On November 16, 2016 Therapeutic Proteins International (TPI) reported that it will change its name to Adello Biologics, LLC, effective immediately (Press release, Therapeutic Proteins International, NOV 16, 2016, View Source;s%20Interest-,Therapeutic%20Proteins%20International%20Renames%20Company%20to%20Adello%20Biologics%2C%20LLC%3B%20Relocates,Headquarters%20to%20Piscataway%2C%20New%20Jersey&text=CHICAGO%2C%20Nov.,Biologics%2C%20LLC%2C%20effective%20immediately [SID1234563291]). The name change accompanies the move of its corporate headquarters to Piscataway, New Jersey. Along with all corporate functions, the 50,000 sq. ft. facility will house the company’s new R&D lab. The company plans to complete the move by the end of the year.

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 new name aligns with our company’s vision; To become the trusted choice of high-quality, affordable biosimilars for patients worldwide," said Dr. Peter Moesta, Chief Executive Officer of Adello. "We are fully focused on developing a robust portfolio of biosimilars, and our move to New Jersey is an effort to further enhance our R&D bench strength, drawing on the scientific talent pool in the area."

The Chicago site will remain the company’s key manufacturing facility in the U.S. with around 100 employees supporting operations. Adello is currently actively recruiting positions for the R&D function in Piscataway. With capacity for 70 scientists, the group will continue to be led by Chief Scientific Officer, Dr. Michael Washabaugh.

On November 16, 2016 PharmaCyte Biotech (OTCQB: PMCB) reported that it has arrived at the door of U.S. FDA and awaits a pre-IND meeting with the agency (Press release, PharmaCyte Biotech, NOV 16, 2016, View Source [SID1234516661]). After years of surrounding its signature live-cell encapsulation technology, Cell-in-a-Box, with some of the brightest minds in pancreatic cancer and fine-tuning its therapy and clinical trial design, the small biotech has reached the final test before it can begin its pivotal clinical trial in advanced pancreatic cancer.

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!

PharmaCyte made two recent announcements that would be big for any company, but for a small biotech, the announcements are big news for shareholders who have been patiently waiting. First, it announced that oncologist, Dr. Manuel Hidalgo, who is the Chief of the Division of Hematology-Oncology at Harvard Medical School’s Beth Israel Deaconess Medical Center, has accepted the role of Principal Investigator for PharmaCyte’s planned clinical trial. And the company followed up that news with the announcement that it has requested a pre-IND meeting with the FDA for its upcoming pancreatic cancer clinical trial.

In PharmaCyte’s clinical trial, Dr. Hidalgo will once again be teamed up with renowned pancreatic cancer expert Dr. Daniel Von Hoff. Dr. Von Hoff is the Chief Development Officer at Translational Drug Development (TD2), the nation’s premiere oncology CRO and the company responsible for organizing and conducting PharmaCyte’s clinical trial.

Dr. Von Hoff and Dr. Hidalgo worked together on the clinical trials that brought the industry what is now the gold standard and the FDA approved treatment for advanced pancreatic cancer, Abraxane plus gemcitabine.

PharmaCyte has already named a handful of clinical trial sites that are being considered which include the Mayo Clinic in Scottsdale, Arizona, the Beth Israel Deaconess Cancer Center in Boston, the Dana-Farber Cancer Institute in Boston, the Baylor Cancer Center in Dallas, the City of Hope Cancer Center in Los Angeles and sites in Germany and Spain.

Creating an "Artificial Liver" to Target Pancreatic Cancer

PharmaCyte’s pancreatic cancer therapy is made up of pinhead-sized, porous capsules that are filled with thousands of genetically modified cells that act as a type of "artificial liver."

PharmaCyte’s Cell-in-a-Box is not a drug delivery system. There are no drugs encapsulated inside the porous capsules for any of its treatments. Instead, the capsules are filled with about 10,000 live cells that are capable of converting an inactive chemotherapy drug (ifosfamide) into its active cancer-killing form — just as the enzyme system in a patient’s liver would normally do.

Because the chemotherapy drug ifosfamide is a prodrug or an inactive drug, it can travel all over the body and have no effect whatsoever until it is activated in the liver. PharmaCyte’s therapy essentially moves the "normal" conversion site of that inactive drug (the patient’s liver) closer to the cancerous tumor by using Cell-in-a-Box capsules and the live cells inside them to do the job of the patient’s liver or to act as an "artificial liver."

How Does PharmaCyte Biotech Do It

The encapsulated live cells (Cell-in-a-Box capsules) are placed as close to the patient’s cancerous tumor as possible. Once implanted, ifosfamide, the aforementioned chemotherapy drug that needs to be activated in the body, is given to the patient intravenously at one-third the normal dose. The ifosfamide is then carried by the circulatory system to where the encapsulated cells have been placed.

When the ifosfamide, which is normally activated in the liver, comes in contact with the encapsulated live cells in the Cell-in-a-Box capsules, the chemotherapy drug is activated into its cancer-killing form right at the site of the cancer. This is "targeted chemotherapy" in the truest sense, and the company’s therapy has proven effective and safe to use in past clinical trials.

Chemotherapy with No Side Effects

The obvious question is why move the conversion site of the chemotherapy drug at all. Well, there are actually a number of reasons to move the activation site closer to the tumor. We’ll start with the chemotherapy drug itself.

Ifosfamide, when activated, has a very short half-life (time before it decays and no longer offers any effect), so by using the cells inside the Cell-in-a-Box capsules to activate the drug at the site of the tumor, ifosfamide can immediately be the most effective when it’s the most potent before dying off minutes later.

Without a treatment like PharmaCyte’s, ifosfamide would be given to the patient intravenously and then activated "normally" in the liver, the activated drug would then affect tissues and organs other than the pancreas, and by the time it reached the pancreas, it undoubtedly would have lost much of its effectiveness. So, to be effective against a pancreatic tumor when the Cell-in-a-Box capsules are not used, a large dose of the drug has to be administered.

Using ifosfamide in such large doses has proven to be damaging for tissues and organs including the patient’s liver, and because the activated drug would come in contact with such other organs and good cells throughout the body on its way to the pancreas, the side effects would be intolerable; in fact, this is known to be the case.

By moving the conversion site as close to the tumor as possible, PharmaCyte is able to give a much smaller dose of the chemotherapy drug (one-third the normal dose), which patient’s are able to tolerate, and because of the smaller dose, the treatment can be administered without any side effects from the chemotherapy.

Next Stop FDA Clinical Trial

With a list of oncologists and clinicians that reads like a who’s who now in place to lead PharmaCyte’s clinical trial, the company is now awaiting a pre-IND meeting with the FDA. After submitting questions to the FDA as part of a pre-IND meeting request where aspects of the content of the Investigational New Drug (IND) application itself (CMC section, clinical trial description, etc.) will be discussed, PharmaCyte is ready to fully engage with the FDA on its way to receiving the final approval it needs to begin its planned clinical trial in pancreatic cancer.

Once PharmaCyte navigates the pre-IND process and files its IND application, then the FDA will have 30 days to make comments, and if no comments are made, then PharmaCyte is effectively "approved" to begin its pivotal clinical trial.

On November 16, 2016 ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA), a rare cancer-focused innovative biotechnology company, reported that clinical data on brigatinib, its investigational anaplastic lymphoma kinase (ALK) inhibitor, will be presented at the International Association for the Study of Lung Cancer (IASLC) 17th World Conference on Lung Cancer (WCLC) being held in Vienna, December 4 to 7, 2016 (Press release, Ariad, NOV 16, 2016, View Source;p=RssLanding&cat=news&id=2223132 [SID1234516644]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited that updated data from the ALTA trial on brigatinib in patients with ALK-positive non-small cell lung cancer will be presented at WCLC this year. We continue to be encouraged by the activity and safety profile seen in the ALTA trial, and especially the correlation between investigator and independent review assessments of response and response durability. ALTA data to be presented at the meeting will include approximately three months of additional follow-up as compared to the abstract," stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD.

The ALTA trial

The ALTA (ALK in Lung Cancer Trial of AP26113) trial enrolled 222 patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC) who had been treated with and experienced disease progression on their most recent crizotinib therapy. Patients were randomized one-to-one to receive either 90 mg of brigatinib once per day (QD) (Arm A), or 180 mg QD, preceded by a lead-in dose of 90 mg QD for seven days (Arm B). In addition, patients were stratified by presence of brain metastases at baseline and best response to prior crizotinib therapy.

The primary endpoint of the ALTA trial is investigator-assessed confirmed objective response rate (ORR) as measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Key secondary endpoints include progression-free survival (PFS), confirmed ORR assessed by an independent review committee (IRC), CNS response and PFS, duration of response, safety and tolerability.

Brigatinib received Breakthrough Therapy designation from the FDA for the treatment of patients with ALK+ NSCLC whose tumors are resistant to crizotinib, and was granted orphan drug designation by the FDA for the treatment of ALK+ NSCLC. The FDA has accepted brigatinib’s New Drug Application and has granted ARIAD’s request for Priority Review and set an action date of April 29, 2017 under the Prescription Drug User Fee Act (PDUFA). ARIAD intends to submit a Marketing Authorization Application (MAA) for brigatinib to the European Medicines Agency (EMA) in early 2017.

Abstract Highlights on ALTA Trial Update
Data as of February 29, 2016 with Independent Review Committee (IRC) Data as of May 16, 2016

Accepted as a poster presentation, this abstract reports updated clinical data from the ALTA trial. A total of 222 patients with ALK+ NSCLC treated with prior crizotinib therapy were randomized in the study (110 patients in Arm B at the 180 mg dose level with a seven-day lead-in at 90 mg and 112 patients in Arm A at the 90 mg dose level). The last patient was enrolled in the study in September 2015.
The median follow-up was 8.3 months in Arm B and 7.8 months in Arm A.
Investigator-assessed confirmed ORR in Arm B was 54 percent. IRC-assessed confirmed ORR in Arm B was 53 percent. Investigator-assessed confirmed ORR in Arm A was 45 percent. IRC- assessed confirmed ORR in Arm A was 48 percent.
Investigator-assessed median PFS was 12.9 months and 9.2 months in Arm B and Arm A, respectively.
IRC-assessed median PFS was 15.6 months and 9.2 months in Arm B and Arm A, respectively.
The most common treatment-emergent adverse events (AEs), grade 3 or higher, (Arm B/A) were (excluding neoplasm progression): hypertension (6%/6%), increased creatine phosphokinase (CPK) (9%/3%), pneumonia (5%/3%), and increased lipase (3%/4%).
A subset of pulmonary AEs with early onset occurred in six percent of all patients (in 3% of patients, events were grade 3 or higher); no such events occurred after dose escalation to 180 mg QD in Arm B.
Abstract Highlights from Update on Clinical Data from Patients with Baseline CNS Metastases from Phase 1/2 and ALTA Trials
Data as of February 29, 2016 in ALTA Trial, and November 16, 2015 in Phase 1/2 Trial

Accepted as an oral presentation, this abstract reports clinical data from the Phase 1/2 and ALTA trials of brigatinib in patients with ALK+ NSCLC who had brain metastases at baseline.
In the Phase 1/2 trial, patients with advanced malignancies, including ALK+ NSCLC, received 30-300 mg of brigatinib per day. Efficacy in both trials and safety in ALTA are reported for patients with intracranial CNS metastases at baseline.
In the Phase 1/2 trial of brigatinib, 50/79 (63%) of ALK+ NSCLC patients had IRC-assessed baseline brain metastases. In the ALTA trial, 153/222 (69%) of ALK+ NSCLC patients had IRC-assessed baseline brain metastases. The efficacy analysis of Phase 1/2 trial data was based on an evaluable population (patients with at least one on-study brain scan, n=46), and the analysis of ALTA trial data was based on the intention-to-treat (ITT) population (n=153).
For patients with measurable brain lesions, the confirmed intracranial objective response rate was 53 percent (8/15) in the Phase 1/2 trial, and confirmed intracranial objective response rates were 67 percent (12/18) in Arm B and 42 percent (11/26) in Arm A in the ALTA trial.
There were 31 patients in the Phase 1/2 trial with only non-measurable lesions, and of these, 35 percent had complete resolution of lesions. In ALTA, there were 55 patients in Arm B and 54 in Arm A with only non-measurable lesions; of these, 18 percent and seven percent of patients, respectively, had complete resolution of lesions.
For patients with brain metastases at baseline, median intracranial PFS was 15.6 months in the Phase 1/2 trial (n=46); and 12.8 months (95% confidence interval [CI] 11.0 – not reached) and 15.6 months (95% CI 7.3-15.7 months) in ALTA Arm B and Arm A, respectively (n=73/ n=80).
In the ALTA trial, the most common treatment-emergent AEs, grade 3 or higher (excluding neoplasm progression), in patients with baseline brain metastases were (n=151 treated; Arm B/A): increased CPK (11%/1%), hypertension (7%/4%), increased lipase (3%/3%), and pneumonia (4%/1%).
For both presentations, ALTA data to be presented at the conference in Vienna will be based on an updated analysis, with a data cutoff date of May 31, 2016. These updated data will be included in the MAA application.

The schedule and meeting location for the sessions at WCLC, together with the abstract information and ARIAD’s investor event and NSCLC symposium, are listed below (all times are Central European Time Zone):

Brigatinib Oral Presentation

Title:
Brigatinib Activity in Patients with ALK+ NSCLC and Intracranial CNS Metastases in Two Clinical Trials
Abstract No/ID: 4374; Oral ID: OA08.06
Presenter: Scott Gettinger, M.D. (Yale Cancer Center)
Oral Session: Targeted Therapies in Brain Metastases
Session Date & Time: Monday, December 5, 2016, 16:00 – 17:30
Presentation Time: 11:57 a.m. to 12:09 p.m.
Location: Schubert 1

Brigatinib Posters

Title:
Brigatinib in Crizotinib-Refractory ALK+ NSCLC: Central Assessment and Updates from ALTA, a Pivotal Randomized Phase 2 Trial

Abstract No/ID: 4046; Poster ID: P3.02a-013
Presenter: D. Ross Camidge, M.D., Ph.D. (Colorado University Cancer Center)
Poster Session: PS03
Date & Time: Wednesday, December 7, 2016, 14:30 – 15:45
Location:
Hall B, poster area

Title:
Indirect Naive Comparison of Post-Crizotinib Treatments for ALK+ Non–Small Cell Lung Cancer (NSCLC)
Abstract No/ID: 4459; Poster ID: P3.02a-017
Presenter: Karen L. Reckamp, M.D. (City of Hope)
Poster Session: PS03
Date & Time: Wednesday, December 7, 2016, 14:30 – 15:45
Location: Hall B, poster area

AP32788 Poster

Title:
A Phase 1/2 Trial of the Oral EGFR/HER2 Inhibitor AP32788 in Non–Small Cell Lung Cancer (NSCLC)
Abstract No/ID: 5047; Poster ID: P2.06-007
Presenter: Robert C. Doebele, M.D., Ph.D. (University of Colorado)
Poster Session: PS02
Date & Time: Tuesday, December 6, 2016, 14:30 – 15:45
Location: Hall B, poster area

Investor and Analyst Briefing and Webcast

A webcast briefing will be held to review the updated brigatinib clinical data from the WCLC. Details will be provided at a later date.

NSCLC Global Symposium at WCLC

ARIAD will host a symposium titled, "Current and emerging treatments for patients with ALK+ NSCLC," that is open to all registered WCLC attendees. This symposium will be co-hosted by D. Ross Camidge, M.D., Ph.D., director of thoracic oncology at the University of Colorado and Professor Christoph Zielinski, M.D., Ph.D., chairman of the Clinical Division of Oncology, Medical University Vienna, Austria. They will be joined by Pasi A. Jänne, M.D., Ph.D., professor of medicine at the Dana Farber Cancer Institute, Boston, MA, USA, to review ALK inhibitor sequencing, the role of mutation testing, and current and future potential ALK inhibitors.

Date: Sunday, December 4, 2016
Time: 12:00 to 13:30 p.m. (CET)
Location: Strauss 3, Messe Wien Exhibition & Congress Center, Vienna
Congress:
17th World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer (www.IASLC.org)

On November 16, 2016 Novartis reported that it will present data demonstrating the latest advancements from its oncology research program at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, San Diego, December 3-6, and the San Antonio Breast Cancer Symposium (SABCS), San Antonio, December 6-10 (Press release, Novartis, NOV 16, 2016, View Source [SID1234516642]). Presentations will focus on a number of cancers, including leukemia, lymphoma, myelofibrosis and breast cancer, as well as chronic iron overload. The data reinforce Novartis’ dedication to developing transformative therapies and treatment strategies to improve and extend the lives of people living with these diseases.

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!

"Novartis continues to invest in not only creating new medicines for underserved patient communities, but also in redefining cancer treatment goals," said Bruno Strigini, CEO, Novartis Oncology. "Our ASH (Free ASH Whitepaper) and SABCS data, including personalized cell and targeted therapies of the future, underscore our core belief in treating each patient as an individual, not just the disease."

Most notable among Novartis’ clinical data to be featured at the two meetings are from the ongoing registrational trials for investigational CTL019* and LEE011** (ribociclib). The CTL019 data will be included in upcoming regulatory submissions. Novartis also recently received US Food and Drug Administration Priority Review for LEE011 (ribociclib) plus letrozole as first-line treatment for postmenopausal women with HR+/HER2- advanced or metastatic breast cancer, based on results from the MONALEESA-2 study.

Analysis of a Global Registration Trial of the Efficacy and Safety of CTL019 in Pediatric and Young Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) (Abstract #221, Oral Presentation, Saturday, December 3, 5:00 pm PST)
First-Line Ribociclib Plus Letrozole in Patients with De Novo HR+/HER2- Advanced Breast Cancer (ABC): A Subgroup Analysis of the MONALEESA-2 Trial (Abstract #P4-22-05, Poster Presentation, Friday, December 9, 7:30 – 9:00 am CST)
First-Line Ribociclib Plus Letrozole in Patients with HR+/HER2- Advanced Breast Cancer (ABC) Presenting with Liver and/or Lung Metastases or Bone-Only Disease: A Subgroup Analysis of the MONALEESA-2 trial (Abstract #P4-22-16, Poster Presentation, Friday, December 9, 7:30 – 9:00 am CST)
Novartis will also be presenting safety, efficacy and quality of life data at ASH (Free ASH Whitepaper) from its hematology portfolio, including an investigational use for Tasigna (nilotinib). Five-year pooled overall survival data for Jakavi (ruxolitinib)*** in patients with myelofibrosis and patient-reported health-related outcomes from patients with chronic immune thrombocytopenia taking Revolade (eltrombopag)**** will also be presented.

Treatment-Free Remission in Patients with Chronic Myeloid Leukemia in Chronic Phase According to Reasons for Switching from Imatinib to Nilotinib: Subgroup Analysis from ENESTop (Abstract #792, Oral Presentation, Monday, December 5, 11:45 am PST)
A Pooled Overall Survival Analysis of 5-Year Data from the COMFORT-I and COMFORT-II Trials of Ruxolitinib for the Treatment of Myelofibrosis (Abstract #3110, Poster Presentation, Sunday, December 4, 6:00 – 8:00 pm PST)
The Impact of Myeloproliferative Neoplasms (MPNs) on Patients’ Quality of Life and Productivity: Results from the International MPN LANDMARK Survey (Abstract #4267, Poster Presentation, Monday, December 5, 6:00 – 8:00 pm PST)
Patient-Reported Health-Related Quality of Life Improves Over Time in Patients with Chronic Immune Thrombocytopenia Receiving Long-Term Treatment with Eltrombopag (Abstract #3750, Poster Presentation, Monday, December 5, 6:00 – 8:00 pm PST)
Sandoz, a Novartis division, the pioneer and global leader in biosimilars, will present pivotal Phase III safety and efficacy data for its proposed biosimilar rituximab.

A Phase III Efficacy and Safety Study of the Proposed Rituximab Biosimilar GP2013 versus Rituximab in Patients with Previously Untreated Advanced Follicular Lymphoma (Abstract #1809, Poster Presentation, Saturday, December 3, 5:30 – 7:30 pm PST)
Additional abstracts of note from each meeting are as follows.

ASH: Data for investigational therapies

ABL001

Expanded Phase I Study Update of ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Reveals Significant and Durable Responses in Patients with CML-Chronic Phase with Failure of Prior TKI Therapy (Abstract #625, Oral Presentation, Monday, December 5, 7:00 am PST)
CTL019

Efficacy and Safety of CTL019 in the First US Phase II Multicenter Trial in Pediatric Relapsed/Refractory Acute Lymphoblastic Leukemia: Results of an Interim Analysis (Abstract #2801, Poster Presentation, Sunday, December 4, 6:00 – 8:00 pm PST)
Treatment with Chimeric Antigen Receptor Modified T Cells Directed Against CD19 (CTL019) Results in Durable Remissions in Patients with Relapsed or Refractory Diffuse Large B Cell Lymphomas of Germinal Center and Non-Germinal Center Origin, "Double Hit" Diffuse Large B Cell Lymphomas, and Transformed Follicular to Diffuse Large B Cell Lymphomas (Abstract #3026, Poster Presentation, Sunday, December 4, 6:00 – 8:00 pm PST)
PKC412 (midostaurin)

Radius: A Phase II, Randomized Trial of Standard of Care (SOC) with or without Midostaurin to Prevent Relapse Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients with FLT3-ITD Mutated Acute Myeloid Leukemia (Abstract #2248, Poster Presentation, Saturday, December 3, 5:30 – 7:30 pm PST)
ASH: Data for approved therapies

Exjade/Jadenu(TM) (deferasirox)

Improved Patient-Reported Outcomes with a Film-Coated Versus Dispersible Tablet Formulation of Deferasirox: Results from the Randomized, Phase II ECLIPSE Study (Abstract #850, Oral Presentation, Monday, December 5, 3:30 pm PST)
New Film-Coated Tablet Formulation of Deferasirox is Well Tolerated in Patients with Thalassemia or MDS: Results of the Randomized, Phase II ECLIPSE Study (Abstract #1285, Poster Presentation, Saturday, December 3, 5:30 – 7:30 pm PST)
Jakavi (ruxolitinib)

Effects of Long-Term Ruxolitinib (RUX) on Bone Marrow (BM) Morphology in Patients with Myelofibrosis (MF) Enrolled in the COMFORT-I Study (Abstract #1949, Poster Presentation, Saturday, December 3, 5:30 – 7:30 pm PST)
Safety and Efficacy of Ruxolitinib for the Final Enrollment of JUMP: An Open-Label, Multicenter, Single-Arm, Expanded-Access Study in Patients with Myelofibrosis (N = 2233) (Abstract #3107, Poster Presentation, Sunday, December 4, 6:00 – 8:00 pm PST)
ASH: Investigational use of approved therapies

Revolade/Promacta (eltrombopag)

Thrombopoietin (TPO) Receptor Agonist Eltrombopag in Combination with Azacitidine (AZA) for Primary Treatment of Myelodysplastic Syndromes (MDS) Patients with Thrombocytopenia: Outcomes from the Randomized, Placebo-Controlled, Phase III SUPPORT Study (Abstract #163, Oral Presentation, Saturday, December 3, 2:00 pm PST)
Tasigna (nilotinib)

ENESTPath: A Phase III Study to Assess the Effect of Nilotinib Treatment Duration on Treatment-Free Remission (TFR) in Patients with Chronic Phase-Chronic Myeloid Leukemia Previously Treated with Imatinib: 24-Month Analysis of the First 300 Patients in the Induction/Consolidation Phase (Abstract #3094, Poster Presentation, Sunday, December 4, 6:00 – 8:00 pm PST)
SABCS: Data for investigational therapies

LEE011 (ribociclib)

Ribociclib + Fulvestrant in Postmenopausal Women with HR+/HER2- Advanced Breast Cancer (ABC) (Abstract #P4-22-12, Poster Presentation, Friday, December 9, 7:30 – 9:00 am CST)
Phase Ib Safety, Efficacy and Molecular Analysis of Ribociclib (LEE011) plus Letrozole for the Treatment of ER+/HER2- Advanced Breast Cancer (Abstract #P4-22-18, Poster Presentation, Friday, December 9, 7:30 – 9:00 am CST)
BKM120 (buparlisib)

BELLE-3: A Phase III Study of Buparlisib + Fulvestrant in Postmenopausal Women with HR+/HER2-, Aromatase Inhibitor-Treated, Locally Advanced or Metastatic Breast Cancer, who Progressed on or after mTOR Inhibitor-Based Treatment (Abstract #S4-07, Oral Presentation, Thursday, December 8, 4:45 pm CST)
SABCS: Investigational use of approved therapies

Afinitor (everolimus)

PrECOG 0102: A Randomized, Double-Blind, Phase II Trial of Fulvestrant Plus Everolimus or Placebo in Postmenopausal Women with Hormone Receptor (HR)-Positive, HER2-Negative Metastatic Breast Cancer (MBC) Resistant to Aromatase Inhibitor (AI) Therapy (Designed and conducted independently by PrECOG, LLC with partial support from Novartis) (Abstract S1-02, Oral Presentation, Wednesday, December 7, 9:00 am CST)
Novartis Oncology will host dedicated content on the company website (View Source) throughout ASH (Free ASH Whitepaper) and SABCS, featuring unique insights and perspectives on emerging areas of cancer care and research. Additionally, follow @NovartisCancer on Twitter for the latest oncology news and insights on cancer research.

Product Information
Approved indications for products vary by country and not all indications are available in every country. The product safety and efficacy profiles have not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that the compounds will become commercially available with additional indications.

For full prescribing information, including approved indications and important safety information about globally marketed products, please visit
View Source

Because CTL019, LEE011 (ribociclib), ABL001, PKC412 (midostaurin) and BKM120 (buparlisib) are investigational compounds, the safety and efficacy profiles have not yet been fully established. Access to these investigational compounds is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the compounds. Because of the uncertainty of clinical trials, there is no guarantee that CTL019, LEE011 (ribociclib), ABL001, PKC412 (midostaurin) and BKM120 (buparlisib) will ever become commercially available anywhere in the world.

On November 16, 2016 Bristol-Myers Squibb Company (NYSE:BMY) reported new data to be presented at the International Association for the Study of Lung Cancer (IASLC) 17th World Conference on Lung Cancer (WCLC) in Vienna, Austria from December 4-7 (Press release, Bristol-Myers Squibb, NOV 16, 2016, View Source [SID1234516636]). Among the key data to be presented, studies evaluating Opdivo (nivolumab) monotherapy and in combination with Yervoy (ipilimumab) in two types of lung cancer highlight the company’s commitment to addressing high unmet medical needs.

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!

Fouad Namouni, M.D., head of development, Oncology, Bristol-Myers Squibb, commented, "We believe Immuno-Oncology combinations may help improve outcomes for patients with lung cancer and have a strong scientific rationale for studying the Opdivo and Yervoy combination therapy. At the WCLC meeting, we will share data investigating this regimen in first-line non-small cell lung cancer and previously treated small cell lung cancer, as well as other important data from our broad thoracic development program."

The full set of Bristol-Myers Squibb-sponsored data to be presented include:

First-line Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Patients With Advanced NSCLC: Long-term Outcomes From CheckMate -012
Presenter: S. Gettinger
Oral Session: Immunotherapy Checkpoint Inhibitors in Advanced NSCLC; Monday, December 5, 11:00 CET, Room C8
Nivolumab Alone or With Ipilimumab in Recurrent Small Cell Lung Cancer: Two-year Survival and Updated Analyses From the CheckMate -032 Trial
Presenter: M. Hellmann
Mini Oral Session: Immunotherapy Combinations; Tuesday, December 6, 14:50 CET, Room Strauss 2
Analysis of Early Survival in Patients With Advanced Non-squamous NSCLC Treated With Nivolumab vs Docetaxel in CheckMate -057
Presenter: S. Peters
Oral Session: Immunotherapy Checkpoint Inhibitors in Advanced NSCLC; Monday, December 5, 11:45 CET, Room C8
Is Nivolumab Safe and Effective in Elderly and PS2 Patients With Non-small Cell Lung Cancer? Results of CheckMate -153
Presenter: D. Spigel
Poster Session with Presenters: Wednesday, December 7, 14:30 CET, Hall B
Demonstrating Life Expectancy Gains With Immuno-Oncology Therapies
Presenter: R. Figlin
Mini Oral Session: Immunotherapy in Advanced NSCLC: Biomarkers and Costs; Tuesday, December 6, 17:00 CET, Room Strauss 2
Prognostic Factors for Overall Survival Among Patients With Advanced/Metastatic Non-small Cell Lung Cancer
Presenter: K. Verleger
Poster Session with Presenters: Tuesday, December 6, 14:30 CET, Hall B
Checkmate 384: A Phase 3b/4 Dose-frequency Optimization Trial of Nivolumab in Advanced or Metastatic Non-small Cell Lung Cancer
Presenter: R. Harris
Poster Session with Presenters: Wednesday, December 7, 14:30 CET, Hall B
Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation

At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents, including the first combination of two I-O agents in metastatic melanoma, and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 11 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.

We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part, but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 57 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 47 countries, including the United States and the European Union.

U.S. FDA APPROVED INDICATIONS FOR OPDIVO

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO (nivolumab) is indicated for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

Please refer to the end of the Important Safety Information for a brief description of the patient populations studied in the CheckMate trials.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests at baseline and before each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of patients.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 4.9% (13/263) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 3.4% (9/263) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=8).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated hepatitis occurred in 13% (51/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the ULN or total bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in 0.4%.

Immune-Mediated Neuropathies

In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported.

Immune-Mediated Endocrinopathies

OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO with YERVOY, hypophysitis occurred in 9% (36/407) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO with YERVOY, adrenal insufficiency occurred in 5% (21/407) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. 6 of the 9 patients were hospitalized for severe endocrinopathies.

Immune-Mediated Nephritis and Renal Dysfunction

OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients.

Immune-Mediated Skin Adverse Reactions and Dermatitis

OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated rash occurred in 22.6% (92/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of toxic epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.

Immune-Mediated Encephalitis

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.

Other Immune-Mediated Adverse Reactions

Based on the severity of adverse reaction, permanently discontinue or withhold treatment, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO the following clinically significant immune-mediated adverse reactions occurred in <1.0% of patients receiving OPDIVO: uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), myositis, myocarditis, rhabdomyolysis, motor dysfunction, vasculitis, and myasthenic syndrome.

Infusion Reactions

OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy, infusion-related reactions occurred in 6.4% (127/1994) of patients. In patients receiving OPDIVO with YERVOY, infusion-related reactions occurred in 2.5% (10/407) of patients.

Complications of Allogeneic HSCT after OPDIVO

Complications, including fatal events, occurred in patients who received allogeneic HSCT after OPDIVO. Outcomes were evaluated in 17 patients from Checkmate 205 and 039, who underwent allogeneic HSCT after discontinuing OPDIVO (15 with reduced-intensity conditioning, 2 with myeloablative conditioning). Thirty-five percent (6/17) of patients died from complications of allogeneic HSCT after OPDIVO. Five deaths occurred in the setting of severe or refractory GVHD. Grade 3 or higher acute GVHD was reported in 29% (5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome, without an identified infectious cause, was reported in 35% (n=6) of patients. Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic encephalitis without an identified infectious cause, and Grade 3 (n=1) suspected viral encephalitis. Hepatic veno-occlusive disease (VOD) occurred in one patient, who received reduced-intensity conditioned allogeneic HSCT and died of GVHD and multi-organ failure. Other cases of hepatic VOD after reduced-intensity conditioned allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor blocking antibody before transplantation. Cases of fatal hyperacute GVHD have also been reported. 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.

Embryo-Fetal Toxicity

Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of OPDIVO.

Lactation

It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment. Advise women to discontinue nursing during treatment with YERVOY and for 3 months following the final dose.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO . The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73% and 37%), adverse reactions leading to permanent discontinuation (43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4 adverse reactions (72% and 44%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, among all patients (safety population [n=263]), adverse reactions leading to discontinuation (4.2%) or to dosing delays (23%) occurred. The most frequent serious adverse reactions reported in ≥1% of patients were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis. Ten patients died from causes other than disease progression, including 6 who died from complications of allogeneic HSCT. Serious adverse reactions occurred in 21% of patients in the safety population (n=263) and 27% of patients in the subset of patients evaluated for efficacy (efficacy population [n=95]). In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO. The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infections, and sepsis.

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and dyspnea (20%). The most common (≥20%) adverse reactions in the OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%), and nausea (28%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, among all patients (safety population [n=263]) and the subset of patients in the efficacy population (n=95), respectively, the most common adverse reactions (≥20%) were fatigue (32% and 43%), upper respiratory tract infection (28% and 48%), pyrexia (24% and 35%), diarrhea (23% and 30%), and cough (22% and 35%). In the subset of patients in the efficacy population (n=95), the most common adverse reactions also included rash (31%), musculoskeletal pain (27%), pruritus (25%), nausea (23%), arthralgia (21%), and peripheral neuropathy (21%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO were cough and dyspnea at a higher incidence than investigator’s choice.

In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

CheckMate Trials and Patient Populations
Checkmate 067 – advanced melanoma alone or in combination with YERVOY; Checkmate 037 and 066 – advanced melanoma; Checkmate 017 – squamous non-small cell lung cancer (NSCLC); Checkmate 057 – non-squamous NSCLC; Checkmate 025 – renal cell carcinoma; Checkmate 205/039 – classical Hodgkin lymphoma; Checkmate 141 – squamous cell carcinoma of the head and neck.
Please see U.S. Full Prescribing Information, including Boxed WARNING regarding immune-mediated adverse reactions, for YERVOY.

Please see U.S. Full Prescribing Information for OPDIVO.