On August 8, 2016 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported financial results for the quarter ended June 30, 2016 (Press release, Inovio, AUG 8, 2016, View Source [SID:1234514352]). The following financial results provide a year-over-year comparison of the second quarter in 2016 and 2015. Total revenue was $6.2 million compared to $5.3 million. Total operating expenses were $24.4 million compared to $20.4 million. The net loss attributable to common stockholders was $18.7 million, or $0.26 per share, compared to $6.2 million, or $0.09 per share.

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!

Revenue

The increase in revenue was primarily due to an increase in development payments from our DARPA Ebola grant.

Operating Expenses

Research and development expenses were $19.6 million compared to $16.7 million. The increase was primarily related to increased investment in our product development programs. General and administrative expenses were $5.8 million compared to $4.7 million.

Capital Resources

As of June 30, 2016, cash and cash equivalents and short-term investments were $134.5 million compared with $163.0 million as of December 31, 2015. There were 73.5 million shares outstanding and 81.2 million fully diluted.

The Company sold 119,400 shares of common stock at an average price of $11.12 per share, for net proceeds of $1.3 million, under the ATM common stock sales agreement implemented during the period.

Inovio’s balance sheet and statement of operations are provided below. Form 10-Q providing the complete 2016 second quarter financial report can be found at: View Source

Corporate Update

Clinical Development

The FDA and European Medicines Agency provided an affirmative path toward an indication for VGX-3100 to treat HPV-16/18-related high grade cervical dysplasia in a pivotal phase III registration study. We completed major commercial device design and manufacturing process development efforts, and are in the final stage of testing. Completion of this extensive work will enable us to then submit our final package to the FDA in order to start the phase III in 4Q 2016.
Received approval from the FDA to initiate a phase I human trial to evaluate Inovio’s Zika DNA vaccine (GLS-5700). This phase I, open-label, dose-ranging study with 40 healthy subjects is evaluating the safety, tolerability and immunogenicity of GLS-5700. Subsequent to the quarter Inovio announced the dosing of the first subject in this study. We expect to report interim immune response and safety data in 4Q 2016.
Inovio will continue to develop its hepatitis B DNA immunotherapy (INO-1800) independently following Roche’s notice that it will discontinue its collaboration with Inovio and its development of INO-1800. INO-1800 was licensed to Roche from Inovio in 2013. All of Roche’s rights to INO-1800, including the right to license the product to other parties, will be returned. Inovio will continue to advance its current phase I study of INO-1800, which is enrolling as planned in 30 clinical sites in the U.S. and Asia-Pacific regions. Inovio anticipates completing enrollment in the first half of 2017 and expects results in the second half of 2017.
The study has completed interim safety reviews with a favorable safety profile to date. Immunology analyses are planned after completion of enrollment.
Partnered with the National Cancer Institute and Mayo Clinic to initiate a phase I trial of our immunotherapy for hepatitis C (INO-8000). The dose escalation study will enroll patients in the early stages of chronic HCV infection to determine the therapy’s ability to decrease and potentially eliminate HCV viral load, measure HCV specific immune responses and durability of these immune responses, and evaluate safety and tolerability.
Completed enrollment of 94 subjects in the phase I study of our PENNVAX-GP HIV immunotherapy. After completing extensive immunogenicity analyses, we expect to report data in 1H 2017.
Completed enrollment of 22 subjects in the phase I study of our HPV-driven cancer immunotherapy, INO-3112, in head & neck cancer patients. We expect to report additional immune response and safety data in 4Q 2016.
Completed enrollment of 62 subjects in the phase I study of our INO-5150 prostate cancer immunotherapy. We expect to report interim immune response and safety data in 4Q 2016.
Completed enrollment of 75 subjects in the phase I study of our GLS-5300 MERS vaccine. We expect to report interim immune response and safety data in 4Q 2016.
Corporate Development

Inovio completed the acquisition of all of Bioject Medical Technologies Inc.’s assets, including pioneering needle-free jet injection technology, devices, and intellectual property, for $5.5 million in cash and stock.
Inovio’s DNA-based monoclonal antibody technology will be deployed to develop new immunotherapy approaches to treat HIV. This work will be funded by a $23 million grant, called BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy, from the National Institutes of Health to The Wistar Institute, an Inovio collaborator, and more than 30 of the nation’s leading HIV investigators.
Preclinical Development

Preclinical testing of our Zika virus synthetic vaccine induced robust and durable immune responses in mice and in non-human primates (monkeys).

On August 8, 2016 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported financial results for the second quarter of 2016, recapped recent progress against the Company’s multi-year vision and provided an update on clinical data timelines (Press release, Epizyme, AUG 8, 2016, View Source [SID:1234514351]).

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!

"We are pleased with our continued momentum in the clinical development of tazemetostat in non-Hodgkin lymphoma, or NHL, and genetically defined solid tumors, as well as the expansion of the tazemetostat clinical development program into mesothelioma," said Robert Bazemore, President and Chief Executive Officer of Epizyme. "For the remainder of the year, our focus is on the continued enrollment in and execution of our Phase 2 NHL and solid tumor studies to generate mature objective response and durability data, and to assess the differences in activity between study arms. With a robust clinical program underway for tazemetostat, and advancements in our preclinical and discovery efforts, we believe we are further solidifying Epizyme’s position as the leader in epigenetic drug discovery and development."

Advancing the Clinical Development of Tazemetostat for the Treatment of Non-Hodgkin Lymphoma (NHL) and Genetically Defined Solid Tumors

In June, Epizyme presented positive, early findings from its ongoing Phase 2 study of tazemetostat in patients with relapsed or refractory NHL at the American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting on Lymphoma Biology. As of the data cutoff date in late May, approximately 30 percent of the planned 270 patients were enrolled into the study. Tazemetostat demonstrated clinical activity, including objective responses, in all five arms of the study and a favorable safety profile in a heavily pre-treated, multiply relapsed and highly refractory patient population. Overall patient enrollment is proceeding according to internal projections, and the study is now open for enrollment in the U.S.

Overall patient enrollment is also on-track in the Company’s ongoing Phase 2 clinical study in adult patients and Phase 1 study in pediatric patients with INI-1 negative tumors or synovial sarcoma.

Epizyme plans to provide data on the efficacy and safety of tazemetostat from both the NHL and solid tumor Phase 2 studies in the first half of 2017. The Company plans to meet with regulatory authorities, beginning with the U.S. Food and Drug Administration (FDA) in mid-2017, to review data from all cohorts of its Phase 2 solid tumor study and discuss registration strategies based on these data. Epizyme also expects to meet with FDA to review Phase 2 NHL data and discuss registration strategies in 2017.

In June, Epizyme participated in FDA’s Pediatric Subcommittee of the Oncologic Drugs Advisory Committee (ODAC) meeting, which reviewed select novel, targeted agents for the treatment of pediatric cancer. Epizyme was one of five invited innovators, and presented on its ongoing pediatric clinical program. The Company received valuable feedback and support from Committee members on the development of tazemetostat as a treatment for rare and extremely aggressive cancers in pediatric patients.
Broadening Scope of Tazemetostat Clinical Program

In August, Epizyme initiated a global study of tazemetostat in patients with mesothelioma. This is a multi-center Phase 2 study evaluating tazemetostat as a monotherapy treatment for patients with mesothelioma characterized by BAP1 loss-of-function. The study is open for enrollment in the U.S., with an accepted Investigational New Drug application, and is expected to open in international sites shortly. This study marks the first of five new indications into which the Company plans to expand tazemetostat in the clinic by the end of 2020.

In June, Epizyme entered into a collaboration agreement with Genentech, a member of the Roche Group, to conduct a clinical trial to investigate tazemetostat and Genentech’s recently approved anti-PD-L1 cancer immunotherapy, Tecentriq (atezolizumab), when used in combination for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. The study will be conducted by Genentech and is expected to begin in the second half of 2016.

In May, Epizyme entered into a collaboration agreement with the Lymphoma Study Association (LYSA), a premier cooperative group in France dedicated to clinical and translational research for lymphoma, to investigate the combination of tazemetostat with R-CHOP as a front-line treatment in elderly, high-risk patients with DLBCL. The study will be conducted by LYSA and is expected to be initiated in the second half of 2016.

Second Quarter 2016 Financials Results and Guidance

Collaboration revenue was $0.5 million and $0.9 million for the three and six months ended June 30, 2016, respectively, compared to $0.7 million and $1.6 million for the three and six months ended June 30, 2015, respectively. The period-over-period decreases reflect decreased recognition of deferred revenue from upfront payments and research and development revenue related to the Company’s collaboration with GlaxoSmithKline, partially offset by increased recognition of deferred revenue from upfront payments from its Celgene collaboration.

Research and development (R&D) expenses were $21.5 million and $39.2 million for the three and six months ended June 30, 2016, respectively, compared to $20.6 million and $77.6 million for the three and six months ended June 30, 2015, respectively. During the three months ended June 30, 2016, R&D expenses increased due to external and internal costs associated with the expansion of the tazemetostat program, which more than offset the period-over-period reduction of pinometostat-related costs. The period-over-period decrease from the six months ended June 30, 2015 was driven by the first quarter 2015 payment to Eisai of $40.0 million for the reacquisition of the worldwide rights, excluding Japan, to tazemetostat. Epizyme expects that R&D expenses will increase significantly in the remainder of 2016. This will be driven by the planned expansion of clinical trial activity for tazemetostat, including initiation of the mesothelioma study, initiation of the two combination trials in DLBCL, and expansion of the Company’s ongoing studies in NHL and solid tumors. In addition, discovery and preclinical research costs are expected to increase as Epizyme advances its wholly owned small molecule programs against multiple novel epigenetic targets and continues its research efforts under its Celgene collaboration.

General and administrative (G&A) expenses were $7.4 million and $13.3 million for the three and six months ended June 30, 2016, respectively, as compared to $6.0 million and $11.2 million for the three and six months ended June 30, 2015, respectively. The period-over-period increases in G&A expenses were largely due to staffing key leadership roles in the second quarter. Epizyme expects that G&A spend will increase modestly over the remainder of 2016.

Net loss was $28.0 million and $50.9 million for the three and six months ended June 30, 2016, respectively, compared to a net loss of $25.8 million and $87.1 million for the three and six months ended June 30, 2015, respectively.

Cash, cash equivalents and marketable securities were $288.6 million as of June 30, 2016, as compared to $208.3 million as of December 31, 2015.

Epizyme has established an operating plan and investment strategy designed to support its objectives through 2020 and extend its runway. Based on the updated operating plan, the Company now believes that its cash, cash equivalents and marketable securities as of June 30, 2016 will be sufficient to fund the Company’s planned operations into at least the second quarter of 2018.

On August 8, 2016 Adaptimmune Therapeutics plc (Nasdaq:ADAP) ("Adaptimmune" or the "Company"), a leader in T-cell therapy to treat cancer, reported financial results for the second quarter ended June 30, 2016 (Press release, Adaptimmune, AUG 8, 2016, View Source;p=RssLanding&cat=news&id=2193633 [SID:1234514347]).

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!

Recent Corporate and Clinical Highlights:

Received access to Priority Medicines (PRIME) regulatory support from the European Medicines Agency for NY-ESO SPEAR (Specific Peptide Enhanced Affinity Receptor) T-cell therapy;
Received orphan medicinal product designation for SPEAR T-cell therapy targeting NY-ESO for the treatment of soft tissue sarcoma in the European Union from the European Commission;
Received orphan drug designation for SPEAR T-cell therapy targeting NY-ESO for the treatment of soft tissue sarcoma from the U.S. Food and Drug Administration (FDA);
Finalized commercial development and supply agreement for Thermo Fisher Scientific’s DynaBeads CD3/CD28 Cell Therapy System for use in manufacturing Adaptimmune’s SPEAR T-cell therapies;
Announced new preclinical and clinical data at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting, including: data showing that the incidence of cytokine release syndrome appears to be of lower frequency and severity with NY-ESO SPEAR T-cell therapy compared to that reported with CD19 CAR-T therapy; data describing robust clinical responses including a 50 percent response rate (60 percent at the target dose) in synovial sarcoma, and a 91 percent response rate in multiple myeloma; and that Adaptimmune’s extensive preclinical safety package is capable of preclinically validating TCRs with enhanced affinity for target proteins; and
Expanded synovial sarcoma trials to sites outside of the United States with submissions made to the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom, and to Health Canada which has now approved the clinical trial application.
"The last six months were a period of strong progress for Adaptimmune on a number of fronts," commented James Noble, Adaptimmune’s Chief Executive Officer. "Among our accomplishments, we continued to advance our NY-ESO SPEAR T-cell program toward pivotal studies in sarcoma, received orphan drug and Breakthrough Therapy designation in the U.S. and received both PRIME regulatory eligibility and orphan medicinal product designation in Europe. We also presented important new clinical data at the 2016 ASCO (Free ASCO Whitepaper) meeting and at our analyst and investor day in April 2016 that continue to differentiate our SPEAR T-cell products from other therapies in the space."

Mr. Noble continued, "Still, this period has not been without its challenges. As we previously announced, the FDA placed a partial clinical hold on our planned pivotal study of NY-ESO SPEAR T-cell therapy in myxoid round cell liposarcoma and requested additional information prior to trial commencement. We will provide a full response to the FDA shortly. Separately, the initiation of the pivotal study in synovial sarcoma has been delayed until mid-2017. In addition, slower than anticipated enrollment in non-small cell lung cancer (NSCLC) for our MAGE-A10 and NY-ESO SPEAR T-cell therapies has also pushed the timelines for these data readouts into 2017. Notwithstanding these challenges, the breadth and depth of our clinical pipeline mean that, by early 2017, our clinical efforts could involve SPEAR T-cell therapies directed against four separate targets in as many as 10 different tumor types; we anticipate that our data readouts throughout 2017 may validate the targets themselves and, more broadly, our SPEAR T-cell platform in additional solid tumors beyond sarcoma."

Financial Results for the three-month period ended June 30, 2016

Cash / liquidity position: As of June 30, 2016, Adaptimmune had $150.9 million of cash and cash equivalents and $55.0 million of short-term deposits representing a total liquidity position1 of $205.9 million. For the three months ended June 30, 2016, the decrease in cash and cash equivalents was $12.9 million and the decrease in short-term deposits was $7.3 million, representing a decrease in total liquidity position of $20.2 million.
Revenue: For the three months ended June 30, 2016, revenue was $0.3 million compared to $2.8 million for the three months ended June 30, 2015. This decrease was primarily due to a change in the estimate of the period over which the revenue relating to the GSK Collaboration and License Agreement is being recognized.
Research and development ("R&D") expenses: R&D expenses increased to $16.2 million for the three months ended June 30, 2016 from $8.4 million for the three months ended June 30, 2015, primarily due to increased period-over-period costs associated with: ongoing clinical trials of the Company’s NY-ESO and MAGE-A10 SPEAR T-cell therapies; preparation for a study with the Company’s SPEAR T-cell therapy targeting AFP; and personnel expenses for an increased number of employees engaged in R&D.
General and administrative ("G&A") expenses: G&A expenses were $6.8 million for the three months ended June 30, 2016 compared to $5.5 million for the three months ended June 30, 2015. The increase was primarily due to increased personnel costs, increased property costs and other costs associated with being a public company, partially offset by a decrease in share-based compensation expenses.
Net loss: Net loss attributable to holders of the Company’s ordinary shares was $22.1 million for the three months ended June 30, 2016. This equates to $(0.05) per ordinary share or $(0.31) per American Depositary Share.
1 Total liquidity position is a non GAAP financial measure, which is explained and reconciled to the most directly comparable financial measures prepared in accordance with GAAP below.

Financial Guidance

Adaptimmune is reiterating its guidance. For the full year 2016, the Company expects its decrease in total liquidity position to be between $80 and $100 million and expects its total liquidity position at December 31, 2016, including cash, cash equivalents and short term deposits, to be at least $150 million. This guidance excludes the effect of any potential new business development activities.

Pipeline Review
Adaptimmune is providing an update below on each cohort of its clinical pipeline and the timing of anticipated milestones.

NY-ESO SPEAR T-cell Therapy
Synovial sarcoma:
Cohort 1 (high NY-ESO expression, cyclophosphamide + fludarabine) is complete, and was initially reported at the 2015 American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting. Updates on cohorts 2 (low NY-ESO expression, cyclophosphamide + fludarabine) and 3 (cyclophosphamide) will be presented at the 2016 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting. Cohort 4 (modified cyclophosphamide + fludarabine) is on schedule to initiate in 2H 2016.

The Company submitted to the IND its proposed pivotal study in myxoid round cell liposarcoma and received a partial clinical hold notice from the FDA. The notice was received prior to the study being opened at any clinical site. This communication from the FDA was not related to concerns on safety, but rather to the request for additional information on CMC about manufacturing changes introduced in the pivotal program, and information on and modification of some clinical trial design features. The Company intends to submit its full response shortly; the agency will then have 30 days to respond. In addition, enrollment into the pivotal synovial sarcoma study will begin in mid-2017 to allow for the submission of a Special Protocol Assessment requested by FDA and characterization of the revised commercial manufacturing process to be employed in the pivotal studies. If the discussions with the FDA on MRCLS are concluded within the 30-day review window, the Company would expect to initiate the study as planned in Q4 2016/Q1 2017; if it takes longer, then this study will be on a similar timeline to the synovial sarcoma study.

Multiple myeloma:
The 25-patient study with autologous stem cell transplant is complete and has been published (Rapoport; Nat Med, 2015). The Company expects to agree terms for a combination study with a PD-1 receptor inhibitor using cyclophosphamide and fludarabine conditioning in 2016, with initiation of the study occurring in 1H 2017.

Ovarian cancer:
The Company reported data from this six-patient study at the 2016 ASCO (Free ASCO Whitepaper) meeting showing no objective response in the absence of fludarabine. The Company is evaluating a preconditioning regimen consisting of modified doses of cyclophosphamide and fludarabine and intends to enroll patients in 2H 2016 with this regimen.

Melanoma:
The Company reported data at the 2016 ASCO (Free ASCO Whitepaper) meeting showing no objective response in the absence of fludarabine in six patients who had progressed after treatment with immune check point inhibitors. The Company is considering a study with a new preconditioning regimen including fludarabine in combination with check point inhibitors in 2017.

Non-small cell lung cancer:
A study is open and actively screening patients; data are anticipated in 2017. The chemotherapy conditioning for this trial is being modified in an amendment to consist of cyclophosphamide and fludarabine instead of cyclophosphamide alone.

MAGE-A10 SPEAR T-cell Therapy
Non-small cell lung cancer:
A study is open and actively screening patients; data are anticipated in 2017. Chemotherapy conditioning for this trial is being modified in an amendment to consist of cyclophosphamide and fludarabine instead of cyclophosphamide alone.

Bladder, melanoma, and ovarian cancer:
The Company is on track to initiate this study, including a preconditioning regimen of cyclophosphamide and fludarabine, in 2016 with data anticipated in 2017.

AFP SPEAR T-cell Therapy
Hepatocellular cancer:
The investigational new drug application (IND) is open, and the Company anticipates that enrollment will begin in 1H 2017.

MAGE-A4 SPEAR T-cell Therapy
Multiple tumor types:
The Company is on track for an IND submission in 1Q 2017.

Generation 2 TCRs
Multiple tumor types:
The Company is on track to submit INDs from 2017 onwards.

On August 8, 2016 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA (pembrolizumab), the company’s anti-PD-1 (programmed death receptor-1) therapy, at a fixed dose of 200 mg every three weeks, for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy (Press release, Merck & Co, AUG 8, 2016, View Source [SID:1234514343]). Under the FDA’s accelerated approval regulations, this indication for KEYTRUDA is approved based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. For HNSCC patients, PD-L1 testing is not needed prior to use of KEYTRUDA.

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!

The approval is based on data from the KEYNOTE-012 study, which included patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy or following platinum-containing chemotherapy administered as part of induction, concurrent, or adjuvant therapy and ECOG performance status (PS) of zero or one. The data showed an objective response rate (ORR) of 16 percent (95% CI: 11, 22), complete response rate of five percent, with responses of six months or longer observed in 82 percent (n=23/28) of the responding patients. ORR and duration of response were similar regardless of human papilloma virus (HPV) status.

Immune-mediated adverse reactions occurred with KEYTRUDA including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Female patients of reproductive potential should be advised of the potential hazard to a fetus. For more information regarding immune-mediated adverse reactions and use in pregnancy, see "Selected Important Safety Information" below.

"Today’s approval represents a meaningful advance for the oncology community, as well as for our head and neck cancer clinical program," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. "Together with prior approvals in the treatment of other tumor types, today’s action by the FDA underscores our tireless commitment to addressing the unmet needs of patients suffering from a broad range of cancers."

KEYNOTE-012 was the first clinical study to investigate the role of a PD-1 inhibitor in patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy. Merck currently has the largest immuno-oncology clinical development program, including multiple registration-enabling studies in head and neck cancer, and is conducting research investigating KEYTRUDA (pembrolizumab) as a monotherapy, as well as in combination with chemotherapy compared to the current standard of care.

"Head and neck cancer is a complex disease that historically has been associated with high recurrence rates and poor long-term outcomes, highlighting the critical need for new treatment options," said Dr. Tanguy Seiwert, associate director of the Head and Neck Cancer Program and assistant professor of medicine at The University of Chicago. "The approval of KEYTRUDA for previously treated patients with recurrent or metastatic head and neck squamous cell carcinoma is an important step forward in treating this disease."

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

"Head and neck squamous cell carcinoma presents unique challenges including limited treatment options, especially for patients with recurrent or metastatic disease," said Holly Boykin, executive director, Head and Neck Cancer Alliance. "We welcome the approval of KEYTRUDA as a new treatment option for people whose lives are impacted by this devastating disease."

Data Supporting the Approval

The accelerated FDA approval was based on a multicenter, nonrandomized, open-label, multi-cohort phase 1b study, KEYNOTE-012, that evaluated safety in 192 patients with recurrent or metastatic HNSCC and ECOG PS of zero or one; efficacy was evaluated in 174 of these patients who had disease progression on or after platinum-containing chemotherapy administered for recurrent or metastatic HNSCC or following platinum-containing chemotherapy administered as part of induction, concurrent, or adjuvant therapy. Patients were enrolled regardless of tumor HPV status (33% were HPV-positive). The median number of prior lines of therapy administered for the treatment of HNSCC was two. Nearly all (95%) of the patients enrolled had prior radiation therapy. Patients received KEYTRUDA (pembrolizumab) at a dose of 10 mg/kg every two weeks (n=53) or a 200 mg fixed dose every three weeks (n=121) until unacceptable toxicity or disease progression. Patients without disease progression were treated for up to 24 months. Treatment with KEYTRUDA could be reinitiated for subsequent disease progression and administered for up to one additional year. The primary efficacy outcome measures were ORR according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by blinded independent central review (BICR), and duration of response.

Efficacy analysis showed an ORR of 16 percent (95% CI: 11, 22) with a complete response rate of five percent. The median follow-up time was 8.9 months. Among the 28 responding patients, the median duration of response had not been reached (range 2.4+ to 27.7+ months), with 23 patients having responses of six months or longer. The ORR and duration of response were similar irrespective of dosage regimen (10 mg/kg every 2 weeks or 200 mg every 3 weeks) or HPV status.

In HNSCC, serious adverse reactions occurred in 45 percent of patients receiving KEYTRUDA. The most frequent serious adverse reactions reported in at least two percent of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The incidence of adverse reactions, including serious adverse reactions, was similar between dosage regimens (10 mg/kg every 2 weeks or 200 mg every 3 weeks). The most common adverse reactions (reported in at least 20% of patients) were fatigue (46%), decreased appetite (22%), and dyspnea (20%). Adverse reactions in patients with HNSCC were generally similar to those occurring in patients with melanoma and non-small cell lung cancer (NSCLC), with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3-4) and new or worsening hypothyroidism.

About KEYTRUDA (pembrolizumab)

KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.

KEYTRUDA Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks.

Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy, at a dose of 2 mg/kg every three weeks. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA (pembrolizumab). This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy at a fixed dose of 200 mg every three weeks. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

Immune-mediated pneumonitis, including fatal cases, occurred in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging and administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-mediated colitis occurred in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-mediated hepatitis occurred in patients receiving KEYTRUDA. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hypophysitis occurred in patients receiving KEYTRUDA. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

New or worsening hypothyroidism occurred in 28 (14.6%) of 192 patients, including Grade 3 (0.5%) hypothyroidism. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA (pembrolizumab) for Grade 3 or 4 hyperthyroidism.

Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in patients receiving KEYTRUDA. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer anti-hyperglycemics in patients with severe hyperglycemia.

Immune-mediated nephritis occurred in patients receiving KEYTRUDA. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Other clinically important immune-mediated adverse reactions can occur. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

Severe and life-threatening infusion-related reactions have been reported in 3 (0.1%) of 2117 patients. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

KEYTRUDA (pembrolizumab) was discontinued due to adverse reactions in 17 percent of 192 patients. Serious adverse reactions occurred in 45 percent of patients. The most frequent serious adverse reactions reported in at least 2 percent of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (reported in at least 20% of patients) were fatigue (46%), decreased appetite (22%), and dyspnea (20%).

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck Oncology, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology, with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes more than 300 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials

On August 8, 2016 Storm Therapeutics, a spin-out company based upon the ground-breaking work of its founders, CRUK-funded Professor Tony Kouzarides and Professor Eric Miska, reported that it has secured £12 million in series ‘A’ funding (Press release, Cancer Research Technology, AUG 8, 2016, View Source [SID1234523500]). Cancer Research Technology has also granted Storm Therapeutics rights to license specific IP arising out of further research from Professors Kouzarides and Miska’s labs at the Gurdon Institute, University of Cambridge.

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!

The series ‘A’ funding, from investors Imperial Innovations, Cambridge Innovation Capital, Merck Ventures and Pfizer Venture Investments, will be used to identify small molecule modulators of novel targets in RNA modification pathways and develop them into new classes of anti-cancer treatments.

Professors Tony Kouzarides and Eric Miska, co-founders of Storm Therapeutics, commented: "The work that our research groups are undertaking on non-coding RNA and the enzymes that modify this RNA is giving us incredibly interesting insights into how gene expression can be modified at a cellular level. The funding and support that Storm Therapeutics has received from its investors will allow the development of these insights into a new class of therapeutics ready to be taken into clinical trials."