On June 14, 2019 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated therapeutics targeting the underlying mechanisms of cancer, reported that new preclinical data for CG-806, its oral, first-in-class pan-FLT3/pan-BTK inhibitor, is being presented in a poster presentation today at the 24th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Amsterdam, the Netherlands (Press release, Aptose Biosciences, JUN 14, 2019, View Source [SID1234537082]).

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The poster, CG-806, preclinical in vivo efficacy and safety profile as a pan-FLT3 / pan-BTK inhibitor, highlights the in vivo anti-leukemic efficacy of CG-806 and its GLP toxicology and toxicokinetic profile. In a preclinical MV4-11 FLT3-ITD AML xenograft mouse model, CG-806 suppressed leukemia growth at all doses tested throughout the 28-day period of dosing. After dosing was halted, tumors treated with 10 mg/kg and 30 mg/kg resumed growth but responded again when CG-806 dosing was restarted. In the mice treated with 100 mg/kg, 5 of 11 (45%) were cured through day 120, and in the 300 mg/kg group, 10 of 11 (91%) of the mice were cured. Retreating the "uncured’ mice in these two dose groups for an additional 28 days beginning on day 88 led to rapid and robust antitumor response resulting in "cures" in all retreated mice through day 120. In the "re-treated" mice, no drug resistance and no toxicities were observed. GLP 28-day toxicology and TK studies mice and dogs showed no adverse CG-806-related effects on body weight, ophthalmic, respiratory or neurological examinations, clinical pathology (coagulation, clinical chemistry, or urinalysis), organ weight or macroscopic evaluations. No CG-806-related cardiovascular effects were noted in the 28-day GLP toxicology study or in a separate preclinical cardiovascular safety study.

The poster and abstract can be accessed here or at the publications and presentations section of Aptose’s website www.aptose.com.

"The wealth of preclinical data supporting CG-806 continues to grow and differentiate the molecule from other drugs on the market or in development," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "We are pleased to have reached the clinic with this compound and are hopeful that clinical testing will prove it to be an effective therapy for hematologic malignancy patients greatly in need of new treatment options."

About CG-806
CG-806 is an oral, first-in-class pan-FLT3/pan-BTK multi-cluster kinase inhibitor in Phase 1 clinical development for hematologic malignancies. This small molecule, in-licensed from CrystalGenomics Inc. in Seoul, South Korea, demonstrates potent inhibition of wild type and all mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), cures animals of acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser (C481S) mutant forms of the BTK enzyme, as well as other oncogenic pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL/SLL, FL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors. Because CG-806 targets key kinases/pathways operative in malignancies derived from the bone marrow, it is in development for B-cell cancers and AML.

On June 14, 2019 Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a physician-led biopharmaceutical company focused on immuno-inflammatory and dermatological diseases, reported that management will present a company overview at the 2019 JMP Securities Life Sciences Conference on Thursday, June 20, 2019 at 11:30 AM ET at the St. Regis Hotel in New York, New York (Press release, Aclaris Therapeutics, JUN 14, 2019, View Source [SID1234537081]).

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A live audio webcast of the presentation may be accessed through the Company’s web site, www.aclaristx.com, on the ‘Events’ section. An archived version of the presentation will be available for 30 days.

On June 14, 2019 Xynomic Pharmaceuticals Holdings, Inc. ("Xynomic", Nasdaq: XYN), a clinical stage US-China oncology drug development company, reported that Xynomic has dosed the first patient in a Phase 1/2 trial that combines abexinostat with ibrutinib in patients with relapsed/refractory mantle cell lymphoma ("r/r MCL") or relapsed/refractory diffuse large B-cell lymphoma ("r/r DLBCL") at Memorial Sloan Kettering Cancer Center (MSK) (Press release, Xynomic Pharmaceuticals, JUN 14, 2019, View Source [SID1234537078]). This trial will enroll approximately 40 patients to assess the safety and efficacy of the combination in patients with r/r MCL or r/r DLBCL. This trial will also explore the biologic predictors of response and resistance to dual B-cell receptor (BCR) and histone deacetylase (HDAC) inhibition. Janssen Biotech, Inc. is providing ibrutinib as part of the study, with Xynomic providing abexinostat and funding support for the trial being conducted at MSK.

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Mantle cell lymphoma (MCL) has an annual incidence of approximately 6,500 in G7 countries, according to DR/Decision Resources, LLC. Ibrutinib has been approved by the United States Food and Drug Administration (FDA) for relapsed MCL and has response rates of 60-70% and median duration of response of 18 months. Abexinostat as a mono therapy has been shown to have response rate of 15.4% (7.7% complete response and 7.7% partial response) in r/r MCL patients. Researchers at MSK are testing whether abexinostat/ibrutinib combo could potentially improve response rates and duration of responses in r/r MCL patients, subject to the assessment upon the completion of the trial.

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin’s lymphoma (NHL) subtype according to the Leukemia & Lymphoma Society (LLS). Researchers at MSK have shown preclinical data demonstrating that dual targeting of Bruton’s tyrosine kinase (BTK) in the BCR pathway with ibrutinib and inhibition of MyD88-driven NF-kB activation with a HDAC inhibitor lead to synergistic anti-lymphoma activity in MyD88 mutated, ABC-subtype DLBCL both in vitro and in vivo.

Abexinostat is a novel HDAC inhibitor in global pivotal trials against NHL and renal cell carcinoma. Ibrutinib is a first-in-class BTK inhibitor jointly developed and commercialized as IMBRUVICA by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company and has been approved for multiple hematological malignances and chronic graft-versus-host-disease (cGVHD).

On June 14, 2019 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, reported updated interim data from the ongoing Phase 2 clinical trial of its lead drug candidate, tipifarnib, in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) (Press release, Kura Oncology, JUN 14, 2019, View Source [SID1234537077]).

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The results, which will be presented during an oral session at 16:45 CET / 10:45 am ET tomorrow at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in Amsterdam, demonstrate ongoing anti-tumor activity and a manageable safety profile in advanced patients with angioimmunoblastic T-cell lymphoma (AITL) as well as non-AITL PTCL. A copy of the presentation is available on the Company’s website at www.kuraoncology.com.

"With additional follow up and new patients enrolled in the ongoing Phase 2 study, tipifarnib continues to demonstrate encouraging clinical activity in patients with relapsed or refractory PTCL who have experienced a median of three prior lines of therapy," said Francine Foss, M.D., professor of medicine at the Yale Cancer Center, and a principal investigator in the trial. "Given the grim prognosis for late-stage PTCL patients, these data are exciting because they further validate tipifarnib as a targeted therapy and the potential for CXCL12 pathway biomarkers as effective enrichment strategies in late-stage PTCL patients with few therapeutic options."

The multi-center, single-arm, open-label Phase 2 trial was designed to determine the efficacy, safety and biomarkers of activity of tipifarnib in patients with relapsed or refractory PTCL. Initially, patients were enrolled without selection in the Phase 2 trial. Based upon molecular characterization of the initial patients, the Phase 2 trial was amended to include two expansion cohorts: 1) patients with AITL, an aggressive form of T-cell lymphoma often characterized by high levels of CXCL12 expression (the AITL expansion cohort), and 2) patients with PTCL who lack a single nucleotide variation (rs2839685 A>G) in the 3’-untranslated region of the CXCL12 gene (the CXCL12 SNP+ expansion cohort).

As of the May 24, 2019 data cutoff, a total of 50 relapsed/refractory PTCL patients with a median number of three prior regimens have been enrolled in all stages of the Phase 2 trial. Key preliminary findings include:

The primary efficacy endpoint was achieved in each of the AITL and CXCL12+ expansion cohorts. Sixteen patients were treated in the AITL cohort and 15 in the CXCL12 SNP+ cohort. Among the 11 evaluable patients in the AITL extension cohort, three achieved a complete response (CR) and two achieved a partial response (PR), for an objective response rate (ORR) of 45% (31% ORR on a modified intent-to-treat basis, mITT). Among the 12 evaluable patients in the CXCL12+ expansion cohort, three achieved a CR and two achieved a PR, for an ORR of 42% (33% ORR by mITT). Two of the five responders in the CXCL12+ expansion cohort were AITL patients.

When all AITL patients (N=23) and all PTCL not otherwise specified (PTCL-NOS) with available rs2839695 data and absence of this 3’UTR variant (N=17) enrolled in all portions were taken into account, ORR were 53%/39% (PPS/mITT) for AITL and 20%/18% for CXCL12 SNP+ PTCL-NOS.

Thirty-four patients had available gene expression data. Patients with a high ratio of CXCL12 expression to its receptor CXCR4 (N=17) experienced an ORR of 47% and a clinical benefit rate of 82% (CR+PR+SD) with tipifarnib.

Next-generation sequencing of 16 AITL patients revealed a high rate of mutation/variation (50%) of the killer cell immunoglobulin-like receptors, including KIR3DL2. KIR3DL2 mutation at C336R was concurrent with Q386E and was associated with outcome from tipifarnib therapy. Four of the eight KIR3DL2 C336R/Q386E patients achieved a CR, two achieved a PR and two achieved stable disease (SD) for a CR rate of 50%, an ORR of 75% and a clinical benefit rate of 100%. Furthermore, high KIR3DL2 mutant variant allele frequency KIR3DL2 was predictive of complete response to tipifarnib in AITL. Tumors with KIR3DL2 mutations expressed low levels of CXCL5 and its receptor CXCR1 and CXCR2, a potential mechanism of resistance to tipifarnib.

Tipifarnib was generally well-tolerated in this Phase 2 trial, with adverse events consistent with its known safety profile. The most frequently observed treatment-related adverse events (grade ≥ 3) were hematology-related, including thrombocytopenia, neutropenia, leukopenia, anemia, febrile neutropenia and lymphopenia.
"We believe that these data validate our prior observations of tipifarnib as a CXCL12 pathway inhibitor and constitute the first clinical proof-of-concept of farnesyl transferase inhibitors in CXCL12-driven tumors. AITL and related lymphomas encompass approximately one-third of PTCL cases and represent a significant unmet medical need," said Antonio Gualberto, M.D., Ph.D., Head of Development and Chief Medical Officer of Kura Oncology. "We are also very encouraged by the discovery of KIR3DL2 mutations, the characterization of mechanisms of sensitivity and resistance to tipifarnib in lymphoma, and the development of robust molecular tools for the selection and/or stratification of PTCL patients. These findings are a testimony of the potential for success of our precision medicine approaches."

Poster Presentation Explores CXCL12 Overexpression in Tipifarnib Responders

Separately, Kura has been evaluating the potential to use CXCL12 pathway biomarkers to enrich for clinical activity in other hematologic malignancies. In addition to AITL, high CXCL12 expression was observed in tumors from other lymphoma patients, including patients with PTCL-NOS, diffuse large B-cell lymphoma (DLBCL) and mycosis fungoides, the most common form of cutaneous T-cell lymphoma (CTCL). Lymphoma patients with CXCL12 reference sequences also appeared to have a higher chance of clinical benefit from tipifarnib treatment. The identification of these CXCL12 reference sequences in responders to tipifarnib across multiple hematologic malignancies will be presented in a poster presentation at 17:30 CET / 11:30 am ET tomorrow at the EHA (Free EHA Whitepaper) Annual Congress in Amsterdam. A copy of the poster is also available on the Company’s website at www.kuraoncology.com.

"These data represent the first prospective validation of CXCL12 pathway biomarkers to enrich for clinical activity of tipifarnib in PTCL. We believe these data support the potential to register tipifarnib in both the AITL and PTCL-NOS patient populations, and we look forward to seeking regulatory feedback on next steps for this program," said Troy Wilson, Ph.D., President and CEO of Kura Oncology. "In addition, based on our growing body of clinical and preclinical data, we believe CXCL12 pathway biomarkers may have the potential to unlock the therapeutic value of farnesyl transferase inhibition across multiple hematologic and solid tumor indications, including DLBCL, acute myeloid leukemia (AML), CTCL and pancreatic cancer."

Conference Call and Webcast

Kura’s management will host a webcast and conference call at 8:00 a.m. ET today, June 14, 2019 to discuss the results from the Company’s Phase 2 trial of tipifarnib in PTCL. The live call may be accessed by dialing (877) 516-3514 for domestic callers or +1 (281) 973-6129 for international callers and using conference ID #1273055. A live webcast of the call will be available from the Investors and Media section of the Company’s website at www.kuraoncology.com, and will be archived there for 30 days.

About Peripheral T-Cell Lymphoma

PTCL is a rare and diverse group of aggressive lymphomas that develop from white blood cells called NK/T-cells that grow abnormally. The term PTCL is sometimes used to describe a heterogeneous group of T-cell lymphomas. The most common types of PTCL are PTCL-NOS and AITL. Significant advances in the genetic landscape of T-cell and NK-cell neoplasms as the result of genomic studies, as well as the introduction of more powerful diagnostic technologies have led to revisions in the classification and introduction of new entities. Many of the same genetic changes observed in AITL are also observed in cases of PTCL-NOS that manifest a T follicular helper (TFH) phenotype. This common genotype/phenotype has led to follicular T-cell lymphoma (FTCL) and AITL being unified under a common heading. Cases of nodal PTCL with TFH phenotype are now included in the same grouping as well. As a result, patients with the PTCL-NOS phenotype are increasingly being characterized as having AITL and/or related tumors.

Recently, the U.S. Food and Drug Administration (FDA) approved ADCETRIS (brentuximab vedotin) in combination with chemotherapy for previously untreated systemic ALCL or other CD30-expressing PTCL, including AITL and PTCL-NOS. This was the first FDA-approved frontline treatment for PTCL. Previously approved therapies in relapsed or refractory PTCL were based on single-arm clinical trials of 130 patients or fewer with response rates in the range of 25-27% and limited duration of clinical benefit in unselected populations.

About CXCL12

CXCL12 is a stroma-derived chemokine that promotes the progression of lymphoma as well as other hematological and solid tumors carrying the CXCR4 receptor. Results from ancillary studies show that high CXCL12 expression is a negative prognostic factor for standard-of-care PTCL therapy. Approximately 50% of the AITL patients and 35% of the non-AITL patients in Kura’s Phase 2 trial of tipifarnib in PTCL overexpressed CXCL12.

About Tipifarnib

Kura Oncology’s lead drug candidate, tipifarnib, is a potent, selective and orally bioavailable inhibitor of farnesyl transferase in-licensed from Janssen in December 2014. Previously, tipifarnib was studied in more than 5,000 cancer patients and showed compelling and durable anti-cancer activity in certain patient subsets; however, no molecular mechanism of action had been determined that could explain its clinical activity across a range of solid tumor and hematologic indications. Leveraging advances in next-generation sequencing as well as emerging information about cancer genetics and tumor biology, Kura is seeking to identify those patients most likely to benefit from tipifarnib. In November 2018, following an end of Phase 2 meeting with the FDA, Kura initiated its first registration-directed trial of tipifarnib in patients with recurrent or metastatic HRAS mutant head and neck squamous cell carcinoma (HNSCC).

In 2018, the U.S. Patent and Trademark Office issued new patents for tipifarnib as a method of treating patients certain CXCL12-expressing cancers, including PTCL, and as a method of treating patients with AITL. Both patents expand protection for tipifarnib, providing exclusivity in the United States to 2037.

On June 14, 2019 Bristol-Myers Squibb Company (NYSE: BMY) reported the presentation of updated data from ELOQUENT-3, the international randomized Phase 2 study evaluating Empliciti (elotuzumab) plus pomalidomide and dexamethasone (EPd) versus pomalidomide and dexamethasone (Pd) alone in patients with relapsed or refractory multiple myeloma (RRMM) (Press release, Bristol-Myers Squibb, JUN 14, 2019, View Source [SID1234537076]). In a non-prespecified analysis conducted to provide a descriptive assessment of overall survival (OS) after extended follow-up of at least 18.3 months, patients treated with EPd continued to experience sustained and clinically relevant OS and progression-free survival (PFS) benefits compared with patients treated with Pd.

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Treatment with EPd was associated with a 46% reduction in risk of death [Hazard Ratio (HR) 0.54; 95% Confidence Interval (CI): 0.30 to 0.96] versus treatment with Pd alone. At 18 months, rates of OS, a secondary endpoint, were 68% for patients treated with EPd compared to 49% for patients treated with Pd. Median OS was not reached with EPd [95% CI: 24.9 months, Not Estimable (NE)] at the time of analysis and was 17.4 months (95% CI: 13.8, NE) among patients receiving Pd. Eighteen-month PFS rates were 34% among patients randomized to EPd compared to 11% among patients randomized to Pd. Safety results for EPd were consistent with the primary analysis and with prior findings for Empliciti and pomalidomide regimens.

These data will be presented at the 24th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Amsterdam in a poster display (Abstract #PS1370) on Saturday, June 15 from 5:30-7 PM CEST.

"Multiple myeloma is a disease characterized by relapse, making it all the more important to have effective options available for patients after initial treatments. With 18 months of follow-up from the ELOQUENT-3 trial, we continue to see meaningful improvements across key endpoints with EPd versus Pd alone, including a positive trend in overall survival," said Meletios A. Dimopoulos, M.D., professor and chairman of the Department of Clinical Therapeutics at Kapodistrian University of Athens School of Medicine. "These data point to the potential for this combination to become a new standard of care for patients with multiple myeloma that returned after or did not respond to prior therapies, including lenalidomide and a proteasome inhibitor."

"The extended follow-up results from ELOQUENT-3 reinforce the EPd combination’s sustained efficacy and favorable safety profile in patients with relapsed or refractory multiple myeloma," said Fouad Namouni, M.D., head, Oncology Development, Bristol-Myers Squibb. "These data, along with our overall presence at EHA (Free EHA Whitepaper), underscore our commitment to leading innovative research in hematology and developing therapies that can improve long-term survival for patients with different types of blood cancer."

Data from the primary analysis of ELOQUENT-3 were published in the New England Journal of Medicine in November 2018 and supported the approval of EPd by the U.S. Food and Drug Administration for the treatment of adult patients with RRMM who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.

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

About ELOQUENT-3

The Phase 2 ELOQUENT-3 trial randomized 117 patients with RRMM who received two or more prior therapies and were either refractory or relapsed and refractory to lenalidomide and a proteasome inhibitor. Patients were randomized 1:1 to receive either EPd (n=60) or Pd (n=57) in 28-day cycles until disease progression or unacceptable toxicity. Patients in both the EPd and Pd arms received 4 mg of pomalidomide for days 1-21 of each cycle, and the weekly equivalent of 40 mg or 20 mg dexamethasone for patients ≤75 years or >75 years, respectively. In the EPd arm, Empliciti was administered intravenously at the dose of 10 mg/kg weekly for the first 2 cycles and 20 mg/kg every four weeks starting from cycle 3. The primary endpoint of the study was investigator-assessed PFS.

In the 18-month follow-up analysis, adverse events (AEs) were comparable between treatment arms and consistent with the primary analysis. The most common grade 3-4 AEs were infections (22% among patients receiving EPd, 24% among patients receiving Pd), neutropenia (13%, 29%), anemia (10%, 22%), thrombocytopenia (10%, 7%) and hyperglycemia (8%, 11%). Grade 5 all-cause AEs occurred in seven patients (12%) who received EPd and nine patients (16%) who received Pd.

Bristol-Myers Squibb: Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do. The focus of our research is to increase quality, long-term survival for patients and make cure a possibility. Through a unique multidisciplinary approach powered by translational science, we harness our deep scientific experience in oncology and Immuno-Oncology (I-O) research to identify novel treatments tailored to individual patient needs. Our researchers are developing a diverse, purposefully built pipeline designed to target different immune system pathways and address the complex and specific interactions between the tumor, its microenvironment and the immune system. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines, like I-O, a reality for patients.

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.

Empliciti was initially approved by the FDA in 2015 in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.

U.S. FDA-APPROVED INDICATIONS FOR EMPLICITI

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

EMPLICITI (elotuzumab) is indicated in combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

IMPORTANT SAFETY INFORMATION

Infusion Reactions

Infusion reactions were reported in 10% of patients treated with EMPLICITI in the ELOQUENT-2 trial [EMPLICITI + lenalidomide + dexamethasone (ERd) vs lenalidomide + dexamethasone (Rd)] and 3.3% in the ELOQUENT-3 trial [EMPLICITI + pomalidomide + dexamethasone (EPd) vs pomalidomide + dexamethasone (Pd)].

In the ELOQUENT-2 trial, all infusion reactions were Grade 3 or lower, with Grade 3 infusion reactions occurring in 1% of patients. The most common symptoms included 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.

In the ELOQUENT-3 trial, the only infusion reaction symptom was chest discomfort (2%), which was Grade 1. All the patients who experienced an infusion reaction had them during the first treatment cycle.

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 EMPLICITI infusion.

Infections

In the ELOQUENT-2 trial (N=635), infections were reported in 81% of patients in the ERd arm and 74% in the Rd arm. Grade 3-4 infections were 28% (ERd) and 24% (Rd). Discontinuations due to infections were 3.5% (ERd) and 4.1% (Rd). Fatal infections were 2.5% (ERd) and 2.2% (Rd). Opportunistic infections were reported in 22% (ERd) and 13% (Rd). Fungal infections were 10% (ERd) and 5% (Rd). Herpes zoster was 14% (ERd) and 7% (Rd).

In the ELOQUENT-3 trial (N=115), infections were reported in 65% of patients in both the EPd arm and the Pd arm. Grade 3-4 infections were reported in 13% (EPd) and 22% (Pd). Discontinuations due to infections were 7% (EPd) and 5% (Pd). Fatal infections were 5% (EPd) and 3.6% (Pd). Opportunistic infections were reported in 10% (EPd) and 9% (Pd). Herpes zoster was reported in 5% (EPd) and 1.8% (Pd).

Monitor patients for development of infections and treat promptly.

Second Primary Malignancies

In the ELOQUENT-2 trial (N=635), invasive second primary malignancies (SPM) were 9% (ERd) and 6% (Rd). The rate of hematologic malignancies was 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).

In the ELOQUENT-3 trial (N=115), invasive SPMs were 0% (EPd) and 1.8% (Pd).

Monitor patients for the development of SPMs.

Hepatotoxicity

In the ELOQUENT-2 trial (N=635), AST/ALT >3X the upper limit, total bilirubin >2X the upper limit, and alkaline phosphatase <2X the upper limit were 2.5% (ERd) vs 0.6% (Rd). Of 8 patients experiencing hepatotoxicity, 2 patients discontinued treatment while 6 patients had resolution and continued. Monitor liver enzymes periodically. Stop EMPLICITI upon ≥Grade 3 elevation of liver enzymes. Continuation of treatment may be considered after return to baseline values.

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 available data on EMPLICITI use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage.

There is a risk of fetal harm, including severe life-threatening human birth defects, associated with lenalidomide and pomalidomide, and they are contraindicated for use in pregnancy. Refer to the respective product 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

ELOQUENT-2 trial:

Serious adverse reactions were 65% (ERd) and 57% (Rd). The most frequent serious adverse reactions in the ERd arm compared to the Rd arm were: pneumonia (15%, 11%), pyrexia (7%, 5%), 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 (62%, 52%), diarrhea (47%, 36%), pyrexia (37%, 25%), constipation (36%, 27%), cough (34%, 19%), peripheral neuropathy (27%, 21%), nasopharyngitis (25%, 19%), upper respiratory tract infection (23%, 17%), decreased appetite (21%, 13%), and pneumonia (20%, 14%).
ELOQUENT-3 trial:

Serious adverse reactions were 22% (EPd) and 15% (Pd). The most frequent serious adverse reactions in the EPd arm compared to the Pd arm were: pneumonia (13%, 11%) and respiratory tract infection (7%, 3.6%).
The most common adverse reactions in EPd arm (≥20% EPd) and Pd, respectively, were constipation (22%, 11%) and hyperglycemia (20%, 15%).