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Additional Phase 1 Data from ECHO-202 Reinforce Durability of Response in Patients with Treatment-naive Advanced or Metastatic Melanoma Treated with Epacadostat in Combination with Keytruda® (pembrolizumab)

On October 7, 2016 Incyte Corporation (Nasdaq:INCY) reported that updated data from the Phase I portion of the ECHO-202 trial evaluating the safety and efficacy of epacadostat, Incyte’s selective IDO1 enzyme inhibitor, in combination with pembrolizumab (Keytruda)*, Merck’s anti-PD-1 therapy, have been published as a poster at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress 2016 in Copenhagen, Denmark (Press release, Incyte, OCT 7, 2016, View Source [SID:SID1234515643]).

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Further to the previously published abstract, today’s updated data show that among patients with treatment-naïve advanced melanoma (n=19), the combination of epacadostat plus pembrolizumab resulted in progression-free survival (PFS) rates of 74 percent and 57 percent at 6 months and 12 months, respectively. Median PFS has not been reached. The updated data also show an increase in the complete response (CR) rate to 26 percent. The objective response rate (ORR) and disease control rate (DCR) remained consistent with the previously published abstract data, at 58 percent and 74 percent, respectively. All responses are confirmed and ongoing (median follow-up among responders 56 plus [range of 46 to 90 plus] weeks).

"We are excited to share further data with additional follow-up from the Phase 1 portion of the ECHO-202 study," said Steven Stein, M.D., Incyte’s Chief Medical Officer. "The durable responses seen in patients with treatment-naïve advanced or metastatic melanoma reaffirm the activity of this immunotherapy combination, and we look forward to the read-out of ECHO-301, the ongoing, pivotal Phase 3 trial."

Epacadostat in combination with pembrolizumab was well tolerated in the Phase 1 population (n=62). The most common (≥15%) all grade treatment-related AEs (TRAEs) were fatigue, rash, pruritus, arthralgia, diarrhea and nausea. Grade ≥3 TRAEs were observed in 19 percent of patients; the most common were rash (8%) and increased lipase (5%). Five patients (8%) discontinued treatment due to TRAEs.

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

Vaccinex Announces Clinical Collaboration with Merck KGaA, Darmstadt, Germany, to Evaluate the Combination of VX15/2503, and Avelumab in Non-Small Cell Lung Cancer

On October 6, 2016 Vaccinex, Inc. reported it has entered into a collaboration agreement with Merck KGaA, Darmstadt, Germany, to evaluate VX15/2503, an investigational humanized anti-semaphorin 4D IgG4 monoclonal antibody, in combination with avelumab*, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in patients with advanced non-small cell lung cancer (NSCLC) who have not previously received immunotherapy (Press release, Vaccinex, OCT 6, 2016, View Source [SID:SID1234515654]). Vaccinex will be responsible for conducting the planned Phase Ib/II clinical trial.

"Immunotherapies have shown promise in how we treat cancer, and the investigation of combination therapies may uncover additional possibilities. We look forward to working with Merck KGaA, Darmstadt, Germany to explore how we can bring the potential of immunotherapy to more patients, especially considering a
Phase 1 study of monotherapy with VX15/2503 in patients with solid tumors has already suggested its potential for use in combination therapies," said Dr. Maurice Zauderer, CEO of Vaccinex.

In preclinical studies, anti-semaphorin 4D antibodies have been shown to increase infiltration of tumoricidal immune cells while simultaneously reducing multiple types of immunosuppressive cells in tumors. Anti-semaphorin 4D antibody was found to synergize with a checkpoint inhibitor antibody to promote tumor eradication.

"Non-small cell lung cancer continues to be one of the most challenging of cancers worldwide, and we believe in investigating promising avenues to address this need," said Alise Reicin, M.D., Head of Global Clinical Development in the biopharma business of Merck KGaA, Darmstadt, Germany. "Through this partnership with Vaccinex, we are exploring an innovative combination with avelumab that we hope will provide a new option for patients with this deadly cancer."

Further details of the collaboration were not disclosed.

*Avelumab is jointly developed by Merck KGaA, Darmstadt, Germany and Pfizer.

About Non-Small Cell Lung Cancer

Globally, lung cancer is the most common cause of cancer-related deaths in men and the second most common in women1, responsible for more deaths than colon, breast and prostate cancer combined.2 NSCLC is the most common type of lung cancer, accounting for 80 to 85 percent of all lung cancers.3 The five-year survival rate for people diagnosed with late-stage lung cancer that has spread (metastasized) to other areas of the body is 4 percent.4

About Avelumab

Avelumab (also known as MSB0010718C) is an investigational, fully human antibody specific for a protein found on tumor cells called PD-L1, or programmed death ligand-1. Avelumab is thought to have a dual mechanism of action which may enable the immune system to find and attack cancer cells. By binding to PD-L1, avelumab is thought to prevent tumor cells from using PD-L1 for protection against white blood cells such as T-cells, exposing them to anti-tumor responses. Avelumab may also help white blood cells such as natural killer (NK) cells find and attack tumors in a process known as ADCC, or antibody-dependent cell-mediated cytotoxicity. In November 2014, Merck KGaA, Darmstadt, Germany, the science and technology company, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

PRIMA ABSTRACTS ACCEPTED FOR POSTER PRESENTATION
AT ESMO SYMPOSIUM ON IMMUNO-ONCOLOGY

On October 6, 2016 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) ("Prima", the "Company") reported that an abstract for each of its two clinical trials for IMP321 has been accepted for Poster presentation (display) during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Symposium on ‘Immuno-Oncology—Advances in cancer immunotherapy; From vaccines to antibodies and cell therapies’ from 4-6 November 2016 in Lausanne, Switzerland (Filing, 6-K, Prima Biomed, OCT 6, 2016, View Source [SID:SID1234515644]).
The abstract titles are:

• TACTI-mel (Two ACTive Immunotherapeutics in melanoma): A Phase 1 trial in patients with unresectable or metastatic melanoma receiving IMP321 (LAG-3Ig fusion protein) as an adjunctive therapy to anti-PD-1 therapy with pembrolizumab (Poster #155); and

• AIPAC (Active Immunotherapy PAClitaxel): A Phase IIb trial in hormone receptor-positive metastatic breast carcinoma patients receiving IMP321 (LAG-3Ig fusion protein) or placebo as adjunctive to a standard chemotherapy regimen of paclitaxel (Poster #145).

Both posters will be on display for the duration of the Symposium. The Poster viewing session will take place over lunch from 13:00-14:15 on Saturday 5 November 2016. The abstracts will also be published in the ESMO (Free ESMO Whitepaper) Symposium on Immuno-Oncology 2016 Abstract Book, a supplement to the official ESMO (Free ESMO Whitepaper) journal "Annals of Oncology".
For more schedule information see View Source

COHERUS BIOSCIENCES ANNOUNCES FDA ACCEPTANCE OF 351(K) BIOLOGICS LICENSE APPLICATION TO U.S. FOOD AND DRUG ADMINISTRATION FOR CHS-1701 (PEGFILGRASTIM BIOSIMILAR CANDIDATE)

On October 6, 2016 Coherus BioSciences, Inc. (NASDAQ:CHRS), a leading pure-play, global biosimilar company with late-stage clinical products, reported that the U.S. FDA has accepted the filing of 351(k) Biologics License Application for CHS-1701, a pegfilgrastim (Neulasta) biosimilar candidate (Press release, Coherus Biosciences, OCT 6, 2016, View Source;p=irol-newsArticle&ID=2210016 [SID:SID1234515636]).

The BLA submission is supported by similarity data from analytical, pharmacokinetic, pharmacodynamic and immunogenicity studies comparing CHS-1701 and Neulasta. The biosimilar user fee act (BSUFA) action date is June 9, 2017.

Cerulean Announces Data Presentations at the 2016 European Society for Medical Oncology Annual Meeting

On October 6, 2016 Cerulean Pharma Inc. (NASDAQ:CERU), a clinical-stage company developing nanoparticle-drug conjugates (NDCs), reported it will present clinical data from its CRLX101 and CRLX301 programs at the 2016 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting being held in Copenhagen, Denmark on October 7-11 (Press release, Cerulean Pharma, OCT 6, 2016, View Source [SID:SID1234515635]). Details of the ESMO (Free ESMO Whitepaper) poster presentations are as follows:

Title: A phase 1b/2 study of the nanoparticle-drug conjugate CRLX101 in combination with weekly paclitaxel in patients with platinum-resistant ovarian cancer
Date and time: Saturday, October 8 – 13:00 to 14:00 pm Central European Time
Abstract number: 1483
Location: Hall E
Poster board number: 864P
Summary: CRLX101 is an investigational NDC containing the payload camptothecin. This Phase 1b/2 trial evaluates the potential synergy of CRLX101, a topoisomerase 1 inhibitor, in combination with paclitaxel, a standard of care taxane, in patients with platinum-resistant ovarian cancer (PROC). In this trial, CRLX101 is dosed every other week at 12 or 15 mg/m2 in conjunction with weekly paclitaxel at 80 mg/m2. Data from the nine patients in the Phase 1b portion of the trial suggest CRLX101 administered every other week in combination with weekly paclitaxel demonstrate antitumor activity. Additionally, the combination has been generally well tolerated with no dose-limiting toxicities reported. Early data from the first nine patients in the Phase 2 portion of the trial also show activity and tolerability.

Title: Evaluation of weekly dosing of CRLX101 alone and in combination with bevacizumab in patients with advanced solid tumors
Date and time: Monday, October 10 – 13:00 to 14:00 pm Central European Time
Abstract number: 1781
Location: Hall E
Poster board number: 393P
Summary: CRLX101, an investigational NDC containing the payload camptothecin, has been shown to be active in different tumor types as a topoisomerase 1 inhibitor. This study evaluated the dosing and tolerability of a weekly dosing schedule of CRLX101 alone and in combination with bevacizumab. In arm 1, CRLX101 was administered intravenously as a monotherapy at 12 or 15 mg/m2 weekly; in arm 2, this same dosing regimen was administered in combination with every other week dosing of bevacizumab at 10 mg/kg. In arm 1, the maximum tolerated dose for CRLX101 weekly monotherapy is 15 mg/m2. In arm 2, the maximum tolerated dose for CRLX101 in combination with bevacizumab is either 12 mg/m2 weekly or 15 mg/m2 for 3 of 4 weeks. Partial responses were observed in three patients. There was increased cystitis, but no new safety concerns were observed.

Title: Pharmacokinetics of CRLX101 administered weekly in patients with advanced solid tumors
Date and time: Monday, October 10 – 13:00 to 14:00 pm Central European Time
Abstract number: 1767
Location: Hall E
Poster board number: 394P
Summary: CRLX101 is an investigational NDC containing the payload camptothecin. This study evaluated the pharmacokinetics of CRLX101 in patients with advanced solid tumors. CRLX101 was administered intravenously at 12 or 15 mg/m2 on a weekly dosing schedule. The data suggest CRLX101 exhibits high drug retention in the plasma, slow clearance and controlled slow release of camptothecin from the NDC without drug accumulation, supporting weekly dosing of CRLX101 at 15 mg/m2, which represents a 100% increase in dose intensity when compared to a dosing schedule of every other week.

Title: A dose-escalation study of weekly intravenous CRLX301 in patients with advanced solid tumor malignancies
Poster presentation: Monday, October 10 – 13:00 to 14:00 pm Central European Time
Abstract number: 1793
Location: Hall E
Poster board number: 413Tip
Summary: CRLX301 is an investigational NDC containing the payload docetaxel currently being investigated in a Phase 1/2a trial of patients with advanced solid tumors. The first portion of the trial determined the maximum tolerated dose for IV CRLX301 administered every three weeks to be 75 mg/m2. The second portion of the trial is evaluating the maximum tolerated dose for weekly administration of CRLX301. Based on data from the first portion of this trial, the weekly starting dose was 25 mg/m2. This dose escalating trial also evaluates safety, PK and antitumor activity.

Electronic copies of the posters will be available upon request following ESMO (Free ESMO Whitepaper) by emailing [email protected].

About CRLX101

CRLX101 is a nanoparticle-drug conjugate (NDC) designed to concentrate in tumors and slowly release its anti-cancer payload, camptothecin, inside tumor cells. CRLX101 inhibits topoisomerase 1 (topo 1), which is involved in cellular replication. CRLX101 has shown activity in multiple tumor types, both as monotherapy and in combination with other cancer treatments. CRLX101 is in Phase 2 clinical development and has been dosed in more than 400 patients. The U.S. FDA has granted CRLX101 Orphan Drug designation for the treatment of ovarian cancer, Fast Track designation in combination with paclitaxel for platinum-resistant ovarian carcinoma, fallopian tube or primary peritoneal cancer, and Fast Track designation in combination with Avastin in metastatic renal cell carcinoma.

About CRLX301

CRLX301 is a dynamically tumor-targeted NDC designed to concentrate in tumors and slowly release its anti-cancer payload, docetaxel, inside tumor cells. In preclinical studies, CRLX301 delivers up to 10 times more docetaxel into tumors, compared to an equivalent milligram dose of commercially available docetaxel and was similar to or better than docetaxel in seven of seven animal models, with a statistically significant survival benefit seen in five of those seven models. In addition, preclinical data show that CRLX301 had lower toxicity than has been reported with docetaxel in similar preclinical studies. CRLX301 is in Phase 1/2a clinical development.