which was partially offset by an increase in expenses related to professional fees.

Cash, cash equivalents and investments were $127.6 million at March 31, 2017, compared to
$163.3 million at March 31, 2016, and $138.2 million at December 31, 2016.

Financial Expectations

The company anticipates its cash balance at the end of 2017 to be approximately $100 million.

About EC1169 and EC0652

EC1169 is an investigational therapeutic SMDC constructed of a high affinity prostate specific membrane antigen (PSMA)-targeting ligand conjugated through a bioreleasable linker system to a potent microtubule inhibitor, tubulysin B hydrazide (TubBH). Patient PSMA-status is determined using the investigational companion imaging agent, EC0652.

About EC1456 and etarfolatide

EC1456 is an investigational therapeutic SMDC constructed of a high affinity FR-targeting ligand conjugated through a spacer and bioreleasable linker system to a potent cytotoxic microtubule inhibitor, TubBH. Patient FR-status is determined using the investigational companion imaging agent, etarfolatide.