On December 11, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the Phase III IMmotion151 study met its co-primary endpoint of investigator-assessed progression-free survival (PFS) and demonstrated that the combination of Tecentriq (atezolizumab) and Avastin (bevacizumab) provided a statistically significant and clinically meaningful reduction in the risk of disease worsening or death (PFS) in people whose disease expressed the PD-L1 (programmed death-ligand 1: Expression ≥1%) protein compared with sunitinib for the first-line treatment of people who have advanced or metastatic renal cell carcinoma (mRCC) (Press release, Hoffmann-La Roche, DEC 11, 2017, View Source [SID1234522504]).

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!

Observations of a pre-specified subgroup analysis of the Tecentriq and Avastin combination indicated that, in people whose disease expressed PD-L1, a numerical difference favouring Tecentriq was seen across all patient risk factor groups (favourable, intermed­iate and poor) compared to sunitinib; however, due to the study design these data could not be assessed for statistical significance and are descriptive only. Assessment of secondary endpoints is ongoing. Safety for the Tecentriq and Avastin combination appeared consistent with the known safety profile of the individual medicines and what was previously reported in the Phase II IMmotion150 study. No new safety signals were identified with the combination.

Results will be presented at an upcoming oncology conference in 2018. Top-line results from the co-primary endpoint of overall survival (OS) are not mature.

"We are encouraged by these results as they add to the emerging body of evidence that supports our rationale for this combination. We believe that the regimen of Tecentriq and Avastin may enhance the potential of the immune system in the initial treatment of advanced kidney cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We will discuss these data with health authorities globally and hope to bring this combination forward as a potential new treatment option to patients as soon as possible.’’
IMmotion151 is the second successive positive Phase III study of Tecentriq that includes an Avastin combination component as an initial treatment. This follows the positive Phase III non-squamous non-small cell lung cancer (NSCLC) IMpower150 study that showed Tecentriq and Avastin plus chemotherapy demonstrated a PFS advantage over Avastin plus chemotherapy.

About the IMmotion151 study
IMmotion151 is a Phase III multicentre, randomised, open-label study to evaluate the efficacy and safety of Tecentriq and Avastin versus sunitinib in people with inoperable, locally advanced or metastatic renal cell carcinoma (RCC) who have not received prior systemic active or experimental therapy. It enrolled 915 people globally who were randomised 1:1 to receive Tecentriq and Avastin, or sunitinib alone.

People in the Tecentriq and Avastin arm received Tecentriq at a fixed dose of 1200 milligrams (mg) and Avastin at a dose of 15 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 3 weeks until loss of clinical benefit or unacceptable toxicity. People in the sunitinib arm received sunitinib 50 mg orally, once daily for 4 weeks followed by 2 weeks rest until loss of clinical benefit or unacceptable toxicity.

The co-primary endpoints were PFS, as determined by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in people whose tumours expressed PD-L1 [PD-L1 expression ≥1 percent on immune cells (IC)], and OS in the overall study population (intention-to-treat, ITT). PD-L1 expression was prospectively assessed using an immunohistochemistry (IHC) test (SP142) developed by Roche Tissue Diagnostics.
Stratification factors included the presence or absence of liver metastases; level of IC staining for PD-L1 (≥1 percent vs. <1 percent) and Memorial Sloan-Kettering Cancer Center (Motzer) risk score. The Motzer prognostic scoring system predicts for OS based upon an individual’s baseline clinical and laboratory characteristics.
Depending on the presence of one or several of five variables (risk factors), patients are classified in one of the three risk groups: ‘Favourable’ with 0 risk factors, ‘Intermediate’ with 1–2 risk factors and ‘Poor’ with ≥ 3 risk factors.

About RCC
Kidney cancer remains one of the most common cancers in the world, accounting for over 140,000 deaths worldwide each year,1 with renal cell carcinoma (RCC) accounting for approximately 90% of all cases.2 Over 300,000 people are diagnosed with RCC every year and currently only about 1 in 10 people are alive beyond 5 years following diagnosis of metastatic disease.

RCC occurs when abnormal cells develop in the tissue of the kidneys, specifically in the small tubes (also known as tubules) where our blood is filtered.4 Typically, RCC is a single tumour in one kidney but, in rare cases, there can be multiple tumours, which can occur in one or both kidneys.

Despite recent progress in the field of kidney cancer, treatment options for people with the disease remains limited.

About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Tecentriq is already approved in the European Union, United States and more than 50 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer (mUC) who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

About Avastin (bevacizumab) in RCC
Avastin (bevacizumab) is an anti-VEGF inhibitor. VEGF (vascular endothelial growth factor) is a protein that stimulates the formation and maintenance of blood vessels and has been shown to play a key role in the development of RCC.
RCC tumours are highly vascularised, meaning they have many blood vessels and also exhibit a high concentration of VEGF5. There is, therefore a strong rationale for medicines such as Avastin that block the VEGF pathway. Avastin is the only currently available treatment for patients with mRCC that directly inhibits VEGF.

There is a strong scientific rationale to support further investigation of Tecentriq and Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat first-line advanced NSCLC and mRCC. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.
To learn more about the Roche approach to cancer immunotherapy please follow this link:
View Source

On December 11, 2017 Celgene Corporation (NASDAQ: CELG) and bluebird bio, Inc. (Nasdaq: BLUE) reported that updated results from the ongoing CRB-401 Phase 1 clinical study of bb2121, an investigational anti-B-cell maturation antigen (BCMA) CAR T cell therapy, in 21 patients with late-stage relapsed/refractory multiple myeloma will be presented in an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, Georgia (Press release, bluebird bio, DEC 11, 2017, View Source [SID1234522486]).

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 objective of this Phase 1 dose-escalation study is to evaluate safety and efficacy of bb2121 and determine a recommended Phase 2 dose.

"Celgene has a longstanding commitment to patients with multiple myeloma through our extensive research efforts in this deadly blood cancer," said Nadim Ahmed, President, Hematology and Oncology for Celgene. "Looking ahead, we see BCMA as an important target in this disease and we believe bb2121 has the potential to create significant impact on the treatment approach and outcomes for these patients."

"The growing body of bb2121 clinical data are building a compelling story, further supporting the importance of the therapy’s unique features," said Dave Davidson, M.D., chief medical officer, bluebird bio. "The responses achieved in this relapsed and refractory patient population, combined with the generally tolerable safety profile, reinforce the potential role of bb2121 as a groundbreaking CAR T therapy in multiple myeloma."

Durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma: Updated results from a multicenter study of bb2121 anti-BCMA CAR T cell therapy (Abstract #740)

Presenter: James Kochenderfer, M.D., the Center for Cancer Research at the National Cancer Institute in Bethesda, Maryland

Date: Monday, December 11, 3:00 pm (Oral presentation)
Location: Hall C1 (Georgia World Congress Center)

Session Title: Myeloma: Therapy, excluding Transplantation I

The open-label Phase 1 CRB-401 study (NCT02658929) is evaluating the preliminary safety and efficacy of bb2121 anti-BCMA CAR T cell in patients with relapsed and/or refractory multiple myeloma. The study also evaluated the recommended dose of bb2121 for future studies.

Patients on study were heavily pre-treated, with a median of 7 prior therapies (range: 3 – 14):

100% previously treated with lenalidomide and bortezomib
91% previously treated with pomalidomide and carfilzomib
71% previously treated with daratumumab
29% of patients were penta-refractory (bortezomib, lenalidomide, carfilzomib, pomalidomide, daratumumab)
All patients had at least one prior autologous stem cell transplant (ASCT).
As of the October 2, 2017 data cut-off, 21 patients had been enrolled and dosed in the dose-escalation phase of the study, in four dose cohorts: 50 x 106, 150 x 106, 450 x 106 and 800 x 106 CAR+ T cells. This multi-center study has enrolled patients at nine sites in the U.S with central manufacturing performed at Celgene.
Patients received a conditioning regimen of cyclophosphamide and fludarabine, followed by an infusion of bb2121 anti-BCMA CAR T cells. The CAR T cells were produced from each patient’s own blood cells, which were modified using a proprietary lentiviral vector encoding the anti-BCMA CAR.

Results in the active dose cohorts (150 x 106, 450 x 106 and 800 x 106 CAR+ T cells; N=18) were:

Median follow-up was 40 weeks (range: 6.6-69)
17/18 (94%) patients achieved an objective response
16/18 (89%) patients achieved at least a very good partial response (VGPR)
10/18 (56%) patients achieved a complete response (CR, N = 7), or unconfirmed complete response (N = 3)
9 of 10 patients who were evaluable for MRD status were found to be MRD-negative
Median PFS has not been reached in the active dose cohorts. The PFS at 6 months and 9 months was 81% and 71%, respectively.
Three patients in the dose-escalation who responded to therapy subsequently experienced disease progression.
In the dose-escalation phase, 15/21 (71%) of patients had cytokine release syndrome (CRS), mostly Grade 1 & 2, with 2 patients experiencing Grade 3 CRS (9%). Four patients received tocilizumab, 1 (Grade 2 CRS) received steroids and in each case the CRS resolved within 24 hours. The most common treatment-emergent Grade 3-4 AEs in 21 infused patients were cytopenias commonly associated with lymphodepleting chemotherapy including neutropenia (86%), anemia (57%) and thrombocytopenia (43%). There were two deaths in the active cohorts at 22 and 69 weeks following infusion, respectively. The first was due to cardiac arrest and the second was due to myelodysplastic syndrome; both subjects were in a myeloma CR at their last study assessment prior to death. Based on the findings during dose escalation, a dose expansion phase of 12 subjects has started testing doses between 150-450 x 106 CAR+ T cells. In the dose expansion phase, one patient treated at the 450 x 106 CAR+ T cells dose experienced Grade 4 neurotoxicity including focal cerebral edema and subarachnoid hemorrhage. This patient had a high tumor burden, and a history of subarachnoid hemorrhage. The event was successfully managed, and the patient remains in the response group. No other Grade 3/4 neurotoxicity was observed in the escalation or expansion cohort.

"To see these types of responses after one treatment with bb2121 in a heavily pre-treated patient population is very promising, and we are hopeful that CAR T therapy with bb2121 may become an important therapy in the fight against multiple myeloma, which remains an insidious and incurable disease," said James Kochenderfer, M.D., the Center for Cancer Research at the National Cancer Institute in Bethesda, Maryland and a primary investigator in the study."

bb2121 is an investigational compound that is not approved for any use in any country. bb2121 recently received Breakthrough Therapy Designation from the U.S. FDA and PRIME eligibility from the EMA. Celgene has also sponsored an open-label, single-arm phase 2 study (KarMMa), which is open to recruitment, to evaluate bb2121 further in patients with relapsed/refractory multiple myeloma. (NCT03361748)

About Celgene

Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more information, please visit www.celgene.com. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.

On December 11, 2017 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported initial data from the ongoing Phase 1b trial of its investigational Bruton’s Tyrosine Kinase (BTK) inhibitor, zanubrutinib (BGB-3111), in combination with its investigational anti-PD-1 antibody, tislelizumab (BGB-A317), in patients with B-cell malignancies at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, GA (Press release, BeiGene, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322104 [SID1234522525]). The initial dose escalation data suggest that the combination of zanubrutinib and tislelizumab had a manageable toxicity profile and anti-tumor activity in patients with B-cell malignancies.

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 initial data from this Phase 1b trial indicate that the combination of zanubrutinib and tislelizumab is tolerable with adverse events generally consistent with each therapeutic class. With only a short follow-up time, we have observed objective responses across different malignancy types in this heavily pre-treated population," commented Constantine Tam, MD, Disease Group Lead for Low Grade Lymphoma and Chronic Lymphocytic Leukemia at Peter MacCallum Cancer Centre, Director of Haematology at St. Vincent’s Hospital, Australia, and lead author of the presentation.

"Based on pre-clinical data suggesting the synergy of this combination, we are hopeful that this clinical trial will help to characterize the combination’s potential in treating patients with B-cell malignancies, particularly aggressive lymphomas," commented Jane Huang, MD, Chief Medical Officer, Hematology at BeiGene.

Summary of Results from the Ongoing Phase 1b Trial

The open-label, multi-center Phase 1b trial of zanubrutinib in combination with tislelizumab consists of a dose escalation portion to be followed by a dose expansion portion. Data presented at ASH (Free ASH Whitepaper) include patients enrolled at the first two dose levels of the dose escalation phase: dose 1 cohort of zanubrutinib at 320 mg once a day (QD) with tislelizumab at 2 mg/kg every three weeks (Q3W), and dose 2 cohort of zanubrutinib at 320 mg QD with tislelizumab at 5 mg/kg Q3W. Patients in the third dose cohort will receive zanubrutinib at 160 mg twice daily with tislelizumab at 200 mg Q3W.

As of September 15, 2017, the date of the most recent data cutoff, 25 patients, including 15 patients in the dose 1 cohort and 10 patients in the dose 2 cohort, had been enrolled. There were 13 patients with indolent lymphoma, including chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), marginal zone lymphoma (MZL), and Waldenström’s macroglobulinemia (WM), and 12 patients with aggressive lymphoma, including diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and transformed lymphoma. The median follow-up time was 5.1 months (0.4-14.1 months). Two cases of autoimmune hemolysis occurred in patients with WM in the dose 2 cohort, and one qualified as a dose-limiting toxicity (DLT). These events were not associated with a positive direct antiglobulin test and resolved with immunosuppressive therapy, but resulted in the decision to exclude further enrollment of WM patients in the trial. No further DLTs were observed after WM patients were excluded.

Among patients with indolent lymphoma, the most common adverse events (AEs) (occurring in ≥ 20% of patients) of any attribution were petechiae/purpura/contusion (31%) and thrombocytopenia (23%). Grade 3-4 AEs of any attribution reported in at least two patients included thrombocytopenia, anemia, and hemolysis (15% each). Besides the two cases of autoimmune hemolysis, there was one more immune-related event, a grade 4 autoimmune encephalitis. The patient was treated with aggressive immunosuppressive therapy and gradually improved over time.

Among patients with aggressive lymphoma, the most common AEs (occurring in ≥ 20% of patients) of any attribution were diarrhea, fatigue, pyrexia, upper respiratory tract infection (33% each), cough (25%), and nausea (25%). Grade 3-4 AEs of any attribution reported in at least two patients included pyrexia (17%). There was one patient with multiple occurrences of grade 2 and 3 pneumonitis.

At the time of data cutoff, the efficacy-evaluable population consisted of 25 patients. The median follow-up time was 5.1 months (0.4-14.1 months). Objective responses were observed in 10 patients (40%). By tumor type, two partial responses (PRs) were observed out of five patients with CLL, one complete response (CR) and one PR were observed out of five patients with FL, one very good partial response and one minor response were observed out of two patients with WM, one CR was observed out of five patients with DLBCL, and three PRs were observed out of five patients with transformed lymphoma.

About Zanubrutinib

Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of BTK that has demonstrated higher selectivity against BTK than ibrutinib (a BTK inhibitor currently approved by the U.S. Food and Drug Administration and the European Medicines Agency) based on biochemical assays, higher exposure than ibrutinib based on their respective Phase 1 experience in separate studies, and sustained 24-hour BTK occupancy in both the peripheral blood and lymph node compartments.

About Tislelizumab

Tislelizumab (BGB-A317) is an investigational humanized monoclonal antibody that belongs to a class of immuno-oncology agents known as immune checkpoint inhibitors. It is designed to bind to PD-1, a cell surface receptor that plays an important role in downregulating the immune system by preventing the activation of T-cells. Tislelizumab has high affinity and specificity for PD-1. It is differentiated from the currently approved PD-1 antibodies in an engineered Fc region, which is believed to minimize potentially negative interactions with other immune cells. Tislelizumab is being developed as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers. BeiGene and Celgene Corporation have a global strategic collaboration for tislelizumab for solid tumors.

On December 11, 2017 The OHSU Knight Cancer Institute and Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the presentation of preclinical data demonstrating that CG’806, a pan-FLT3/pan-BTK inhibitor, has broad and potent drug activity against acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and other hematologic disease subtypes (Press release, Aptose Biosciences, DEC 11, 2017, View Source [SID1234522544]). The data were highlighted in a poster presentation on Monday, December 11, 2017 at the American Society of Hematology (ASH) (Free ASH Whitepaper) 59th Annual Meeting & Exposition, being held December 9-12 in Atlanta, GA.

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 poster CG’806, a First-in-Class Pan-FLT3/BTK Inhibitor, Exhibits Potent Growth Inhibition as a Single Agent and in Combination with a BET Bromodomain Inhibitor and a Bcl2 Inhibitor Against AML and CLL Patient Samples, evaluated the activity of CG’806 on various hematologic malignancy cell lines and patient primary bone marrow specimens through the Beat AML Initiative. CG’806 exhibited broad and potent activity against primary patient samples over a diverse range of hematologic malignancy subtypes, including AML, CLL, myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN), and acute lymphoblastic leukemia (ALL).

The poster presentation can be accessed on the Events & Presentations section of the Aptose website at the following link.

"In patient samples and cultured cell lines, CG’806 demonstrated potent and broad inhibitory activity against hematologic malignancies alone and in combination," said Stephen E. Kurtz, Ph.D., lead author and Research Assistant Professor at the OHSU Knight Cancer Institute. "Both AML and CLL are in urgent need of effective therapies that provide more durable clinical responses. CG’806 represents a potential new treatment approach that warrants further development."

OHSU researchers used an ex vivo drug sensitivity assay to determine the activity of CG’806 as a single agent and in combination with the BET bromodomain inhibitor OTX-015 or the Bcl2 inhibitor venetoclax on freshly isolated primary patient samples. Across the four general subtypes of hematologic malignancies in the dataset with patient samples, there was broad sensitivity to CG’806, with 55% (90/164) AML, 48% (46/96) CLL, 22% (6/27) ALL, and 53% (14/26) MDS/MPN cases exhibiting an IC50 < 100nM. CG’806 demonstrated median IC50 values of 70nM and 140nM against primary AML and CLL cells, respectively. CG’806 also exerted potent picomolar to low-nanomolar IC50 anti-proliferative activity against human AML, B-ALL, mantle-cell lymphoma, Burkitt’s lymphoma, and diffuse large B-cell lymphoma cell lines. CG’806 in combination with OTX-015 demonstrated median IC50 values of 20nM and 40nM against primary AML and CLL cells, respectively. CG’806 in combination with venetoclax demonstrated median IC50 values of 20nM and 10nM against primary AML and CLL cells, respectively.

"Collaborating with OHSU and the Beat AML initiative has provided us an exceptional opportunity to explore the activity of CG‘806 against a large and diverse set of freshly isolated patient bone marrow samples from patients with AML, CLL and other hematologic malignancies," commented William G. Rice, Ph.D., Chairman and Chief Executive Officer of Aptose. "CG’806 continues to reveal compelling preclinical results that are superior to other FLT3 or BTK inhibitors, and we are eagerly preparing CG’806 for clinical studies and look forward to an IND submission in 2018."

Separately, Aptose and The University of Texas MD Anderson Cancer Center researchers also presented new data on CG’806 at ASH (Free ASH Whitepaper) (see press release here).

In addition to the abstracts that were presented at ASH (Free ASH Whitepaper), two additional abstracts on CG’806 and two abstracts on APTO-253, Aptose’s small molecule c-Myc Inhibitor, have been published on the ASH (Free ASH Whitepaper) abstracts site. All abstracts will become part of the permanent ASH (Free ASH Whitepaper) and Blood abstracts archive.

For more information on Beat AML refer to View Source

About CG’806

CG‘806 is an oral, first-in-class pan-FLT3/pan-BTK inhibitor. This small molecule demonstrates potent inhibition of all wild type and mutant forms of FLT3 tested (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinases operative in B cell malignancies, suggesting CG’806 may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.

On December 11, 2017 Kura Oncology, Inc. (Nasdaq:KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, today reported new findings supporting the development of lead candidate tipifarnib, a potent and selective inhibitor of farnesyl transferase, in the treatment of certain bone marrow cancers (Press release, Fate Therapeutics, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322103 [SID1234522555]). These results were featured in presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Atlanta. Copies of the posters are now available on the company’s website at www.kuraoncology.com.

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!

Among the findings presented at ASH (Free ASH Whitepaper) were the identification of CXCR4/CXCR2 expression ratio and bone marrow homing of myeloid cells as potential biomarkers of tipifarnib activity across the bone marrow cancers, myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML), further showing that the CXCL12/CXCR4 pathway is a potential therapeutic target of farnesyl transferase inhibitors.

"Although tipifarnib has previously demonstrated clinical responses in certain patients with AML and MDS, no molecular mechanism of action was identified that could explain the activity of the drug candidate in those patient populations," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "These new findings are exciting because they may define potential biomarkers for tipifarnib in bone marrow tumors and characterize a subgroup of patients that are most likely to derive clinical benefit from a targeted therapy such as tipifarnib."

Previously, Kura Oncology reported preliminary results from an ongoing Phase 2 clinical trial of tipifarnib in patients with peripheral T-cell lymphoma (PTCL) identifying the CXCL12/CXCR4 pathway as a potential target of tipifarnib. Specifically, high levels of CXCL12 gene expression and absence of single nucleotide gene variations in the 3′-untranslated region of the CXCL12 gene were associated with observed clinical activity of tipifarnib in these PTCL patients.

In the ASH (Free ASH Whitepaper) presentation entitled, "The CXCL12/CXCR4 Pathway As a Potential Target of Tipifarnib: Preliminary Results from an Open-Label, Phase II Study in Relapsed or Refractory Peripheral T-Cell Lymphoma," Kura Oncology extends these observations and provides data supporting the observed tipifarnib-derived clinical benefit for the CXCL12-positive population.

CXCL12 is a chemokine that is secreted in large amounts by lymph nodes, bone marrow stroma, liver, and lung, and plays key roles in tumor invasion, bone marrow homing and site of metastasis. Among its multiple functions, CXCL12 is essential for homing of myeloid cells to the bone marrow and lymphoid cells to lymph nodes and other organs.

Based on its initial observations in PTCL, the company investigated a role for the CXCL12/CXCR4 pathway and bone marrow homing of myeloid cells as biomarkers of tipifarnib activity in AML and MDS studies.

In the ASH (Free ASH Whitepaper) presentation entitled, "The CXCL12/CXCR4 Pathway As a Potential Target of Tipifarnib in Acute Myeloid Leukemia and Myelodysplastic Syndromes," Kura Oncology presented results that identify the ratio of CXCR4/CXCR2 gene expression and bone marrow homing of myeloid cells as potential biomarkers of the activity of tipifarnib in certain bone marrow tumors. The results were obtained by analyzing data from previous studies of tipifarnib in AML and MDS, as well as data from the ongoing Phase 2 clinical trial of tipifarnib in CMML.

"We were very encouraged to identify CXCR4/CXCR2 expression ratio and bone marrow homing as markers of tipifarnib’s activity in MDS, AML and CMML," said Antonio Gualberto, M.D., Ph.D., Chief Medical Officer at Kura Oncology. "Although our analysis is retrospective, the fact that we observe a consistent clinical benefit across different endpoints, treatment settings and indications gives us increased confidence in the potential for these biomarkers. Based on our preliminary data, we believe CXCL12/CXCR4 may have the potential to unlock the therapeutic value of farnesyl transferase inhibition across multiple bone marrow neoplasias."

About Tipifarnib

Kura Oncology’s lead candidate, tipifarnib, is a potent and selective inhibitor of the enzyme farnesyl transferase, a key cell signaling process implicated in cancer initiation and development. Tipifarnib has previously been studied in more than 5,000 patients in more than 70 clinical trials has a well-established safety profile and has demonstrated compelling and durable anti-cancer activity in certain patient subsets.

Leveraging advances in next-generation sequencing as well as emerging information about cancer genetics and tumor biology, Kura Oncology is seeking to identify patients most likely to benefit from tipifarnib. The company is conducting clinical and preclinical studies in multiple disease indications where tipifarnib has previously shown signs of activity with the goal of identifying and validating biomarkers associated with the observed clinical activity of tipifarnib.

In September 2017, Kura Oncology reported that its Phase 2 trial of tipifarnib in patients with HRAS mutant head and neck squamous cell carcinomas (HNSCC) achieved its primary efficacy endpoint prior to the completion of patient enrollment. The company is now planning to initiate a registration-enabling study of tipifarnib in HRAS mutant HNSCC in 2018.