On October 6, 2016 Cellectar Biosciences, Inc. (Nasdaq: CLRB) (the "company"), an oncology-focused clinical stage biotechnology company, reported the enrollment of the first patient into Cohort 3 of the company’s Phase I clinical study of CLR 131 in patients with relapsed or refractory multiple myeloma (Filing, 8-K, Cellectar Biosciences, OCT 6, 2016, View Source [SID:SID1234515634]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Cohort 3 of the Phase 1 study of CLR 131 will consist of at least three patients with relapsed or refractory multiple myeloma that have been treated previously with at least one proteasome inhibitor and one immunomodulatory agent. Patients in this cohort will receive 25mCi/m2 of CLR 131 as a single dose infusion, which represents a 33 percent increase in the dose from the previous cohort.

"We are highly encouraged with CLR 131’s safety profile, overall clinical activity and PFS observed from a single dose infusion, particularly in such a heavily pretreated patient population. The PFS demonstrated in Cohort 2 already compares favorably to other treatments that require multiple doses, either daily or weekly," said Jim Caruso, president and CEO of Cellectar Biosciences. "We plan to accelerate Cohort 3 enrollment as well as initiate a Phase II study in the first half of 2017 to further define the clinical benefits of this novel compound in selected hematologic malignancies with limited treatment options."

In this multi-center, open label Phase I dose escalation study, CLR 131 is administered as a single dose, 30-minute infusion. The primary study objective is to characterize the safety and tolerability of CLR 131 in patients with relapsed or refractory multiple myeloma. Secondary study objectives include establishment of a recommended Phase II dose, both with and without dexamethasone, as well as an assessment of therapeutic activity, including progression-free survival (PFS) and efficacy endpoints.

About CLR 131
CLR 131 is an investigational compound under development for a range of hematologic malignancies. It is currently being evaluated in a Phase I clinical trial in patients with relapsed or refractory multiple myeloma. The company plans to initiate a Phase II clinical study to assess efficacy in a range of B-cell malignancies in the first half of 2017. Based upon pre-clinical and interim Phase I study data, treatment with CLR 131 provides patients with a novel approach to treating hematological diseases and may provide patients with an improvement in progression-free survival and overall quality of life. CLR 131 utilizes the company’s patented PDC tumor targeting delivery platform to deliver a cytotoxic radioisotope, iodine-131 directly to tumor cells. The FDA has granted Cellectar an orphan drug designation for CLR 131.

About Phospholipid Drug Conjugates (PDCs)
Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). Its phospholipid ether (PLE) carrier platform was deliberately designed to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in over 70 different xenograft models of cancer.

About Relapsed or Refractory Multiple Myeloma
Multiple myeloma is the second most common blood or hematologic cancer with approximately 30,000 new cases in the United States every year. It affects a specific type of blood cells known as plasma cells. Plasma cells are white blood cells that produce antibodies to help fight infections. While treatable for a time, multiple myeloma is incurable and almost all patients will relapse or the cancer will become resistant/refractory to current therapies.

On October 6, 2016 Teva Pharmaceutical Industries Ltd. (NYSE and TASE:TEVA), Celltrion, Inc. and Celltrion Healthcare reported that the companies have entered into an exclusive partnership to commercialize two of Celltrion’s mAb biosimilar candidates in the U.S. and Canada (Press release, Teva, OCT 6, 2016, View Source [SID:SID1234515633]). CT-P10 is a proposed mAb biosimilar to Rituxan (rituximab), which is used to treat patients with Non-Hodgkin’s Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), Rheumatoid Arthritis (RA), Wegener’s Granulomatosis and Microscopic Polyangiitis (MPA). CT-P6 is a proposed mAb biosimilar to Herceptin (trastuzumab), which is used for the treatment of HER2-overexpressing breast cancer and for the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. Combined annual net sales for Rituxan and Herceptin are approximately $6.5 billion in the U.S. and Canada.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This commercial partnership with Celltrion enables Teva to expand into the upcoming wave of biosimilars and build on its strong position in the biosimilar space," said Siggi Olafsson, President & CEO of Global Generic Medicines, Teva Pharmaceuticals. "The introduction of two additional mAb biosimilar candidates into our near-term pipeline bolsters our biosimilar portfolio and continues to leverage Teva’s unique cross-functional capabilities across both specialty and generic medicines. We look forward to our partnership with Celltrion with its expertise in mAb biosimilar development and manufacturing."

Both CT-P10 and CT-P6 are currently in late-stage Phase III development and their primary endpoints have been successfully achieved. CT-P10 was submitted by Celltrion to the European Medicines Agency (EMA) for review in October 2015. In the meantime, Celltrion is preparing CT-P6 for submission in Europe seeking approval from the EMA this quarter. As part of the agreement, Teva will be responsible for all commercial activities in the U.S. and Canada, pending regulatory approvals for both products. Celltrion has responsibility for completing all clinical development and regulatory activities.

"With Teva’s strong legacy and U.S. commercial presence in Oncology, we are pleased to partner with Celltrion to bring additional biosimilar treatment options to patients," said Rob Koremans, M.D., President and Chief Executive Officer, Global Specialty Medicines, Teva Pharmaceuticals. "By bringing two near-term treatment options into our product offering, we will continue our commitment to serving those dealing with cancer and other serious diseases."

"As a global biopharmaceutical leader with established products as well as a robust biosimilar pipeline and novel drugs, we are very excited about our new partnership with Teva," said HyoungKi Kim, Chief Executive Officer, Celltrion, Inc. "Following on the heels of our global success with Remsima (Inflectra), our infliximab biosimilar, which has brought affordable and effective biologic treatment to many patients around the world with proven record of quality, efficacy and safety to the reference product, we are confident that we will be able to repeat the same success in the U.S and Canada with CT-P10 and CT-P6 through our partnership with Teva."

Under the terms of the agreement, Teva will pay Celltrion Healthcare $160 million upfront of which up to $60 million is refundable or creditable under certain circumstances. Teva and Celltrion Healthcare will share profit from the commercialization of the mAb biosimilars.

On October 6, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported The New England Journal of Medicine has published data from the Phase III POLLUX (MMY3003) study of daratumumab (Press release, Genmab, OCT 6, 2016, View Source [SID:SID1234515622]). The POLLUX data were presented at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in June. Daratumumab was granted a Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration (FDA) based on these data in July 2016.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Phase III POLLUX study enrolled 569 patients who had relapsed or refractory multiple myeloma. Patients were randomized to receive either daratumumab combined with lenalidomide (an immunomodulatory drug) and dexamethasone (a corticosteroid), or lenalidomide and dexamethasone alone. The study met the primary endpoint of improving progression-free survival (PFS) (Hazard Ratio (HR) = 0.37; 95% CI 0.27-0.52; p<0.001) for patients treated with daratumumab versus patients who did not receive daratumumab. Patients who received treatment with daratumumab in combination with lenalidomide and dexamethasone had a 63% reduction in risk of their disease progressing, compared to those who did not receive daratumumab. The median PFS for patients treated with daratumumab in combination with lenalidomide and dexamethasone has not been reached, compared to an estimated median PFS of 18.4 months for patients who received lenalidomide and dexamethasone alone. The overall response rate was 93% in the group of patients treated with daratumumab versus 76% in the group that did not receive daratumumab. The rates of very good partial response or better (76% vs 44%) and complete response or better (43% vs 19%) were also higher for the group treated with daratumumab. Of patients treated with daratumumab, 22% were minimal residual disease negative, versus 5% in those who did not receive daratumumab; negative minimal residual disease translated into improved outcomes. The most common grade 3 or 4 adverse events in patients treated with daratumumab in combination with lenalidomide and dexamethasone versus those who received only lenalidomide and dexamethasone were neutropenia (51.9% vs 37.0%), thrombocytopenia (12.7% vs 13.5%), and anemia (12.4% vs 19.6%). Daratumumab-associated infusion-related reactions occurred in 48% of patients, were mostly grade 1/2, and occurred predominantly during the first infusion. Overall, the safety profile was consistent with known toxicities of daratumumab monotherapy and combination therapy of lenalidomide and dexamethasone.

Data from another Phase III study (CASTOR) of daratumumab combined with subcutaneous bortezomib (a type of chemotherapy, called a proteasome inhibitor) and dexamethasone (a corticosteroid) compared with bortezomib and dexamethasone alone in patients with relapsed or refractory multiple myeloma was also recently published in the New England Journal of Medicine.1
"Following the publication of the Phase III CASTOR data, we are pleased that the positive data from the Phase III POLLUX study has now also been published in the New England Journal of Medicine," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "The data from this study formed the basis, along with data from the CASTOR study, of two regulatory submissions in August; the supplemental Biologics License Application submitted to the U.S. Food and Drug Administration and the submission of the variation to the Marketing Authorization to the European Medicines Agency."

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.2 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.3 Approximately 30,330 new patients are expected to be diagnosed with multiple myeloma and approximately 12,650 people are expected to die from the disease in the U.S. in 2016.4 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.5 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.6 Patients who relapse after treatment with standard therapies, including proteasome inhibitors or immunomodulatory agents, have poor prognoses and few treatment options.7

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.8 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through programmed cell death, or apoptosis,8,9 and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity,8,9 antibody-dependent cellular phagocytosis10,11 and antibody-dependent cellular cytotoxicity.8,9 In addition, daratumumab therapy results in a reduction of immune-suppressive myeloid derived suppressor cells (MDSCs) and subsets of regulatory T cells (Tregs) and B cells (Bregs), all of which express CD38. These reductions in MDSCs, Tregs and Bregs were accompanied by increases in CD4+ and CD8+ T cell numbers in both the peripheral blood and bone marrow.8,12

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, non-Hodgkin’s lymphoma and a solid tumor.

On October 6, 2016 Kite Pharma, Inc. (Nasdaq:KITE) reported the first patient was enrolled in ZUMA-6, a Phase 1b/2 clinical study of KTE-C19 in combination with atezolizumab, Genentech’s anti-PD-L1 cancer immunotherapy (Press release, Kite Pharma, OCT 6, 2016, View Source [SID:SID1234515618]). The trial is designed to evaluate the safety and efficacy of the combination in patients with refractory diffuse large B-cell lymphoma (DLBCL).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

PD-L1 expression in DLBCL is associated with high-risk disease and poor outcomes. The interaction of PD-L1 and PD-1, which is expressed on KTE-C19, may dampen T-cell activity in some patients. As a result, use of the two compounds in combination could provide a synergistic effect since inhibiting PD-L1 with atezolizumab may enhance and prolong the activity and proliferation of KTE-C19.

"The ZUMA-6 combination study is a core element of our broad strategy to optimize KTE-C19 treatment outcomes and to significantly extend the important potential benefits of KTE-C19 monotherapy," said David Chang, M.D., Ph.D., Kite’s Executive Vice President, Research and Development, and Chief Medical Officer. "We view the scientific rationale for this combination study as compelling and look forward to advancing the study based on our extensive clinical experience."

Kite entered a clinical collaboration in March 2016 with Genentech, a member of the Roche Group, to evaluate the safety and efficacy of KTE-C19 in combination with atezolizumab. The first ZUMA-6 patient was enrolled at the end of September 2016.

About ZUMA-6

ZUMA-6 is the first industry-sponsored clinical trial to enroll patients to study the combination of an anti-CD19 engineered chimeric antigen receptor (CAR) T-cell and a checkpoint inhibitor. The study will proceed as a single-arm, open-label, multi-center study in patients with chemotherapy-refractory DLBCL. The Phase 1b portion of ZUMA-6 will assess the safety of KTE-C19 and atezolizumab given in sequence. The primary objective of the Phase 2 portion is to evaluate the combination’s safety and efficacy. The study also includes secondary analyses of key biomarkers of T-cell activity and other safety and efficacy endpoints. Kite will be the sponsor of the study, and the results will be used to evaluate options for further development of the combination. Additional information about the ZUMA-6 study will be available at www.clinicaltrials.gov by searching on NCT02926833.

About KTE-C19

Kite Pharma’s lead product candidate, KTE-C19, is an investigational therapy in which a patient’s T-cells are engineered to express a CAR to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T-cells to kill cancer cells. KTE-C19 has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.