On June 1, 2018 Bristol-Myers Squibb Company (NYSE: BMY) reported that the U.S. Food and Drug Administration (FDA) lifted a partial clinical hold placed on CA209-602 (CheckMate -602), a randomized, open-label Phase 3 study evaluating the addition of Opdivo (nivolumab) to pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (Press release, Bristol-Myers Squibb, JUN 1, 2018, View Source [SID1234527061]). The decision follows consultation with the FDA and agreement on amendments to the study protocol.

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Three trials evaluating Opdivo-based combinations in relapsed or refractory multiple myeloma were placed on partial clinical hold in September 2017 as an FDA precaution following risks identified in trials studying another anti–PD-1 agent, pembrolizumab, in patients with multiple myeloma. CheckMate -602 is the last of the three trials to have its partial clinical hold lifted following a similar FDA action announced in December 2017, when the agency lifted partial holds on CA209-039 (CheckMate -039) and CA204-142.

Bristol-Myers Squibb is committed to improving outcomes for patients with multiple myeloma.

About Opdivo

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

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

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

U.S. FDA-APPROVED INDICATIONS FOR OPDIVO

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

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

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

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

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

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with intermediate or poor-risk, previously untreated advanced renal cell carcinoma (RCC).

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 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 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. This indication is approved under accelerated approval based on tumor response rate and duration of response. 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 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.

OPDIVO (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

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

OPDIVO (10 mg/mL) is an injection for intravenous (IV) use.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

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

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

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

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated pneumonitis occurred in 6% (25/407) of patients. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated pneumonitis occurred in 4.4% (24/547) of patients.

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: Grade 3 (n=1) and Grade 2 (n=12).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated colitis occurred in 10% (52/547) of patients.

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

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. For patients without HCC, withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4. For patients with HCC, withhold OPDIVO and administer corticosteroids if AST/ALT is within normal limits at baseline and increases to >3 and up to 5 times the upper limit of normal (ULN), if AST/ALT is >1 and up to 3 times ULN at baseline and increases to >5 and up to 10 times the ULN, and if AST/ALT is >3 and up to 5 times ULN at baseline and increases to >8 and up to 10 times the ULN. Permanently discontinue OPDIVO and administer corticosteroids if AST or ALT increases to >10 times the ULN or total bilirubin increases >3 times the ULN. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated hepatitis occurred in 13% (51/407) of patients. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated hepatitis occurred in 7% (38/547) of patients.

In Checkmate 040, immune-mediated hepatitis requiring systemic corticosteroids occurred in 5% (8/154) of patients receiving OPDIVO.

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

Immune-Mediated Neuropathies

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

Immune-Mediated Endocrinopathies

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

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, hypophysitis occurred in 9% (36/407) of patients. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypophysitis occurred in 4.6% (25/547) of patients In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, adrenal insufficiency occurred in 5% (21/407) of patients. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, adrenal insufficiency occurred in 7% (41/547) 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 1 mg/kg with YERVOY 3 mg/kg, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving this dose of OPDIVO with YERVOY. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (119/547) of patients. Hyperthyroidism occurred in 12% (66/547) of patients receiving this dose of OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, diabetes occurred in 1.5% (6/407) of patients. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, diabetes occurred in 2.7% (15/547) of patients.

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

Immune-Mediated Nephritis and Renal Dysfunction

OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated nephritis and renal dysfunction occurred in 4.6% (25/547) of patients.

Immune-Mediated Skin Adverse Reactions and Dermatitis

OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg, immune-mediated rash occurred in 22.6% (92/407) of patients. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, immune-mediated rash occurred in 16.6% (91/547) of patients.

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

Immune-Mediated Encephalitis

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg (0.2%) after 1.7 months of exposure. Encephalitis occurred in one patient receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg (0.2%) after approximately 4 months of exposure.

Other Immune-Mediated Adverse Reactions

Based on the severity of the adverse reaction, permanently discontinue or withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO monotherapy or in combination with YERVOY, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1.0% of patients receiving OPDIVO: myocarditis, rhabdomyolysis, myositis, 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), motor dysfunction, vasculitis, aplastic anemia, pericarditis, and myasthenic syndrome.

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 and may require treatment with systemic steroids to reduce the risk of permanent vision loss.

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 as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate study 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. In patients receiving OPDIVO 1 mg/kg with ipilimumab 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related reactions occurred in 5.1% (28/547) of patients.

Complications of Allogeneic HSCT after OPDIVO

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

Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.

Embryo-Fetal Toxicity

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

Lactation

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

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO . The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73% and 37%), adverse reactions leading to permanent discontinuation (43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4 adverse reactions (72% and 44%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY and in 43% of patients receiving sunitinib. The most frequent serious adverse reactions reported in at least 2% of patients were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis; in patients treated with sunitinib, they were pneumonia, pleural effusion, and dyspnea. In Checkmate 205 and 039, adverse reactions leading to discontinuation occurred in 7% and dose delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in ≥1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural effusion, pneumonitis, and rash. Eleven patients died from causes other than disease progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection 8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=236). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. In Checkmate 040, serious adverse reactions occurred in 49% of patients (n=154). The most frequent serious adverse reactions reported in at least 2% of patients were pyrexia, ascites, back pain, general physical health deterioration, abdominal pain, and pneumonia. In Checkmate 238, Grade 3 or 4 adverse reactions occurred in 25% of OPDIVO-treated patients (n=452). The most frequent Grade 3 and 4 adverse reactions reported in at least 2% of OPDIVO-treated patients were diarrhea and increased lipase and amylase. Serious adverse reactions occurred in 18% of OPDIVO-treated patients.

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and dyspnea (20%). The most common (≥20%) adverse reactions in the OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%), and nausea (28%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were fatigue (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 214, the most common adverse reactions (≥20%) reported in patients treated with OPDIVO plus YERVOY (n=547) vs sunitinib (n=535) were fatigue (58% vs 69%), rash (39% vs 25%), diarrhea (38% vs 58%), musculoskeletal pain (37% vs 40%), pruritus (33% vs 11%), nausea (30% vs 43%), cough (28% vs 25%), pyrexia (25% vs 17%), arthralgia (23% vs 16%), and decreased appetite (21% vs 29%). In Checkmate 205 and 039, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=266) were upper respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%) and pruritus (20%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO (n=236) were cough and dyspnea at a higher incidence than investigator’s choice. In Checkmate 275, the most common adverse reactions (≥ 20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In Checkmate 040, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=154) were fatigue (38%), musculoskeletal pain (36%), abdominal pain (34%), pruritus (27%), diarrhea (27%), rash (26%), cough (23%), and decreased appetite (22%). In Checkmate 238, the most common adverse reactions (≥20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%). The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%). 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, headache, and abdominal pain.

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

Checkmate Trials and Patient Populations

Checkmate 067–advanced melanoma alone or in combination with YERVOY (ipilimumab); Checkmate 037 and 066–advanced melanoma; Checkmate 017–squamous non-small cell lung cancer (NSCLC); Checkmate 057–non-squamous NSCLC; Checkmate 025–renal cell carcinoma; Checkmate 205/039–classical Hodgkin lymphoma; Checkmate 141–squamous cell carcinoma of the head and neck; Checkmate 275–urothelial carcinoma; Checkmate 040–hepatocellular carcinoma, Checkmate 238–adjuvant treatment of melanoma.

Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY.

On June 1, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported the first data from the ongoing Phase 1 study evaluating single agent AG-881 in advanced glioma and other solid tumors (Press release, Agios Pharmaceuticals, JUN 1, 2018, View Source [SID1234527131]). The data were featured in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. AG-881 is an investigational, oral, selective, potent inhibitor of mutant isocitrate dehydrogenase-1 (IDH1) and IDH2 enzymes, which was designed for enhanced brain penetrance for development in IDH-mutant glioma.

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"IDH mutant glioma is a distinct disease where patients are typically diagnosed in their thirties and forties and endure a deteriorating quality of life from the side effects associated with multiple rounds of surgery, radiation and chemotherapy and ultimately die of their disease," said Ingo Mellinghoff, M.D., Memorial Sloan Kettering Cancer Center, an investigator for the study. "The AG-881 Phase 1 dose-escalation data are encouraging, as they demonstrate a favorable safety profile at lower dose levels and show signals of clinical activity that support further evaluation of the role of inhibiting mutant IDH in low-grade glioma."

"With no curative or approved targeted therapies for low-grade glioma and a poor long-term prognosis, we are committed to exploring the novel mechanism of action of our IDH inhibitors in this indication," said Chris Bowden, M.D., chief medical officer at Agios. "Data from our ivosidenib and AG-881 Phase 1 trials and the ongoing perioperative study, combined with feedback from regulators and the neurology community, will inform our pivotal development plan."

The ongoing Phase 1 dose-escalation trial is assessing the safety and tolerability of AG-881 in IDH1/2 mutant advanced solid tumors, including glioma. As of the March 29, 2018 data cut-off, 93 patients (52 with glioma and 41 with other solid tumors) have been treated with single agent AG-881. Enrollment is complete and 17 glioma patients and 1 non-glioma solid tumor patient remain on treatment. Study design, status and baseline characteristics for the 52 glioma patients are reported below.

Forty-eight percent of patients (n=25) had World Health Organization (WHO) classified Grade 2 tumors, 42% (n=22) had Grade 3 tumors, 8% (n=4) had Grade 4 tumors and 2% (n=1) was unknown.
LOGO

Ninety-two percent of patients (n=48) had an IDH1 mutation and 6% (n=3) had an IDH2 mutation. One patient did not have a biopsy but was confirmed as IDH mutant positive due to 2-HG elevation by magnetic resonance spectroscopy (MRS).

The median age of these patients is 42.5 years (ranging from 16-73 years).

Patients received a median of two prior systemic therapies (ranging from one to six).

Seventy-three percent of patients (n=38) had previously received temozolomide and 58% percent (n=30) had previously received radiotherapy.

Patients received daily doses of AG-881 ranging from 10 mg to 300 mg.

The median treatment duration was seven months (ranging from 0-27 months) for all glioma patients, 12 months (ranging from 1-27 months) for non-enhancing glioma and 3 months (ranging from 0- 27 months) for patients with enhancing disease.
Safety Data

The safety analysis conducted for all 93 treated patients as of the data cut-off demonstrated that AG-881 has a favorable safety profile at dose levels below 100 mg.

The majority of adverse events (AEs) reported by investigators were mild to moderate, with the most common (>33%) being fatigue, nausea, increases in alanine aminotransferase (ALT) and increases in aspartate aminotransferase (AST).

Grade 3 or higher AEs were observed in 33% of all patients (n=31).

Dose limiting toxicities (DLTs) of Grade 2 or higher elevated transaminases occurred in five glioma patients at the higher dose levels (³100 mg) and resolved to Grade £1 with dose modification or discontinuation. There were no treatment-related on-treatment deaths.

A maximum tolerated dose (MTD) was not reached by Bayesian model; the doses chosen for further clinical development were based on safety, pharmacokinetics and pharmacodynamics data.
Efficacy Data

Efficacy data from the 52 glioma patients (23 with non-enhancing and 29 with enhancing disease) as of the data cut-off showed:

One patient with non-enhancing disease and a 1p19q co-deletion had a sustained minor response according to the investigator by Response Assessment in Neuro-Oncology for low grade glioma (RANO-LGG) and remains on treatment.

Seventy-five percent of patients (n=39) had a best response of stable disease, including 20 patients with non-enhancing disease.

Thirty-five percent of patients (n=18, including 13 patients with non-enhancing disease) remained on treatment for ³1 year.
Efficacy data from the 41 patients with non-glioma solid tumors as of the data cut-off showed:

One patient with cholangiocarcinoma had a partial response, 37% of patients (n=15) had stable disease and 44% (n=18) had progressive disease.

The median treatment duration was 2 months (ranging from 0-18 months).
Ongoing Perioperative Study in Glioma

A perioperative ‘window’ trial with ivosidenib and AG-881 (10 mg and 50 mg) in up to 45 IDH1m non-enhancing low-grade glioma patients is ongoing. The goal of the trial is to confirm CNS penetrance and tumor 2-HG suppression of ivosidenib and AG-881 as part of the strategy to finalize pivotal development plans by year-end 2018.

About Glioma

Glioma presents in varying degrees of tumor aggressiveness, ranging from slower growing (low grade glioma) to rapidly progressing (high grade glioma-Glioblastoma Multiforme). Common symptoms include seizures, memory disturbance, sensory impairment and neurologic deficits. The long-term prognosis is poor with a five-year survival rate of 33 percent. Approximately 11,000 low-grade glioma patients are diagnosed annually in the U.S. and EU and approximately 80 percent have an IDH1 mutation.

On June 1, 2018 Exact Sciences Corp. (Nasdaq: EXAS) reported that company management will be presenting at the following investor conferences during June and invited investors to participate by webcast (Press release, Exact Sciences, JUN 1, 2018, View Source [SID1234527026]).

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Jefferies 2018 Global Healthcare Conference, New York Presentation on Tuesday, June 5, 2018, at 9 a.m. EDT

William Blair 38th Annual Growth Stock Conference, Chicago Presentation on Tuesday, June 12, 2018, at 4:10 p.m. CDT

Goldman Sachs 39th Annual Global Healthcare Conference, Rancho Palos Verdes, Calif. Fireside chat on Wednesday, June 13, 2018, at 8 a.m. PDT

On June 1, 2018 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported it will present data evaluating certain biomarkers as potential predictors of survival in patients with previously untreated metastatic pancreatic ductal adenocarcinoma at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, which takes place June 1-5 in Chicago (Press release, Halozyme, JUN 1, 2018, View Source [SID1234527045]). In addition, Halozyme partner Janssen will present five posters of clinical studies involving subcutaneous daratumumab using Halozyme ENHANZE technology.

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"Our goal at Halozyme is to develop new therapies for cancer patients, while minimizing the burden and impact of treatment on their lives," said Helen Torley, president and chief executive officer. "The exploratory plasma biomarker data may support efforts to identify patients who benefit from our investigational drug, PEGPH20, through a simple blood draw rather than a needle biopsy.

"Our ENHANZE technology allows certain drugs to be given subcutaneously in a shorter, simpler injection than when the drug is delivered intravenously, thereby reducing the treatment burden for patients. We are delighted that Janssen will be presenting five posters on their exploration of a subcutaneous version of daratumumab that can be given in 5 minutes or less using our ENHANZE technology."

The Halozyme research of peptide biomarkers measured maturation and degradation of type III collagen, a key component of the extracellular matrix, using baseline plasma samples from patients in Halozyme’s HALO-202 Phase 2 clinical study of PEGPH20 (pegvorhyaluronidase alfa) in combination with ABRAXANE (nab-paclitaxel) and gemcitabine (PAG arm) as compared to ABRAXANE and gemcitabine only (AG arm).

Highlights from the Halozyme biomarker analysis include:

In the Discovery cohort (Stage 1), median progression-free survival (PFS) was 8.0 months in the PAG arm versus 5.3 months in the AG arm for patients whose biomarker scores were equal or above a specific cut-off value. The proportion of this patient population to all subjects tested in Stage 1 is 50 percent.
In the Validation cohort (Stage 2), patients whose biomarker scores were equal to or above the cut-off value derived from the Discovery cohort experienced a median PFS of 8.8 months in the PAG arm versus 3.4 in the AG arm, as well as overall survival of 13.8 months in the PAG arm versus 8.5 months in the AG arm. The proportion of this patient population to all subjects tested in Stage 2 is 47 percent.
PEGPH20 is a proprietary enzyme that targets and degrades hyaluronan (HA), a glycosaminoglycan or naturally occurring sugar in the body. HA accumulates in higher concentrations around many solid tumors, potentially constricting blood vessels, impeding the immune response and the access of other therapies.

Janssen’s daratumumab
Janssen (Janssen Research & Development, LLC) presentations will highlight development of subcutaneous daratumumab using Halozyme ENHANZE technology. Results from the Phase 1b PAVO study of patients with relapsed or refractory multiple myeloma showed daratumumab co-formulated with ENHANZE enabled dosing in 3 to 5 minutes and was well tolerated with low infusion-related reactions.

Additional Updates and Presentations at ASCO (Free ASCO Whitepaper)
In an update on the HALO-101 Lung/Gastric Phase 1b study, Halozyme said that in light of the evolution in the standard of care in first-line non-small-cell lung cancer, it is closing enrollment in the lung cohort in the study. Investigators are being given the option to continue treatment of ongoing patients, and data will be submitted to medical forum later this year.

Halozyme’s ASCO (Free ASCO Whitepaper) abstracts include:

Extracellular matrix (ECM) circulating peptide biomarkers as potential predictors of survival in patients (pts) with untreated pancreatic ductal adenocarcinoma (mPDA) receiving pegvorhyaluronidase alfa (PEPGH20), nab-paclitaxel (A), and gemcitabine (G). Abstract 12030. Monday, June 4, 1:15 to 4:45 p.m. CT.

Tumor hyaluronan (HA) as a novel biomarker to taxane therapy in non-small cell lung cancer (NSCLC). Publication only.

A Pilot study of Gemcitabine, Nab-paclitaxel, PEGPH20 and Rivaroxaban for Advanced Pancreatic Adenocarcinoma: Interim Safety and Efficacy Analysis. Publication only.

Pegvorhyaluronidase alfa (PEPGH20) enhances FOLFIRINOX efficacy in a preclinical model of human pancreatic ductal adenocarcinoma. Publication only.

Affinity histochemical evaluation of hyaluronan accumulation in solid malignancies of the digestive system. Publication only.

About PEGPH20
PEGPH20 (pegvorhyaluronidase alfa) is an investigational PEGylated form of Halozyme’s proprietary recombinant human hyaluronidase under clinical development for the potential systemic treatment of tumors that accumulate hyaluronan. PEGPH20 is an enzyme that temporarily degrades HA, a dense component of the tumor microenvironment that can accumulate in higher concentrations around certain cancer cells, potentially constricting blood vessels and impeding the access of other therapies. In January, Halozyme announced the positive topline results as of December 2016 of its randomized phase 2 HALO-202 study of PEGPH20 in combination with ABRAXANE (nab-paclitaxel) and gemcitabine chemotherapy in metastatic pancreatic cancer. In the study, PEGPH20 met key endpoints, including in the targeted HA-High patient population.

FDA granted orphan drug designation to PEGPH20 for treatment of pancreas cancer and fast track for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic pancreas cancer. Additionally, the European Commission, acting on the recommendation from the Committee for Orphan Medicinal Products of the European Medicines Agency, designated investigational drug PEGPH20 an orphan medicinal product for the treatment of pancreas cancer.

On June 1, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported that four posters will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2018 Annual Meeting taking place June 1-5, 2018 in Chicago (Press release, Karyopharm, JUN 1, 2018, View Source [SID1234527027]). Among the poster presentations will be clinical results from the Phase 2 portion of the Company’s Phase 2/3 SEAL study evaluating selinexor, its lead, oral SINE compound, in patients with advanced unresectable dedifferentiated liposarcoma. The remaining posters will highlight data from ongoing investigator-sponsored trials evaluating selinexor in combination with approved anti-cancer agents in hematologic and solid tumor malignancies.

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"In the Phase 2 portion of the SEAL study, patients treated with oral selinexor achieved progression-free survival (PFS) of 5.5 months, compared to 2.7 months for placebo-treated patients, an increase of 2.8 months," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "Dedifferentiated liposarcoma is particularly difficult to treat because it is resistant to both standard chemotherapy and radiation and there is a significant unmet need for therapies with a novel mechanism that can help these patients with few effective treatment options. The Phase 3 portion of the SEAL study is currently ongoing and we are anticipating top-line data by the end of 2019. Other selinexor data presented at ASCO (Free ASCO Whitepaper) from ongoing investigator-sponsored research continue to highlight early signs of clinical activity and good tolerability when selinexor is combined with approved agents in soft tissue sarcoma (STS) and acute myeloid leukemia (AML), and additional compelling evidence for selinexor’s potential combinability with checkpoint inhibitors, in this case in AML."

Phase 2 Portion of the Phase 2/3 SEAL Study Evaluating Selinexor in Patients with Liposarcoma

In the poster presentation titled, "Phase 2 results of selinexor in advanced dedifferentiated (DDLS) liposarcoma (SEAL) study: A phase 2/3, randomized, double blind, placebo controlled cross-over study," (Abstract #11512) Mrinal Gounder, MD, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College and lead investigator of the SEAL study, presented detailed clinical data from the successful Phase 2 portion of the randomized, double-blind, placebo-controlled Phase 2/3 SEAL study evaluating oral selinexor (60mg twice weekly) in 56 patients with previously treated, advanced unresectable dedifferentiated liposarcoma (median 2 prior regimens (range 1-9)). Patients on placebo with confirmed progressive disease are permitted to cross over to the selinexor treatment arm.

For the primary endpoint of PFS, oral selinexor showed superiority over placebo, achieving a median PFS of 5.5 months, compared to 2.7 months for placebo with a hazard ratio (HR) of 0.67, representing a 33% reduction in the risk of progression or death. PFS was assessed by Independent Central Radiological Review based on RECIST v1.1. Additional efficacy assessments included PFS by World Health Organization (WHO) response criteria. PFS per WHO criteria achieved a HR of 1.02. Oral selinexor demonstrated an expected and manageable safety profile, primarily with nausea, fatigue, anorexia and weight loss, with low levels of Grade 3/4 cytopenias, and no new or unexpected safety signals identified. The majority of treatment-related adverse events (AEs) were low grade and reversible with dose modifications and/or standard supportive care. These data from the Phase 2 portion of the SEAL study, which is now complete, demonstrate that treatment with selinexor improves PFS (RECIST v1.1) and supports the currently ongoing Phase 3 portion of the study using RECIST v1.1 response criteria [only], and for which top-line data are expected by the end of 2019.

Dr. Gounder stated, "Extending PFS in patients with recurrent, unresectable DDLS is an important clinical goal and these data highlight that oral selinexor continues to demonstrate an expected and manageable safety profile, along with the ability to prolong PFS. We are pleased to share these data with the medical community at ASCO (Free ASCO Whitepaper) this year and look forward to further elucidating selinexor’s efficacy and safety in the already ongoing Phase 3 portion of the SEAL study."

Selinexor in Combination with Immunotherapy or Standard of Care Agents in Other Hematologic and Solid Tumor Malignancies

In the poster presentation titled, "Phase 1b study of selinexor, a first in class selective inhibitor of nuclear export (SINE) compound, in combination with doxorubicin in patients (pts) with locally advanced or metastatic soft tissue sarcoma (STS)," (Abstract #11562) Eoghan Ruadh Malone, MB BCh, BAO, BA, MSc, MRCPI, Princess Margaret Cancer Centre, presented results from an investigator-sponsored Phase 1b clinical study evaluating selinexor in combination with doxorubicin in 17 patients with locally advanced or metastatic STS. Disease subtypes included leiomyosarcoma (n=6), undifferentiated pleomorphic sarcoma (n=3), liposarcoma (n=2), malignant peripheral nerve sheath tumor (n=3) and other sarcomas (n=3). Preliminary data from this study show that the combination of selinexor plus doxorubicin has a manageable tolerability profile, along with early signals of anti-tumor activity, including partial responses (n=3). Median time on treatment is 20 weeks. Enrollment in the study is ongoing.

In the poster presentation titled, "Phase 1 study of selinexor plus mitoxantrone, etoposide, and cytarabine in acute myeloid leukemia," (Abstract #7048) Bhavana Bhatnagar, DO, Ohio State University Comprehensive Cancer Center, presented results from an investigator-sponsored Phase 1 clinical study evaluating selinexor in combination with mitoxantrone, etoposide and cytarabine (MEC) in patients with relapsed or refractory AML. Of the 23 evaluable patients, ten responded for an overall response rate of 44%, including six patients (26%) achieving complete remission (CR), two patients (9%) achieving CR with incomplete count recovery (CRi), and two patients (9%) achieving a morphologic leukemia-free state (MLFS). The tolerability of this combination regimen was similar to cytotoxic chemotherapy alone. The most common Grade ≥3 adverse events were febrile neutropenia (48%), catheter related infection (26%), diarrhea (26%), hyponatremia (22%), sepsis (22%), fatigue (13%), hyperglycemia (13%), and hypotension (13%). The RP2D of selinexor in in this combination regimen was established to be 60mg twice weekly. Six responders proceeded to allogeneic stem cell transplantation without evidence of AML at the time of transplant.

In the poster presentation titled, "Profiling the immune checkpoint pathway in acute myeloid leukemia," (Abstract #7015) Paola Dama, PhD, University of Chicago, presented results from an investigator-sponsored study assessing the expression of immune checkpoint biomarkers in AML patients treated with the combination of selinexor, high-dose cytarabine (HiDAC) and mitoxantrone. Data from this study demonstrated high level expression of Gal9 in CD34- cells at diagnosis in patients who failed induction chemotherapy, compared to those in complete remission. There was no difference in PD-L1 expression between the two patient groups. Increased expression of Tim 3 on CD4 and CD8 T cells and high PD-1 in peripheral CD4+ T cell were observed at disease remission suggesting an exhausted immune status at the time of disease remission on the selinexor + HiDAC + mitoxantrone combination, which the researchers believe could be targeted with the addition of checkpoint inhibitors.

Details for the ASCO (Free ASCO Whitepaper) 2018 selinexor presentations are as follows:

Company-sponsored Trials

Title:Phase 2 results of selinexor in advanced de-differentiated (DDLS) liposarcoma (SEAL) study: A phase 2/3, randomized, double blind, placebo controlled cross-over study
Lead author:Mrinal Gounder, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College
Poster Board #: 257
Abstract #: 11512
Poster Discussion Session: Sarcoma
Poster Discussion Presenter:Mark Andrew Dickson
Date and Time:Saturday, June 2, 2018; 8:00 AM – 11:30 AM CT; Discussion from 3:18 – 3:30PM CT
Location: Hall A

Investigator-sponsored Trials

Title:Phase 1 study of selinexor plus mitoxantrone, etoposide, and cytarabine in acute myeloid leukemia
Lead author:Bhavana Bhatnagar, Ohio State University Comprehensive Cancer Center
Poster Board #: 108
Abstract: 7048
Poster Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Date and Time:Monday, June 4, 2018; 8:00 AM – 11:30 AM CT
Location: Hall A

Title:Phase 1b study of selinexor, a first in class selective inhibitor of nuclear export (SINE) compound, in combination with doxorubicin in patients (pts) with locally advanced or metastatic soft tissue sarcoma (STS)
Lead author: Eoghan Ruadh Malone, Princess Margaret Cancer Centre
Poster Board #: 307
Abstract: 11562
Poster Session: Sarcoma
Date and Time:Saturday, June 2, 2018; 8:00 AM – 11:30 AM CT
Location: Hall A

Title:Profiling the immune checkpoint pathway in acute myeloid leukemia
Lead author:Paola Dama, University of Chicago
Poster Board #: 75
Abstract: 7015
Poster Discussion Session: Hematologic Malignancies – Leukemia, Myelodysplastic Syndromes, and Allotransplant
Date and Time:Monday, June 4, 2018; 8:00 AM – 11:30 AM CT; Discussion from 11:30 AM – 12:45 PM CT
Location: Hall A

About Selinexor

Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,400 patients have been treated with selinexor. In April 2018, Karyopharm reported positive top-line data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with penta-refractory multiple myeloma. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) during the second half of 2018, with a request for accelerated approval for oral selinexor as a new treatment for patients with penta-refractory multiple myeloma. The Company also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in early 2019 with a request for conditional approval. Selinexor is also being evaluated in several other mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON) and as a potential backbone therapy in combination with approved therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), liposarcoma (SEAL), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.