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Aduro Biotech Completes Enrollment in Phase 2b ECLIPSE Trial in Metastatic Pancreatic Cancer

On September 8, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that it has completed enrollment in the Phase 2b ECLIPSE trial of its novel LADD and GVAX immunotherapies being developed for the treatment of metastatic pancreatic cancer. The randomized, controlled three-arm trial enrolled 303 patients in the United States and Canada (Press release, Aduro BioTech, SEP 8, 2015, View Source;p=RssLanding&cat=news&id=2085917 [SID:1234507460]). Top line results are expected in the first half of 2016.

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ECLIPSE was designed to evaluate the safety, immune response and efficacy of the combination immunotherapy of CRS-207 and GVAX Pancreas compared to chemotherapy. The trial also included a treatment arm to evaluate CRS-207 as a monotherapy. The primary endpoint of the trial is overall survival in the primary cohort of patients who have received two or more prior therapies for metastatic disease. A second cohort of patients who received one prior therapy for metastatic disease is also being evaluated.

"This is a significant clinical trial in the pancreatic cancer field which has the potential to yield important information on the role of Aduro’s immunotherapy combination in this indication," said Vincent Picozzi, M.D., director of the Pancreatic Center of Excellence at the Virginia Mason Clinic. "Very few therapeutic options exist for metastatic pancreatic cancer patients, especially after initial chemotherapy, and this field could benefit greatly from more varied and attractive therapy options."

"The fight against metastatic pancreatic cancer continues to be arduous," said Dirk G. Brockstedt, Ph.D., senior vice president of research and development at Aduro. "We are encouraged by data from long-term survivors in our Phase 2a clinical trial and look forward to results from our Phase 2b ECLIPSE trial. We would like to thank our investigators, and more importantly the patients and their families, for their participation and support in our trials and development of our technologies in this indication."

The ECLIPSE trial was initiated following a Phase 2a trial which demonstrated efficacy of the immunotherapy combination with CRS-207 and GVAX Pancreas compared to GVAX Pancreas alone in a randomized, controlled, multi-center trial in metastatic pancreatic cancer patients. Results of the Phase 2a clinical trial, published in the Journal of Clinical Oncology (JCO), indicated the median overall survival of Arm A patients receiving the combination regimen of CRS-207 and GVAX Pancreas was 6.1 months compared to 3.9 months for Arm B patients receiving GVAX monotherapy (HR=0.5930, one-sided p=0.0172).

Overall, the combination immunotherapy was well-tolerated. Of the 93 patients enrolled, the most common Grade 3 adverse events were transient lymphopenia, fevers, elevated liver enzymes and fatigue.

In 2014, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for Aduro’s pancreatic cancer combination treatment consisting of CRS-207 and GVAX Pancreas based on results from the Phase 2a clinical trial of patients with metastatic pancreatic cancer. According to the FDA, Breakthrough Therapy designation is for a drug candidate that treats a serious or life-threatening condition for which preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinically significant endpoint over available therapies.

About CRS-207

CRS-207 is one of a family of product candidates based on Aduro’s live-attenuated, double-deleted (LADD) Listeria monocytogenes immuno-oncology platform that are designed to induce potent innate and adaptive immune responses. CRS-207 has been engineered to express the tumor-associated antigen mesothelin, which is over-expressed in many cancers including mesothelioma and pancreatic, non-small cell lung, ovarian and gastric cancers.

About GVAX Pancreas

GVAX Pancreas is one of a family of GVAX immunotherapies derived from human cancer cell lines that are genetically modified to express granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune system-stimulating cytokine. GVAX Pancreas is derived from human pancreatic cancer cell lines and is designed to activate specific T cell immunity to pancreatic cancer antigens, including mesothelin.

Five Prime Therapeutics Initiates Patient Dosing in Phase 1a/1b Trial Evaluating the Immunotherapy Combination of FPA008 and OPDIVO (nivolumab) in Six Tumor Types

On September 8, 2015 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing novel protein therapeutics for cancer and inflammatory diseases, reported that it has initiated patient dosing in the Phase 1a/1b clinical trial evaluating the immunotherapy combination of FPA008, Five Prime’s monoclonal antibody that inhibits colony stimulating factor-1 receptor (CSF1R), with OPDIVO (nivolumab), Bristol-Myers Squibb’s PD-1 immune checkpoint inhibitor, in six tumor types (Press release, Five Prime Therapeutics, SEP 8, 2015, View Source [SID:1234507422]).

FPA008 and OPDIVO are part of a new class of cancer treatments known as immunotherapies that are designed to harness the body’s own immune system to fight cancer. FPA008 targets macrophages and monocytes, which are activated or elevated in multiple disease settings. In cancer, tumor-associated macrophages suppress the immune system’s ability to kill cancer cells. OPDIVO is approved in the United States, Japan and the European Union for metastatic melanoma, and in the United States and European Union for squamous non-small cell lung cancer. OPDIVO is being evaluated as a mono therapy, as well as in combination with other agents, across multiple tumor types in more than 50 clinical trials. Preclinical data suggest that combining antibodies targeting PD-1 and CSF1R may lead to an enhanced anti-tumor immune response compared to either drug alone.

"We hope that targeting tumor suppressing macrophages in addition to a known immune checkpoint will allow us to harness more of the immune system’s anticancer activity, and will make durable responses a reality for more of our patients," said Julie Brahmer, M.D., Associate Professor of Oncology and Interim Director at the Sidney Kimmel Comprehensive Cancer Center (Johns Hopkins Bayview campus) and a Principal Investigator for the trial. "We look forward to participating in this trial, which will generate important information about the potential of this immunotherapy combination across a number of tumor types, including many where patients have few effective treatments."

"We are excited about the potential of FPA008 as a novel immuno-oncology therapeutic and about combining it with OPDIVO in this clinical collaboration with Bristol-Myers Squibb. We believe that targeting the CSF1R and PD-1 pathways in tandem may produce a synergistic treatment effect against a variety of tumors," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "Five Prime looks forward to enrolling this study, as it will provide us a wealth of information about this novel therapeutic combination and will further guide our development of FPA008 in oncology."

During Phase 1a, Five Prime will evaluate the safety, pharmacokinetics and biomarkers of escalating doses of FPA008 as a monotherapy, as well as in combination with the approved 3 mg/kg dose of nivolumab. Approximately 30 patients with advanced cancers are expected to be enrolled during the Phase 1a part of the study and both drugs will be administered every two weeks. In the Phase 1b part of the study, Five Prime will evaluate the safety, tolerability and preliminary efficacy of the selected dose of FPA008 in combination with nivolumab in approximately 240 patients, as a front-line therapy for melanoma; as second-line therapy for squamous cell carcinoma of the head and neck, pancreatic cancer, and malignant glioma; as a second- or third-line therapy for non-small cell lung cancer (NSCLC); and as a third-line therapy for colorectal cancer. Tumor biopsies will be obtained both pre-treatment and one month post-treatment in a subset of patients to analyze the immune response within the tumor microenvironment, and Five Prime will use this analysis to further guide FPA008’s development in oncology.

Under the terms of the clinical collaboration, BMS made a one-time payment of $30 million to Five Prime and is responsible for external study costs, the costs for OPDIVO, and half of the costs for FPA008 used in the Phase 1b part of the trial. The study design will be described in further detail in a trial-in-progress presentation at the International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper), to be held September 16-19, 2015 in New York City. Five Prime expects to complete Phase 1a dose escalation and expand into Phase 1b with the selected dose of FPA008 in late 2015 or early 2016.

About FPA008

FPA008, Five Prime’s antibody that inhibits colony stimulating factor-1 receptor (CSF1R), targets macrophages and monocytes, which are activated or elevated in multiple disease settings. In cancer, tumor-associated macrophages suppress the immune system’s ability to kill cancer cells. In joint diseases, such as PVNS and RA, synovial macrophages play a central role in the disease process. Five Prime is evaluating the immunotherapy combination of FPA008 and OPDIVO (nivolumab), Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor, in six tumor types in a Phase 1a/1b clinical trial. Five Prime is also conducting a Phase 1/2 trial of FPA008 in pigmented villonodular synovitis (PVNS), a joint tumor driven by the CSF1 pathway and an orphan disease, and a Phase 1 study in rheumatoid arthritis.

FDA grants Roche's alectinib Priority Review for specific type of ALK-positive lung cancer

On September 8, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s New Drug Application (NDA) and granted Priority Review for alectinib (known as Alecensa in Japan and the U.S.), an oral investigational anaplastic lymphoma kinase (ALK) inhibitor, for the treatment of people with ALK-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib (Press release, Hoffmann-La Roche , SEP 8, 2015, View Source [SID:1234507421]). Alectinib was granted Breakthrough Therapy Designation by the FDA in June 2013 for people with ALK-positive NSCLC whose disease progressed on crizotinib.

"Alectinib was granted Priority Review by the FDA based on results from two studies showing the medicine shrank tumours in people with ALK-positive NSCLC that progressed on crizotinib," said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head of Global Product Development. "There is a need for new treatment options in this patient population, especially because the disease often spreads to the brain at progression."

A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. The NDA for alectinib includes data from two Phase II studies (NP28761 and NP28673), and the FDA will make a decision on approval by 4 March 2016.

ALEX, an ongoing, global randomised Phase III study is comparing alectinib to crizotinib as an initial (first-line) treatment for people with advanced NSCLC whose tumours were characterised as ALK-positive by a companion immunohistochemistry (IHC) test developed by Roche Diagnostics.

About the NP28761 and NP28673 Studies
Results from the Phase II NP28761 and NP28673 studies were recently presented at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper).

NP28761 is a North American, single-arm, open-label, multicentre trial evaluating the safety and efficacy of alectinib in 87 people with ALK-positive NSCLC whose disease progressed on crizotinib.

– Response assessment by an independent review committee (IRC) showed that alectinib shrank tumours (objective response rate, ORR) in 47.8% (95% confidence interval [CI] 35.6%-60.2%) of people treated with alectinib, as measured by Response Evaluation Criteria in Solid Tumours (RECIST v1.1).
– Investigator assessment showed that alectinib shrank tumours in this group of people with a similar response rate (ORR of 46.0%, [95% CI 35.2%-57.0%]).

– Activity was also observed in the central nervous system (CNS), as shown by a CNS ORR by IRC of 68.8% (95% CI 41.3%-89.0%) in people whose disease had already spread to the brain or other parts of the CNS at study entry.

– People whose tumours shrank in response to alectinib continued to respond for a median of 7.5 months (duration of response [DOR], immature data).

– The immature median progression-free survival (PFS) was 6.3 months (95% CI 5.5 months–not estimable) based on 40% of events.

In study NP28761, alectinib demonstrated a safety profile consistent with that observed in previous studies.
– The most common Grade 3 or higher adverse events were increased muscle enzymes (increased blood levels of creatine phosphokinase; 8%), increased liver enzymes (alanine aminotransferase; 6%, and aspartate aminotransferase; 5%) and shortness of breath (dyspnea; 3%).

NP28673 is a global, single-arm, open-label, multicentre trial evaluating the safety and efficacy of alectinib in 138 people with ALK-positive NSCLC whose disease progressed on crizotinib.

– An IRC analysis showed that alectinib shrank tumours (ORR of 50.0%, [95% CI 40.8%-59.1%]) in this group of people, as measured by RECIST.

– Assessment by investigator was consistent with the IRC and also showed that alectinib shrank tumours in this group of people (ORR of 47.8%, [95% CI 39.3%-56.5%]).

– Activity was also observed in the CNS, as shown by a CNS ORR by IRC of 57.1% (95% CI 39.4%-73.7%) in people whose disease had already spread to the brain or other parts of the CNS at study entry.

– People who achieved a response continued to respond for a median of 11.2 months (DOR, immature data based on 33% of events, [95% CI 9.6 months-not estimable]).

– The median PFS for people who received alectinib was 8.9 months (95% CI 5.6 months-11.3 months) based on 58% of events.
Alectinib demonstrated a safety profile in study NP28673 consistent with that observed in previous studies.
– The most common Grade 3 or higher adverse event was shortness of breath (dyspnea; 4%).

About alectinib
Alectinib (RG7853/AF-802/RO5424802/CH5424802) is an oral medicine created at Chugai Kamakura Research Laboratories for certain people with NSCLC whose tumours are identified as ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history. The people whose NSCLC is ALK-positive almost always have adenocarcinoma.
Early studies with alectinib have shown activity on brain metastases, indicating that the drug may be taken up in the brain. The brain is protected by the Blood-Brain Barrier, a network of tightly joined cells that line the inside of the blood vessels in the brain and spinal cord. One of the ways the Blood-Brain Barrier prevents molecules from affecting the brain is to actively eject them from the barrier through a process known as ‘active efflux’. The active efflux system does not recognise alectinib, which means that it may travel into and throughout brain tissue.

The Global Phase III studies of alectinib include a companion test developed by Roche Diagnostics. Alectinib is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.

About Roche in lung cancer
Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have two approved medicines to treat certain kinds of lung cancer and more than 10 medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

DelMar Pharmaceuticals Presents Clinical Protocol for Advancement of VAL-083 into Phase IV Studies as a Treatment for Non-Small Cell Lung Cancer

On September 8, 2015 DelMar Pharmaceuticals, Inc. (OTCQX: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported an overview of its planned clinical trial protocol for Company’s lead product candidate VAL-083 (dianhydrogalactitol) in the treatment of non-small cell lung cancer (NSCLC) (Press release, DelMar Pharmaceuticals, SEP 8, 2015, http://ir.delmarpharma.com/news/detail/779/delmar-pharmaceuticals-presents-clinical-protocol-for-advancement-of-val-083-into-phase-iv-studies-as-a-treatment-for-non-small-cell-lung-cancer [SID:1234507420]).

The Company presented the VAL-083 NSCLC clinical development plan in a poster entitled, "Post-Market Clinical Trial of Dianhydrogalactitol in the Treatment of Relapsed or Refractory Non-Small Cell Lung Cancer" at the 16th World Conference on Lung Cancer in Denver, Colorado.

VAL-083 is a "first-in-class" bi-functional alkylating agent meditating inter-strand DNA crosslinks at N7 of guanine that has been approved by the Chinese Food and Drug Administration (CFDA) for the treatment of lung cancer. However, use of VAL-083 in China has been limited by a lack of modern data, poor distribution, and preference for targeted therapies such as tyrosine kinase inhibitors (TKIs) in the modern era.

The study will enroll up to 20 adult patients with NSCLC in an open-label post market Phase IV clinical trial to investigate the activity of VAL-083 in NSCLC patients who have failed standard platinum doublet therapy. The primary goal is the assessment disease control rate, defined as objective response rate, complete (CR) and partial (PR) response rates, and stable disease (SD). Secondary endpoints will include evaluation of progression free survival (PFS) and overall survival (OS). Results will provide guidance to treating physicians under the context of VAL-083’s current approval in China and clinical proof-of-concept to support DelMar’s global development of VAL-083 as a potential new treatment for NSCLC.

The clinical trial will be initiated in Shanghai under the terms of DelMar’s collaboration with Guangxi Wuzhou Pharmaceutical (Group) Co., Ltd. Under the terms of the collaboration, Guangxi Wuzhou Pharmaceuticals is responsible for funding VAL-083 clinical research in China and DelMar is responsible for management of the clinical trials.

"Earlier this year, we presented preclinical data supporting the potential of VAL-083 as a valuable therapeutic option in the modern treatment of lung cancer, particularly in patients who have failed or are unlikely to respond to current standard of care. Our research also suggests that the combination of VAL-083 with either cisplatin or oxaliplatin provides a super-additive (synergistic) effect against NSCLC cell lines, including those resistant to TKI therapy in vitro," stated Jeffrey Bacha, president & CEO of DelMar Pharmaceuticals. "The upcoming Phase IV trial will further evaluate VAL-083’s potential to address a significant unmet need in platinum drug-resistant NSCLC. The clinical outcomes from this study will be important in developing additional CFDA treatment guidelines to expand VAL-083 beyond its currently approved indication in lung cancer in China."

"Importantly, we believe data from this post-market study in China will also establish global proof-of-concept to support a global clinical development program with VAL-083 in NSCLC," Mr. Bacha added.

The trial will follow the dosing regimen in accordance with the approved label in China. Patients will receive VAL-083 intravenous (IV) dose of 40 mg/day for five consecutive days, with one to two weeks rest, for two courses, followed by maintenance therapy 40 mg/day IV for five consecutive days every 28 days. Patients will continue to receive treatment until withdrawal criteria are met or the patient receives up to 12 cycles of therapy, whichever comes first. Patients will be monitored for objective responses, progression-free survival, survival, and quality-of-life. Following tumor assessments at screening, evaluation of tumor response conforming to RECIST v1.1 will be documented prior to every other new 28-day maintenance treatment cycle, commencing with maintenance Cycle #2.

PHASE IV CLINICAL STUDY OF DIANHYDROGALACTITOL (VAL-083) IN RELAPSED OR REFRACTORY NSCLC

Protocol Summary

This is an open label post-market Phase IV study of VAL-083 in treatment of NSCLC patients who have failed standard platinum doublet therapy. Up to 20 patients will be enrolled into the study. Study patients will receive VAL-083 intravenous (IV) dose of 40 mg/day for five consecutive days, with 1-2 weeks rest, for two courses, followed by maintenance therapy 40 mg/day IV for five consecutive days every 28 days. Patients will continue to receive treatment until withdrawal criteria are met or the patient receives up to 12 cycles of therapy, whichever comes first. Patients will be monitored for objective responses, progression-free survival, survival, and quality-of-life (using a quality-of-life instrument for patients with lung cancer). Following tumor assessments at screening, evaluation of tumor response conforming to RECIST v1.1 will be documented prior to every other new 28-day maintenance treatment cycle, commencing with maintenance Cycle #2.

Primary goals
To determine activity of VAL-083 in NSCLC patients who have failed standard platinum doublet therapy, as assessed by disease control rate, defined as objective response rate, complete (CR) and partial (PR) response rates, and stable disease (SD) in order to provide guidance to treating physicians under the context of VAL-083’s current approval in China.

Secondary goals
To determine the progression-free survival rate of NSCLC patients who have failed standard platinum doublet therapy when treated with VAL-083; to determine the overall survival of NSCLC patients who have failed standard platinum doublet therapy when treated with VAL-083; and to evaluate the quality of life and impact on disease symptoms following treatment with VAL-083.

Study duration
The study will be considered complete when the last patient either experiences disease progression or an intolerable toxicity, or withdraws from the study. The study is anticipated to take approximately 1-2 years.

The Company’s poster presentation on the Phase IV post-market clinical protocol for VAL-083 in the treatment of relapsed or refractory non-small cell lung cancer may be found on DelMar’s website under View Source

About Lung Cancer
Lung cancer is a leading cause of cancer-related mortality around the world. In general, prognosis for lung cancer patients remain poor, with 5-year relative survival less than 14% among males and less than 18% among females in most countries. Globally, the market for lung cancer treatments may exceed $7 billion by 2019 according to report published by Transparency Market research. Non-small cell lung cancer is the most common type of lung cancer, accounting for 85% of all lung cancer cases in the United States and approximately 90% of lung cancer cases diagnosed in China. NSCLC is usually treated with surgery followed by treatment with either tyrosine kinase inhibitors (TKIs) or platinum-based chemotherapy regimens. TKI resistance has emerged as a significant unmet medical need, and long-term prognosis with platinum-based therapies is poor.

About VAL-083
VAL-083 is a "first-in-class", small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated safety and efficacy in treating a number of cancers including lung, brain, cervical, ovarian tumors and leukemia. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia (CML) and lung cancer and has received orphan drug designation in Europe and the U.S. for the treatment of gliomas.

DelMar is currently studying VAL-083 in a multi-center Phase I/II clinical trial for patients with refractory GBM in accordance with the protocol that has been filed with the U.S. Food and Drug Administration (FDA) at five clinical centers in the United States: Mayo Clinic (Rochester, MN); UCSF (San Francisco, CA) and three centers associated with the Sarah Cannon Cancer Research Institute (Nashville, TN, Sarasota, FL and Denver, CO). As a potential treatment for glioblastoma, VAL-083’s mechanism of action appears to be unaffected by the expression of MGMT, a DNA repair enzyme that is implicated in chemotherapy resistance and poor outcomes following front-line treatment with Temodar (temozolomide).

Chugai’s ALK Inhibitor “Alectinib,” New Drug Application Submitted for ALK Positive Advanced Non-Small Cell Lung Cancer in the United States

On September 9, 2015 Chugai Pharmaceutical Co., Ltd. [Main Office: Chuo-ku, Tokyo. Chairman & CEO: Osamu Nagayama] (Chugai) (TOKYO: 4519) and F. Hoffmann-La Roche Ltd. [Head Office: Basel, Switzerland. CEO: Severin Schwan] (Roche) reported that Genentech, Inc. [Head Office: California, U.S., CEO: Ian T. Clark], a member of the Roche Group, has filed a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) and the FDA has accepted the NDA, for ALK (Anaplastic Lymphoma Kinase) inhibitor "alectinib hydrochloride" (alectinib) for the treatment of patient with ALK positive advanced non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib in September (Press release, Chugai, SEP 8, 2015, View Source [SID:1234507419]).

Alectinib was granted Breakthrough Therapy Designation by FDA in June 2013 for patients with ALK positive NSCLC who have progressed on crizotinib.

Alectinib is a highly selective, CNS-active ALK inhibitor created by Chugai. Alectinib matches with the Personalized Healthcare Strategy promoted by Chugai and Roche. It has been reported that 2 to 5 percent of patients with NSCLC express a chromosomal rearrangement which leads to fusion of the ALK gene with another gene1. ALK kinase signaling is constantly active in cells with such fusion genes, resulting in uncontrolled growth of tumor cells and transforming the cells into tumor cells2, 3. Alectinib exerts its anti-tumor effect by selectively inhibiting ALK kinase activity to inhibit tumor cell proliferation and induce cell death4. In addition, alectinib is not recognized by the transporter proteins in the blood brain barrier that actively pump molecules out of the brain.

Alectinib is active in the central nervous system and has proven activity against brain metastases.

In Japan, alectinib [brand name; Alecensa capsule 20mg and 40mg] was become available to patients with "ALK fusion gene positive unresectable, recurrent/advanced NSCLC" in September 2014 and is marketed by Chugai. The rights for Alecensa in overseas countries including Europe and the US were out-licensed to Roche, and clinical trials of Alecensa (Roche Development Code: RG7853) for patients with NSCLC who have ALK mutation are currently ongoing in the US, Europe and other countries.

Two pivotal clinical phase I/II trials formed the basis for the new drug application.

NP28673 study
NP28673 is a phase I/II global, single arm, open-label, multicentre trial evaluating the safety and efficacy of alectinib in 138 people with ALK positive NSCLC whose disease progressed on crizotinib.

The study showed by assessment of an independent review committee an ORR in 50.0% of people treated with alectinib, as measured by RECIST criteria.

An investigator assessment also showed tumours shrank in 47.8% of people who received alectinib.

CNS tumours shrank in response to alectinib in 57.1% of people whose disease had spread to the brain or other parts of the CNS.
In addition, the people whose tumours shrank in response to alectinib continued to respond for a median of 11.2 months (Duration of Response (DOR), immature data).

The median progression-free survival (PFS) for people who received alectinib was 8.9 months.

Alectinib demonstrated a safety profile consistent with that observed in previous studies.

The most common (occurring in at least 2% of people) Grade 3 or higher adverse event was shortness of breath (dyspnoea; 4%).
NP28761 study
NP28761 is a phase I/II North American, single arm, open-label, multicentre trial evaluating the safety and efficacy of alectinib in 87 people with ALK positive NSCLC whose disease progressed on crizotinib.

The study showed by assessment of an independent review committee an ORR in 47.8% of people treated with alectinib, as measured by RECIST criteria.

An investigator assessment showed tumours shrank in 46.0% of people who received alectinib.

CNS tumours shrank in response to alectinib in 68.8% of people whose disease had spread to the brain or other parts of the CNS.
In addition, the people whose tumours shrank in response to alectinib continued to respond for a median of 7.5 months (DOR, immature data).

The immature median PFS was 6.3 months.
Alectinib demonstrated a safety profile consistent with that observed in previous studies.
The most common (occurring in at least 2% of people) Grade 3 or higher adverse events were an increase in muscle enzymes (increased blood levels of creatine phosphokinase; 8%), increased liver enzymes (alanine aminotransferase; 6%, and aspartate aminotransferase; 5%) and shortness of breath (dysponea; 3%).