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Cellular Biomedicine Group (CBMG) Approved to Commence Phase I Trial (CALL-1) for C-CAR011 in Adult Patients with Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia (ALL) in China

On January 9, 2017 Cellular Biomedicine Group Inc. (CBMG) ("CBMG" or the "Company"), a clinical-stage biomedicine firm engaged in the development of effective immunotherapies for cancer and stem cell therapies for degenerative diseases, reported the approval and commencement of patient enrollment in China for its CALL-1 ("CAR-T against Acute Lymphoblastic Leukemia") Phase I clinical trial utilizing its optimized proprietary C-CAR011 construct of CD19 chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of patients with relapsed or refractory (r/r) CD19+ B-cell Acute Lymphoblastic Leukemia (ALL) (Press release, Cellular Biomedicine Group, JAN 9, 2017, View Source [SID1234517313]). The CALL-1 trial has begun enrollment with final data expected to be available at the end of 2017. Depending on the Phase I CALL-1 results, CBMG expects to initiate a larger Phase II clinical trial as soon as practicable.

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"Our CALL-1 trial represents the second CBMG-sponsored clinical trial after the recent launch of our CARD-1 trial in refractory DLBCL patients. This is another major corporate milestone and demonstrates CBMG’s ability to execute on our immuno-oncology plan and to forward our prioritized assets into clinical development in China," said Tony (Bizuo) Liu, Chief Executive Officer of CBMG.

CBMG’s CALL-1 Phase I dose-escalation trial will use the 3+3 design to evaluate the safety, efficacy and persistence of C-CAR011 in CD19+ r/r ALL patients.

"Relapsed or refractory CD19+ adult ALL patients have limited options and poor prognosis," said Dr. Li Yu from the PLA General Hospital ("PLAGH"), the Principal Investigator for the CALL-1 trial. "I am excited to be able to participate in the trial of C-CAR011 which may someday provide a treatment option for these patients."

"We are excited to launch this trial to better understand the potential C-CAR011 can have to address a large cancer population in China," said Dr. Yihong Yao, Chief Scientific Officer of CBMG.

About the CALL-1 Clinical Trial
CALL-1 is a Phase I single-site, single-arm dose-escalating trial consisting of three patient cohorts using escalating C-CAR011 cell dosing levels with three patients in each cohort. Phase I dose expansion will enroll an additional 6-12 patients to confirm the optimal dose. The primary end points are Dose-Limiting Toxicity (DLT) and Treatment Emergent Adverse Events (TEAE). Secondary endpoints will measure Overall Response Rate (CR + CRi, complete remission with incomplete hematopoietic recovery), MRD-CR rate at 8 weeks according to the NCCN Guideline Version 2.2016, Acute Lymphoblastic Leukemia, and overall survival at 6 months.

Dr. Li Yu, Director emeritus, Professor and Chief Physician of the Department of Hematology at the PLAGH in Beijing, China will conduct the trial. The PLAGH was founded in 1953 and is a top-ranking medical center in China, integrating medical care, education and research. The PLAGH has 125 clinical, medical and technological departments, 4,000 patient beds with annual volumes of more than 3.8 million outpatient visits, 110,000 admissions and over 65,000 surgical operations performed.

About C-CAR011
CBMG’s proprietary anti-CD19 chimeric antigen receptor T-cell (CAR-T) construct represents advancement over CBMG’s prior CBM-C19.1 construct, which completed a human proof-of-concept trial demonstrating an optimistic response rate with controllable toxicities. C-CAR011 is entirely engineered and manufactured in CBMG’s own GMP manufacturing facility in China.

About Acute Lymphoblastic Leukemia (ALL)
Acute Lymphoblastic Leukemia (ALL), also called acute lymphocytic leukemia, starts from the early type of white blood cells called lymphocytes in the bone marrow. The leukemia cells then invade the blood fairly quickly and may spread to other parts of the body, including the lymph nodes, liver, spleen, central nervous system (brain and spinal cord), and testicles (in males). The World Health Organization defines "acute" when greater than 20% of the cells in the bone marrow are blasts, which can progress quickly, and if untreated, would likely be fatal within months. According to the U.S. National Cancer Institute, 6,600 patients are diagnosed with ALL in the U.S. annually. Additionally, it is estimated that 27,000 patients in China will be diagnosed with ALL annually. While pediatric patients make up approximately 60% of the total and achieve an 85% effective cure rate, only 40% of Adult ALL patients achieve long-term disease-free survival.

Innate Pharma receives $15 million milestone payment from Bristol-Myers Squibb for continued exploration of lirilumab in combination with Opdivo

On January 9, 2017 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that, per the licensing agreement for lirilumab, Bristol-Myers Squibb has paid Innate Pharma a US$15 million milestone payment for the continued exploration of lirilumab in combination with Opdivo (nivolumab) (Press release, Innate Pharma, JAN 9, 2017, View Source [SID1234517308]).

This milestone payment follows the presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting (November 2016) of encouraging preliminary activity results from the cohort of patients with Squamous Cell Cancer of the Head and Neck (SCCHN) of a Phase I/II trial. These interim efficacy results – the first report for the combination of an anti-KIR antibody and an anti-PD-1 therapy – indicate that targeting both pathways with lirilumab and nivolumab respectively may provide enhanced clinical activity, particularly in PD-L1 positive tumors, with deep and durable responses in some patients.

Pierre Dodion, Chief Medical Officer at Innate Pharma, said: "The combination of lirilumab with nivolumab showed encouraging early efficacy signals in the initial part of the trial which support the strategy of simultaneously targeting the KIR and PD-1 pathways with lirilumab and nivolumab, respectively; the reported data point to broader potential for lirilumab. We look forward to further investigation of the combination in the Phase II part of this trial."

In total, Bristol-Myers Squibb is currently investigating lirilumab in six trials, across a range of solid and hematological cancer indications, in monotherapy and in combination with other agents, and Innate Pharma is responsible for conducting the EffiKIR trial, a randomized Phase II trial evaluating lirilumab as a single agent in patients with acute myeloid leukemia (see on clinicaltrials.gov).

About CA223-001: A Phase I/II Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of Anti-KIR (Lirilumab) Administered in Combination With Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors
CA223-001 is a Phase I/II dose escalation and cohort expansion study of lirilumab in combination with nivolumab in patients with advanced solid tumors.
During the dose escalation, patients with advanced solid tumors who progressed after ≥ 1 prior therapy received lirilumab 0.1–3.0 mg/kg once every 4 weeks (Q4W) plus nivolumab 3.0 mg/kg Q2W. Cohort expansion was initiated at the maximum dose of lirilumab 3.0 mg/kg Q4W plus nivolumab 3.0 mg/kg Q2W in patients with advanced solid tumors. The data reported at SITC (Free SITC Whitepaper) pertain to an expansion cohort in SCCHN. Key study endpoints include safety (primary), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and biomarker assessments.

The purpose of this Phase I/II open label study is to determine the safety of the combination of lirilumab and nivolumab and to explore the preliminary anti-tumor activity of the combination in patients with a range of advanced solid tumors.

FDA grants Roche’s cancer immunotherapy TECENTRIQ(atezolizumab) Priority Review in additional type of advanced bladder cancer

On January 9, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for TECENTRIQ (atezolizumab) for the treatment of people with locally advanced or metastatic urothelial carcinoma (mUC) who are ineligible for cisplatin chemotherapy, and are either previously untreated (first-line) or have disease progression at least 12 months after receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant) (Press release, Hoffmann-La Roche, JAN 9, 2017, View Source [SID1234517307]). Urothelial carcinoma accounts for 90 percent of all bladder cancers and can also be found in the renal pelvis, ureter and urethra.

"In May 2016, TECENTRIQ became the first treatment approved by the FDA for people with previously treated advanced bladder cancer in more than 30 years," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "We are committed to continue working with the FDA to make TECENTRIQ available to more people with this type of advanced bladder cancer, specifically those who are unable to tolerate cisplatin-based chemotherapy as an initial treatment."

This sBLA submission for TECENTRIQ is based on results from the Phase II IMvigor210 study, and the FDA will make a decision on approval by 30 April 2017. A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention or diagnosis of a serious disease.
TECENTRIQ is currently approved by the FDA to treat people with locally advanced or mUC who have disease progression during or following platinum-based chemotherapy or whose disease has worsened within 12 months of neoadjuvant or adjuvant platinum-based chemotherapy. TECENTRIQ is approved under accelerated approval for this indication based on tumour response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. TECENTRIQ is also approved for the treatment of people with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumour has EGFR or ALK gene abnormalities.

About the IMvigor210 study
IMvigor210 is an open-label, multicenter, single-arm Phase II study that evaluated the safety and efficacy of TECENTRIQ in people with locally advanced or mUC, regardless of PD-L1 expression. People in the study were enrolled into one of two cohorts. Cohort 1, upon which this sBLA submission is based, consisted of people who were ineligible for first-line cisplatin-based chemotherapy, and who had received no prior chemotherapies for locally advanced or mUC (i.e., first-line) or had disease progression at least 12 months after neoadjuvant or adjuvant chemotherapy. Cohort 2, which served as the basis for the FDA’s accelerated approval of TECENTRIQ in May 2016, included people whose disease had progressed during or following previous treatment with a platinum-based chemotherapy regimen, or who had disease progression within 12 months of treatment with a platinum-based neoadjuvant or adjuvant chemotherapy regimen. The primary endpoint of the study was objective response rate (ORR). Secondary endpoints included duration of response (DOR), overall survival (OS), progression-free survival (PFS) and safety.

About metastatic urothelial carcinoma
Metastatic urothelial cancer (mUC) is associated with a poor prognosis and limited treatment options. It is a disease that has seen no major advances for more than 30 years. UC is the ninth most common cancer worldwide, with 430,000 new cases diagnosed in 2012, and it results in approximately 145,000 deaths globally each year. Men are three times more likely to suffer from UC, compared with women, and the disease is three times more common in developed countries than in less developed countries.

About TECENTRIQ (atezolizumab)
TECENTRIQ is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death-ligand 1), which is expressed on tumour cells and tumour-infiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this interaction, TECENTRIQ may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells. TECENTRIQ is currently only approved in the US.

Amgen and Immatics Enter Strategic Collaboration to Develop Novel Bispecific Cancer Immunotherapies

On January 9, 2017 Amgen (NASDAQ:AMGN) and Immatics Biotechnologies GmbH, a leading company in the field of cancer immunotherapy, reported a research collaboration and exclusive license agreement to develop next-generation, T-cell engaging bispecific immunotherapies targeting multiple cancers (Press release, Amgen, JAN 9, 2017, View Source [SID1234517306]).

The collaboration will combine Immatics’ world-leading XPRESIDENT target discovery and T-cell receptor (TCR) capabilities with Amgen’s validated Bispecific T-cell Engager (BiTE) technology with the aim of creating novel oncology drugs. Amgen will be responsible for the clinical development, manufacturing and commercialization worldwide.

Under the terms of the agreement, Immatics will receive an upfront fee of $30 million and is eligible to receive over $500 million in development, regulatory and commercial milestone payments for each program and tiered royalties up to a double-digit percentage of net sales.

"We are very pleased to be entering this strategic collaboration with Amgen, which is contributing its bispecific T-cell engagers expertise, as together we look to develop novel immunotherapies that will deliver a step change in the treatment of several cancers. This collaboration also demonstrates Amgen’s confidence in Immatics’ world-leading immune-oncology target and TCR discovery capabilities," said Carsten Reinhardt, M.D., Ph.D., managing director and chief medical officer at Immatics.

"The intersection of immunology and oncology represents a promising and rapidly developing approach that can have a significant impact for patients with cancer," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We look forward to collaborating with Immatics to translate their unique target and TCR discovery capabilities combined with Amgen’s validated BiTE technology into novel therapies."

About T-cell Engaging Bispecific Cancer Immunotherapies

T-cell engaging bispecifics leverage the body’s immune system by redirecting the T-cell response towards cancer cells expressing specific tumor antigens. Immatics’ TCR-bispecifics and Amgen’s BiTE antibody constructs each possess two or more binding domains. One such binding domain specific to an intracellular antigen discovered by XPRESIDENT presented on the surface of a cancer cell; another such binding domain is designed to recognize a T-cell activator, such as CD3. This approach allows every T-cell to become activated and able to attack the tumor, independent of the T-cells’ intrinsic specificity. This bispecific approach is designed to improve the immunotherapies’ ability to eradicate malignant cells while avoiding damage to healthy tissues.

CTI BioPharma Announces Progress Of Lead Programs And Strategic Objectives For 2017

On January 9, 2017 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) reported positive progress on its lead programs in addition to key business priorities for 2017 (Press release, CTI BioPharma, JAN 8, 2017, View Source;p=RssLanding&cat=news&id=2234839 [SID1234517386]).

"Throughout 2016 we maintained our commitment to bringing new therapies to patients with unmet medical needs, and were successful in working with the FDA to remove the full clinical hold on pacritinib and get it back on the development track for the benefit of myelofibrosis patients," said Richard Love, Interim President and Chief Executive Officer of CTI BioPharma. "The PERSIST-2 clinical trial of pacritinib was highlighted as one of six late-breaking data presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) conference in December. We believe this oral presentation was well received by the hematology/oncology community, which recognizes the unmet need for myelofibrosis patients who are ineligible to receive or are not benefitting from the approved JAK1/JAK2 inhibitor, ruxolitinib. Additionally, the PIX306 confirmatory trial of our commercial product PIXUVRI(R)(pixantrone) continues to progress toward an announcement of top-line results later this year. If positive, this trial could provide the opportunity for full approval and label expansion by EMA, and discussions with the FDA about accelerated PIXUVRI approval in the US for the treatment of patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. We have also made significant effort at reducing our expenses and believe we are well positioned moving into 2017."

Recent Progress Update

Pacritinib

In January 2017, CTI BioPharma announced the U.S. Food and Drug Administration (FDA) removed the full clinical hold on studies being conducted under the Investigational New Drug (IND) application for pacritinib.

In December 2016, data from the randomized Phase 3 PERSIST-2 clinical trial comparing pacritinib with physician-specified best available therapy (BAT), including ruxolitinib, for treatment of patients with myelofibrosis whose baseline platelet counts are less than 100,000 per microliter was one of six late-breaking oral presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Patients in the trial were randomized to receive 200 mg pacritinib twice daily (BID), 400 mg pacritinib once daily (QD), or BAT. In those patients who had a chance to reach Week 24 (the primary analysis time point) at the time the clinical hold was imposed, the trial showed a statistically significant response rate in spleen volume reduction (SVR) in patients treated with pacritinib compared to BAT irrespective of prior treatment with ruxolitinib. The co-primary endpoint of reduction of Total Symptom Score (TSS) was not achieved but trended toward improvement in TSS. Although secondary objectives could not be evaluated formally due to the study not achieving one of the primary objectives, when the two pacritinib dosing arms were evaluated separately versus BAT, pacritinib BID showed a higher percent of SVR and TSS responses compared to BAT; whereas, pacritinib given QD showed only a higher percent SVR responses compared to BAT. There was no significant difference in overall survival (OS) across treatment arms, censored at the time of clinical hold. The most common treatment-emergent adverse events (AEs), occurring in 20 percent or more of patients treated with pacritinib within 24 weeks, of any grade, were gastrointestinal (generally manageable diarrhea, nausea and vomiting) and hematologic (anemia and thrombocytopenia) and were generally less frequent for BID versus QD administration. The most common serious treatment-emergent AEs (incidence of ≥5 percent reported in any treatment arm irrespective of grade) were anemia, thrombocytopenia, pneumonia and acute renal failure none of which exceeded 8 percent individually in any arm. The presentation was also selected to be part of the "2017 Highlights of ASH (Free ASH Whitepaper)" program designed to review significant scientific updates presented at ASH (Free ASH Whitepaper) with hematologists/oncologists at five locations across the U.S.

PIXUVRI

In January 2017, CTI BioPharma received a €7.5 million milestone payment from its partner Servier following achievement of a milestone associated with patient enrollment in the Phase 3 PIX306 clinical trial of PIXUVRI. The trial is a post-authorization trial as part of the conditional marketing authorization of PIXUVRI in the European Union (E.U.) The PIX306 is comparing PIXUVRI and rituximab with gemcitabine and rituximab in the setting of aggressive B-cell non-Hodgkin lymphoma (NHL). The trial continues to enroll patients.

2017 Key Objectives

Advance Marketing Authorization Application in E.U. and define regulatory pathway in U.S. for pacritinib. CTI BioPharma continues to have dialogue with the European Medicines Authority (EMA) on the Marketing Authorization Application (MAA) for pacritinib that had been previously filed by its former partner, Baxalta. At the time of the filing only data from the first Phase 3 clinical trial of pacritinib, PERSIST-1, was available. With the availability of results from the PERSIST-2 clinical trial and the recent completion of the PERSIST-2 clinical study report, CTI BioPharma believes that the best strategy currently to achieve marketing authorization is to utilize the combined clinical evidence from both Phase 3 trials. Accordingly, CTI BioPharma is evaluating whether to update the current application with the additional data from PERSIST-2 or to resubmit the MAA. Under either plan, CTI BioPharma would expect to pursue marketing authorization for the treatment of patients with myelofibrosis who are ineligible to receive, intolerant of or have insufficient response to the approved JAK1/JAK2 inhibitor, ruxolitinib.

CTI BioPharma also intends to discuss with the FDA the future development of pacritinib.

Initiate PAC203 trial. CTI BioPharma expects to initiate the PAC203 trial in the second quarter of 2017. The trial plans to enroll up to approximately 105 patients with primary myelofibrosis who have failed prior ruxolitinib therapy to evaluate the safety and the dose response relationship for efficacy (spleen volume reduction at 24 weeks) of three dose regimens: 100 mg once-daily, 100 mg twice-daily (BID) and 200 mg BID.

Secure ex-U.S. partner for pacritinib. CTI BioPharma intends to secure a partnership for the development and commercialization of pacritinib in certain territories outside the U.S.

Release top-line results of PIX306. CTI BioPharma expects to complete enrollment in the ongoing PIX306 trial of PIXUVRI and release top-line results by the end of 2017.

Financial

CTI BioPharma’s preliminary, unaudited estimates of its cash and cash equivalents balance as of December 31, 2016 is approximately $44.0 million. In January 2017, we received a €7.5 million milestone payment from Servier. CTI BioPharma expects that its cash burn (a non-GAAP financial measure), excluding cash inflows from future business development activities and proceeds from capital markets financing activities, would be approximately $65-75 million for 2017. The Company expects to meet its cash requirements for 2017 with existing cash and by partnering one or more product assets during the course of the year.

About Pacritinib

Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia and lymphoma. In addition to myelofibrosis, the kinase profile of pacritinib suggests its potential therapeutic utility in conditions such as acute myeloid leukemia, or AML, myelodysplastic syndrome, or MDS, chronic myelomonocytic leukemia, or CMML, and chronic lymphocytic leukemia, or CLL, due to its inhibition of c-fms, IRAK1, JAK2 and FLT3.

In August 2014, pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high risk myelofibrosis including, but not limited to, patients with disease-related thrombocytopenia (low platelet counts); patients experiencing treatment-emergent thrombocytopenia on other JAK2 inhibitor therapy; or patients who are intolerant of, or whose symptoms are not well controlled (sub-optimally managed) on other JAK2 therapy.

Pacritinib was evaluated in two Phase 3 clinical trials, known as the PERSIST program, for patients with myelofibrosis, with one trial in a broad set of patients without limitations on platelet counts, the PERSIST-1 trial; and the other in patients with low platelet counts, the PERSIST-2 trial. The PERSIST-1 trial met its primary endpoint of spleen volume reduction (35 percent or greater from baseline to Week 24 by MRI/CT scan). The PERSIST-2 trial met one of its co-primary endpoints, that of spleen volume reduction. The co-primary endpoint of reduction of Total Symptom Score (TSS) was not achieved but trended toward improvement in TSS.

Clinical studies under the investigational new drug (IND) for pacritinib were subject to a full clinical hold issued by the FDA in February 2016. In January 2017, the FDA removed the full clinical hold and stated that clinical trials may be resumed.

About PIXUVRI (pixantrone)

PIXUVRI is a novel aza-anthracenedione with unique structural and physiochemical properties. In May 2012, the European Commission granted conditional marketing authorization for PIXUVRI as a monotherapy for the treatment of adult patients with multiply relapsed or refractory B-cell aggressive NHL. The benefit of PIXUVRI treatment has not been established in patients when used as fifth line or greater chemotherapy in patients who are refractory to last therapy. The Summary of Product Characteristics (SmPC) has the full prescribing information, including the safety and efficacy profile of PIXUVRI in the approved indication. The SmPC is available at www.pixuvri.eu. PIXUVRI does not have marketing approval in the United States.

In September 2014, CTI BioPharma entered into an exclusive license and collaboration agreement, with Servier with respect to the development and commercialization of PIXUVRI. Under the agreement, CTI BioPharma retains full commercialization rights to PIXUVRI in Austria, Denmark, Finland, Germany, Israel, Norway, Sweden, Turkey, the United Kingdom and the U.S. while Servier has exclusive rights to commercialize PIXUVRI in all other countries.