Gemcitabine Hydrochloride

- Announced first patient dosed in Phase 1/2a clinical trial of GLIX1 for treatment of glioblastoma (GBM) - - Announced new GLIX1 data demonstrating potent anti-tumor effect in GBM across multiple in-vivo studies, including a temozolomide (TMZ)-resistant patient-derived xenograft model - - Management to host conference call today, May 27, at 8:30 am EDT - TEL AVIV, Israel, May 27, 2026 /PRNewswire/ -- BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, today reported its unaudited financial results for the quarter ended March 31, 2026, and provided a corporate update. "Since our last quarterly update, we achieved a significant milestone for our company and for the GLIX1 development program with the dosing of the first patient in our Phase 1/2a clinical trial of GLIX1 in glioblastoma," stated Philip Serlin, Chief Executive Officer of BioLineRx. "We are also very encouraged by compelling new pre-clinical data showing that GLIX1 demonstrated robust dose-dependent tumor-growth inhibition and survival benefit in orthotopic cell-derived xenograft (CDX) GBM models. Furthermore, in a newly completed subcutaneous TMZ-resistant patient-derived xenograft (PDX) GBM model, GLIX1 demonstrated a robust anti-tumor effect while no effect was observed with TMZ, highlighting the potential to address the very high unmet need in GBM." "In the coming days, we look forward to engaging with the broader oncology community at this year's ASCO meeting with two abstracts featuring GLIX1. The abstracts highlight its novel mechanism of action and provide strong rationale for the development of GLIX1 in GBM as well as in other cancers. They also highlight that in safety studies in animals GLIX1 was safe up to the highest feasible doses tested, supporting the combination with other anti-cancer agents. Furthermore, the abstracts highlight the compelling mechanistic rationale for combining GLIX1 with PARP inhibitors supported by synergistic effect in cell lines across diverse cancers including from tumor types typically less responsive to PARP inhibition." Financial Updates With $17.4 million on its balance sheet as of March 31, 2026, BioLineRx is maintaining its cash runway guidance into the first half of 2027. Development Updates GLIX1 Phase 1/2a clinical trial of GLIX1 in glioblastoma and other cancers initiated in March 2026. The first patient was dosed at NYU Langone Health under the supervision of Dr. Alexandra Miller, Chief of Neuro-Oncology & Co-Director of Brain and Spine Tumor Center, Perlmutter Cancer Center. Two additional leading cancer centers are participating in the study: Northwestern University, led by Dr. Roger Stupp and Dr. Ditte Primdahl; and Moffit Cancer Center, led by Dr. Patrick Grogan. Additional sites may be added to the study at a later date. The Phase 1 part of the trial is expected to recruit up to 30 patients with recurrent and progressive GBM and other high-grade gliomas. The objective is to establish a maximum tolerated dose (MTD) and/or a recommended dose based on safety, PK/PD and preliminary efficacy. The Phase 2a expansion part of the trial is planned to include additional indications, including newly diagnosed GBM, as well as select cancers, with GLIX1 as monotherapy or in combination with standard of care (including in combination with PARP inhibitors). These cohorts are expected to identify preliminary efficacy, PD assessments and dose optimization data, serving as the basis for a rapid and effective advanced clinical development plan. Announced new GLIX1 data demonstrating potent anti-tumor effect in GBM across multiple in-vivo studies, including a temozolomide (TMZ)-resistant patient-derived xenograft model Announced two abstracts on GLIX1 that were selected for publication during the American Society of Clinical Oncology (ASCO) Annual Meeting, which is scheduled for May 29-June 2, in Chicago, IL. Pre-clinical activities in support of clinical development for GLIX1 in additional cancer indications, including in combination with PARP inhibitors, are ongoing. Motixafortide Pancreatic Ductal Adenocarcinoma (mPDAC) Enrollment is continuing in the CheMo4METPANC Phase 2b clinical trial, which is being led by Columbia University, and supported by both Regeneron and BioLineRx. The trial is evaluating motixafortide in combination with the PD-1 inhibitor cemiplimab and standard chemotherapy (gemcitabine and nab-paclitaxel). A prespecified interim/futility analysis is planned when 40% of progression-free survival (PFS) events are observed, which the Company continues to anticipate will occur in 2026. APHEXDA Performance Update APHEXDA sales for the first quarter of 2026 were $2.7 million, which provided royalty revenues to the company of $0.5 million. Financial Results for the Quarter ended March 31, 2026 Revenues for the three months ended March 31, 2026 were $0.5 million, an increase of $0.2 million, compared to revenues of $0.3 million for the three months ended March 31, 2025. The increase in revenues from 2025 to 2026 reflects an increase in royalties paid by Ayrmid from the commercialization of APHEXDA. Cost of revenues for the three months ended March 31, 2026 was $0.1 million, compared to immaterial cost of revenues for the three months ended March 31, 2025. The cost of revenues reflects sub-license fees on royalties paid by Ayrmid from the commercialization of APHEXDA. Research and development expenses for the three months ended March 31, 2026 were $2.5 million, an increase of $0.9 million, or 55.8%, compared to $1.6 million for the three months ended March 31, 2025. The increase resulted primarily from expenses related to the new GLIX1 project. General and administrative expenses for the three months ended March 31, 2026 were $0.9 million, a decrease of $0.1 million, or 13.3%, compared to $1.0 million for the three months ended March 31, 2025. The decrease resulted primarily from a decrease in legal expenses, as well as a decrease in a number of other general and administrative expenses. Net non-operating income amounted to $0.5 million for the three months ended March 31, 2026, compared to net non-operating income of $7.6 million for the three months ended March 31, 2025. Non-operating income for the periods primarily relates to non-cash fair-value adjustments of warrant liabilities, as a result of changes in the Company's share price, offset by warrant offering expenses. Net financial expenses for the three months ended March 31, 2026 were immaterial compared to net financial expenses of $0.1 million for the three months ended March 31, 2025. Net financial expenses for the periods primarily relate to interest paid on loans, partially offset by investment income earned on bank deposits. Net loss for the quarter ended March 31, 2026 was $2.6 million, compared to net income of $5.1 million for the quarter ended March 31, 2025. As of March 31, 2026, the Company had cash, cash equivalents, and short-term bank deposits of $17.4 million. Conference Call and Webcast Information To access the conference call, please dial +1-888-407-2553 from the U.S. or +972-3-918-0685 internationally. A live webcast and a replay of the call can be accessed through the event page on the Company's website. Please allow extra time prior to the call to visit the site and download any necessary software to listen to the live broadcast. The call replay will be available approximately two hours after completion of the live conference call. A dial-in replay of the call will be available until May 28, 2026; please dial +1-888-295-2634 from the US or +972-3-925-5904 internationally. About BioLineRx BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX) is a clinical-stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases. The Company's lead development asset is GLIX1, a first-in-class, oral, small molecule targeting DNA damage response in glioblastoma and other solid tumors, for which a Phase 1/2a clinical trial was initiated in the first quarter of 2026. GLIX1 is being developed under a collaboration with Hemispherian AS. The Company's first approved product, APHEXDA® (motixafortide), is indicated in the U.S. for stem cell mobilization for autologous transplantation in multiple myeloma, and is being commercialized by Ayrmid Ltd. (globally, except Asia) and developed by Gloria Biosciences (in Asia). BioLineRx has retained the rights to develop motixafortide in metastatic pancreatic cancer (PDAC) and has a Phase 2b PDAC trial currently ongoing under a collaboration with Columbia University. Learn more about who we are, what we do, and how we do it at , or on LinkedIn. Forward Looking Statement Various statements in this release concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "anticipates," "believes," "could," "estimates," "expects," "intends," "may," "plans," "potential," "predicts," "projects," "should," "will," and "would," and describe opinions about future events. These include statements regarding management's expectations, beliefs and intentions regarding, among other things, the expectations with regard to the planned Phase 1/2a GLIX1 clinical trial, expected timing of a clinical readout, and BioLineRx's business strategy. These forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Factors that could cause BioLineRx's actual results to differ materially from those expressed or implied in such forward-looking statements include, but are not limited to: the clinical development, commercialization and market acceptance of GLIX1 and motixafortide including the degree and pace of market uptake of APHEXDA for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients; the initiation, timing, progress and results of BioLineRx's preclinical studies, clinical trials and other therapeutic candidate development efforts; BioLineRx's ability to advance GLIX1 and motixafortide into clinical trials or to successfully complete its preclinical studies or clinical trials; whether the clinical trial results for GLIX1 and motixafortide will be predictive of real-world results; BioLineRx's receipt of regulatory approvals for GLIX1 and motixafortide and the timing of other regulatory filings and approvals; whether access to GLIX1 and motixafortide is achieved in a commercially viable manner and whether GLIX1 and motixafortide receives adequate reimbursement from third.-party payors; BioLineRx's ability to establish, manage, and maintain corporate collaborations, as well as the ability of BioLineRx's collaborators to execute on their development and commercialization plans; BioLineRx's ability to integrate new therapeutic candidates and new personnel, as well as new collaborations; the interpretation of the properties and characteristics of BioLineRx's therapeutic candidates and of the results obtained with its therapeutic candidates in preclinical studies or clinical trials; the implementation of BioLineRx's business model and strategic plans for its business and therapeutic candidates; the scope of protection that BioLineRx's is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; estimates of BioLineRx's expenses, future revenues, capital requirements and its need for and ability to access sufficient additional financing; risks related to changes in healthcare laws, rules and regulations in the United States or elsewhere; competitive companies, technologies and BioLineRx's industry; BioLineRx's ability to maintain the listing of its ADSs on Nasdaq; statements as to the impact of the political and security situation in Israel on BioLineRx's business which may exacerbate the magnitude of the factors discussed above. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on March 23, 2026. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law. Contacts: United States Chuck Padala LifeSci Advisors, LLC [email protected] Israel Moran Meir LifeSci Advisors, LLC [email protected] Logo - SOURCE BioLineRx Ltd. 21% more press release views with Request a Demo

First-ever immunotherapy combination approved in Europe for adult and adolescent patients, ages 12 and older, with previously untreated Stage III or IV classical Hodgkin Lymphoma (cHL) PRINCETON, N.J.--(BUSINESS WIRE)-- $BMY #HodgkinLymphoma -- Bristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has approved Opdivo ® (nivolumab) in combination with doxorubicin, vinblastine and dacarbazine (AVD) for the treatment of adult and adolescent patients 12 years of age and older with previously untreated Stage III or IV classical Hodgkin Lymphoma (cHL). This approval marks a significant milestone, establishing the Opdivo plus AVD combination as the first immunotherapy-based regimen available in the European Union (EU) for newly diagnosed advanced cHL. 1 This new EC approval reinforces the expanding impact of Opdivo in cHL, building upon the U.S. Food and Drug Administration (FDA) approval of Opdivo in combination with AVD for previously untreated Stage III or IV cHL in adults and pediatric patients 12 years and older, granted in March 2026. 2 Earlier this year, the EC also approved Opdivo in combination with brentuximab vedotin for the treatment of children 5 years of age and older, adolescents, and adults up to 30 years of age with relapsed or refractory cHL after one prior line of therapy. 1 “Today’s approval of Opdivo in combination with AVD for previously untreated advanced classical Hodgkin Lymphoma marks an important advancement for patients in the European Union, 1 ” said Monica Shaw, MD, senior vice president of Oncology Commercialization, Bristol Myers Squibb. “For decades, patients newly diagnosed with this aggressive blood cancer have faced intensive treatment approaches. 3,4 This approval underscores the benefit and critical role of immunotherapy-based approaches in hematologic cancers like cHL and reflects our continued commitment to bringing these innovative options to patients earlier in their treatment journey across cancer types.” The EC approval is based on data from the Phase 3 SWOG 1826 (Study CA2098UT) which demonstrated a 58% reduction in the risk of disease progression or death with Opdivo in combination with AVD versus brentuximab vedotin plus AVD, as determined per investigator (Hazard Ratio [HR] 0.42; 95% Confidence Interval [CI] 0.27-0.67; P =<0.0001).The trial demonstrated a statistically significant improvement in the primary endpoint of progression-free survival (PFS), based on a median follow-up of 13.7 months in the intent to treat population. After a median follow-up of 36.7 months, the median overall survival (OS) had not been reached in either treatment arm with a total of 26 deaths: 9 (1.8%) deaths in the Opdivo in combination with AVD arm and 17 (3.4%) deaths in the standard of care over brentuximab vedotin plus AVD arm. 5 “For patients with newly diagnosed Stage III or IV classical Hodgkin Lymphoma, finding an effective and tolerable first-line treatment remains crucial to achieving long-term remission, especially for adolescents and the elderly,” said Franck Morschhauser, MD, PhD, Professor of Hematology at the University of Lille and Hospital Claude Huriez. “The SWOG 1826 study provided compelling data demonstrating that nivolumab-based combination therapy significantly improved progression-free survival compared with the standard of care. The availability of the first-ever IO combination in this earlier setting and across a broad spectrum of ages offers a potentially practice-changing approach to the treatment of frontline cHL.” This approval by the EC for Opdivo plus AVD for the treatment of adult and adolescent patients 12 years of age and older with previously untreated Stage III or IV cHL is valid in all 27 member states of the EU, as well as Iceland, Liechtenstein and Norway. In addition to this approval in cHL, Opdivo- based options are also approved for treatment of multiple tumor types in the EU. Bristol Myers Squibb thanks the SWOG Cancer Research Network and its investigators for leading the Phase 3 SWOG 1826 (CA2098UT) trial and the patients for their important contributions to this study. About SWOG 1826 (CA2098UT) SWOG 1826, also known as CA2098UT, is a randomized, multicenter, Phase 3 study evaluating Opdivo ® (nivolumab) in combination with doxorubicin, vinblastine and dacarbazine (AVD) for adult and pediatric (12 years and older) patients with previously untreated Stage III or IV classical Hodgkin Lymphoma (cHL). 3 The study is designed to assess progression-free survival as the primary endpoint, with key secondary endpoints that include overall survival and other measures of efficacy and safety. 3 The SWOG 1826 study is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH) under a Cooperative Research and Development Agreement with Bristol Myers Squibb and conducted in the NCI National Clinical Trials Network (NCTN) led by the SWOG Cancer Research Network in collaboration with the Children’s Oncology Group (COG). 3 It is the largest cHL study conducted in the NCTN. 3 Bristol Myers Squibb co-sponsored the study and supplied Opdivo to the NCI through a Cooperative Research and Development Agreement. 3 Select Safety Pro SWOG 1826 (CA2098UT) Serious adverse reactions occurred in 39% of patients receiving Opdivo in combination with doxorubicin, vinblastine and dacarbazine (AVD) (n=490). The most frequent serious adverse reactions reported in ≥5% patients who received Opdivo in combination with AVD were neutropenia (7%), pyrexia (7%), febrile neutropenia (6%), and nausea (6%). Fatal adverse reactions occurred in 3 patients (0.6%), all from sepsis. The most common adverse reactions were nausea (70%), neutropenia (61%), fatigue (59%), anemia (51%), constipation (49%), leukopenia (44%), musculoskeletal pain (42%), transaminases increase (41%), peripheral neuropathy (41%), vomiting (33%), and stomatitis (30%). About Classical Hodgkin Lymphoma Hodgkin lymphoma (HL), also known as Hodgkin disease, is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system. 6 HL is the most common cancer diagnosed in adolescents (ages 15-19). 7 It is most often diagnosed in early adulthood (ages 20-39) and late adulthood (older than 55 years of age). 8 Classical Hodgkin lymphoma is the most common type of HL, accounting for 95% of cases. 9 Despite progress in frontline therapy, advanced-stage HL still carries a substantial risk of relapse, highlighting the need for innovative approaches that deliver durable remission for patients. 8 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 treated more than 35,000 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 65 countries, including the United States, the European Union, Japan and China. 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 50 countries, including the United States and the European Union. INDICATIONS OPDIVO ® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. OPDIVO ® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma. OPDIVO ® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC). OPDIVO ® (nivolumab) in combination with platinum-doublet chemotherapy, is indicated for neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, followed by single-agent OPDIVO ® as adjuvant treatment after surgery. OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. OPDIVO ® (nivolumab) is indicated for the treatment of adult 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), in combination with YERVOY ® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM). OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC). OPDIVO ® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). OPDIVO ® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. OPDIVO ® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. 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 adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy. OPDIVO ® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. OPDIVO ® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC. OPDIVO ® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC). OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC). OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. OPDIVO ® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy. OPDIVO ® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT). OPDIVO ® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1). OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1). OPDIVO ® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma whose tumors express PD-L1 (≥1). 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 or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. 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 and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY 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 and YERVOY 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%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 7% (31/456) of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2 (4.4%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 3.9% (26/666) of patients, including Grade 3 (1.4%) and Grade 2 (2.6%). In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, immune-mediated pneumonitis occurred in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3 (3.5%), and Grade 2 (4.0%). Four patients (0.7%) died due to pneumonitis. In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO, including Grade 3 (n=1) and Grade 2 (n=12). Immune-Mediated Colitis OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. 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%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated colitis occurred in 9% (60/666) of patients, including Grade 3 (4.4%) and Grade 2 (3.7%). Immune-Mediated Hepatitis and Hepatotoxicity OPDIVO and YERVOY 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%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), Grade 3 (4.9%), and Grade 2 (0.4%). OPDIVO in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to OPDIVO alone. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. In patients receiving OPDIVO and cabozantinib, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. Immune-Mediated Endocrinopathies OPDIVO and YERVOY 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 and YERVOY 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 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456) of patients, including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, adrenal insufficiency occurred in 7% (48/666) of patients, including Grade 4 (0.3%), Grade 3 (2.5%), and Grade 2 (4.1%). In patients receiving OPDIVO and cabozantinib, adrenal insufficiency occurred in 4.7% (15/320) of patients, including Grade 3 (2.2%) and Grade 2 (1.9%). 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 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456) of patients, including Grade 3 (2.4%) and Grade 2 (6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypophysitis occurred in 4.4% (29/666) of patients, including Grade 4 (0.3%), Grade 3 (2.4%), and Grade 2 (0.9%). In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, thyroiditis occurred in 2.7% (22/666) of patients, including Grade 3 (4.5%) and Grade 2 (2.2%). 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 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3 (0.9%) and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hyperthyroidism occurred in 12% (80/666) of patients, including Grade 3 (0.6%) and Grade 2 (4.5%). 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 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypothyroidism occurred in 18% (122/666) of patients, including Grade 3 (0.6%) and Grade 2 (11%). 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. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2. Contacts Bristol Myers Squibb M edia Inquiries: media@bms.com Investors: investor.relations@bms.com Read full story here