On December 5, 2016 ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA), a rare cancer-focused innovative biotechnology company, reported clinical data on brigatinib, its investigational anaplastic lymphoma kinase (ALK) inhibitor, from the ongoing Phase 1/2 and pivotal ALTA trials in patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC) and intracranial central nervous system (CNS) metastases (Press release, Ariad, DEC 5, 2016, View Source;p=RssLanding&cat=news&id=2227425 [SID1234516925]). These data, being presented today at the International Association for the Study of Lung Cancer (IASLC) 17th World Conference on Lung Cancer (WCLC) being held in Vienna, showed that in patients with measurable brain metastases, the confirmed intracranial objective response rate (ORR) was 53 percent in the Phase 1/2 trial, and the confirmed intracranial ORR was 67 percent in Arm B (brigatinib 180 mg with seven-day lead-in at 90 mg once daily) in the ALTA trial. Median intracranial progression-free survival (PFS) in ALTA Arm B was 18.4 months.

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"Although crizotinib is initially effective in most patients with advanced ALK rearranged lung cancer, patients eventually develop resistance to crizotinib, often with new or progressive brain metastases," said presenting author Scott N. Gettinger, M.D., associate professor of medicine at Yale Cancer Center. "We are clearly encouraged by these data that demonstrate efficacy in the brain, with median intracranial PFS of over one and a half years, in patients with crizotinib refractory disease."

The ALTA Trial

The ALTA (ALK in Lung Cancer Trial of AP26113) trial enrolled 222 patients with ALK+ NSCLC who had been treated with and experienced disease progression on their most recent crizotinib therapy. Patients were randomized one-to-one to receive either 90 mg of brigatinib once per day (QD) (Arm A), or 180 mg QD with a seven-day lead-in at 90 mg QD (Arm B). In addition, patients were stratified by presence of brain metastases at baseline and best response to prior crizotinib therapy. Patient enrollment is complete, with the last patient enrolled in September 2015. Median follow-up in all patients with intracranial CNS metastases at baseline enrolled in the ALTA trial was 10.7 months as of May 31, 2016.

Phase 1/2 Study

The Phase 1/2 study of brigatinib included a dose-escalation portion that enrolled patients with advanced solid tumors, particularly those with NSCLC, who were either refractory to available therapies or had no standard treatment available to them. The Phase 2 portion of the trial includes five expansion cohorts. The trial enrolled 137 patients with 79 patients having ALK+ NSCLC. All but eight ALK+ NSCLC patients had failed prior crizotinib therapy. Patient enrollment in the trial is complete, with the last patient enrolled in July 2014. Median follow-up in ALK+ NSCLC patients with intracranial CNS metastases at baseline in the Phase 1/2 study was 24.9 months as of May 31, 2016.

Key Data from Oral Presentation on Patients with Baseline CNS Metastases from Phase 1/2 and ALTA Trials

Follow-up Data as of May 31, 2016; Last IRC Data in ALTA Trial was July 13, 2016, and Last Brain Scan in Phase 1/2 Trial was October 8, 2015

In the Phase 1/2 trial of brigatinib, 50/79 (63%) of ALK+ NSCLC patients had IRC-assessed baseline brain metastases. In the ALTA trial, 153/222 (69%) of ALK+ NSCLC patients had IRC-assessed baseline brain metastases. The efficacy analysis of Phase 1/2 trial data was based on an evaluable population (patients with at least one on-study brain scan, n=46), and the analysis of ALTA trial data was based on the intention-to-treat (ITT) population (n=153).
As of May 31, 2016, 42 percent and 55 percent of ALK+ NSCLC patients with brain metastases at baseline remained on study in the Phase 1/2 and ALTA populations respectively.
For patients with measurable brain lesions, the confirmed intracranial ORR was 53 percent (8/15) in the Phase 1/2 trial, and confirmed intracranial ORRs were 67 percent (12/18) in Arm B and 46 percent (12/26) in Arm A in the ALTA trial.
There were 31 patients in the Phase 1/2 trial with only non-measurable brain lesions, and of these, 35 percent had complete resolution of lesions. In ALTA, there were 55 patients in Arm B and 54 in Arm A with only non-measurable lesions; of these, 18 percent and seven percent of patients, respectively, had complete resolution of lesions.
For patients with any brain metastases at baseline:
Median duration of intracranial response in confirmed responders was 11.4 months in the Phase 1/2 trial (n=19); and was not yet reached in either arm of the ALTA trial (n=22 in Arm B and n=16 in Arm A).
Median intracranial PFS was 14.6 months in the Phase 1/2 trial (n=46); and 18.4 months (95% confidence interval [CI] 12.8 – not reached) and 15.6 months (95% CI 9.0-18.3 months) in ALTA Arm B and Arm A, respectively (n=73/n=80).
In the Phase 1/2 trial (n=46), for patients with any brain metastases at baseline, investigator-assessed whole-body ORR was 74 percent, median duration of response was 24 months and median PFS was 14.5 months. In ALTA (Arms B and A, respectively), for patients with any brain metastases at baseline, investigator-assessed whole-body ORR was 58 percent and 39 percent, median duration of response was not yet reached and 12 months, and median PFS was 12.9 months and 9.2 months.
In patients with any brain metastases at baseline in the ALTA trial, the most common treatment-emergent adverse events (AEs), grade 3 or higher (excluding neoplasm progression), were (n=151 treated; Arm B/A): increased creatine phosphokinase (CPK) (12%/1%), hypertension (7%/4%), increased lipase (3%/4%), malignant pleural effusion (1%/4%) and pneumonia (4%/1%).
The oral presentation, "Brigatinib Activity in Patients with ALK+ NSCLC and Intracranial CNS Metastases in Two Clinical Trials," (Abstract #4374, Oral ID OA08.06) will be presented today, Monday, December 5, 2016 in the Schubert 1 Auditorium at 11:57 am ET/16:57 GMT.

Investor and Analyst Briefing and Webcast

Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer of ARIAD will host an investor and analyst briefing on Wednesday, December 7 at 4:00 p.m. Central European Time (10:00 a.m. Eastern Time) to discuss the data presented at WCLC. Dr. Clackson will be joined by Karen Reckamp, M.D., associate professor in the Department of Medical Oncology & Therapeutics Research and co-director of the Lung Cancer and Thoracic Oncology Program at City of Hope Comprehensive Cancer Center (COHCCC).

The live webcast can be accessed by visiting the investor relations section of the Company’s website at View Source The call can be accessed by dialing 844-249-9386 (domestic) or 270-823-1534 (international) five minutes prior to the start time and providing the pass code 20888507. A replay of the call will be available on the ARIAD website approximately two hours after completion of the call and will be archived for three weeks.

About Brigatinib

Brigatinib is an investigational, targeted cancer medicine discovered internally at ARIAD. Brigatinib received Breakthrough Therapy designation from the FDA for the treatment of patients with ALK+ NSCLC whose tumors are resistant to crizotinib, and was granted orphan drug designation by the FDA for the treatment of ALK+ NSCLC. The FDA has accepted brigatinib’s New Drug Application based on data from an earlier datacut, and has granted ARIAD’s request for Priority Review. The FDA has set an action date of April 29, 2017 under the Prescription Drug User Fee Act (PDUFA). ARIAD intends to submit a Marketing Authorization Application (MAA) for brigatinib to the European Medicines Agency (EMA) in early 2017, based on this datacut.

ARIAD has also initiated the Phase 3 ALTA 1L trial to assess the efficacy and safety of brigatinib in comparison to crizotinib in patients with locally advanced or metastatic ALK+ NSCLC who have not received prior treatment with an ALK inhibitor. More information on brigatinib clinical trials, as well as the expanded access program (EAP) for ALK+ NSCLC can be found here.

On December 5, 2016 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported key presentations of clinical and scientific data related to its products at the San Antonio Breast Cancer Symposium (SABCS), being held in San Antonio, Texas, from December 6-10, 2016 (Press release, Spectrum Pharmaceuticals, DEC 5, 2016, View Source [SID1234516921]).

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For more information about the SABCS meeting and for a complete list of abstracts, please refer to the conference website at View Source

The following are key ROLONTISTM (eflapegrastim) related abstracts being presented at the SABCS meeting:

Abstract # Type Title First Author Date/Time
Location: Hall 1
OT1-01-11 Poster
Randomized phase 3 study of a novel, long-acting G-CSF (eflapegrastim) versus pegfilgrastim in the management of chemotherapy-induced neutropenia in early-stage breast cancer patients receiving docetaxel and cyclophosphamide (TC) (ADVANCE study)

Schwartzberg Wednesday, Dec 7
5:00 PM
P5-11-09 Poster
Sustained efficacy of eflapegrastim in breast cancer patients in a phase 2, open-label, dose-ranging study

Vacirca Friday, Dec 9
5:00 PM
P5-11-07 Poster
Pharmacokinetics of eflapegrastim in a phase 2 open-label dose-ranging study in breast cancer patients receiving TC regimen

Vacirca Friday, Dec 9
5:00 PM
P5-11-08 Poster
Immunogenicity of eflapegrastim in a Phase 2 Open-Label Dose-Ranging Study of eflapegrastim in Breast Cancer Patients Receiving TC Regimen

Vacirca Friday, Dec 9
5:00 PM
The following key poziotinib related abstract will be presented at the SABCS meeting:

Abstract # Type Title First Author Date/Time
Location: Hall 1
OT1-02-10 Poster
A phase 2 study of poziotinib in patients with HER2-positive metastatic breast cancer (MBC) who have received prior HER2 regimens for MBC

Lathrop Wednesday, Dec 7
5:00 PM

On December 5, 2016 Oxford BioMedica plc ("Oxford BioMedica" or "the Group") (LSE: OXB), a leading gene and cell therapy group, reported the findings from Novartis on their clinical trial (ELIANA) evaluating the efficacy and safety of CTL019, an investigational chimeric antigen receptor T cell (CAR T) therapy, in relapsed/refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL). Oxford BioMedica produces the lentiviral vector expressing CTL019 and has a CAR-T partnership with Novartis.

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The findings were presented during an oral session on Saturday 3rd December 2016 at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting (Abstract #221, December 3, 4:00-5:30 p.m.). Novartis reported that the global Phase II study found that 82% (41 of 50) of infused patients achieved complete remission or complete remission with incomplete blood count recovery at three months post CTL019 infusion. For all patients with complete remission, no minimal residual disease was detected. In addition, the estimated relapse-free rate among responders was 60% (95% CI: 36, 78) six months after infusion with CTL019. Novartis confirmed their intention to file CTL019 with the US Food and Drug Administration (FDA) in early 2017 for pediatric and young adult patients with r/r B-cell ALL.

John Dawson, Chief Executive Officer of Oxford BioMedica, commented: "We are pleased that Novartis has reported exciting progress with its investigational therapy CTL-019, and that Novartis confirm their commitment to advancing CTL019 and working closely with the FDA and EMA in the coming months."

On December 5, 2016 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported the presentation of data from a Phase 2 clinical trial of oral rigosertib and azacitidine in higher-risk myelodysplastic syndromes (HR-MDS) at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California (Press release, Onconova, DEC 5, 2016, View Source [SID1234516918]).

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"The complete remission rate amongst HMA-naïve HR-MDS patients is higher and responses occur more rapidly and durably with the oral rigosertib combination compared to historic single-agent azacitidine," commented Lewis R. Silverman, M.D., lead investigator in the trial and Associate Professor of Medicine, Hematology and Medical Oncology, at the Icahn School of Medicine at Mount Sinai. "Furthermore, the addition of oral rigosertib to azacitidine does not substantially change the adverse event profile of single-agent azacitidine, and thus may overcome the limitations identified in other HMA-based combinations."

The current standard of care for higher-risk MDS patients is one of two approved hypomethylating agents (azacitidine and decitabine, approved by the FDA in 2004 and 2006). Although these drugs are currently the standard of care in HR-MDS therapy, their overall response rate and duration of benefit is limited to a subset of eligible patients and all responding patients ultimately progress. Thus, there is an urgent need for improving therapeutic options for newly diagnosed HR-MDS patients. The 09-08 trial tested oral rigosertib in combination with injectable azacitidine in a dose ranging study (Phase 1), followed by an expansion cohort (Phase 2) to evaluate the efficacy and safety of the combination. Both 1st-line and 2nd-line HR-MDS patients were included in the study.

Summary of Presented Data from the 09-08 Combination Therapy Trial

Patient Demographics:

Thirty-three of 40 MDS patients enrolled were evaluable for response at the time of this analysis.
The median age was 66, with 73% of male patients. ECOG performance status was 0 or 1 in 95% of the patients. IPSS-R distribution was: 7.5% Low, 12.5% Intermediate, 37.5% High, 32.5% Very High and 10% unknown.
Safety/Tolerability of the Combination:

Oral rigosertib (560 mg qAM, 280 mg qPM) was administered on Day 1-21 of a 28-day cycle. Azacitidine 75 mg/m2/day SC or IV was administered for 7 days starting on Day 8.
The combination of oral rigosertib and azacitidine was well tolerated.
Adverse events of Grade ≥3 experienced across all cycles with the combination included thrombocytopenia (33%), neutropenia (30%), haematuria (13%), dysuria (8%), diarrhoea (3%) and arthralgia (3%).
Notably, the side effects were similar to those previously reported for azacitidine administered alone.
Efficacy of the Combination:

Thirty-three (20 HMA naïve; 13 HMA resistant) MDS patients were evaluable for efficacy analysis per IWG 2006 criteria (Cheson et al., Blood 2006).
25 of 33 (76%) patients responded per IWG — 85% of HMA naïve patients experienced a response and 62% of HMA resistant patients experienced a response.
7 of 20 (35%) HMA naïve and 1 of 13 (8%) HMA-resistant patients achieved a complete remission (CR). The median duration of CR was 8.0 months, which compares very favorably to the historic duration of CR and PR with single-agent azacitidine of 3.2 months1.
Hematologic improvement (HI) was observed in 11 of 33 patients (33%) and the median duration of response was 7.4 months for erythroid response, 8 months for platelet response, and 6.2 months for neutrophil response. Marrow CR was observed in 16 of 33 (48%) patients and the median duration of response was 12.3 months. Marrow CR combined with HI was observed in 10 of 33 (30%) patients.
The poster entitled, "Combination of Oral Rigosertib and Injectable Azacitidine in Patients with Myelodysplastic Syndromes (MDS): Results from a Phase II Study," was presented by Dr. Shyamala Navada of Mount Sinai School of Medicine at the Myelodysplastic Syndromes Session on Sunday, December 4, 2016 at the ASH (Free ASH Whitepaper) Annual Meeting in San Diego, California. A copy of the poster is available by visiting the Scientific Presentations section under the Investors & Media tab of Onconova’s website.

"We are pleased by the positive efficacy signal observed over extended periods of treatment, and the acceptable tolerability of oral rigosertib and azacitidine in 1st-line HR-MDS," stated Ramesh Kumar, Ph.D., President and CEO of Onconova. "We presented Phase 2 data to the FDA as part of our End-of-Phase 2 meeting in September 2016, and based on these discussions, we are designing a randomized, placebo controlled Phase 3 clinical trial comparing the combination of oral rigosertib plus azacitidine to azacitidine plus placebo in 1st-line HR-MDS patients with the primary composite endpoint of CR and PR rate per 2006 IWG criteria. Based on our discussions with the FDA the primary efficacy endpoint of this trial will be composite response and not survival, permitting accelerated evaluation of outcomes."

Comprehensive Safety Assessment of Rigosertib in MDS Patients

In a second poster at the conference a safety review of 557 MDS/AML patients treated with rigosertib in clinical studies, including the randomized Phase 3 ONTIME trial was presented. The poster entitled, "Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)," can be accessed by visiting the Scientific Presentations section under the Investors & Media tab of Onconova’s website.

On December 5, 2016 Dynavax Technologies Corporation (NASDAQ: DVAX) reported clinical data from an ongoing Phase 1/2, two-part clinical trial evaluating intratumoral administration of SD-101 in the treatment of low-grade lymphoma (Press release, Dynavax Technologies, DEC 5, 2016, View Source [SID1234516916]). The combination of intratumoral SD-101 and low-dose irradiation resulted in tumor regression in untreated tumor sites as well as in the treated tumors. Treatment was well-tolerated and changes in T cell populations consistent with stimulation of anti-tumor immunity were observed in the treated lesions. These data were presented in a poster session on Sunday at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California.

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Data from the dose escalation and expansion phase of the study were reported from 28 evaluable patients. None of the patients had received prior treatment for their low-grade lymphoma. The primary endpoints of the trial are maximum tolerated dose (MTD) and evaluation of the safety of intratumoral SD-101 in combination with low dose radiotherapy. In addition, the trial is evaluating anti-tumor activity, pharmacodynamics, and duration of response. Doses ranged from 1 mg to 8 mg per injection in successive cohorts.

Key findings presented include:

Of the 28 evaluable patients treated across all dose levels, 3 had a partial response (PR) and1 had a complete response (CR) as measured by Cheson criteria.
Durable abscopal tumor shrinkage was observed in the majority of patients.
Confirming observations in the dose escalation phase, the most common treatment-related treatment emergent adverse events (TEAEs) in the expansion phase were flu-like symptoms, consistent with the engagement of TLR9 and the induction of interferon-alpha.
Increases in CD8+ cells were observed in the injected tumor, and correlated with an increased abscopal tumor shrinkage
"The clinical data emerging from our SD-101 program continues to be encouraging. We look forward to providing updates from our ongoing clinical trials," stated Eddie Gray, chief executive officer of Dynavax Technologies. "We will discuss this program and our oncology pipeline in our cancer R&D Day which will be webcast live on December 9th at 8:30 a.m. EST."

About SD-101

SD-101 is Dynavax’s proprietary, second-generation, Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide. SD-101 is being studied for its multiple anti-tumor activities in innate immune cells and activation of plasmacytoid dendritic cells to stimulate T cells specific for antigens released from dying tumor cells. TLR9 agonists such as SD-101 enhance T and B cell responses and provide potent Type 1 interferon induction and maturation of plasmacytoid dendritic cells to antigen-presenting cells. SD-101 is being evaluated in several Phase 1/2 oncology studies to assess its safety and activity.

For information about SD-101 trials that are currently recruiting patients, please visit www.clinicaltrials.gov.