On July 31, 2017 Generex Biotechnology Corporation (www.generex.com) (OTCPink:GNBT) reported that its wholly-owned subsidiary, Antigen Express, Inc. (www.antigenexpress.com) has entered into a clinical trial collaboration agreement with Merck (known as MSD outside the United States and Canada), through a wholly-owned subsidiary, to evaluate Antigen’s AE37 cancer vaccine in combination with Merck’s anti-PD-1 (programmed death receptor-1) therapy, KEYTRUDA (pembrolizumab), in patients with metastatic triple-negative breast cancer (Filing, 8-K, Generex, AUG 1, 2017, View Source [SID1234519959]). The study will evaluate preliminary safety and efficacy of the combination in a Phase II trial.

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The combination of AE37 plus KEYTRUDA follows previous studies, in which both therapies have individually shown encouraging results in patients with triple-negative breast cancer. In a controlled, randomized trial of AE37 in 300 breast cancer patients, the most encouraging results were observed in those with triple-negative breast cancer. Similarly, KEYTRUDA has shown encouraging activity in patients with metastatic triple-negative breast cancer. The attractiveness of the combination lies in the different mechanisms of action of the two immunotherapeutic drugs: AE37 specifically activates T cells to attack cancer cells while KEYTRUDA increases the ability of the body’s immune system to help detect and fight tumor cells.

"We are excited to be collaborating with Merck, a clear leader in cancer immunotherapy, to advance this important treatment modality in patients with triple negative breast cancer," said Dr. Eric von Hofe, Ph.D., President of Antigen Express. "Both the clinical data as well as mechanistic data on the activity of AE37 and KEYTRUDA in patients strongly argue for the potential benefit of this combination study."

Dr. Samuel Jacobs, MD of the NSABP Foundation, which is collaborating in this study with Antigen Express and Merck, noted that "with single agent immunotherapy in metastatic TNBC the response rate is low, but the benefit in responding patients is strikingly prolonged. We are hoping that with this combination we will see both an increase in the response rate and extended duration of benefit."

CMO and CSO of Generex, Dr. Jason Terrell, added, "This trial unveils our incredibly diverse Ii-key hybrid vaccine platform. AE37 is a hybrid vaccine combining the potent immune-stimulating Ii-key molecule with a breast cancer specific target. Ii-key can similarly be combined with virtually any target to create vaccines across the spectrum of disease processes."

"The agreement with Merck is a pivotal milestone in the advancement of our immunotherapy assets and marks a new phase of Antigen Express clinical development" said Joe Moscato, CEO of Generex. "Given that AE37 alone showed statistically significant efficacy in the triple-negative subpopulation of our prior Phase 2 study," he continued, "we anticipate important new development opportunities when coupled with KEYTRUDA. In particular, this combination study will highlight the unique value of AE37 and pave the way for additional development opportunities in other cancers. We are excited to move this study into the clinic and reinvigorate our immunotherapy work as we approach the end of our company reorganization. This collaboration highlights our commitment to Antigen Express and its assets into the future."

The collaboration agreement is between Antigen Express and Merck. Under the terms of the agreement, the trial will be sponsored by Antigen Express. Additional details were not disclosed.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

About the NSABP Foundation

The NSABP Foundation is an outgrowth of the National Surgical Adjuvant Breast and Bowel Project, instituted in 1958 as part of the National Cancer Institute’s clinical trials program. The founder, Bernard Fisher, MD, was one of the first cancer researchers to realize the value of the randomized clinical trial in answering questions about the development, progression, and treatment of this disease. From the time of the NSABP’s first studies, the randomized trial has been its primary research tool, and over the years has established record of designing and conducting clinical trials that have changed the way breast cancer is treated and prevented.

In its history the NSABP has enrolled more than 110,000 women and men in clinical trials in breast and colorectal cancer. It has research sites at nearly 700 major medical centers, university hospitals, large oncology practice groups, and health maintenance organizations in the United States, Canada, and Ireland. At those sites and their satellites, about 5000 physicians, nurses, and other medical professionals conduct NSABP treatment and prevention trials.

On August 1, 2017 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, and US Oncology Research, one of the nation’s largest networks of independent, community-based oncology practices dedicated to advancing high-quality treatments through clinical trials, reported a collaboration to screen and identify relapsed or refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) patients with EZH2 mutations (Press release, Epizyme, AUG 1, 2017, View Source [SID1234519958]). Once identified, eligible candidates will be directed to Epizyme’s ongoing Phase 2 clinical trial of tazemetostat, the Company’s first-in-class EZH2 inhibitor, as a single-agent treatment for relapsed or refractory patients with FL or DLBCL.

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"Relapsed follicular lymphoma and DLBCL are difficult diseases for which there is generally poor prognosis and limited treatment options for patients," said Michael Seiden, M.D., Ph.D. chief medical officer, US Oncology Research. "Physicians affiliated with US Oncology Research strive to provide access to the treatment strategies that are best suited to each patient. Given the encouraging clinical activity and favorable safety profile demonstrated by tazemetostat in these patient populations, US Oncology Research is pleased to work with Epizyme to offer this screening process so that appropriate patients being treated by an affiliated physician can be promptly directed to a clinical trial evaluating an investigational therapy that is targeted to their cancer."

Under the collaboration, US Oncology Research will implement a separate screening protocol in 68 locations in the U.S. to identify relapsed or refractory FL and DLBCL patients with tumors bearing EZH2 mutations who may be candidates for enrollment in Epizyme’s ongoing Phase 2 clinical trial. US Oncology Research will direct identified patients to the tazemetostat Phase 2 clinical trial for protocol screening and potential enrollment into the trial. Sites began screening patients in July 2017.

"We are pleased that US Oncology Research, a program recognized for tremendous success in oncology clinical trials and for providing patients with access to novel treatments, is joining our effort to develop a targeted treatment for lymphoma patients with EZH2 mutations," said Peter Ho , chief medical officer of Epizyme. "This collaboration significantly expands our clinical trial footprint within the United States and is expected to further enhance our enrollment of patients whose tumors harbor an EZH2 mutation for our ongoing Phase 2 study of tazemetostat. We believe that tazemetostat has the potential to play a very important role in the targeted treatment of these patients in the future."

About Follicular Lymphoma (FL) and Diffuse Large B-Cell Lymphoma (DLBCL)
FL, an indolent form of non-Hodgkin lymphoma (NHL), is considered to be incurable with existing treatments and is characterized by cycles of relapse that become increasingly difficult to treat with each disease progression. Approximately 25,000 patients in the U.S. and major European countries are diagnosed with FL every year1, of which 15 to 20 percent are estimated to have an EZH2 mutation. There are no approved treatments indicated for patients with FL with an EZH2 mutation. In April 2017, the FDA granted Fast Track designation to tazemetostat for FL regardless of EZH2 mutational status.

DLBCL is an aggressive form of NHL that, once diagnosed, typically requires immediate treatment. Approximately 45,000 patients are diagnosed with DLBCL in the U.S. and major European countries every year2. Among patients with germinal center DLBCL, an estimated 15 to 20 percent have an EZH2 mutation. Forty to 50 percent of patients will relapse on their first-line treatment, which is most commonly the chemotherapy regimen R-CHOP, and there are few treatment options for patients who relapse or become refractory to chemotherapy. In November 2016, the FDA granted Fast Track designation to tazemetostat for DLBCL with EZH2 mutations.

About the Tazemetostat Clinical Trial Program
Tazemetostat, a first-in-class EZH2 inhibitor, is currently being studied in ongoing Phase 2 programs in both follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) forms of non-Hodgkin lymphoma; certain molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors; and mesothelioma, as well as in combination studies in DLBCL. Tazemetostat has been granted Fast Track designation by the U.S. Food and Drug Administration for FL regardless of EZH2 mutation and for DLBCL with EZH2-activating mutations, as well as Orphan Drug designation for soft tissue sarcoma and malignant rhabdoid tumors.

On August 1, 2017 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported that it has completed enrollment of more than 80 patients in the phase 2 portion of its FOCUS study evaluating CA4P in combination with bevacizumab (Avastin) and physician’s choice chemotherapy for the treatment of platinum-resistant ovarian cancer.

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"Interest in this clinical trial has been significant from the oncology community. The enthusiasm of our investigators has helped us complete enrollment well in advance of our year-end 2017 goal," said William D. Schwieterman, M.D., President and Chief Executive Officer of Mateon. "We thank patients and investigators for their support, as completing enrollment in the first part of our phase 2/3 study is an important milestone. We look forward to the multiple upcoming data readouts expected over the next several months."

The next (second) interim analysis of FOCUS is anticipated in mid-August, the third in September, and the fourth and final interim analysis in November 2017. The company expects these analyses to provide preliminary information on objective response rate (ORR) for 40, 60 and all 80-plus patients, respectively, as well as provide early data on progression-free survival (PFS), the primary endpoint of the study. The study’s final analysis is scheduled to occur when disease has progressed in 75% of enrolled patients.

Patients in FOCUS have ovarian cancer that has progressed within six months of treatment with a platinum-based chemotherapy. All patients are receiving the current standard of care for platinum-resistant ovarian cancer, bevacizumab (Avastin) and physician’s choice chemotherapy, with or without CA4P.

On August 1, 2017 CTI BioPharma Corp. (NASDAQ and MTA: CTIC) reported that the first patient has been enrolled in PAC203, a Phase 2 clinical trial of pacritinib in patients with primary myelofibrosis who have failed prior ruxolitinib therapy (Press release, CTI BioPharma, AUG 1, 2017, View Source [SID1234519954]). PAC203 is designed to evaluate the dose response relationship for safety and efficacy (spleen volume reduction at 12 and 24 weeks) of three dose regimens: 100 mg once-daily, 100 mg twice-daily (BID) and 200 mg BID. The 200 mg BID dose regimen was used in the Phase 3 PERSIST-2 trial of pacritinib in patients with myelofibrosis. The trial is expected to enroll up to approximately 105 patients.

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About Pacritinib

Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia and lymphoma. In addition to myelofibrosis, the kinase profile of pacritinib suggests its potential therapeutic utility in conditions such as acute myeloid leukemia, or AML, myelodysplastic syndrome, or MDS, chronic myelomonocytic leukemia, or CMML, and chronic lymphocytic leukemia, or CLL, due to its inhibition of c-fms, IRAK1, JAK2 and FLT3.

Pacritinib was evaluated in two Phase 3 clinical trials, known as the PERSIST program, for patients with myelofibrosis, with one trial in a broad set of patients without limitations on platelet counts, the PERSIST-1 trial; and the other in patients with low platelet counts, the PERSIST-2 trial. The PERSIST-1 trial met its primary endpoint of spleen volume reduction (35 percent or greater from baseline to Week 24 by MRI/CT scan). The PERSIST-2 trial met one of its co-primary endpoints, that of spleen volume reduction. The co-primary endpoint of reduction of Total Symptom Score (TSS) was not achieved but trended toward improvement in TSS.

Clinical studies under the investigational new drug (IND) for pacritinib were subject to a full clinical hold issued by the FDA in February 2016. In January 2017, the FDA removed the full clinical hold and stated that clinical trials may resume. CTI BioPharma is conducting the PAC203 trial which was a condition of the clinical hold being removed.

On August 1, 2017 Bristol-Myers Squibb Company (NYSE:BMY) reported the U.S. Food and Drug Administration (FDA) has approved Opdivo (nivolumab) injection for intravenous use for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan (Press release, Bristol-Myers Squibb, AUG 1, 2017, View Source [SID1234519953]).2 Approval for this indication has been granted under accelerated approval based on overall response rate (ORR) and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The recommended dose is 240 milligrams administered as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity.2 In the CheckMate -142 trial, among patients (53/74) who received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, 28% (95% CI: 17-42; 15/53) responded to treatment with Opdivo. The percentage of patients with a complete response was 1.9% (1/53) and the percentage of patients with a partial response was 26% (14/53). Among these responders, the median duration of response was not reached (range: 2.8+-22.1+ months).2 Among all enrolled patients, 32% (95% CI: 22-44; 24/74) responded to treatment with Opdivo; 2.7% (2/74) experienced a complete response, 30% (22/74) experienced a partial response.2

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Opdivo is associated with the following Warnings and Precautions including immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions; infusion reactions; and embryo-fetal toxicity.2 Please see the Important Safety Information section below.

"As part of our commitment to address hard-to-treat cancers, with today’s approval, Opdivo provides a new treatment option for these patients who have historically faced a poor prognosis,"3,4,5 said Chris Boerner, president, U.S. Commercial, Bristol-Myers Squibb. "This approval is one example of how our commitment to translational medicine and investigating predictive biomarkers may help us discover treatment approaches to address different patients’ unique needs."

"Patients with metastatic colorectal cancer who have dMMR or MSI-H tumors are less likely to respond to conventional chemotherapy,"3,4,5 said Heinz-Josef Lenz, M.D., FACP, J. Terrence Lanni Chair in Gastrointestinal Cancer Research, University of Southern California. "While the challenges of treating these patients have been significant, tumors characterized by these biomarkers are immunogenic.3,6 Therefore, advances in immunotherapy research are encouraging in presenting new treatment options for appropriate patients with MSI-H metastatic colorectal cancer."

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) recommend universal MMR or MSI testing for all patients with a personal history of colon or rectal cancer to inform use of immunotherapy in patients with metastatic disease. The National Comprehensive Cancer Network (NCCN) panel recommends nivolumab (OPDIVO) as a category 2A treatment option in patients with metastatic deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer in second- or third-line therapy.7

Approval Based on Notable Tumor Response Rate and Duration of Response

CheckMate -142 is a Phase 2, multicenter, open-label, single-arm study evaluating Opdivo in patients with locally determined dMMR or MSI-H mCRC whose disease had progressed during, after, or were intolerant to, prior treatment with fluoropyrimidine-, oxaliplatin-, or irinotecan-based chemotherapy.1,2 In this study, 74 patients received Opdivo 3 mg/kg administered intravenously every two weeks.2 The recommended dose is 240 mg administered as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity.2 Across the 74 patients, 72% received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.2 Efficacy outcome measures included independent radiographic review committee-assessed confirmed ORR per RECIST 1.1, and duration of response.2 More than half of patients (51%) had a BRAF (16%) or KRAS (35%) mutation.1

In this trial, Opdivo demonstrated an ORR of 28% (95% CI: 17-42; 15/53) in patients who received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, including a 1.9% complete response rate (1/53) and a 26% partial response rate (14/53). Median duration of response in these patients was not reached (range: 2.8+-22.1+ months).2 Among all enrolled patients, 32% (95% CI: 22-44; 24/74) responded to treatment with Opdivo, including a 2.7% complete response rate (2/74) and a 30% partial response rate (22/74). The median duration of response was not reached (range: 1.4+-26.5+ months).2 Data from CheckMate -142 were published in The Lancet Oncology in July.

"As the third most common type of cancer in the United States, our view is that colorectal cancer – particularly for those with dMMR or MSI-H metastatic disease – has been in need of new research and treatments.8 The approval of Opdivo for appropriate patients with this disease gives the community more hope," said Michael Sapienza, chief executive officer of the Colon Cancer Alliance.

Select Safety Profile

The most common adverse reactions (≥20%) in patients who received Opdivo as a single agent were fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia.2 Please see additional Important Safety Information below.

About dMMR or MSI-H Colorectal Cancer

Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system.9 In the United States, CRC is the third most common cancer, in 2017 it is estimated that there will be approximately 135,000 new cases of the disease and that it will be the second leading cause of cancer-related deaths among men and women combined.8,10 Approximately 5% of metastatic CRC patients have mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) tumors.3

Mismatch repair deficiency occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, which leads to MSI-H tumors in certain types of cancer, including CRC.5,11 Patients with dMMR or MSI-H metastatic CRC are less likely to benefit from conventional chemotherapy and typically have a poor prognosis.3,4,5 Routine testing to confirm dMMR or MSI-H status should be conducted for all metastatic CRC patients.7

INDICATION

OPDIVO (nivolumab) is indicated for the treatment of adults and pediatric (12 years and older) patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

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.

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. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients.

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.

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 monotherapy, adrenal insufficiency occurred in 1% (20/1994) 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 monotherapy, diabetes occurred in 0.9% (17/1994) of patients.

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.

Immune-Mediated Skin Adverse Reactions

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.

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.

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.

Embryo-Fetal Toxicity

Based on its mechanism of action, 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 an OPDIVO- containing regimen and for at least 5 months after the last dose of OPDIVO.

Lactation

It is not known whether OPDIVO 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.

Common Adverse Reactions

The most common adverse reactions (≥20%) in patients who received OPDIVO as a single agent were fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia.2

Please see U.S. Full Prescribing Information for OPDIVO

About the Opdivo Clinical Development Program

Bristol-Myers Squibb’s global development program founded on scientific expertise in the field of Immuno-Oncology includes a broad range of clinical trials studying Opdivo, 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.