Numab Therapeutics Completes Oversubscribed CHF 100 Million
Series C Financing

On May 20, 2021 Numab Therapeutics AG, a clinical stage biopharmaceutical company developing next-generation multispecific antibody-based immunotherapies for cancer and inflammation, reported the closing of a CHF 100 million (approximately USD 110 million) Series C financing (Press release, Numab, MAY 20, 2021, View Source [SID1234580359]). The financing was co-led by new investors Novo Holdings and HBM Partners, with participation from additional new investors Forbion via its Forbion Growth Opportunities Fund, Cormorant Asset Management, BVF Partners L.P., RTW Investments L.P., funds and accounts under the management of BlackRock, Octagon Capital Advisors, and existing investors. Concurrent with the financing, Nanna Lüneborg from Novo Ventures, Matthias Fehr from HBM Partners, and Carlo Incerti from Forbion have been appointed to Numab’s Board of Directors.

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Proceeds will support acceleration and expansion of the clinical development of Numab’s lead program NM21-1480 into multiple cancer indications, and the advancement of the company’s pipeline of multi-specific antibodies in oncology and inflammation, into clinical trials.

"We are thrilled to be supported by such a strong group of investors who share our vision for the company’s future," said David Urech, Ph.D., Founder and Chief Executive Officer of Numab Therapeutics. "Combining PD-L1 blockade with tumor localized 4-1BB co-stimulation in a single molecule emerges as an attractive next-generation therapeutic strategy in solid tumors, and Numab’s lead compound NM21-1480 has best-in-class potential. The financing will help us to maximize the value of this asset by significantly expanding the clinical development program and accelerating toward phase 2 proof-of-concept."

"We are impressed by the biological insights that went into the engineering of NM21-1480 and by the innovative pipeline that Numab has established. We believe that Numab’s Lambda-capTM and MATCHTM technologies can provide treatment options with favorable benefit-to-risk profiles," said Matthias Fehr, Head Private Equity at HBM Partners.

"Backing companies built on clearly differentiated science in areas of major unmet medical need is at the heart of Novo Holdings’ investment strategy. We are thus thrilled to co-lead Numab’s Series C financing to support the company at a pivotal stage in growth," commented Nanna Lüneborg, Partner at Novo Ventures.

EXACT THERAPEUTICS ABSTRACT ON ITS PHASE I ACTIVATE STUDY TO BE PRESENTED AT THE 2021 ASCO ANNUAL MEETING

On May 20, 2021 Exact Therapeutics AS (Euronext Growth: EXTX), a clinical stage precision medicine company utilizing Acoustic Cluster Therapy (ACT) to harness the power of ultrasound in therapeutic amplification across multiple therapeutic areas and product classes, reported that an abstract describing the background and methodology of its Phase I study, ACTIVATE, has been released for publication at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Exact Therapeutics, MAY 20, 2021, View Source [SID1234580358]).

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The ACTIVATE Study (NCT04021277) is the first in a series of clinical investigations planned of the Company’s Acoustic Cluster Therapy (ACT) platform technology for targeted therapeutic enhancement.

Abstract Title: Phase I trial of acoustic cluster therapy (ACT) with chemotherapy in patients with liver metastases of gastrointestinal origin (ACTIVATE study)

Oral Abstract Session: Trials in Progress, Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Abstract: TPS3145

Lead Author: Professor Udai Banerji, NIHR Professor of Molecular Cancer Pharmacology at The Institute of Cancer Research and Honorary Consultant in Medical Oncology, The Royal Marsden NHS Foundation Trust.

Cellectar Announces Poster Presentation of CLR 131 Data in Waldenstrom’s Macroglobulinemia at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting

On May 20, 2021 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery and development of drugs for the treatment of cancer, reported a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting to be held virtually June 4-8, 2021 (Press release, Cellectar Biosciences, MAY 20, 2021, View Source [SID1234580355]).

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The poster presentation on June 4th will provide an in-depth update of the six patients reported in the Abstract from the company’s Phase 2a study of CLR 131 in Waldenstrom’s macroglobulinemia (WM). A copy of the Abstract, entitled: Treatment Free Remission (TFR) and Overall Response Rate (ORR) Results in Patients with Relapsed/Refractory Waldenstrom’s Macroglobulinemia (WM) Treated with CLR 131 is available on ASCO (Free ASCO Whitepaper)’s website www.asco.org.

In conjunction with the poster presentation, management is hosting a KOL call with Dr. Sikander Ailawadhi, M.D., the lead investigator for the company’s Phase 2 CLOVER-1 study of CLR 131 in patients with relapsed/refractory B-cell hematologic cancers. Dr. Ailawadhi is a Professor of Medicine, Lead, International Cancer Center, Division of Hematology/Oncology, Departments of Medicine and Cancer Biology at Mayo Clinic Florida. He was awarded the 2013 NCI CCITLA as an Assistant Professor of Medicine at the Norris Cancer Center, University of Southern California (USC), Los Angeles, CA. Subsequently, he joined the Division of Hematology and Oncology at Mayo Clinic in Florida as a Senior Consultant in order pursue his career goal of clinical, translational and outcomes-based research in B-cell malignancies.

About the Pivotal Trial of CLR 131 in Waldenstrom’s macroglobulinemia (WM)
The pivotal trial is designed as a global, non-comparator, single arm, expansion cohort of the currently ongoing Phase 2 CLOVER-1 study of CLR 131. The study will enroll 50 WM patients. Patients in the trial will receive up to four doses of CLR 131 over two cycles (cycle one days 1, 15, and cycle two days 57, 71). The primary endpoint of the trial is response rate as defined as a partial response (a minimum of a 50% reduction in the biological marker IgM) or better in patients that receive a minimum total body dose of 60 mCi with secondary endpoints of treatment free survival, duration of response and progression free survival. An independent data monitoring committee (iDMC) will perform an interim safety and futility evaluation on the first 10 patients enrolled. The assessment will occur patient by patient and will conclude after the tenth patient is evaluated; there is no planned study stoppage.

About Waldenstrom’s macroglobulinemia
Waldenstrom’s macroglobulinemia (WM) is a rare and incurable disease defined by specific genotypic subtypes that defines patient responses and long-term outcomes. The annual incidence is 6,500 with prevalence of approximately 60,000 patients globally. WM is a lymphoma, or cancer of the lymphatic system. The disease occurs in a type of white blood cell called a B-lymphocyte or B-cell, which normally matures into a plasma cell whose job is to manufacture immunoglobulins (antibodies) to help the body fight infection. In WM, there is a malignant change to the B-cell in the late stages of maturing, and it continues to proliferate into a clone of identical cells, primarily in the bone marrow but also in the lymph nodes and other tissues and organs of the lymphatic system. These clonal cells over-produce an antibody of a specific class called IgM.

WM cells have characteristics of both cancerous B-lymphocytes (NHL) and plasma cells (multiple myeloma), and they are called lymphoplasmacytic cells. For that reason, WM is classified as a type of non-Hodgkin’s lymphoma called lymphoplasmacytic lymphoma (LPL). About 95% of LPL cases are WM; the remaining 5% do not secrete IgM and consequently are not classified as WM.

There is no standard treatment for WM. Several drugs have demonstrated activity either alone or in combinations, but only a single drug has received regulatory approval. Treatment is mainly focused on the control of symptoms and the prevention of organ damage. Front-line treatments for WM include rituximab alone or in combination with other agents. In the salvage therapy (second line or later) setting, ibrutinib, combinations of proteosome inhibitors and immunomodulatory drugs and stem cell transplantation are considered. Ibrutinib is the only drug to receive regulatory approval (2015) as a salvage therapy; in late 2019, it was approved for front-line treatment in combination with rituximab. Factors such as long-term cytopenias, age, hyper viscosity, the need for quick disease control, lymphadenopathy, co-morbidities, and IgM-related end-organ damage are key consideration in the choice of treatment.

Cardiff Oncology to Present at the Jefferies Virtual Healthcare Conference

On May 20, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company developing onvansertib to treat cancers with the greatest medical needs for new treatment options, including KRAS-mutated colorectal cancer, pancreatic cancer and castrate-resistant prostate cancer, reported that Dr. Mark Erlander, chief executive officer of Cardiff Oncology, will present and participate in one-on-one investor meetings at the Jefferies Virtual Healthcare Conference taking place June 1-4, 2021 (Press release, Cardiff Oncology, MAY 20, 2021, View Source [SID1234580354]).
Presentation details can be found below.
Date: Tuesday, June 1, 2021 Time: 4:00 PM ET Webcast Link:
View Source

A replay of the presentation will be available by visiting the "Events" section of the Cardiff Oncology website after the conclusion of the presentation and will be archived on the Company website for 30 days.

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U.S. Food and Drug Administration Approves Opdivo® (nivolumab) as Adjuvant Treatment of Completely Resected Esophageal or Gastroesophageal Junction Cancer in Patients who have Received Neoadjuvant Chemoradiotherapy

On May 20, 2021 Bristol Myers Squibb (NYSE: BMY) reported that the U.S. Food and Drug Administration (FDA) has approved Opdivo (nivolumab, injection for intravenous use) for the adjuvant treatment of completely resected esophageal or gastroesophageal junction (GEJ) cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy (CRT) (Press release, Bristol-Myers Squibb, MAY 20, 2021, View Source [SID1234580353]).1 The approval is based on results from the Phase 3 CheckMate -577 trial that evaluated Opdivo (n=532) compared to placebo (n=262) in esophageal or GEJ cancer patients with residual pathologic disease following neoadjuvant CRT and complete resection.1,2

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In the trial, among patients who received Opdivo, median disease-free survival (DFS) was twice as long as in those who received placebo (22.4 months [95% Confidence Interval [CI]: 16.6 to 34.0] compared to 11.0 months [95% CI: 8.3 to 14.3]).1Opdivo reduced the risk of disease recurrence or death by 31% compared to placebo (Hazard Ratio [HR] 0.69; 95% CI: 0.56 to 0.85; P=0.0003).1 In an exploratory analysis, among patients with adenocarcinoma (n=563, 70.9%), mDFS was 19.4 months (95% CI: 15.9 to 29.4) with Opdivo versus 11.1 months (95% CI: 8.3 to 16.8) with placebo (unstratified HR 0.75; 95% CI: 0.59 to 0.96), and among squamous cell carcinoma patients (n=230, 29%), mDFS was 29.7 months (95% CI: 14.4 to NE) with Opdivo versus 11.0 months (95% CI: 7.6 to 17.8) with placebo (unstratified HR 0.61; 95% CI: 0.42 to 0.88).3

"Locally advanced esophageal and gastroesophageal junction cancers are aggressive tumor types that often require multiple approaches to address the disease, including chemotherapy, radiation and surgery," said Ronan J. Kelly M.D., MBA., director, Baylor Scott & White Charles A. Sammons Cancer Center, and W.W. Caruth Jr. Endowed Chair of Immunology at Baylor University Medical Center.3,4,5,6,7,8 "Even after neoadjuvant CRT followed by surgery, there may be a high risk of recurrence for patients who do not achieve a pathologic complete response.2,3,7 In the CheckMate -577 trial, we saw a doubling in median disease-free survival compared to placebo, which suggests that Opdivo could become a new standard of care for these patients.1,9 This is exciting news, providing renewed hope."

Opdivo is associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis and renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.1Please see the Important Safety Information section below, as well as select safety information from CheckMate -577.

"Esophageal and GEJ cancer patients with residual pathologic disease following neoadjuvant CRT and complete resection face a high risk of disease recurrence; however, the predominant option for these patients has been surveillance," said Adam Lenkowsky, senior vice president and general manager, U.S. Cardiovascular, Immunology and Oncology, Bristol Myers Squibb.3,7,9 "Today’s news marks an important step for patients as well as meaningful progress toward our commitment to pioneering immunotherapy treatment options in earlier stages of disease where there is the potential to reduce the risk of recurrence."1

This application was reviewed under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible.10 The review was also conducted under the FDA’s Project Orbis initiative, which enabled concurrent review by the health authorities in Australia, Canada and Switzerland.

About CheckMate -577

CheckMate -577 was a Phase 3 randomized, placebo-controlled, double-blind, multi-center trial, evaluating Opdivo as an adjuvant treatment in patients with esophageal or GEJ cancer with residual pathologic disease following neoadjuvant CRT and complete resection.1,2 The trial excluded patients who did not receive CRT prior to surgery, had stage IV resectable disease, autoimmune disease, or any condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications.1 The primary endpoint of the trial was DFS (investigator assessed).1 Following neoadjuvant CRT and complete tumor surgical resection (also known as trimodality therapy), a total of 794 patients were randomized to receive either Opdivo 240 mg (n=532) or placebo (n=262) by intravenous infusion every two weeks for 16 weeks, followed by Opdivo 480 mg or placebo by intravenous infusion every four weeks beginning at week 17.1,2 Treatment was until disease recurrence, unacceptable toxicity, or for up to one year in total duration.1

The FDA-approved dosing for Opdivo (injection for intravenous use) for adjuvant treatment of patients with resected esophageal or GEJ cancer is 240 mg intravenous infusion over 30 minutes every two weeks or 480 mg intravenous infusion over 30 minutes every four weeks until disease progression or unacceptable toxicity for a total treatment duration of one year.1

Select Safety Profile from CheckMate -577 Study

Opdivo was discontinued in 12% of patients and was delayed in 28% of patients for an adverse reaction.1 Serious adverse reactions occurred in 33% of patients receiving Opdivo.1 A serious adverse reaction reported in ≥ 2% of patients who received Opdivo was pneumonitis.1 A fatal adverse reaction of myocardial infarction occurred in one patient who received Opdivo.1 The most common adverse reactions reported in ≥20% of patients treated with Opdivo were fatigue (34%), diarrhea (29%), nausea (23%), rash (21%), musculoskeletal pain (21%) and cough (20%).1

About Esophageal and Gastroesophageal Junction Cancers

Esophageal and gastroesophageal junction cancers are classified as upper gastrointestinal cancers.11

Esophageal cancer is a type of gastrointestinal cancer that starts in the inner layer of the esophagus (the mucosa) and grows.11 In the United States, it is estimated there will be approximately 19,260 new cases of esophageal cancer diagnosed and 15,530 deaths resulted from the disease in 2021.12 The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma.11
The gastroesophageal junction (GEJ) is the area of the body that connects the lower part of the esophagus to the stomach.11 The prevalence of GEJ cancer has continued to rise.13,14
INDICATIONS

OPDIVO (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy (CRT).

OPDIVO (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO. Early identification and management are essential to ensure safe use of OPDIVO. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment with OPDIVO. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue OPDIVO depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%).

Immune-Mediated Hepatitis and Hepatotoxicity

OPDIVO can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%).

Immune-Mediated Endocrinopathies

OPDIVO can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.

In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%).

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%).

In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%).

In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%).

In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%).

In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis.

Immune-Mediated Nephritis with Renal Dysfunction

OPDIVO can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%).

Immune-Mediated Dermatologic Adverse Reactions

OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.

Withhold or permanently discontinue OPDIVO depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients, including Grade 3 (1.1%) and Grade 2 (2.2%).

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO monotherapy or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica; endocrine: hypoparathyroidism; other (hematologic/immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, which has been observed in patients receiving OPDIVO, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.

Infusion-Related Reactions

OPDIVO can cause severe infusion-related reactions. Discontinue OPDIVO in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with OPDIVO. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between OPDIVO and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal studies, OPDIVO 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 OPDIVO and for at least 5 months after the last dose.

Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone

In randomized clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Lactation

There are no data on the presence of OPDIVO in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 5 months after the last dose.

Serious Adverse Reactions

In Checkmate 577, serious adverse reactions occurred in 33% of patients receiving OPDIVO (n=532). Serious adverse reactions reported in ≥2% of patients who received OPDIVO was pneumonitis. A fatal reaction of myocardial infarction occurred in one patient who received OPDIVO.

Common Adverse Reactions

In Checkmate 577, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=532) were fatigue (34%), diarrhea (29%), nausea (23%), rash (21%), musculoskeletal pain (21%), and cough (20%).

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

Clinical Trials and Patient Populations

Checkmate 577—adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238—adjuvant treatment of melanoma

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

About Bristol Myers Squibb’s Patient Access Support

Bristol Myers Squibb remains committed to providing assistance so that cancer patients who need our medicines can access them and expedite time to therapy.

BMS Access Support, the Bristol Myers Squibb patient access and reimbursement program, is designed to help appropriate patients initiate and maintain access to Bristol Myers Squibb medicines during their treatment journey. BMS Access Support offers benefit investigation, prior authorization assistance, as well as co-pay assistance for eligible, commercially insured patients. More information about our access and reimbursement support can be obtained by calling BMS Access Support at 1-800-861-0048 or by visiting www.bmsaccesssupport.com.

About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.