Investigational Data Presented at ASCO GI Evaluate ABRAXANE® Regimen for Patients with Locally Advanced Pancreatic Cancer

On January 19, 2018 Celgene Corporation (NASDAQ: CELG) reported primary endpoint findings and updated results of secondary endpoints from the phase II international LAPACT trial of ABRAXANE (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) plus gemcitabine in patients with locally advanced pancreatic cancer (Press release, Celgene, JAN 19, 2018, View Source [SID1234523366]). The results were presented today at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco, California.

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An analysis of patients with newly diagnosed, locally advanced pancreatic cancer treated with up to 6 cycles of ABRAXANE + gemcitabine as an investigational induction therapy (n=106) found that patients had a median time to treatment failure (TTF) of 8.8 months (90% CI: 6.67-9.82), which exceeded the protocol-specified target of 6.6 months (primary endpoint). Secondary endpoints included evaluation of the disease control rate (DCR), overall response rate (ORR), progression free survival (PFS) and overall survival (OS) in patients treated with an ABRAXANE + gemcitabine induction therapy. The updated analysis found a 77.6% DCR ≥ 16 wks (DCR ≥ 16 wks: stable disease (SD) ≥ 16 wks = 44.9%, CR = 0%, PR = 32%) and 65.4% DCR ≥ 24 wks (DCR ≥ 24 wks: SD ≥ 24 wks = 32.7%, CR = 0%, PR = 32%). The ORR was 32% (CR=0%, PR=32%), the median PFS was 10.8 months (9,26-11.63; 90% CI) and 12-month estimated OS was 72% (64.5% – 78.9%; 90% CI). One or more treatment emergent adverse event occurred in 99% of patients during induction. The most common Grade ≥ 3 adverse events (AE) (≥10%) were neutropenia (42%), anemia (11%), and fatigue (10%).

"Pancreatic cancer remains an extremely challenging disease to treat because it is often diagnosed at the metastatic stage, and even those diagnosed with locally advanced disease typically have a poor prognosis," said Dr. Pascal Hammel, Gastroenterologist/Oncologist, Hôpital Beaujon, Clichy France. "Disease control is key in our patients with locally advanced disease, as it may lead to opportunities for additional treatment interventions, including radiotherapy, or even, in some favorable cases, surgical resection. The results from this study are encouraging, as it shows that induction therapy has the potential to help us achieve disease control in these locally advanced patients."

In this prospective, phase II trial conducted in the US, Canada and Europe, patients with protocol-defined locally advanced, unresectable pancreatic cancer received an induction regimen of up to 6 cycles of ABRAXANE + gemcitabine, followed by the investigator’s choice (IC) of either (a) continuation of the ABRAXANE + gemcitabine regimen, (b) treatment with chemoradiation, or (c) surgery. More than half of patients (57.5%, n = 61/106) completed the induction phase with ABRAXANE + gemcitabine treatment. Forty two percent (45/106) of patients did not complete induction treatment and the reasons for treatment discontinuation during induction included adverse events (n = 20), progressive disease (n = 8), protocol non-compliance (n = 5), physician decision (n = 6), death (n = 2), and other reasons (n = 4). At the time of data cut-off, 45 patients in the intent to treat cohort received IC therapy after induction: 11% (12/106) of patients continued ABRAXANE + gemcitabine per the protocol; 16% (17/106) received chemoradiation; and 15% of patients (16/106) with unresectable disease at the start of the study underwent tumor resection surgery following ABRAXANE + gemcitabine induction therapy. The LAPACT presentation also reported patient-reported quality of life findings across twenty-nine different symptom measures using the EORTC QLQ-C30 questionnaires.

Other relevant grade ≥3 TEAEs included thrombocytopenia (7.5%), peripheral sensory neuropathy (3.8%), diarrhea (3.8%), and febrile neutropenia (3.8%). AEs of any grade included: neutropenia (58.5%), fatigue (50%), anemia (47.2%), diarrhea (46.2%), thrombocytopenia (41.5%), peripheral sensory neuropathy (23.6%), and febrile neutropenia (3.8%).

"Since its approval to treat metastatic pancreatic cancer in 2013, the ABRAXANE + gemcitabine regimen has become a standard of care in first-line metastatic pancreatic cancer," said Nadim Ahmed, President, Hematology and Oncology for Celgene. "The findings from LAPACT offer insight into the potential of ABRAXANE-based treatment for locally advanced pancreatic cancer patients and it’s encouraging to see a nearly 9-month time to treatment failure in these patients treated with an ABRAXANE regimen."

ABRAXANE is not indicated for the first-line treatment of locally advanced pancreatic cancer.

ABOUT LAPACT,

LAPACT is an international, non-randomized, open-label, multi-center, phase II clinical trial conducted at 42 centers in 5 countries. The study evaluated the safety and efficacy of the investigational use of ABRAXANE in combination with gemcitabine as a first-line treatment of patients with locally advanced pancreatic cancer who were not eligible for resection surgery at trial initiation.

The trial evaluated 106 patients with locally advanced pancreatic cancer who had not received prior treatment for their pancreatic cancer and were classified as unresectable at the start of the trial. Patients were given ABRAXANE 125 mg/m2 followed by gemcitabine 1000 mg/m2 on days 1, 8 and 15 of a 28-day cycle for up to six cycles. Patients completing six cycles of treatment were given subsequent investigator-determined treatment of either: continuation of the ABRAXANE + gemcitabine regimen; chemoradiation therapy with capecitabine or gemcitabine + radiation; or surgical intervention. The median age of the patients was 65 years.

Currently, there are more than 130 studies evaluating the use of ABRAXANE in patients with pancreatic cancer in combination with more than 50 novel agents.

ABOUT ABRAXANE

ABRAXANE is indicated for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine.

Important Safety Information

WARNING – NEUTROPENIA

Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE
Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS
CONTRAINDICATIONS

Neutrophil Counts

ABRAXANE should not be used in patients who have baseline neutrophil counts of < 1500 cells/mm3
Hypersensitivity

Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS

Hematologic Effects

Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In clinical studies, Grade 3-4 neutropenia occurred in 47% of patients with non-small cell lung cancer (NSCLC) and 38% of patients with pancreatic cancer
Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15 for NSCLC and for pancreatic cancer
Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1500 cells/mm3
In patients with adenocarcinoma of the pancreas, withhold ABRAXANE and gemcitabine if the ANC is less than 500 cells/mm3 or platelets are less than 50,000 cells/mm3 and delay initiation of the next cycle if the ANC is less than 1500 cells/mm3 or platelet count is less than 100,000 cells/mm3 on Day 1 of the cycle. Resume treatment with appropriate dose reduction if recommended
Nervous System

Sensory neuropathy is dose- and schedule-dependent
The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification
If ≥ Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment until resolution to ≤ Grade 1 for NSCLC and pancreatic cancer followed by a dose reduction for all subsequent courses of ABRAXANE
Sepsis

Sepsis occurred in 5% of patients with or without neutropenia who received ABRAXANE in combination with gemcitabine
Biliary obstruction or presence of biliary stent were risk factors for severe or fatal sepsis
If a patient becomes febrile (regardless of ANC), initiate treatment with broad-spectrum antibiotics
For febrile neutropenia, interrupt ABRAXANE and gemcitabine until fever resolves and ANC ≥1500 cells/mm3, then resume treatment at reduced dose levels
Pneumonitis

Pneumonitis, including some cases that were fatal, occurred in 4% of patients receiving ABRAXANE in combination with gemcitabine
Monitor patients for signs and symptoms and interrupt ABRAXANE and gemcitabine during evaluation of suspected pneumonitis
Permanently discontinue treatment with ABRAXANE and gemcitabine upon making a diagnosis of pneumonitis
Hypersensitivity

Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug
Hepatic Impairment

Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution
Patients with hepatic impairment may be at an increased risk of toxicity, particularly from myelosuppression, and should be monitored for development of profound myelosuppression
For pancreatic adenocarcinoma, ABRAXANE is not recommended for patients with moderate to severe hepatic impairment (total bilirubin > 1.5 x ULN and AST ≤10 x ULN)
Albumin (Human)

ABRAXANE contains albumin (human), a derivative of human blood
Use in Pregnancy: Pregnancy Category D

ABRAXANE can cause fetal harm when administered to a pregnant woman
If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus
Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE
Use in Men

Men should be advised not to father a child while receiving ABRAXANE
ADVERSE REACTIONS

Among the most common (≥20%) adverse reactions in the phase III study, those with a ≥5% higher incidence in the ABRAXANE/gemcitabine group compared with the gemcitabine group are neutropenia (73%, 58%), fatigue (59%, 46%), peripheral neuropathy (54%, 13%), nausea (54%, 48%), alopecia (50%, 5%), peripheral edema (46%, 30%), diarrhea (44%, 24%), pyrexia (41%, 28%), vomiting (36%, 28%), decreased appetite (36%, 26%), rash (30%, 11%), and dehydration (21%, 11%)
Of these most common adverse reactions, those with a ≥2% higher incidence of Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared with the gemcitabine group, respectively, are neutropenia (38%, 27%), fatigue (18%, 9%), peripheral neuropathy (17%, 1%), nausea (6%, 3%), diarrhea (6%, 1%), pyrexia (3%, 1%), vomiting (6%, 4%), decreased appetite (5%, 2%), and dehydration (7%, 2%)
Thrombocytopenia (all grades) was reported in 74% of patients in the ABRAXANE/gemcitabine group vs 70% of patients in the gemcitabine group
The most common serious adverse reactions of ABRAXANE (with a ≥1% higher incidence) are pyrexia (6%), dehydration (5%), pneumonia (4%), and vomiting (4%)
The most common adverse reactions resulting in permanent discontinuation of ABRAXANE were peripheral neuropathy (8%), fatigue (4%), and thrombocytopenia (2%)
The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (10%) and peripheral neuropathy (6%)
The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (16%), thrombocytopenia (12%), fatigue (8%), peripheral neuropathy (15%), anemia (5%), and diarrhea (5%)
Other selected adverse reactions with a ≥5% higher incidence for all-grade toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine group, respectively, are asthenia (19%, 13%), mucositis (10%, 4%), dysgeusia (16%, 8%), headache (14%, 9%), hypokalemia (12%, 7%), cough (17%, 7%), epistaxis (15%, 3%), urinary tract infection (11%, 5%), pain in extremity (11%, 6%), arthralgia (11%, 3%), myalgia (10%, 4%), and depression (12%, 6%)
Other selected adverse reactions with a ≥2% higher incidence for Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine group are thrombocytopenia (13%, 9%), asthenia (7%, 4%), and hypokalemia (4%, 1%)
Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations

Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied
There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs
There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration
DRUG INTERACTIONS

Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4
USE IN SPECIFIC POPULATIONS

Nursing Mothers

It is not known whether paclitaxel is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother
Pediatric

The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated
Geriatric

Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients ≥65 years of age treated with ABRAXANE and carboplatin in NSCLC
Diarrhea, decreased appetite, dehydration, and epistaxis were more frequent in patients 65 years or older compared with patients younger than 65 years old who received ABRAXANE and gemcitabine in adenocarcinoma of the pancreas
Renal Impairment

There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance < 30 mL/min)
DOSAGE AND ADMINISTRATION

Do not administer ABRAXANE to any patient with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN
Do not administer ABRAXANE to patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment
Dose reductions or discontinuation may be needed based on severe hematologic, neurologic, cutaneous, or gastrointestinal toxicity
Monitor patients closely
Please see full Prescribing Information, including Boxed WARNING.

TRACON Pharmaceuticals Announces Positive Data from Ongoing Phase 1b/2 Trial of TRC105 in Hepatocellular Carcinoma Patients

On January 19, 2018 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer, wet age-related macular degeneration and fibrotic diseases, reported that positive initial clinical data from its ongoing Phase 1b/2 study of TRC105 and Nexavar (sorafenib) in patients with advanced hepatocellular carcinoma (HCC) were presented in a poster presentation at the 2018 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in San Francisco, California (Press release, Tracon Pharmaceuticals, JAN 19, 2018, View Source;p=RssLanding&cat=news&id=2327502 [SID1234523376]).

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Initial data from the ongoing open-label, non-randomized study were presented by Dr. Kanwal Raghav from the University of Texas MD Anderson Cancer Center:

Partial responses by RECIST 1.1 occurred in 2 of 8 (25%) evaluable patients and a reduction of 50% or greater in alpha fetoprotein (AFP) concentration occurred in 3 of 8 (38%) evaluable patients. Reduction in AFP, a tumor marker expressed in patients with HCC, in early treatment may help identify a favorable response to treatment and was observed in both cases of partial response.
Hybrid dosing consisting of four weekly doses of TRC105 at 10 mg/kg followed by every other week dosing at 15 mg/kg thereafter was tolerable when given with the standard Nexavar dose of 400 mg twice daily.
Adverse events typical of each drug did not increase in frequency or severity when the drugs were administered concurrently.
The trial is ongoing, with the completion of the enrollment of approximately 33 patients expected by the end of 2018.
"We continue to be encouraged with the safety and activity of TRC105 in combination with Nexavar in patients with HCC, a tumor type with limited treatment options," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "Importantly, the initial data from the current trial are consistent with the 33% partial response rate by RECIST 1.1 reported in the completed Phase 1/2 study published by the National Cancer Institute in 2017. We expect to complete enrollment of the current multicenter study by the end of 2018, and will discuss a potential registration-enabling study of the combination of TRC105 and Nexavar in HCC with regulatory authorities shortly thereafter."

The poster is available on TRACON’s website at: www.traconpharma.com/publications.php

About Carotuximab (TRC105)

TRC105 is a novel, clinical stage antibody to endoglin, a protein overexpressed on proliferating endothelial cells that is essential for angiogenesis, the process of new blood vessel formation. TRC105 is currently being studied in a pivotal Phase 3 trial in angiosarcoma and multiple Phase 2 clinical trials, in combination with VEGF inhibitors. TRC105 has received orphan designation for the treatment of soft tissue sarcoma in both the U.S. and EU. The ophthalmic formulation of TRC105, DE-122, is currently in a randomized Phase 2 trial for patients with wet AMD. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical_trials.php.

Atreca to Participate in Immunotherapy Showcase at the 2018 Precision Medicine World Conference

On January 19, 2018 Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response, announced today that Norman Michael Greenberg, Ph.D., Senior Vice President and Chief Scientific Officer, will deliver a presentation on the Company’s lead programs in immuno-oncology as part of the Immunotherapy Showcase during the 2018 Precision Medicine World Conference on Wednesday, January 24, 2018, at 1:45 PM PT in Mountain View, CA.

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Dr. Greenberg’s talk, titled "Mining the Immunoresponsome: Anti-Cancer Antibodies from Elite Responder Patients", will take place in the Boole Room, Track 4, in the Computer History Museum.

Atreca to Participate in Immunotherapy Showcase at the 2018 Precision Medicine World Conference

On January 19, 2018 Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response, reported that Norman Michael Greenberg, Ph.D., Senior Vice President and Chief Scientific Officer, will deliver a presentation on the Company’s lead programs in immuno-oncology as part of the Immunotherapy Showcase during the 2018 Precision Medicine World Conference on Wednesday, January 24, 2018, at 1:45 PM PT in Mountain View, CA (Press release, , JAN 19, 2018, View Source [SID1234523452]).

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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

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Dr. Greenberg’s talk, titled "Mining the Immunoresponsome: Anti-Cancer Antibodies from Elite Responder Patients", will take place in the Boole Room, Track 4, in the Computer History Museum.

Rexahn Pharmaceuticals will present clinical result of RX-3117 in metastatic pancreatic cancer

On January 19, 2018 Rexahn Pharmaceuticals, Inc., a Delaware corporation (the "Company"), reported that clinical data from the completed Phase IIa clinical trial of RX-3117 in metastatic pancreatic cancer patients will be presented in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers (ASCO GI) 2018 annual meeting at 11:30 Pacific Time on Friday, January 19, 2018, in San Francisco, California (Press release, Rexahn, JAN 19, 2018, View Source [SID1234523375]). The poster is titled: RX-3117: Activity of an Oral Antimetabolite Nucleoside in Subjects with Pancreatic Cancer — Preliminary Results of Stage II of the Phase Ib/IIa Study

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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

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A copy of the poster being will be available to be viewed on the Company’s website at View Source beginning at 12:00 PM Eastern Time on Friday, January 19, 2018.