On June 3, 2017 TG Therapeutics (NASDAQ: TGTX) reported positive results from its Phase 3 GENUINE trial of TG-1101 (ublituximab) plus ibrutinib in patients with previously treated high risk Chronic Lymphocytic Leukemia (CLL) (Press release, TG Therapeutics, JUN 5, 2017, View Source [SID1234519420]). Data from this trial was presented today by Dr. Jeff Sharman, Medical Director, Hematology Research, US Oncology in an oral session during the 53rd American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.

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Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics stated, "Patients with high-risk CLL have the poorest outcomes on ibrutinib and are in need of a more efficacious treatment. We believe the data presented today demonstrate that the addition of TG-1101 to ibrutinib improves patient outcomes across multiple measures." Mr. Weiss continued, "In addition to increasing the overall number of patients that responded to treatment with ibrutinib, adding TG-1101 to ibrutinib increased the number of patients with bone marrow confirmed CR’s, MRD negativity in peripheral blood, deepened nodal responses, and resulted in fewer patients progressing on therapy. Collectively, we see the consistent pattern of enhanced benefit as providing a compelling case for combining TG-1101 with ibrutinib in these hard to treat patients with high-risk CLL. We look forward to sharing these data with the FDA later this year to discuss filing for accelerated approval. We would like to thank our investigators and their patients for their participation in this important clinical trial."

Highlight’s from this presentation include the following:

Oral Presentation: Ublituximab and ibrutinib for previously treated genetically high-risk chronic lymphocytic leukemia: Results of the GENUINE Phase 3 study

This presentation includes data from the GENUINE Phase 3 trial, a multicenter, randomized trial (NCT02301156), which assessed the efficacy and safety of TG-1101 plus ibrutinib versus ibrutinib alone in patients with high risk CLL. For the trial, high-risk was defined as having any one or more of the following centrally confirmed features: 17p deletion, 11q deletion or p53 mutation. The GENUINE study was designed to demonstrate the value of adding TG-1101, a potent next generation glycoengineered anti-CD20 monoclonal antibody to ibrutinib monotherapy in high-risk CLL, and was powered to show a statistically significant improvement in ORR of 30%, with a minimal absolute detectable difference between the two arms of approximately 20%.

The trial met its primary endpoint, demonstrating a statistically significant improvement in Overall Response Rate (ORR), as assessed by blinded independent central radiology and hematology review by iwCLL (Hallek 2008) criteria, compared to ibrutinib alone in both the Intent to Treat (ITT) population (p=0.001) and Treated population (p<0.001). Per iwCLL guidelines, all responders required confirmation of response for a minimum duration of 2 months. The ITT population includes all 126 randomized patients (64 in the TG-1101 plus ibrutinib arm and 62 in the ibrutinib alone arm) while the Treated population includes all ITT patients that received at least one dose of either study drug (59 in the TG-1101 plus ibrutinib arm and 58 in the ibrutinib alone arm).




Patient Demographics

One hundred and twenty-six (126) patients were randomized on the GENUINE Phase 3 trial. 100% of patients were high-risk and had either 17p deletion, 11q deletion, or p53 mutation. Sixty-four percent (64%) of patients in the TG-1101 plus ibrutinib arm and 66% of patients in the Ibrutinib alone arm had 17p deletion and/or a p53 mutation while 36% and 34% of patients in the TG-1101 plus ibrutinib and ibrutinib alone arms, respectively, had an 11q deletion only. The median age of patients on either arm was 67 years and the median number of prior lines of therapy for either arm was 3.

Safety & Tolerability

One hundred and seventeen (117) patients were evaluable for safety (59 patients in the TG-1101 plus ibrutinib arm, and 58 patients in the ibrutinib alone arm). The combination was well tolerated and, apart from infusion related reactions, the addition of TG-1101 did not appear to alter the safety profile of ibrutinib monotherapy. Neutropenia, occurring in 9% of patients, was the most commonly reported Grade 3/4 Adverse Event (AE) in the combination arm, followed by infusion related reactions and anemia, each reported in 5% of patients. Notably, the majority of infusion related reactions (IRR) were Grade 1 or 2 in severity, with only 5% Grade 3/4 IRR observed. Median follow-up for this study was approximately 11.4 months.

Clinical Activity

Response Rates


TG-1101 plus Ibrutinib
Ibrutinib
P-value
Treated Population (n)
n=59
n=58

Overall Response Rate (ORR)
78%
45%
P<0.001
Complete Response (CR)
7%
0%
NS
MRD-Negative
19%
(n=53) *
2%
(n=53) *
P<0.01
*Patients evaluable for MRD included those enrolled >4 months prior to data cutoff date of February 15, 2017. MRD analyzed by central lab, 7-color flow cytometry


In addition to the improvements in ORR, CR and MRD-negativity, a trend in improvement of Progression Free Survival (PFS) was observed in the combination arm of TG-1101 plus ibrutinib as compared to ibrutinib alone (Hazard Ratio = 0.559; p=NS).

ABOUT THE PHASE 3 GENUINE STUDY

The Phase 3 GENUINE study is a randomized, open label, multicenter clinical trial to evaluate the safety and efficacy of TG-1101 (ublituximab) plus ibrutinib compared to ibrutinib alone in adult patients with high-risk Chronic Lymphocytic Leukemia (CLL) who received at least one prior therapy for their disease.

The study was conducted at 160 clinical trial sites in the US and Israel and randomized 126 patients. Patients received ibrutinib orally at 420 mg once daily in both arms and in the combination arm those patients also received intravenous infusions of TG-1101 at 900 mg dosed on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6. Patients in the combination arm who had not progressed received quarterly infusions of TG-1101 maintenance at 900 mg.

PRESENTATION DETAILS:

The above referenced presentation isnow available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

On June 5, 2017 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported smart chemotherapy DS-8201 demonstrated a favorable safety profile and promising antitumor activity in patients with HER2-expressing tumors, including pre-treated metastatic breast and gastric cancer (Press release, Daiichi Sankyo, JUN 5, 2017, View Source [SID1234519417]). These data were highlighted as part of a Clinical Science Symposium at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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Preliminary results from the dose expansion part of the phase 1 study of DS-8201 in a subgroup analysis of HER2-expressing metastatic breast cancer patients pre-treated with ado-trastuzumab emtansine (T-DM1) and pertuzumab demonstrated a 46.7 percent overall response rate (14 of 30 patients) and a 100 percent disease control rate (30 of 30 patients) to date. An overall response rate of 45.7 percent (16 of 35 patients) and disease control rate of 100 percent (35 of 35 patients) was observed in patients pre-treated with only T-DM1.

Antibody drug conjugates (ADCs) are a type of targeted cancer medicine that deliver cytotoxic chemotherapy ("payload") directly to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Using Daiichi Sankyo’s proprietary ADC technology, DS-8201 is a smart chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor (DXd) payload by a tetrapeptide linker designed to deliver enhanced cancer cell destruction upon release inside the cell and reduce systemic exposure to the cytotoxic payload (or chemotherapy).

"The significant tumor shrinkage and sustained tumor control that was demonstrated by DS-8201 is impressive and further confirms the initial antitumor activity shown in the dose escalation part of this study," said Toshihiko Doi, MD, PhD, Department of Experimental Therapeutics, National Cancer Center Hospital East, and study investigator. "These data suggest that DS-8201 may be a promising potential treatment for patients with HER2-expressing metastatic breast cancer whose tumors are no longer controlled with available treatment options like T-DM1 and pertuzumab."

Thirty-nine of 50 patients with HER2-expressing metastatic breast cancer are continuing to receive treatment. To date, median progression free survival has reached 45.4 weeks (95 percent CI: 32.1, NA). Eleven patients have discontinued treatment due to adverse events (3 patients), progressive disease (6 patients) and other reasons (2 patients).

"These results demonstrate that the smart delivery of chemotherapy by DS-8201 to cancer cells may be effective and safe in treating tumors that express HER2," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "Based on these results, we are accelerating the development of DS-8201 and our ADC technology seeking to bring a unique precision medicine to patients and physicians who have exhausted current treatment options."

About the DS-8201 Phase 1 Study
DS-8201 is currently being evaluated in an open-label two-part phase 1 dosing study in patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerant to standard treatment, or for whom no standard treatment is available. The primary objective of the dose escalation phase of the study was to assess the safety and tolerability of DS-8201 and determine the maximum tolerated dose (MTD). No dose limiting toxicity was seen administering DS-8201 up to 8.0 mg/kg every three weeks and the maximum tolerated dose was not reached.

In the dose expansion part of the study, DS-8201 is given in one of two doses (5.4 mg/kg and 6.4 mg/kg) to patients in one of four cohorts: patients with ado-trastuzumab emtansine (T-DM1)-treated HER2-positive breast cancer; patients with trastuzumab-treated HER2-positive gastric cancer or gastroesophageal junction adenocarcinoma; patients with HER2 low-expressing breast cancer; and patients with other HER2-expressing solid malignant tumors. Patient enrollment in the two breast cancer cohorts is ongoing in the U.S. and Japan. For more information about the study, please visit ClinicalTrials.gov.

A total of 134patients have been treated to date in both the dose escalation (24 patients) and dose expansion (110 patients) parts of the study. The most common any-grade adverse events observed in the study to date included nausea (66.9 percent), decreased appetite (57.9 percent), vomiting (36.8 percent) and decreased platelet count (34.6 percent). Grade 4 adverse events included decreased platelet count (3.8 percent), decreased neutrophil count (3.0 percent), anemia (1.5 percent), and decreased white blood cell count (1.5 percent).

Preliminary results in the overall population of HER-expressing solid tumors demonstrated an overall response rate of 40.2 percent (39 of 97 patients) with a disease control rate of 91.8 percent. In the cohort enrolling patients with trastuzumab-treated HER2-positive gastric or gastroesophageal junction adenocarcinoma, a preliminary overall response rate of 44.4 percent (16 of 36 patients) and a disease control rate of 88.9 percent (32 of 36 patients) was shown to date with DS-8201. In a sub-group of patients pre-treated with CPT-11 (irinotecan), an overall response rate of 44.4 percent (8 of 18 patients) and disease control rate of 94.4 percent (17 of 18 patients) was demonstrated to date. A total of 22 out of 39 patients are still receiving treatment with median progression free survival of 27.3 weeks (95 percent CI: 13.4, NA). Seventeen patients have discontinued treatment due to adverse events (6 patients) and progressive disease (11 patients).

About DS-8201
DS-8201 is the lead product in the Antibody Drug Conjugate (ADC) Franchise of the Daiichi Sankyo Cancer Enterprise. DS-8201 is currently in phase 1 clinical development for HER2-positive advanced or metastatic breast cancer and gastric cancer, HER2-low-expressing breast cancer and other HER2-expressing solid cancers. The U.S. Food and Drug Administration (FDA) granted Fast Track designation to DS-8201 for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including ado-trastuzumab emtansine (T-DM1). DS-8201 has not been approved for any indication in any country.

On June 5, 2017 CEL-SCI Corporation (NYSE MKT: CVM) reported that it has responded to the U.S. Food and Drug Administration’s (FDA) most recent communication from May 2017 about the clinical hold imposed on the Company’s Phase 3 head and neck cancer study with Multikine* (Leukocyte Interleukin, Inj.) (Press release, Cel-Sci, JUN 5, 2017, View Source [SID1234519416]).

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The hold issues addressed in the FDA communication were that the study’s Investigator Brochure (IB) and the "Dear Investigator" letter need to be revised. Specific deficiencies and their locations in each of the documents were identified, and directions were given as to the specific information that should be included in the revisions of these documents. CEL-SCI revised the documents exactly as directed by the FDA. If the FDA finds the revisions made to the two documents to be satisfactory, CEL-SCI is hopeful that all of the clinical hold issues have now been addressed, and the FDA will consider lifting the clinical hold.

As of September 2016, nine hundred twenty-eight (928) head and neck cancer patients have been enrolled and have completed treatment in the Phase 3 study. In accordance with the study protocol, the FDA’s instructions, and subject to the clinical hold, CEL-SCI continues to follow these patients.

The study endpoint is a 10% increase in overall survival of patients between the two main comparator groups in favor of the group receiving the Multikine treatment regimen. The determination if the study end point is met will occur when there are a total of 298 deaths in those two groups.

On June 5, 2017 Abbvie reported that long-term follow-up results from the pivotal Phase 3 RESONATE trial (PCYC-1112) showed continued survival rates in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) treated with IMBRUVICA (ibrutinib) up to four years, according to new data were presented today at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago (poster session: 8:00 a.m. – 11:30 a.m. CDT; poster discussion: 1:15 p.m. – 2:30 p.m. CDT) (Press release, AbbVie, JUN 5, 2017, View Source [SID1234519415]). The data regarding IMBRUVICA, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor and the first chemotherapy-free treatment for patients with CLL, were announced by AbbVie (NYSE: ABBV), a global biopharmaceutical company. IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

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According to the study results, IMBRUVICA was associated with significantly longer progression free survival (PFS; 59 percent) in R/R CLL/SLL with median follow-up of 44 months, including in patient subgroups with genomic abnormalities that are traditionally considered high-risk for poor outcomes. In addition, 3-year overall survival (OS; 74 percent) was longer in IMBRUVICA-treated patients. Further, the overall response rate (ORR) was 91 percent with complete response (CR) rates increasing over time (9 percent) (abstract #7510).1

"These results suggest ibrutinib continues to provide persistent responses over the long-term in patients with chronic lymphocytic leukemia, including those who are difficult to treat," said John C. Byrd, MD, Distinguished University Professor at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and lead investigator of the study.* "As a clinician who has treated patients with CLL for more than 20 years, I’m pleased to see the potential for efficacy and safety responses to continue over an extended period of time."

CLL, the most common form of leukemia in adults, is a type of cancer that starts from cells that become certain white blood cells (called lymphocytes) in the bone marrow. The cancer (leukemia) cells start in the bone marrow but then spread into the blood. There are more than 20,000 newly diagnosed CLL patients every year.2 CLL is predominately a disease of the elderly, with a median age of 71 at diagnosis.2 SLL is similar to CLL and affects the same lymphocytes; the only difference between the two is the location where the cancer primarily occurs.3 To-date, more than 25,000 CLL patients have been treated in the U.S. with IMBRUVICA since approval in 2014.

"The first pivotal RESONATE data on IMBRUVICA were presented three years ago at ASCO (Free ASCO Whitepaper) and represented the promise of a new standard of care in blood cancer treatment. We are pleased to continue to see very favorable responses and survival outcomes to IMBRUVICA in relapsed and refractory CLL patients now into the fourth year of study," said Danelle James, M.D., M.S., Head of Clinical Science, Pharmacyclics LLC, an AbbVie company. "We believe in the potential of IMBRUVICA across a range of blood cancers and other serious diseases, and are continuing to explore its potential as part of our robust clinical research program."

About the Study

Abstract #7510: Long-term efficacy and safety with ibrutinib (ibr) in previously treated chronic lymphocytic leukemia (CLL): Up to four years follow-up of the RESONATE study (Poster Board: #272)

Poster Session on Monday, June 5, 2017, 8:00 a.m. – 11:30 a.m. CDT at Hall A
Poster Discussion on Monday, June 5, 2017, 1:15 p.m. – 2:30 p.m. CDT at E354b
At up to 4 years of follow up, PFS was significantly longer for IMBRUVICA than ofatumumab (median NR versus 8 months, [HR 0.133; P<0.0001]; 3-year PFS 59 percent versus 3 percent). Significant benefit was observed across patient subgroups with genomic abnormalities that are traditionally considered high-risk for poor outcomes. Specifically, the high-risk genomic abnormalities were deletion 11q (del 11q), deletion 17p (del 17p), complex karyotype (CK), unmutated immunoglobulin heavy-chain variable-region (IGHV), NOTCH1 mutation, TP53 mutation, SF3B1 mutation, BIRC3 mutation and XP01 mutation. Patients with del 11q trended to have the most favorable outcome; however, PFS was not statistically different for patients with del 17p or del 11q or without these FISH abnormalities. At analysis, with the majority of patients (68 percent) randomized to ofatumumab crossing over to IMBRUVICA, OS was longer for IMBRUVICA versus ofatumumab (median OS not reached for either arm). The OS rate for IMBRUVICA at 3 years was 74 percent, and ORR was 91 percent, with CR and incomplete bone marrow recovery (CRi) increasing over time (now 9 percent).1

RESONATE is a Pharmacyclics-sponsored, randomized, multi-center, open-label, international Phase 3 study, which enrolled 391 patients with R/R CLL/SLL who had received at least one prior therapy and were not considered appropriate candidates for treatment with a purine analog (median age 67). Patients were administered either 420 mg oral IMBRUVICA (n=195) once-daily until progression or unacceptable toxicity or intravenous ofatumumab for up to 24 weeks (n=196, initial dose of 300 mg followed by 11 doses at 2,000 mg per dose and schedule consistent with local labeling). The study met its primary endpoint, demonstrating improved PFS.1

The adverse event (AE) profile of IMBRUVICA was consistent with previous reports. Major hemorrhage, Grade ≥3 atrial fibrillation, and Grade ≥3 hypertension occurred in 6 percent, 6 percent, and 8 percent of patients, respectively, over a follow-up of up to 4 years. The incidence of most Grade ≥3 AEs decreased from year 1 versus year 2-3: neutropenia (18 percent versus 8 percent); pneumonia (11 percent versus 4 percent); atrial fibrillation (4 percent versus 2 percent), respectively. Discontinuations were most frequently due to progressive disease (27 percent) and AEs (12 percent). At analysis, 90 IMBRUVICA patients (46 percent) continue on therapy in the study.1

About IMBRUVICA
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.4,5 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.4

IMBRUVICA is FDA-approved in five distinct patient populations: CLL, SLL, Waldenström’s macroglobulinemia (WM), along with previously-treated mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL).4

IMBRUVICA was first approved for patients with MCL who have received at least one prior therapy in November 2013.
Soon after, IMBRUVICA was initially approved in CLL patients who have received at least one prior therapy in February 2014. By July 2014, the therapy received approval for CLL patients with 17p deletion, and by March 2016, the therapy was approved as a frontline CLL treatment.
IMBRUVICA was approved for patients with WM in January 2015.
In May 2016, IMBRUVICA was approved in combination with bendamustine and rituximab (BR) for CLL/SLL patients.
In January 2017, IMBRUVICA was approved for patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy.
Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.4

IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA has been granted four Breakthrough Therapy Designations from the FDA, spanning CLL/SLL, WM, MCL and chronic graft-versus-host-disease (cGVHD). In addition, IMBRUVICA is the first standard therapy specifically approved for patients with previously-treated MZL and WM.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry, with approximately 130 ongoing clinical trials. There are a total of 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and approximately 100 investigator-sponsored trials and external collaborations that are active around the world. To date, 70,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage – Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA.

The mechanism for the bleeding events is not well understood. IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre- and postsurgery depending upon the type of surgery and the risk of bleeding.

Infections – Fatal and nonfatal infections have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA. Evaluate patients for fever and infections and treat appropriately.

Cytopenias – Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 13% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 13%) based on laboratory measurements occurred in patients treated with single agent IMBRUVICA. Monitor complete blood counts monthly.

Atrial Fibrillation – Atrial fibrillation and atrial flutter (range, 6% to 9%) have occurred in patients treated with IMBRUVICA, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines.

Hypertension – Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA. Adjust existing antihypertensive medications and/or initiate antihypertensive treatment as appropriate.

Second Primary Malignancies – Other malignancies (range, 3% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 2% to 13%).

Tumor Lysis Syndrome – Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity – Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Advise men to avoid fathering a child during the same time period.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia** (61%), thrombocytopenia** (62%), diarrhea (43%), anemia** (41%), musculoskeletal pain (30%), rash (30%), nausea (29%), bruising (30%), fatigue (29%), hemorrhage (22%), and pyrexia (21%).

** Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).

The most common Grade 3 or 4 non-hematologic adverse reactions (≥5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).

The most common Grade 3 or 4 non-hematologic adverse reactions (≥5%) in MZL patients were pneumonia (10%), fatigue (6%), diarrhea (5%), rash (5%), and hypertension (5%).

Approximately 6% (CLL/SLL), 14% (MCL), 11% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4%-10% (CLL/SLL), 9% (MCL), and 9% (WM [6%] and MZL [13%]) of patients discontinued due to adverse reactions. Most common adverse reactions leading to discontinuation were pneumonia, hemorrhage, atrial fibrillation, rash, and neutropenia (1% each) in CLL/SLL patients and subdural hematoma (1.8%) in MCL patients. The most common adverse reactions leading to discontinuation were interstitial lung disease, diarrhea, and rash (1.6% each) in WM and MZL patients.

DRUG INTERACTIONS

CYP3A Inhibitors – Avoid coadministration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose.

CYP3A Inducers – Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment – Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA dose.

Please see Full Prescribing Information: View Source

On June 5, 2017 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported safety and efficacy data from an ongoing phase 1/2a study of the anti-CD38 antibody MOR202 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2017 Annual Meeting in Chicago (Press release, MorphoSys, JUN 5, 2017, View Source [SID1234519413]). The dose escalation trial comprises three arms: MOR202, MOR202 in combination with the immunomodulatory drug (IMiD) lenalidomide (LEN) and MOR202 in combination with the IMiD pomalidomide (POM), in each case with low-dose dexamethasone (DEX). The trial is being conducted in heavily pre-treated patients with relapsed/refractory multiple myeloma.

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"Antibodies directed against CD38 have been reported as a class of potential therapeutics for patients with relapsed or refractory multiple myeloma. Based on the maturing data generated for MOR202, we will intensify our evaluations to further develop this compound as a representative of this class," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG. "We are optimistic about the responses seen in patients treated with MOR202 plus LEN/DEX and POM/DEX as well as the relatively short infusion time and the occurrence of infusion-related reactions in a low proportion of patients observed. We look forward to results further maturing from patients treated in this ongoing trial and to presenting final data later this year."

MOR202 was given as a 2-hour infusion up to the highest dose of 16 mg/kg. Infusion-related reactions (IRRs) occurred in 6% of patients in the clinically relevant dose cohorts of MOR202 (4 mg/kg, 8 mg/kg, 16 mg/kg) and were limited to grade 1 or 2. The most frequent adverse events of grade 3 or higher were neutropenia, lymphopenia, and leukopenia in 42%, 40%, and 33% of patients respectively. No unexpected safety signals were observed.

Patients treated with MOR202 in combination with LEN/DEX had a median of three prior treatment regimens, 56% being refractory to at least one prior therapy. Median progression-free survival (PFS) was not yet reached, median follow-up was 7.5 months and 9 patients were still on study at data cut-off. 12 out of 17 patients (71%, based on the ITT population) reported an objective response (OR) to treatment, including one complete remission (CR), three very good partial responses (VGPR) and eight partial responses (PR).

Patients receiving MOR202 with POM/DEX, had a median of four prior treatment regimens, all being refractory to at least one prior therapy. Current median PFS is 17.5 months, with a median follow-up of 8.5 months. Eight patients were still on study at data cut-off. 6 out of 13 patients (46%, based on the ITT-population) showed an objective response, with two patients achieving a complete remission (CR).

Patients treated with MOR202 plus DEX had a median of five prior treatment regimens before study entry. Median PFS of this cohort was 4.7 months, with a median follow-up of 22.1 months. 5 out of 18 patients (28%, based on the ITT population) had an objective response.

Details of the MOR202 presentation at ASCO (Free ASCO Whitepaper) 2017

Abstract #8024, poster board #350

MOR202 with low-dose dexamethasone (DEX) and in combination with pomalidomide/DEX and lenalidomide/DEX in relapsed or refractory multiple myeloma (RRMM): Interim analysis of a phase 1/2a dose-escalation study

The poster will be presented during the "Hematologic Malignancies – Plasma Cell Dyscrasia" session on June 5, 2017 (8:00 AM-11:30 AM CDT, poster hall).

MorphoSys will hold an Investor & Analyst Event at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting on June 5, 2017, at 6:30pm CDT (June 6, 2017: 1:30am CEST). Clinical data for MorphoSys’s investigational agents MOR208 and MOR202 will be presented by clinical investigators and company representatives.

A replay and the presentation will be made available at View Source

Live-Webcast: https://services.choruscall.com/dataconf/productusers/morph/mediaframe/19794/indexl.html

About MOR202 and the ongoing phase 1/2a study in multiple myeloma
The investigational drug MOR202 is a fully human HuCAL antibody directed against CD38, a highly expressed and validated target in multiple myeloma. Data are from an ongoing clinical phase 1/2a, open-label, multi-center, dose-escalation study conducted in several sites in Germany and Austria. The study is evaluating the safety and preliminary efficacy of MOR202 with low dose dexamethasone and in combination with the immunomodulatory drugs (IMiDs) pomalidomide (POM) and lenalidomide (LEN) plus DEX in patients with relapsed/refractory multiple myeloma. The primary endpoints of the trial are the safety, tolerability and recommended dose of MOR202 with DEX and in combination with the IMiDs. Secondary outcome measures are pharmacokinetics and preliminary efficacy based on overall response rate, duration of response, time-to-progression, and progression-free survival.