On June 26, 2017 Sumitomo Dainippon Pharma Co., Ltd. (Head Office: Osaka, Japan; President: Masayo Tada) reported that the Company decided to unblind the BRIGHTER study, a phase 3 global study in patients with gastric and gastro-esophageal junction (GEJ) cancer of napabucasin (generic name, product code: BBI608), an investigational cancer stemness inhibitor, based on a recommendation by the study’s independent Data and Safety Monitoring Board (DSMB), following a pre-specified interim analysis (Press release, Dainippon Sumitomo Pharma, JUN 26, 2017, View Source [SID1234519683]).

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The study will be continued as an open label study to follow all endpoints as defined in the protocol.

The DSMB determined that the study was unlikely to reach its primary endpoint of superior overall survival for the napabucasin arm versus the control arm at the conclusion of the study. No safety concerns were identified by the DSMB.

Sumitomo Dainippon Pharma remains committed to other ongoing phase 3 studies (CanStem303C for colorectal cancer, CanStem111P for pancreatic cancer) with an aim to obtain marketing authorization of napabucasin as early as possible.

"Advanced gastric/GEJ cancer is a tumor type with high unmet need, and our hope was to develop a new therapeutic option for these patients. We are disappointed with the results of this interim analysis," said Patricia S. Andrews, Chief Executive Officer, Boston Biomedical, Inc. "We remain committed to our ongoing studies with napabucasin as well as our other first-in-class investigational compounds."

Sumitomo Dainippon Pharma is currently examining the effects that this matter will have on its consolidated business performance and will promptly make an announcement if it finds that there is a need to make further disclosures.

【About napabucasin】
Napabucasin is an investigational first-in-class anti-cancer agent created by Boston Biomedical, Inc., wholly-owned subsidiary of Sumitomo Dainippon Pharma. Napabucasin is an orally administered small molecule agent with a novel mechanism of action designed to inhibit cancer stemness pathways by targeting STAT3. Besides the gastric and GEJ cancer, napabucasin is currently being investigated in phase 3 studies for advanced colorectal and pancreatic cancer.


【About the BRIGHTER study】
The BRIGHTER study is a randomized, double blind global clinical phase 3 study to evaluate the efficacy and safety of administration of napabucasin plus weekly paclitaxel in comparison with weekly paclitaxel alone in the U.S., Japan and etc. A total of 714 patients with advanced gastric and GEJ cancer were previously treated with one prior line of platinum/fluoropyrimidine-containing regimen, randomized in a 1:1 ratio to receive napabucasin plus weekly paclitaxel or weekly paclitaxel alone. The primary endpoint is overall survival (OS) in the general study population; secondary endpoints include progression free survival (PFS), OS and PFS in a predefined biomarker-positive sub-population, objective response rate, disease control rate, and safety. The interim analysis of the BRIGHTER study was performed when the cumulative number of events reached 380.

On June 26, 2017 Bayer reported that the Ministry of Health, Labour and Welfare (MHLW) in Japan has granted marketing authorization for Stivarga (regorafenib) tablets for the second-line treatment of patients with unresectable hepatocellular carcinoma (HCC) who have progressed after treatment with cancer chemotherapy (Press release, Bayer, JUN 26, 2017, View Source [SID1234519682]). Stivarga, an oral inhibitor of multiple kinases involved in normal cellular functioning and in pathological processes such as oncogenesis, tumor angiogenesis, metastasis and tumor immunity, is the first and only treatment to demonstrate significant improvement in overall survival in second-line HCC patients who previously had no other options.

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"The number of patients suffering from liver cancer continues to increase in Japan and for years Nexavar was the first and only approved systemic treament option with proven overall survival benefit to help address this unmet need", said Robert LaCaze, Executive Vice President and Head of the Oncology Strategic Business Unit at Bayer. "The approval of Stivarga in Japan for second-line HCC is a significant step forward for patients and their treating doctors. For the first time, patients have a proven treatment plan involving Stivarga directly after Nexavar which could establish a new standard of care."

Since 1990, the annual mortality rate of liver cancer in Japan has increased by over 50%. Globally it is the second leading cause of cancer-related deaths.

The approval of Stivarga in HCC in Japan marks the third time that this therapy has been granted MHLW approval based on priority review, which is an expedited program given to medicines on the basis of their clinical usefulness and severity of the disease. The product is already approved in more than 90 countries worldwide for metastatic colorectal cancer (CRC), including Japan, and in more than 80 countries globally for the treatment of metastatic gastrointestinal stromal tumors (GIST), including Japan. Additional regulatory filings for Stivarga in HCC are under review in countries around the world and Stivarga in HCC has been approved by the FDA in the U.S.

The HCC approval is based on data from the international, multicenter, placebo-controlled Phase III RESORCE trial, which investigated patients with unresectable HCC whose disease had progressed during treatment with sorafenib. In the trial, regorafenib plus best supportive care (BSC) was shown to provide a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo plus BSC (HR 0.63; 95% CI 0.5-0.79; p<0.0001), which translates to a 37% reduction in the risk of death over the trial period.

The most common treatment-emergent adverse events (regorafenib vs. placebo group) were palmar-plantar erythrodysesthesia syndrome (53% vs. 8%), diarrhea (41% vs. 15%), fatigue (40% vs. 32%) and hypertension (31% vs. 6%).

About Hepatocellular Carcinoma
Hepatocellular carcinoma, or HCC, is the most common form of liver cancer and represents approximately 70-85 percent of liver cancer worldwide. Liver cancer is the sixth most common cancer in the world and the second leading cause of cancer-related deaths globally. More than 780,000 cases of liver cancer are diagnosed worldwide each year (52,000 in the European Union, 501,000 in the Western Pacific region and 30,000 in the United States) and the incidence rate is increasing. In 2012, approximately 746,000 people died of liver cancer including approximately 48,000 in the European Union, 477,000 in the Western Pacific region and 24,000 in the United States.

About Regorafenib (Stivarga)
Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumor immunity (CSF1R).

Regorafenib is approved under the brand name Stivarga in more than 90 countries worldwide, including the U.S., countries of the EU, China and Japan for the treatment of metastatic colorectal cancer (mCRC). The product is also approved in over 80 countries, including the U.S., countries of the EU, China and Japan, for the treatment of metastatic gastrointestinal stromal tumors (GIST). It was recently approved in the U.S. for second-line treatment of HCC and is now approved in Japan in this indication as well. Additional regulatory filings for Stivarga in HCC are under review in countries around the world, including the EU and China.

In the EU, Stivarga is indicated for the treatment of adult patients with mCRC who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy, as well as for the treatment of adult patients with unresectable or metastatic GIST who progressed on or are intolerant to prior treatment with imatinib and sunitinib.

Regorafenib is a compound developed by Bayer. In 2011, Bayer entered into an agreement with Onyx, now an Amgen subsidiary, under which Onyx receives a royalty on all global net sales of regorafenib in oncology.

On June 24, 2017 Verastem, Inc. (NASDAQ: VSTM), focused on discovering and developing drugs to improve the survival and quality of life of cancer patients, reported the presentation of long-term follow-up data from the DYNAMO study, which met its primary endpoint of Overall Response Rate (ORR; p=0.0001) at the final analysis, at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), being held June 22-25, 2017 in Madrid, Spain (Press release, Verastem, JUN 24, 2017, View Source [SID1234519675]). DYNAMO is a Phase 2 clinical study evaluating duvelisib, the Company’s investigational oral monotherapy, dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, in patients with indolent non-Hodgkin lymphoma (iNHL) whose disease is refractory to both rituximab and chemotherapy or radioimmunotherapy. The presentations focus on the subsets of patients with follicular lymphoma (FL) or small lymphocytic lymphoma (SLL) who were enrolled in DYNAMO.

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Oral Duvelisib in Patients with Double-Refractory FL

With 18 months of follow-up, the data continues to be consistent with the primary analysis. Of the 83 patients with double-refractory FL enrolled in DYNAMO (median 3 prior anticancer regimens [range 1-10]), 36 responded, which included 1 (1%) complete response (CR) and 35 (42%) partial responses (PR), for an ORR of 43% as determined by an independent review committee. Responses generally occurred shortly after the start of treatment (median 2 months). Notably, 83% of evaluable patients with FL treated with duvelisib had a reduction in the size of their target lymph nodes. Median duration of response was 7.9 months, median progression-free survival was 8.3 months, and median overall survival was 27.8 months.

The safety profile of duvelisib monotherapy remains consistent with what has been previously reported in iNHL and other advanced hematologic malignancies. In these double-refractory FL patients, the most common Grade ≥3 hematologic adverse events were neutropenia (22%), anemia (13%) and thrombocytopenia (9%). Diarrhea was the most frequently reported nonhematologic adverse event (47%; 16% Grade ≥ 3). As expected in a heavily pretreated and refractory patient population, severe infections were observed (20%). Pneumonitis and colitis remained relatively uncommon (each 5%). Treatment discontinuations attributed to severe adverse events were infrequent, suggesting that these events were generally manageable.

Oral Duvelisib in Patients with Double-Refractory SLL
Of the 28 patients with double-refractory SLL enrolled in DYNAMO (median 3 prior anticancer regimens [range 1-18]), 19 responded, all of which were PRs, for an ORR of 68% as determined by an independent review committee. Responses generally occurred shortly after the start of treatment (median 2 months). Importantly, 100% of evaluable patients with double-refractory SLL treated with duvelisib had a reduction in the size of their target lymph nodes. With a median time on duvelisib of 12 months, median duration of response was 10.1 months, median progression-free survival was 11.7 months, and median overall survival was 28.9 months.

In these double-refractory SLL patients, the most common Grade ≥3 hematologic adverse events were neutropenia (32%), thrombocytopenia (21%) and anemia (21%). The most frequently reported Grade ≥3 nonhematologic adverse events were pneumonia (14%), increases in alanine aminotransferase (7%) and aspartate aminotransferase (11%), and diarrhea (11%). As expected in a heavily pretreated and refractory patient population, severe infections were observed (36%). Colitis occurred in 3 (11%) SLL patients. No double-refractory SLL patients experienced pneumonitis. Treatment discontinuations attributed to the most common adverse events were infrequent, suggesting that these events were generally manageable.

"We believe that oral duvelisib has the potential to be an important new treatment option for lymphoma patients," commented Pier Luigi Zinzani, MD, PhD, of the University of Bologna Institute of Hematology and an Investigator participating in the study. "What I find particularly encouraging are the responses we saw in patients with double-refractory disease, a population with few treatment options left. The data we are presenting at EHA (Free EHA Whitepaper) continue to demonstrate that duvelisib monotherapy can achieve meaningful and durable responses."

Hagop Youssoufian, MSc, MD, Head of Hematology and Oncology Development at Verastem, stated, "The data from DYNAMO remain positive, and reporting the results from long-term follow-up is important for the medical community and for the overall development of duvelisib. Oral duvelisib monotherapy has demonstrated clinical activity across a number of hematologic cancers, including chronic lymphocytic leukemia, iNHL, and T-cell lymphoma. Based on the results we have seen thus far, we remain fully committed to exploring duvelisib’s potential across a wide range of lymphoid malignancies."

Details for the presentations at EHA (Free EHA Whitepaper) 2017 are:
Oral Presentation
Title: DYNAMO: A Phase 2 Study Demonstrating the Clinical Activity of Duvelisib in Patients with Double-Refractory Follicular Lymphoma
Abstract code: S777
Topic: Indolent Non-Hodgkin lymphoma – Clinical
Session title: Follicular lymphoma – Clinical
Location: Hall C
Date and time: Sunday, June 25, 2017, 8:45 – 9:00 CET
A copy of the oral presentation slides will be available here following the conclusion of the oral presentation.
E-Poster Presentation

Title: DYNAMO: The Clinical Activity of Duvelisib in Patients with Double-Refractory Small Lymphocytic Lymphoma in a Phase 2 Study
Abstract code: E1130
Topic: Indolent Non-Hodgkin lymphoma – Clinical
Location: e-poster screens
Date and time: Friday, June 23, 2017 from 9:30 CET to Saturday, June 24, 2017 at 19:00 CET
A copy of the e-poster presentation will be available here following the conclusion of the meeting.

More About the Phase 2 DYNAMO Study
DYNAMO is a Phase 2, single-arm study, which evaluated the efficacy and safety of duvelisib 25 mg twice daily as monotherapy in 129 iNHL patients, including follicular lymphoma (n=83), small lymphocytic lymphoma (n=28), and marginal zone lymphoma (n=18) whose disease has progressed and are refractory to rituximab and to either chemotherapy or radioimmunotherapy. The primary endpoint of the study was ORR as assessed by an independent review committee. DYNAMO met its primary ORR endpoint (p=0.0001) at the final analysis.

About the Tumor Microenvironment
The tumor microenvironment encompasses multiple tumor and non-tumor cell populations and an extracellular matrix that support cancer cell survival. This includes immunosuppressive regulatory T-cells, myeloid-derived suppressor cells, tumor-associated macrophages, cancer-associated fibroblasts, and extracellular matrix proteins that can hamper the entry and therapeutic benefit of cytotoxic T-cells and anti-cancer drugs. In addition to targeting the proliferative and survival signaling of cancer cells, Verastem’s product candidates, including duvelisib and defactinib, also target the tumor microenvironment to potentially improve response to therapy.

About Duvelisib
Duvelisib is an investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells and T-cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib is currently being evaluated in late- and mid-stage clinical trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed or refractory CLL,4 and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory iNHL that achieved its primary endpoint of ORR.5 Duvelisib is also being evaluated for the treatment of hematologic malignancies through investigator-sponsored studies, including T-cell lymphoma.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

On June 24, 2017 Bristol-Myers Squibb Company (NYSE:BMY) reported four-year follow-up data from the Phase 3 ELOQUENT-2 study in which Empliciti (elotuzumab) plus lenalidomide/dexamethasone (ELd) continued to demonstrate efficacy in patients with relapsed/refractory multiple myeloma (RRMM), compared to patients treated with lenalidomide/dexamethasone (Ld) alone (Press release, Bristol-Myers Squibb, JUN 24, 2017, View Source [SID1234519663]). The data also showed a safety profile consistent with prior findings. The results were presented in an oral session today during the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Madrid, Spain and offer the longest follow-up efficacy and safety data of an Immuno-Oncology agent.

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ELd therapy maintained a reduction in the risk of disease progression or death of 29% (HR 0.71; 95% CI: 0.59 to 0.86). At four-years, ELd therapy continued to demonstrate a clinically meaningful and sustained relative improvement of 50% in progression-free survival (PFS) rate, 21% (95% CI: 16.6, 22.3), compared to Ld therapy, 14% (95% CI: 12.1,17.3). PFS benefits seen in patients receiving ELd therapy were consistent across certain patient subsets and sustained through two-year, three-year and four-year follow-up. Patients with high risk* (n=60 ELd, n=66 Ld) showed relative risk reduction of 36% (HR=0.64; 95% CI :0.43 to 0.97) and more than doubling of median PFS (15.2 ELd vs 7.4 Ld) with ELd in comparison to Ld.

Patients receiving ELd therapy demonstrated an overall response rate (ORR) of 79% (253/321 patients, 95% CI: 73.9 to 83.2), compared to 66% (214/325 patients, 95% CI: 60.4 to 71.0) among patients receiving Ld therapy alone. While OS was not pre-specified for the four-year follow-up, Empliciti in combination with Ld data also demonstrated a median overall survival (OS) benefit of 48 months (95% CI: 40.3 to 54.4) in favor of ELd versus a median OS of 40 months for Ld (95% CI: 33.3 to 45.4), a difference of 22% (HR 0.78; 95% CI: 0.63 to 0.96). Early separation of OS Kaplan Meier survival curves was maintained over time in favor of ELd versus Ld.

"These extended four-year follow-up data demonstrated that adding Empliciti to Ld yielded clinically relevant improvements and reductions in the risk of disease progression or death for patients with relapsed/refractory multiple myeloma, compared to Ld alone," Meletios A. Dimopoulos, M.D., ELOQUENT-2 investigator and professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine. "This data at four-year follow-up is particularly notable as it suggests the ability of this Immuno-Oncology agent to build a sustainable immune response in some patients with advanced multiple myeloma."

The rates of adverse events (AE) were similar between patients receiving ELd or Ld therapy and consistent with those reported at two- and three-year follow-up. The most common AEs (all grades) in ELd and Ld, respectively, were diarrhea (49%, 38%), fatigue (48%, 41%), anemia (43%, 38%), pyrexia (40%, 25%), constipation (36%, 28%), neutropenia (35%, 43%), cough (34%, 19%), back pain (31%, 29%), and muscle spasm (31%, 26%).

"The long-term efficacy data for Empliciti in patients with advanced multiple myeloma shows the combination of this Immuno-Oncology agent with standard lenalidomide/dexamethasone treatment can improve patient outcomes," said Jonathan Leith, Ph.D., hematology development lead, Bristol-Myers Squibb. "These findings illustrate Bristol-Myers Squibb’s commitment to exploring how Immuno-Oncology agents might best help appropriate patients."

About ELOQUENT-2

The ELOQUENT-2 trial randomized 646 patients with RRMM who had one to three prior therapies to receive either ELd (321 patients) or Ld (325 patients) in 28-day cycles until their disease progressed, the occurrence of unacceptable toxicity or they withdrew consent. In the ELd arm, patients were administered 10 mg/kg by IV of elotuzumab for weeks one and two of the 28-day cycle and then every other week, along with 25 mg of lenalidomide by mouth for days 1-21 of the cycle and the weekly equivalent of 40 mg of dexamethasone by mouth. In the Ld arm, patients were given 25 mg of lenalidomide by mouth for days 1-21 of the cycle and the weekly equivalent of 40 mg of dexamethasone by mouth.

The occurrence of treatment-related Grade 3–4 AEs in 5% or more of patients were generally comparable between the ELd and Ld groups: vascular diseases (10% vs. 8%; mostly venous-related), second primary malignancies (9% vs. 6%), and cardiac disorders (5% vs. 8%). ELd therapy did have a slightly higher incidence of infection compared to Ld (33% vs. 26%). ELd treatment also had higher overall rates than Ld of any grade infection (84% vs. 75%) and second primary malignancies (17% vs. 11%). However, exposure to ELd was longer than to Ld, with a median treatment cycle of 19 months (9 to 42) compared to 14 months (6 to 25), respectively. While disease progression and infection were major causes of deaths in both groups, fewer were reported with ELd (165) than with Ld (186) treatment.

On November 30, 2015, the U.S. Food and Drug Administration (FDA) approved Empliciti in combination with lenalidomide and dexamethasone in patients with multiple myeloma who have received one to three prior therapies. On May 11, 2016, the European Commission approved Empliciti in combination with lenalidomide and dexamethasone in patients with multiple myeloma who have received at least one prior therapy.

Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines for hard-to-treat cancers that could potentially improve outcomes for these patients.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational compounds and approved agents. Our differentiated clinical development program is studying broad patient populations across more than 50 types of cancers with 14 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O/radiation therapies across multiple tumors and potentially deliver the next wave of therapies with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and how patients’ individual tumor biology can be used as a guide for treatment decisions throughout their journey.

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

About Empliciti

Empliciti is an immunostimulatory antibody that specifically targets Signaling Lymphocyte Activation Molecule Family member 7 (SLAMF7), a cell-surface glycoprotein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 also is expressed on Natural Killer cells, plasma cells and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage.

Empliciti has a dual mechanism-of-action. It directly activates the immune system through Natural Killer cells via the SLAMF7 pathway. Empliciti also targets SLAMF7 on myeloma cells, tagging these malignant cells for Natural Killer cell-mediated destruction via antibody-dependent cellular toxicity.

Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.

U.S. FDA-APPROVED INDICATION FOR EMPLICITI

EMPLICITI (elotuzumab) is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.

IMPORTANT SAFETY INFORMATION

Infusion Reactions

EMPLICITI can cause infusion reactions. Common symptoms include fever, chills, and hypertension. Bradycardia and hypotension also developed during infusions. In the trial, 5% of patients required interruption of the administration of EMPLICITI for a median of 25 minutes due to infusion reactions, and 1% of patients discontinued due to infusion reactions. Of the patients who experienced an infusion reaction, 70% (23/33) had them during the first dose. If a Grade 2 or higher infusion reaction occurs, interrupt the EMPLICITI infusion and institute appropriate medical and supportive measures. If the infusion reaction recurs, stop the EMPLICITI infusion and do not restart it on that day. Severe infusion reactions may require permanent discontinuation of EMPLICITI therapy and emergency treatment.
Premedicate with dexamethasone, H1 Blocker, H2 Blocker, and acetaminophen prior to infusing with EMPLICITI.
Infections

In a clinical trial of patients with multiple myeloma (N=635), infections were reported in 81.4% of patients in the EMPLICITI with lenalidomide/dexamethasone arm (ERd) and 74.4% in the lenalidomide/dexamethasone arm (Rd). Grade 3-4 infections were 28% (ERd) and 24.3% (Rd). Opportunistic infections were reported in 22% (ERd) and 12.9% (Rd). Fungal infections were 9.7% (ERd) and 5.4% (Rd). Herpes zoster was 13.5% (ERd) and 6.9% (Rd). Discontinuations due to infections were 3.5% (ERd) and 4.1% (Rd). Fatal infections were 2.5% (ERd) and 2.2% (Rd). Monitor patients for development of infections and treat promptly.
Second Primary Malignancies

In a clinical trial of patients with multiple myeloma (N=635), invasive second primary malignancies (SPM) were 9.1% (ERd) and 5.7% (Rd). The rate of hematologic malignancies were the same between ERd and Rd treatment arms (1.6%). Solid tumors were reported in 3.5% (ERd) and 2.2% (Rd). Skin cancer was reported in 4.4% (ERd) and 2.8% (Rd). Monitor patients for the development of SPMs.
Hepatotoxicity

Elevations in liver enzymes (AST/ALT greater than 3 times the upper limit, total bilirubin greater than 2 times the upper limit, and alkaline phosphatase less than 2 times the upper limit) consistent with hepatotoxicity were 2.5% (ERd) and 0.6% (Rd). Two patients experiencing hepatotoxicity discontinued treatment; however, 6 out of 8 patients had resolution and continued treatment. Monitor liver enzymes periodically. Stop EMPLICITI upon Grade 3 or higher elevation of liver enzymes. After return to baseline values, continuation of treatment may be considered.
Interference with Determination of Complete Response

EMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.
Pregnancy/Females and Males of Reproductive Potential

There are no studies with EMPLICITI with pregnant women to inform any drug associated risks.
There is a risk of fetal harm, including severe life-threatening human birth defects associated with lenalidomide and it is contraindicated for use in pregnancy. Refer to the lenalidomide full prescribing information for requirements regarding contraception and the prohibitions against blood and/or sperm donation due to presence and transmission in blood and/or semen and for additional information.
Adverse Reactions

Infusion reactions were reported in approximately 10% of patients treated with EMPLICITI with lenalidomide and dexamethasone. All reports of infusion reaction were Grade 3 or lower. Grade 3 infusion reactions occurred in 1% of patients.
Serious adverse reactions were 65.4% (ERd) and 56.5% (Rd). The most frequent serious adverse reactions in the ERd arm compared to the Rd arm were: pneumonia (15.4%, 11%), pyrexia (6.9%, 4.7%), respiratory tract infection (3.1%, 1.3%), anemia (2.8%, 1.9%), pulmonary embolism (3.1%, 2.5%), and acute renal failure (2.5%, 1.9%).
The most common adverse reactions in ERd and Rd, respectively (>20%) were fatigue (61.6%, 51.7%), diarrhea (46.9%, 36.0%), pyrexia (37.4%, 24.6%), constipation (35.5%, 27.1%), cough (34.3%, 18.9%), peripheral neuropathy (26.7%, 20.8%), nasopharyngitis (24.5%, 19.2%), upper respiratory tract infection (22.6%, 17.4%), decreased appetite (20.8%, 12.6%), and pneumonia (20.1%, 14.2%).
Please see the full Prescribing Information for EMPLICITI.