OncoSec Provides Highlights from Research Reception at AACR Annual Meeting 2018

On April 16, 2018 OncoSec Medical Incorporated (OncoSec) (NASDAQ: ONCS), a company developing intratumoral cancer immunotherapies, today provided highlights from its Research Reception held on Sunday, April 15, 2018, during the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018.

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 Research Reception was organized to provide industry experts gathered at the AACR (Free AACR Whitepaper) with a comprehensive overview of OncoSec’s ongoing and anticipated clinical programs involving ImmunoPulse IL-12 (or Intratumoral tavo-EP) in metastatic melanoma and triple-negative breast cancer (TNBC), including an overview of a poster presented at AACR (Free AACR Whitepaper) regarding a Phase 1 pilot study of ImmunoPulse IL-12 in TNBC ("Intratumoral plasmid IL-12 and electroporation in pre-treated inoperable locally advanced or recurrent triple-negative breast cancer (TNBC)" – Poster 055 / Abstract CT022).

ImmunoPulse IL-12 is currently being used in several ongoing clinical trials, with the technology demonstrating evidence of anti-tumor activity in the treatment of various solid tumors, the potential to initiate a systemic immune response, and a favorable safety profile. ImmunoPulse IL-12 combines intratumoral plasmid IL-12 with electroporation to produce a controlled, localized expression of IL-12 in the tumor microenvironment, which in turn, enables the immune system to target and attack tumors throughout the body.
The full webcast and presentation slides from the Research Reception can be accessed via OncoSec’s website: View Source

The following is a recap of key highlights from the event:
Melanoma Data Update: OMS-I100 Monotherapy Study & OMS-I102 Pembrolizumab Combination Study
Led by Alain Algazi, MD of the UCSF Helen Diller Family Comprehensive Cancer Center, the first presentation provided data from the OMS-I100 Phase 2 clinical trial, which demonstrated that ImmunoPulse IL-12 delivered as a monotherapy promoted innate and adaptive immune responses, importantly driving increased CD8+ TIL frequency.
Updated clinical data from the OMS-I100 study demonstrated that, in addition to peripheral immune responses, regression of distal, non-treated lesions were observed on average in 45% of the patients
Also, the treatment-related reshaping of the tumor microenvironment points to amplification of the IFN-γ/IL-12 feedforward loop, which in addition to supporting anti-tumor immunity, triggers adaptive immune resistance (PD-L1 expression) and provides the basis for a combination with IL-12 and anti-PD-1 therapy
Updated data from the OMS-I102 Phase 2 clinical trial (ImmunoPulse IL-12 in combination with pembrolizumab) demonstrated a 57% progression free survival (PFS) rate at 21 months with 100% (11/11) duration of response and median PFS/OS not yet reached

OMS-I140 Protocol; Review of Intratumoral IL-12 Data in TNBC Presented at AACR (Free AACR Whitepaper)
Led by Melinda Telli, MD of the Stanford University Medical Center, the following presentation provided a review of the OMS-I140 Phase 1 pilot study of ImmunoPulse IL-12 in TNBC, including an analysis of initial findings from the study, which were presented as a poster during AACR (Free AACR Whitepaper). The Phase 1 pilot study was designed to determine whether intratumoral plasmid IL-12 with electroporation (ImmunoPulse IL-12) would elicit a pro-inflammatory molecular and histological signature in treated as well untreated sites. Following administration of ImmunoPulse IL-12 on Days 1, 5 and 8 of a single 28-day cycle, data was obtained from five patients of the 10-patient study.
Treatment-related increase in CD8+ TIL density was observed by intratumoral chromogenic staining in 2 of 5 patient tumors (1 treated /1 untreated tumor)
NanoString analysis suggests that 1 cycle of Intratumoral tavo-EP did not globally impact intratumoral immune-related gene expression
Evidence of a treatment-related productive systemic immune response was seen in reduced gMDSCs and increased SLECs in the peripheral blood
Reported treatment-related adverse events included transient pain associated with electroporation and fatigue (both grade 1)

These results suggest that Intratumoral tavo-EP is a safe and tolerable TIL-stimulating therapy of skin and subcutaneous TNBC tumors

Further study of this therapy in combination with anti-PD-1 antibody therapy is warranted
OMS-I141 Protocol; Upcoming Anti-PD-1 Combination Clinical Trial in TNBC
A presentation given by Pamela Munster, MD of the UCSF Helen Diller Family Comprehensive Cancer Center, provided a review of OncoSec’s proposed Phase 2 trial in TNBC involving a combination of ImmunoPulse IL-12 (intratumoral tavo-EP) and an anti-PD-1 antibody therapy. The future Phase 2 trial will be a Simon 2-stage minimax design, non-comparative, open-label, single-arm, multicenter study of ImmunoPulse IL-12 plus an anti-PD-1 antibody therapy.
The study is expected to enroll approximately 25 patients (15 in Stage 1, and, if appropriate, 10 in Stage 2) with TNBC and electroporation accessible cutaneous / subcutaneous tumors

The proposed primary endpoint is to assess efficacy as measured by objective response rate (ORR) by independent central review (ICR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 of intratumoral tavo-EP in combination with an anti-PD-1 antibody therapy in subjects with inoperable locally advanced or metastatic TNBC
OncoSec expects to initiate this proposed study in 2018

PISCES/KEYNOTE-695 Operational Update
Led by OncoSec’s Chief Clinical and Regulatory Officer, Sharron Gargosky, PhD, the final presentation offered an operational assessment of PISCES/KEYNOTE-695, a global, multicenter Phase 2b, open-label trial of ImmunoPulse IL-12 in combination with pembrolizumab in patients with stage III/IV melanoma who have progressed or are progressing on either pembrolizumab or nivolumab treatment. OncoSec expects to report preliminary data at an upcoming medical meeting in 2018.

Navidea Biopharmaceuticals to Present at 2nd Annual NASH Summit

On April 16, 2018 Navidea Biopharmaceuticals (NYSE MKT: NAVB) ("Navidea" or "the Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported it will present at the 2nd Annual NASH Summit in Boston, MA being held April 23-25, 2018 (Press release, Navidea Biopharmaceuticals, APR 16, 2018, View Source [SID1234525353]). Michael Goldberg, President and Chief Executive Officer, will be giving a new presentation focused on Navidea’s NASH research; the presentation will be available on Navidea’s website following the conference.

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!

Event: 2nd Annual NASH Conference
Presentation Date: Wednesday, April 25th
Presentation Time: 11:30am EST
Location: Revere Hotel Boston Common, Boston, MA
To schedule a meeting with Navidea management at the conference, please contact Navidea Investor Relations at [email protected].

Merck’s KEYTRUDA® (pembrolizumab) Plus Pemetrexed (ALIMTA®) and Platinum Chemotherapy Reduced the Risk of Death by Half Compared with Chemotherapy Alone as First-Line Treatment for Advanced Nonsquamous NSCLC in Phase 3 KEYNOTE-189 Study

On April 16, 2018 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported results from KEYNOTE-189, a pivotal Phase 3 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with pemetrexed (ALIMTA) and cisplatin or carboplatin for the first-line treatment of metastatic nonsquamous non-small cell lung cancer (NSCLC) (Press release, Merck & Co, APR 16, 2018, View Source [SID1234525352]). Findings showed that the KEYTRUDA-pemetrexed-platinum chemotherapy combination significantly improved overall survival (OS), reducing the risk of death by half compared with chemotherapy alone (HR=0.49 [95% CI, 0.38-0.64]; p<0.00001). In pre-specified exploratory analyses, an OS benefit was observed regardless of PD-L1 expression in the three PD-L1 categories that were evaluated, including: patients whose tumors were negative for PD-L1 (HR=0.59 [95% CI, 0.38-0.92]); patients whose tumors had PD-L1 tumor proportion scores (TPS) of 1-49 percent (HR=0.55 [95% CI, 0.34-0.90]); and patients who had a TPS of greater than or equal to 50 percent (HR=0.42 [95% CI, 0.26-0.68]). The addition of KEYTRUDA to pemetrexed plus platinum chemotherapy also achieved a significant improvement in progression-free survival (PFS), with a reduction in the risk of progression or death of nearly half for patients in the KEYTRUDA combination arm, compared with chemotherapy alone (HR=0.52 [95% CI, 0.43-0.64]; p<0.00001). A PFS improvement in the KEYTRUDA combination group was observed in patients whose tumors were negative for PD-L1 (HR=0.75 [95% CI, 0.53-1.05]); patients with a TPS of 1-49 percent (HR=0.55 [95% CI, 0.37-0.81]); and patients with a TPS greater than or equal to 50 percent (HR=0.36 [95% CI, 0.25-0.52]). These results are being presented today in a plenary session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 (Abstract #CT075), with simultaneous publication in The New England Journal of Medicine.

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!

"In this trial, KEYTRUDA in combination with pemetrexed and platinum chemotherapy, compared with chemotherapy alone, prolonged overall survival and progression-free survival in patients with advanced nonsquamous non-small cell lung cancer regardless of PD-L1 expression," said Dr. Leena Gandhi, director of thoracic medical oncology at NYU Langone’s Perlmutter Cancer Center and lead author of The New England Journal of Medicine paper. "There is good scientific rationale for combining KEYTRUDA with pemetrexed and platinum chemotherapy, and these clinical data now suggest this combination as a new standard of care for the first-line treatment of these nonsquamous non-small cell lung cancer patients."

"Our goal is to extend the lives of patients with lung cancer, and the unambiguous survival findings from KEYNOTE-189 showing the risk of death was reduced by half in the KEYTRUDA arm are important not only for patients but also for the medical community," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. "The results of this trial have the potential to change the treatment paradigm for patients with nonsquamous non-small cell lung cancer in the first-line setting, including patients whose tumors are either PD-L1 negative or are untested."
KEYTRUDA is the first immunotherapy to significantly extend survival of patients with nonsquamous NSCLC in combination with chemotherapy as a first-line treatment. KEYNOTE-189 is the confirmatory trial for KEYNOTE-021 (Cohort G), a Phase 2 study that made KEYTRUDA the only FDA-approved anti-PD-1 therapy in combination with chemotherapy (pemetrexed plus carboplatin) for the first-line treatment of patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression. Merck is working to submit data from KEYNOTE-189 to regulatory agencies in the United States and around the world.

Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies with KEYTRUDA in combination with other treatments and as monotherapy. The program, which is comprised of nearly 9,000 patients across 15 clinical studies, is evaluating KEYTRUDA across multiple settings and stages of the disease.
"The reality is, there remains a significant need for treatment options for patients with lung cancer. At the Bonnie J. Addario Lung Cancer Foundation (ALCF), we are devoted exclusively to eradicating lung cancer through research, early detection, education and treatment. And, the survival benefit achieved by the KEYTRUDA combination in the KEYNOTE-189 study represents a meaningful advance and may offer hope for patients newly diagnosed with one of the most common and deadly cancers," said Bonnie J. Addario, a 14-year lung cancer survivor and ALCF founder.
Additional Data and Safety Information from KEYNOTE-189 (Abstract #CT075)
KEYNOTE-189, a randomized, double-blind, placebo-controlled, Phase 3 study, evaluated KEYTRUDA in combination with pemetrexed and cisplatin or carboplatin, compared with pemetrexed and cisplatin or carboplatin alone, in 616 untreated patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression. Patients had no sensitizing EGFR or ALK genomic tumor aberrations, and had not previously received systemic therapy for advanced disease. The dual primary endpoints were OS and PFS; secondary endpoints include overall response rate (ORR) and duration of response (DOR).
With a median follow-up of 10.5 months (range, 0.2-20.4), KEYTRUDA in combination with pemetrexed and a platinum chemotherapy demonstrated superior improvements in OS, with a 51 percent reduction in the risk of death, compared with pemetrexed plus platinum chemotherapy alone (HR=0.49 [95% CI, 0.38-0.64]; p<0.00001). This finding includes the 50 percent of patients randomized to the chemotherapy alone group who discontinued all study therapy (n=170) and went on to receive subsequent anti-PD-1 or PD-L1 therapy, including 67 patients who received KEYTRUDA monotherapy as part of study crossover. Median OS was not reached in the KEYTRUDA combination group (95% CI, not estimable) and was 11.3 months in the chemotherapy alone group (95% CI, 8.7-15.1). In the study, 69.2 percent of patients were estimated to be alive at 12 months in the KEYTRUDA treatment group (95% CI, 64.1-73.8%) compared with 49.4 percent in the chemotherapy alone group (95% CI, 42.1-56.2%).
In KEYNOTE-189 there was also a significant improvement in PFS for KEYTRUDA in combination with pemetrexed and platinum chemotherapy with a 48 percent reduction in the risk of progression or death compared with pemetrexed plus platinum chemotherapy alone (HR=0.52 [95% CI, 0.43-0.64]; p<0.00001). The median PFS was 8.8 months for the KEYTRUDA combination (95% CI, 7.6-9.2) compared with 4.9 months for chemotherapy alone (95% CI, 4.7-5.5). The percentage of patients who were alive with no progression of disease at 12 months was 34.1 percent in the KEYTRUDA combination group (95% CI, 28.8-39.5%), which was nearly double the percentage of the pemetrexed plus platinum chemotherapy group (17.3 percent [95% CI, 12.0-23.5%]). In addition, improvements in OS and PFS were observed in other patient subgroups evaluated, including age, sex, EGOG performance-status score, smoking status, brain metastases at baseline and type of platinum chemotherapy prescribed (carboplatin or cisplatin).
In the study, KEYTRUDA plus pemetrexed and a platinum chemotherapy also showed an ORR that was more than double the ORR of chemotherapy alone (47.6 percent [95% CI, 42.6-52.5%] compared to 18.9 percent [95% CI, 13.8-25.0%], respectively, p<0.00001). Among patients in the KEYTRUDA arm, the median duration of response was 11.2 months (range, 1.1+ to 18.0+ months) compared with 7.8 months in the chemotherapy alone group (range, 2.1+ to 16.4+ months). The improvement in response rate occurred in all PD-L1 patient subgroups.
The safety of KEYTRUDA was consistent with what has been seen in previous trials among patients with metastatic NSCLC. Grade 3-5 adverse events from any cause occurred in 67.2 percent of patients in the KEYTRUDA plus pemetrexed and platinum chemotherapy group and 65.8 percent in the chemotherapy alone arm. Adverse events of any grade and from any cause with an incidence of 15 percent or more in the KEYTRUDA group were nausea (55.6%), anemia (46.2%), fatigue (40.7%), constipation (34.8%), diarrhea (30.9%), decreased appetite (28.1%), neutropenia (27.2%), vomiting (24.2%), cough (21.5%), dyspnea (21.2%), asthenia (20.5%), rash (20.2%), pyrexia (19.5%), edema peripheral (19.3%), thrombocytopenia (18.0%) and increased lacrimation (17.0%). The most common immune-mediated adverse events of any grade in patients receiving KEYTRUDA plus pemetrexed and platinum chemotherapy were hypothyroidism (6.7%), pneumonitis (4.4%), hyperthyroidism (4.0%), infusion reactions (2.5%), colitis (2.2%), severe skin toxicity (2.0%), nephritis (1.7%) and hepatitis (1.2%). There were three treatment-related deaths from pneumonitis in the KEYTRUDA plus pemetrexed and platinum chemotherapy group.
About KEYNOTE-189
KEYNOTE-189 (ClinicalTrials.gov, NCT02578680) enrolled 616 patients who were randomized 2:1 to one of two treatment groups, and were treated until disease progression, unacceptable toxicity, physician decision or consent withdrawal, as follows:
KEYTRUDA (200 mg fixed dose every three weeks) plus pemetrexed (500 mg/m2) (with vitamin supplementation) plus cisplatin (75 mg/m2) or carboplatin AUC 5 mg/mL/min on day 1 every three weeks (Q3W) for four cycles, followed by KEYTRUDA 200 mg plus pemetrexed (500 mg/m2) Q3W; or
Saline placebo plus pemetrexed (500 mg/m2) (with vitamin supplementation) plus cisplatin (75 mg/m2) or carboplatin AUC 5 mg/mL/min on day 1 every three weeks (Q3W) for four cycles, followed by placebo plus pemetrexed (500 mg/m2) Q3W.
Patients on the control arm who experienced disease progression, verified by central independent review, were permitted to undergo treatment assignment unblinding and crossover to receive open-label KEYTRUDA. The KEYNOTE-189 study was conducted in collaboration with Eli Lilly and Company, the makers of pemetrexed (ALIMTA).
About Lung Cancer
Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon, breast and prostate cancers combined. The two main types of lung cancer are non-small cell and small cell. NSCLC is the most common type of lung cancer, accounting for about 85 percent of all cases. The five-year survival rate for patients diagnosed in the United States with any stage of lung cancer is estimated to be 18 percent.
Merck Investor Webcast
Merck will hold a live investor audio webcast in conjunction with the AACR (Free AACR Whitepaper) 2018 Annual Meeting on Monday, April 16 at 6:45 p.m. CDT (7:45 p.m. EDT). Those interested in participating can register and join here.
About KEYTRUDA (pembrolizumab) Injection 100mg
KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that 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.
Merck has the industry’s largest immuno-oncology clinical research program, which currently involves more than 700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
KEYTRUDA (pembrolizumab) Indications and Dosing
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.
Lung Cancer
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, as a single agent, is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for pemetrexed and carboplatin.
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. 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. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after three or more prior lines of therapy. 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. In adults with cHL, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
In locally advanced or metastatic urothelial carcinoma, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Microsatellite Instability-High (MSI-H) Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)
solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
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. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.
In adult patients with MSI-H cancer, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In children with MSI-H cancer, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Gastric Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. 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. The recommended dose of KEYTRUDA is 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Selected Important Safety Information for KEYTRUDA
KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. 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.
KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. 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.
KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. 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.
KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. 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.
KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC, occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. 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 for Grade 3 or 4 hyperthyroidism.
KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.
KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. 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.
Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.
KEYTRUDA can cause other clinically important immune-mediated adverse reactions. These immune-mediated reactions may occur in any organ system. 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.
The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.
Solid organ transplant rejection has been reported in postmarketing use of KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment with KEYTRUDA vs the risk of possible organ rejection in these patients.
KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 6 (0.2%) of 2799 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.
Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after being treated with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after treatment with KEYTRUDA on any trial, 6 patients (26%) developed graft-versus-host disease (GVHD), one of which was fatal, and 2 patients (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, one of which was fatal. Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor–blocking antibody before transplantation.
These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT. Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.
In clinical trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled clinical trials.
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.
In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.
In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

In KEYNOTE-021(G1), when KEYTRUDA was administered in combination with carboplatin and pemetrexed (carbo/pem) in advanced nonsquamous NSCLC, KEYTRUDA was discontinued in 10% of 59 patients. The most common adverse reaction resulting in discontinuation of KEYTRUDA (≥2%) was acute kidney injury (3.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 39% of patients; the most common (≥2%) were fatigue (8%), neutrophil count decreased (8%), anemia (5%), dyspnea (3.4%), and pneumonitis (3.4%). The most common adverse reactions (≥20%) with KEYTRUDA compared to carbo/pem alone were fatigue (71% vs 50%), nausea (68% vs 56%), constipation (51% vs 37%), rash (42% vs 21%), vomiting (39% vs 27%), dyspnea (39% vs 21%), diarrhea (37% vs 23%), decreased appetite (31% vs 23%), headache (31% vs 16%), cough (24% vs 18%), dizziness (24% vs 16%), insomnia (24% vs 15%), pruritus (24% vs 4.8%), peripheral edema (22% vs 18%), dysgeusia (20% vs 11%), alopecia (20% vs 3.2%), upper respiratory tract infection (20% vs 3.2%), and arthralgia (15% vs 24%). This study was not designed to demonstrate a statistically significant difference in adverse reaction rates for KEYTRUDA as compared to carbo/pem alone for any specified adverse reaction.

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% 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, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC, with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening hypothyroidism.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL, and treatment was interrupted due to adverse reactions in 26% of patients. Fifteen percent (15%) of patients had an adverse reaction requiring systemic corticosteroid therapy. Serious adverse reactions occurred in 16% of patients. The most frequent serious adverse reactions (≥1%) included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; one from GVHD after subsequent allogeneic HSCT and one from septic shock. The most common adverse reactions (occurring in ≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reactions (in ≥20% of patients) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%). Eighteen patients (5%) died from causes other than disease progression. Five patients (1.4%) who were treated with KEYTRUDA experienced sepsis which led to death, and 3 patients (0.8%) experienced pneumonia which led to death. Adverse reactions leading to interruption of KEYTRUDA occurred in 22% of patients; the most common (≥1%) were liver enzyme increase, diarrhea, urinary tract infection, acute kidney injury, fatigue, joint pain, and pneumonia. Serious adverse reactions occurred in 42% of patients, the most frequent (≥2%) of which were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis.

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Adverse reactions leading to interruption of KEYTRUDA occurred in 20% of patients; the most common (≥1%) were urinary tract infection (1.5%), diarrhea (1.5%), and colitis (1.1%). The most common adverse reactions (≥20%) in patients who received KEYTRUDA vs those who received chemotherapy were fatigue (38% vs 56%), musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%), decreased appetite (21% vs 21%), nausea (21% vs 29%), and rash (20% vs 13%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients, the most frequent (≥2%) of which were urinary tract infection, pneumonia, anemia, and pneumonitis.

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.
There is limited experience in pediatric patients. In a study, 40 pediatric patients (16 children aged 2 years to younger than 12 years and 24 adolescents aged 12 years to 18 years) with advanced melanoma, lymphoma, or PD-L1–positive advanced, relapsed, or refractory solid tumors were administered KEYTRUDA 2 mg/kg every 3 weeks. Patients received KEYTRUDA for a median of 3 doses (range 1–17 doses), with 34 patients (85%) receiving KEYTRUDA for 2 doses or more. The safety profile in these pediatric patients was similar to that seen in adults treated with KEYTRUDA. Toxicities that occurred at a higher rate (≥15% difference) in these patients when compared to adults under 65 years of age were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).

Merck’s Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, 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 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 are 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.

Mateon Therapeutics Raises Net Proceeds of Approximately $2.4 Million in Financing Transaction

On April 16, 2018 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing investigational drugs for the treatment of orphan oncology indications, reported that it has completed a private placement transaction with accredited investors for the sale of 14,625,000 shares of unregistered Mateon common stock at a price of $0.20 per share (Press release, Mateon Therapeutics, APR 16, 2018, View Source [SID1234525351]). Investors in the placement will also receive warrants, with an exercise price of $0.40 per share, for the same number of shares as purchased in the private placement transaction. Gross proceeds of the transaction were $2.925 million, and net proceeds are estimated to be approximately $2.4 million. The transaction closed on April 12, 2018.

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!

Divine Capital Markets LLC acted as the exclusive placement agent for the offering.
Mateon plans to file a registration statement with the SEC to register the shares of common stock issued in the financing as well as shares of common stock issuable upon exercise of the warrants. If all warrants are exercised, Mateon will receive an additional $5.85 million in gross and estimated net proceeds.
This press release does not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein. There shall not be any offer, solicitation of an offer to buy, or sale of securities in any state or jurisdiction in which such an offering, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.24

Mateon Therapeutics Provides Business Update and Reports 2017 Financial Results

On April 16, 2018 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing investigational drugs for the treatment of orphan oncology indications, reported that business update and announced 2017 financial results.

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!

Business Update
Earlier today, Mateon announced the raise of additional capital in a private placement transaction with accredited investors. In addition to general corporate purposes, the additional capital will be prioritized towards the advancement of the company’s two drug development programs:
Using OXi4503 as a treatment for relapsed refractory acute myeloid leukemia
Using CA4P as an immuno-oncology agent as a treatment for advanced melanoma
Both of the company’s clinical development programs have potential to generate additional new clinical data before the end of 2018, with new data from OXi4503 in acute myeloid leukemia (AML) expected before initial data from CA4P as an immuno-oncology agent. The company plans to continue to pursue corporate collaboration opportunities with larger pharmaceutical companies for both of these programs.

The following provides an overview of the company’s two drug development programs:
OXi4503 as a treatment for AML

Mateon has an on-going clinical trial in which its investigational drug OXi4503 is being tested as a new treatment for relapsed/refractory AML and myelodysplastic syndromes (MDS). In this clinical trial, we have completed five ascending dose cohorts using OXi4503 in combination with cytarabine, but subsequently paused enrollment due to lack of sufficient funds. Following the financing announced earlier today, the trial is again opening for patient enrollment. Newly enrolled patients will enter into the trial’s sixth cohort (12.2 mg/m2 of OXi4503; a 25% greater dose than the most recently completed 5th cohort). In the completed fifth cohort, we observed two complete remissions (50%) after one cycle of treatment with 9.76 mg/m2 of OXi4503, and did not observe any dose-limiting toxicities. Among the first four cohorts (lower doses of OXi4503 ranging from 3.75 to 7.81 mg/m2), we observed three complete remissions (18%), each occurring after two cycles of treatment. Because of these promising data, we are planning to enroll a higher number of patients into the sixth cohort in order to better evaluate the potential efficacy of OXi4503. Initial data from the sixth cohort is expected this summer.

CA4P as an Immuno-Oncology Agent
CA4P in combination with immuno-oncology agents is a promising investigational new treatment regimen for patients with advanced cancer who have failed standard therapies. This combination regimen, when studied in animal models of different cancer types, has been shown to increase tumor associated immune responses, tumor regressions, and overall survival compared to immuno-oncology agents alone. While there exist a number of new FDA-approved immuno-oncology agents which have significantly improved treatment options for patients with advanced cancer, unfortunately relatively few of these patients achieve a durable clinical response after treatment with these agents alone. New drugs which enhance the efficacy of these drugs, such as CA4P has been shown to do in animals, are greatly needed.

The mechanism-of-action of CA4P appears to be both unique and promising. CA4P causes rapid and widespread ischemic necrosis of the tumor shortly after infusion. This potent and tumor-specific type of necrosis in turn causes a potent and tumor-specific immune response. Animal models, for example, show that CA4P in combination with an immuno-oncology agent significantly enhances the number and activity of cancer-fighting T-cells within tumors compared to the immuno-oncology agent alone. In these animal models, these cancer-fighting T-cells were shown to be evident throughout the tumor and were associated with twice the amount of tumor necrosis than observed in treatment with the immuno-oncology agent alone. Accordingly, we believe CA4P may result in more and/or better clinical responses in patients with certain advanced cancers, including in patients who either have not experienced a response to immuno-oncology therapy, or in patients who have initially responded but subsequently progressed after treatment.

The next step for establishing CA4P as a safe and effective immuno-oncology agent is to initiate a clinical trial in a setting where immuno-oncology agents are currently used as standard therapy but have historically been associated with a low overall durable response rate. Therefore, Mateon plans to initiate a clinical trial evaluating CA4P in combination with an approved immuno-oncology agent, Opdivo (nivolumab, marketed by Bristol-Myers Squibb), in patients with advanced metastatic melanoma who have previously failed Opdivo and consequently have a poor prognosis. Our goal is to improve the clinical outcomes for these patients, and obtain initial data from the study before the end of the year.

"We are excited about testing the ability of CA4P to enhance the efficacy of Opdivo in advanced melanoma in a new clinical trial," said William D. Schwieterman, M.D., Chief Executive Officer of Mateon Therapeutics. "Because CA4P works rapidly, specifically and powerfully in many tumor types to induce tumor-specific ischemic necrosis, it could be an ideal agent for boosting tumor-specific immune responses and enhancing the efficacy of currently approved immuno-oncology agents.
"
Financial Results
For the year ended December 31, 2017, Mateon reported a net loss of $13.8 million, an increase of $0.1 million from the net loss of $13.7 million for the year ended December 31, 2016. R&D expenses increased to $10.5 million in 2017 compared to $8.8 million in 2016, while general and administrative expenses decreased to $3.4 million in 2017 compared to $5.0 million in 2016.
At December 31, 2017, Mateon had cash and cash equivalents of $1.1 million.