Updated Phase 1 Data Reinforce the Clinical Profile of Epacadostat in Combination with Keytruda® (Pembrolizumab)

On September 28, 2016 Incyte Corporation (Nasdaq: INCY) reported that the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) has published an abstract (#1110PD) containing updated data from the Phase 1 portion of the ECHO-202 trial evaluating the safety and efficacy of epacadostat, Incyte’s selective IDO1 enzyme inhibitor, in combination with Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy (Press release, Incyte, SEP 28, 2016, View Source;p=RssLanding&cat=news&id=2206432 [SID:SID1234515472]). These data will be highlighted in a poster discussion on Monday, 10 October 2016 from 11:00-12:00 CET at the ESMO (Free ESMO Whitepaper) Annual Congress 2016 in Copenhagen, Denmark.

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In patients with treatment-naïve advanced melanoma (n=19), updated data show a disease control rate (DCR) of 74 percent and an overall response rate (ORR) of 58 percent. All responses are confirmed and ongoing (median follow-up 42 weeks); median progression-free survival (PFS) has not been reached.

"We are very pleased that after extended treatment and longer follow-up, these updated Phase 1 data for epacadostat in combination with pembrolizumab demonstrate robust, durable clinical activity in patients with treatment-naïve advanced melanoma and reinforce the promise of IDO1 inhibition in combination with an anti-PD-1 therapy as an important component of immunotherapy," said Steven Stein, M.D., Incyte’s Chief Medical Officer.

Epacadostat in combination with pembrolizumab was well-tolerated. The most common (≥15%) all grade treatment-related adverse events (TRAEs) were fatigue, rash, arthralgia, pruritus, diarrhea and nausea. Grade ≥3 TRAEs were observed in 18% of patients; the most common were rash (8%) and increased lipase (3%).

The ECHO-202 abstract was made available today on the ESMO (Free ESMO Whitepaper) Congress website at View Source

The ECHO-202 poster is expected to be made available to attendees at the ESMO (Free ESMO Whitepaper) Congress on Friday, 7 October 2016, at which time the ECHO-202 poster will be made available via the Events and Presentations tab of the Investor section of www.incyte.com. Incyte will also host an investor conference call and webcast at 14:00 CET (8:00 a.m. ET) on 7 October 2016 which can be accessed via the Events and Presentations tab of the Investor section of www.incyte.com.

About ECHO-202 (KEYNOTE-037)
The ECHO-202 study (NCT02178722) is evaluating the safety and efficacy of epacadostat, Incyte’s selective IDO1 inhibitor, in combination with pembrolizumab. Patients previously treated with anti-PD-1 or anti-CTLA-4 therapies were excluded from this trial. Enrollment is complete for the Phase 1 dose escalation (epacadostat 25, 50, 100 mg BID + pembrolizumab 2 mg/kg IV Q3W and epacadostat 300 mg BID + pembrolizumab 200 mg IV Q3W) and Phase 1 dose expansion (epacadostat 50, 100, and 300 mg BID + pembrolizumab 200 mg IV Q3W) portions of the trial. Enrollment in the Phase 2 tumor-specific cohorts is ongoing.

About ECHO
The ECHO clinical trial program was established to investigate the efficacy and safety of epacadostat as a core component of combination therapy in oncology. Ongoing Phase 1 and Phase 2 studies evaluating epacadostat in combination with PD-1 and PD-L1 inhibitors collectively plan to enroll over 900 patients in a broad range of solid tumor types, as well as hematological malignancies. ECHO-301 (NCT02752074), a Phase 3 randomized, double-blind, placebo-controlled study evaluating pembrolizumab in combination with epacadostat or placebo as first-line treatment for patients with advanced or metastatic melanoma, is also underway. ECHO-301 was initiated in June 2016 and initial data from this study are expected to be available in 2018.

About Epacadostat (INCB024360)
Indoleamine 2,3-dioxygenase 1 (IDO1) is a key immunosuppressive enzyme that modulates the anti-tumor immune response by promoting regulatory T cell generation and blocking effector T cell activation, thereby facilitating tumor growth by allowing cancer cells to avoid immune surveillance. Epacadostat is a first-in-class, highly potent and selective oral inhibitor of the IDO1 enzyme that reverses tumor-associated immune suppression and restores effective anti-tumor immune responses. In single-arm studies, the combination of epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with unresectable or metastatic melanoma. In these studies, epacadostat combined with the CTLA-4 inhibitor ipilimumab or the PD-1 inhibitor pembrolizumab improved response rates compared with studies of the immune checkpoint inhibitors alone.

Clovis Oncology Announces Rucaparib Data Presentations at ESMO 2016 Congress

On September 28, 2016 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that data from its rucaparib program in ovarian cancer will be presented at the annual European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress. ESMO (Free ESMO Whitepaper) will take place October 7-11, 2016 in Copenhagen, Denmark. The data being presented comprise the primary efficacy and safety data included in the New Drug Application (NDA) currently under priority review with the FDA (Press release, Clovis Oncology, SEP 28, 2016, View Source;p=RssLanding&cat=news&id=2206462 [SID:SID1234515469]).

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Rucaparib is the Company’s oral, potent, small molecule inhibitor of PARP1, PARP2 and PARP3 currently being developed for the treatment of advanced ovarian cancer, specifically in patients with tumors with BRCA mutations and other DNA repair deficiencies beyond BRCA (commonly referred to as homologous recombination deficiencies, or HRD). Data from rucaparib studies are the subject of one oral and one poster presentation at the conference:

Abstract 856O – Clinical activity of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib in patients (pts) with high grade ovarian carcinoma (HGOC) and a BRCA mutation (BRCAmut): Analysis of pooled data from Study 10 (parts 1, 2a, and 3) and ARIEL2 (parts 1 and 2)

Rebecca S. Kristeleit, PhD, The University College London, Cancer Institute, London, United Kingdom
Friday, October 7 from 2:45pm-3:00pm CEST
Location: Oslo
Abstract 219TiP – Window study of the PARP inhibitor rucaparib in patients with primary triple negative or BRCA1/2 related breast cancer (RIO)

Christy Toms, PhD, The Institute of Cancer Research, Sutton, United Kingdom
Monday, October 10 from 1:00pm-2:00pm CEST
Location: Hall E, Poster Board #219
About Rucaparib

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed for advanced ovarian cancer.

Specifically, Clovis is developing rucaparib as monotherapy treatment of advanced ovarian cancer in patients with deleterious BRCA-mutated tumors inclusive of both germline and somatic BRCA mutations (as detected by an FDA-approved test) who have been treated with two or more chemotherapies. Rucaparib was granted Breakthrough Therapy Designation for this proposed indication by the FDA in April 2015. In August 2016, the FDA accepted Clovis’ New Drug Application (NDA) submission for accelerated approval of rucaparib and granted priority review status to the application with a PDUFA date of February 23, 2017; and in September 2016, the FDA notified Clovis that the Agency is not planning to hold an advisory committee meeting to discuss the Company’s NDA for rucaparib. The Company’s Marketing Authorization Application (MAA) to the European Medicines Agency for the proposed treatment indication for rucaparib is planned for Q4 2016.

Additionally, Clovis is developing rucaparib as maintenance therapy in the ARIEL3 trial for ovarian cancer patients with tumors with BRCA mutations and other DNA repair deficiencies beyond BRCA (commonly referred to as homologous recombination deficiencies, or HRD). Data from ARIEL3 are expected in Q4 2017, which is expected to be followed by the submission of a supplemental NDA for a second-line or later maintenance indication.

Rucaparib is also being explored in other solid tumor types with BRCA and HRD populations, including breast, prostate and gastroesophageal cancers.

Clovis holds worldwide rights for rucaparib.

Two New Trials of Merck’s KEYTRUDA® (pembrolizumab) as Monotherapy and in Combination with Chemotherapy for First-Line Treatment of Patients with Advanced Non-Small Cell Lung Cancer to be Presented During Presidential Session at ESMO 2016

On September 28, 2016 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that extensive data on KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, have been accepted for presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen, Denmark, Oct. 7 – 11 (Press release, Merck & Co, SEP 28, 2016, View Source [SID:SID1234515465]). In total, findings from 30 studies in 12 cancers from Merck’s industry-leading clinical development program for KEYTRUDA – both as monotherapy and in combination – will be presented at this year’s ESMO (Free ESMO Whitepaper). Two studies of KEYTRUDA in first-line treatment of advanced lung cancer have also been selected for presentation at the Presidential Symposium on Oct. 9: KEYNOTE-024, which studied KEYTRUDA as monotherapy compared to chemotherapy in patients whose tumors express high levels of PD-L1 (tumor proportion score of 50 percent or more), and KEYNOTE-021G, which studied KEYTRUDA plus chemotherapy (carboplatin and pemetrexed) compared to chemotherapy alone in all patients with non-squamous non-small cell lung cancer (NSCLC).

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KEYTRUDA-Related Data at the ESMO (Free ESMO Whitepaper) 2016 Congress

A select listing of the KEYTRUDA late-breaking and oral abstract sessions at ESMO (Free ESMO Whitepaper) 2016 is included below:

Advanced Non-Small Cell Lung Cancer (NSCLC)

At ESMO (Free ESMO Whitepaper), in addition to KEYNOTE-024 and KEYNOTE-021G, which studied KEYTRUDA (pembrolizumab) in previously untreated patients whose tumors were EGFR- and ALK-negative, updated overall survival (OS) data from the phase 2/3 KEYNOTE-010 trial will be presented; KEYNOTE-010 studied previously treated patients with advanced NSCLC whose tumors express PD-L1 (tumor proportion score of one percent or more).

Additional combination data will also be presented from the phase 1b KEYNOTE-098 expansion cohort study investigating KEYTRUDA in combination with the VEGF Receptor 2 antagonist, ramucirumab (under the existing collaboration between Eli Lilly and Company and Merck).

(Abstract #LBA46_PR) Presidential Symposium: Randomized, phase 2 study of carboplatin and pemetrexed with or without pembrolizumab as first-line therapy for advanced NSCLC: KEYNOTE-021 cohort G. C. Langer. Sunday, October 9, 4:25 – 6:20 pm CEST. Location: Copenhagen.
(Abstract #LBA8_PR) Presidential Symposium: KEYNOTE-024: Pembrolizumab (pembro) vs platinum-based chemotherapy (chemo) as first-line therapy for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 50%. M. Reck. Sunday, October 9, 4:25 – 6:20 pm CEST. Location: Copenhagen.
(Abstract #LBA48) Poster Discussion Session: Pembrolizumab (pembro) vs docetaxel (doce) for previously treated, PD-L1–expressing NSCLC: updated outcomes of KEYNOTE-010. R. Herbst. Sunday, October 9, 2:45 – 4:15 pm CEST. Location: Oslo.
(Abstract #LBA38) Poster Discussion Session: Interim safety and clinical activity in patients with advanced NSCLC from a multi-cohort phase 1 study of ramucirumab (R) plus pembrolizumab (P). R. Herbst. Monday, October 10, 9:30 – 10:30 am CEST. Location: Berlin.
Advanced Bladder Cancer

At ESMO (Free ESMO Whitepaper), data investigating the first-line use of KEYTRUDA in patients with unresectable or advanced urothelial (bladder) cancer will be presented from the phase 2 KEYNOTE-052 trial; results will be featured in the official ESMO (Free ESMO Whitepaper) press program. This is the first presentation of data investigating KEYTRUDA in the first-line bladder cancer treatment setting.

(Abstract #LBA32_PR) Proffered Paper Session: Pembrolizumab (pembro) as first-line therapy for advanced/unresectable or advanced urothelial cancer: Preliminary results from the phase 2 KEYNOTE-052 study. A. Balar. Saturday, October 8, 9:15 – 10:30 am CEST. Location: Madrid.
Advanced Melanoma

At ESMO (Free ESMO Whitepaper), final OS data from the phase 2 KEYNOTE-002 trial investigating

KEYTRUDA (pembrolizumab) monotherapy compared to chemotherapy in patients with ipilimumab-refractory advanced melanoma will be presented.

(Abstract #1107O) Proffered Paper Session: Final overall survival for KEYNOTE-002: pembrolizumab (pembro) versus investigator-choice chemotherapy (chemo) for ipilimumab (ipi)-refractory melanoma. O. Hamid. Saturday, October 8, 2:45 – 4:15 pm CEST. Location: Copenhagen.
Additional Data from Merck’s Oncology Portfolio and Pipeline

Data investigating the use of two compounds from Merck’s oncology pipeline and portfolio – EMEND (fosaprepitant dimeglumine), a substance P/neurokinin-1 (NK1) receptor antagonist, and MK-2206, an investigational AKT inhibitor – were also accepted for presentation at this year’s ESMO (Free ESMO Whitepaper). For more information, including a complete list of abstract titles, please visit the ESMO (Free ESMO Whitepaper) website at View Source

About KEYTRUDA (pembrolizumab)

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.

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 (pembrolizumab) 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. 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. Pneumonitis occurred in 32 (2.0%) of 1567 patients with melanoma, including Grade 1 (0.8%), 2 (0.8%), and 3 (0.4%) pneumonitis. Pneumonitis occurred in 19 (3.5%) of 550 patients with NSCLC, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis and more frequently in patients with a history of asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic radiation (6.0%). 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.

Immune-mediated colitis occurred in 31 (2%) of 1567 patients with melanoma, including Grade 2 (0.5%), 3 (1.1%), and 4 (0.1%) colitis. Immune-mediated colitis occurred in 4 (0.7%) of 550 patients with NSCLC, including Grade 2 (0.2%) or 3 (0.4%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-mediated hepatitis occurred in patients receiving KEYTRUDA. Hepatitis occurred in 16 (1%) of 1567 patients with melanoma, including Grade 2 (0.1%), 3 (0.7%), 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.

Hypophysitis occurred in 13 (0.8%) of 1567 patients with melanoma, including Grade 2 (0.3%), 3 (0.3%), and 4 (0.1%) hypophysitis. Hypophysitis occurred in 1 (0.2 %) of 550 patients with NSCLC, which was Grade 3 in severity. 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.

Hyperthyroidism occurred in 51 (3.3%) of 1567 patients with melanoma, including Grade 2 (0.6%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 127 (8.1%) of 1567 patients with melanoma, including Grade 3 (0.1%) hypothyroidism. Hyperthyroidism occurred in 10 (1.8%) of 550 patients with NSCLC, including Grade 2 (0.7%) or 3 (0.3%) hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients with NSCLC, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism. New or worsening hypothyroidism occurred in 28 (14.6%) of 192 patients with HNSCC, 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 for Grade 3 or 4 hyperthyroidism.

Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3 (0.1%) of 2117 patients. 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. Nephritis occurred in 7 (0.4%) of 1567 patients with melanoma including, Grade 2 (0.2%), 3 (0.2%), 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.

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 (pembrolizumab) 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 1567 patients with melanoma: arthritis (1.6%), exfoliative dermatitis, bullous pemphigoid, uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of 550 patients with NSCLC: rash, vasculitis, hemolytic anemia, serum sickness, and myasthenia gravis.

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.

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 (pembrolizumab).

In KEYNOTE-002, KEYTRUDA was discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (≥1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). Adverse reactions leading to interruption of KEYTRUDA occurred in 14% of patients; the most common (≥1%) were dyspnea (1%), diarrhea (1%), and maculopapular rash (1%). The most common adverse reactions with KEYTRUDA vs chemotherapy were fatigue (43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%), constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs 20%), and decreased appetite (20% with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 14% of 550 patients with NSCLC. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. The most common adverse reactions (reported in at least 20% of patients) were fatigue (44%), cough (29%), decreased appetite (25%), and dyspnea (23%).

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 (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 330 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 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.

Cascadian Therapeutics Announces Poster Presentations on Tucatinib at the European Society of Medical Oncology (ESMO) 2016 Congress

On September 28, 2016 Cascadian Therapeutics (NASDAQ:CASC), a clinical-stage biopharmaceutical company, reported two upcoming poster presentations on tucatinib (ONT-380), the Company’s lead product candidate for the treatment of HER2+ breast cancer, at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress being held October 7 -11, 2016 in Copenhagen, Denmark (Press release, Cascadian Therapeutics, SEP 28, 2016, View Source [SID:SID1234515460]).

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Details of Poster Presentations:

Title: Cutaneous responses in Her-2+ metastatic breast cancer (MBC) on phase 1b study of ONT-380, an oral HER2-specific inhibitor in combination with capecitabine (C) and/or trastuzumab (T) in third line or later treatment
Poster Number: 278
Date: Monday, October 10, 2016
Time: 1:00pm — 2:00pm (CEST)

Title: A phase 2 randomized, double-blinded, controlled study of ONT-380 vs. placebo in combination with capecitabine (C) and trastuzumab (T) in patients with pretreated HER2+ unresectable locally advanced or metastatic breast carcinoma (MBC)
Poster Number: 312 (trial in progress)
Date: Monday, October 10, 2016
Time: 1:00pm — 2:00pm (CEST)

CRT Pioneer Fund Licenses Oncology Drug Targeting DNA Damage Response Checkpoint Kinase 1 (Chk1) to ProNAi

On September 28, 2016 ProNAi Therapeutics, Inc. (NASDAQ: DNAI), a clinical-stage drug development company advancing targeted therapeutics for the treatment of patients with cancer, reported that it has obtained an exclusive license from the CRT Pioneer Fund LP for worldwide rights to develop and commercialize PNT737 (formerly CCT245737), a highly selective, orally available, small molecule inhibitor of Checkpoint kinase 1 (Chk1) (Press release, Cancer Research Technology, 28 28, 2016, View Source [SID1234523181]). PNT737 is being investigated in two recently initiated Phase 1 clinical trials, currently sponsored and managed by the Cancer Research UK Centre for Drug Development, led by The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust. (ClinicalTrials.gov identifiers: NCT02797977 and NCT02797964).

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Under the terms of the agreement, ProNAi will pay the CRT Pioneer Fund an upfront payment of US$7.0 million. ProNAi will take on sponsorship and management of the clinical development of the agent from Cancer Research UK’s Centre for Drug Development and pay a fee of up to $2.0 million upon the successful transfer of the two ongoing Phase 1 clinical trials to the Company. Additional payments in the aggregate amount of up to US$319.5 million may become payable upon achievement of certain development, regulatory and commercial milestones. ProNAi will also owe CRT Pioneer Fund high single to low double digit royalties on net sales.

"This transaction adds another high-quality asset to our pipeline. PNT737 targets the DNA Damage Response (DDR) network, a promising approach to treating cancer based on recent leading-edge discoveries in cancer biology," said Dr. Nick Glover, President and CEO of ProNAi. "Cancer cells often depend on activated Chk1, a central cell cycle checkpoint regulator in the DDR network, as a strategy to survive and replicate despite accumulating extensive DNA damage due to replicative stress or in response to chemotherapeutic intervention. PNT737 is a potent and selective inhibitor of Chk1 that targets a potential Achilles’ heel of cancer cell proliferation and survival."

PNT737 was discovered and initially developed by scientists in the Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research (ICR) in collaboration with Sareum Holdings plc (LSE AIM: SAR), with funding provided by Cancer Research UK, the ICR and Sareum. The program was licensed in September 2013 to the CRT Pioneer Fund, a specialist cancer investment fund established by Sixth Element Capital LLP (6EC), Cancer Research Technology (CRT) and the European Investment Fund (EIF) and managed by 6EC.

"This is another significant milestone on the development path for this promising Chk1 inhibitor. We recently initiated a Phase 1 single agent monotherapy study and a Phase 1 study of PNT737 in combination with DNA-targeting chemotherapies. ProNAi has a world-class oncology development team and is well-capitalized, and we believe these studies and the ongoing development strategy for this drug are in excellent hands," added Robert James, Managing Partner of 6EC.

Dr. Udai Banerji, Cancer Research UK Reader in Molecular Cancer Pharmacology at the ICR and Consultant at The Royal Marsden, stated: "This is an exciting opportunity to investigate a novel anticancer agent targeting the aberrant tumor DDR pathway. Two PNT737 clinical trials are now underway and, as Principal Investigator of these studies, I look forward to working closely with ProNAi to optimize the development path for this promising drug candidate."

Professor Paul Workman, Chief Executive and President of The Institute of Cancer Research, London, said: "I’m very pleased that ProNAi has secured the licence to take forward development of PNT737. This drug – which was discovered here at the ICR – represents an exciting new approach to targeting Chk1 and one that holds significant potential for treating several tumor types. I anticipate this agreement will help accelerate development of PNT737 and lead to an expanded program of clinical trials, to maximize the chances of patient benefit as quickly as possible."

Clinical development is currently taking place in facilities funded by Cancer Research UK, the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at The Royal Marsden and ICR, and the Experimental Cancer Medicine Centre Network. ProNAi anticipates expanding on the current clinical program underway for PNT737, including into the United States, with the expectation of filing an Investigational New Drug application in the second half of 2017. To support broader studies, ProNAi plans to conduct research designed to explore markers of sensitivity to PNT737 that may facilitate patient selection and to identify additional therapeutic combination strategies.

"The ICR and The Royal Marsden are world renowned for their work together in cancer research and this is a great opportunity for our team to collaborate on the early clinical development of a promising anti-cancer agent, where we can potentially employ innovative development strategies and leverage emerging science," said Dr. Barbara Klencke, Chief Development Officer of ProNAi. "A possible development path for PNT737 is the treatment of tumors carrying mutations in genes known to contribute to DNA damage and genomic instability – a key hallmark of cancer. The significant and persistent DNA damage caused by these mutations, coupled with Chk1 inhibition, may result in death of the cancer cells, a synergistic effect referred to as ‘synthetic lethality’. Similarly, excessive DNA damage can be induced with certain chemotherapies or radiation, highlighting the potential for synergies between these modalities and Chk1 inhibition."

"ProNAi is also advancing PNT141, a Cdc7 inhibitor that regulates DNA replication and the DDR network in a different, potentially complementary way to PNT737. Inhibiting both Chk1 and Cdc7 simultaneously may be advantageous and presents the potential for novel combination strategies for PNT737 and PNT141," added Dr. Christian Hassig, Senior Vice President, Research at ProNAi.