On December 11, 2015 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the U.S. Food and Drug Administration (FDA) granted accelerated approval to Alecensa (alectinib) for the treatment of people with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib (Press release, Genentech, DEC 11, 2015, View Source [SID:1234508539]). Schedule your 30 min Free 1stOncology Demo! In the pivotal studies, Alecensa shrank tumors in up to 44 percent of people with ALK-positive NSCLC who progressed on crizotinib (objective response rate [ORR] of 38 percent [95 percent CI 28-49] and 44 percent [95 percent CI 36-53]). In a subset of people with tumors that spread to the brain or other parts of the central nervous system (CNS), Alecensa shrank CNS tumors in about 60 percent of people (CNS ORR of 61 percent [95 percent CI 46-74]).
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!
"Alecensa is now approved as a new option for people with ALK-positive NSCLC who progress on or are intolerant to crizotinib," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Sixty percent of people enrolled in our studies had tumors that had spread to their central nervous systems, and Alecensa shrank tumors in many people in a subset of patients with CNS disease."
Possible serious side effects with Alecensa include liver problems, lung problems, slow heartbeat, muscle pain, tenderness and weakness. The most common side effects of Alecensa include tiredness, constipation and swelling in the hands, feet, ankles and eyelids.
The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious condition based on early evidence suggesting clinical benefit. The indication for Alecensa is approved under accelerated approval based on tumor response rate and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Alecensa will be available to people in the United States within two weeks. For those who qualify, Genentech plans to offer patient assistance programs for people taking Alecensa through Genentech Access Solutions. Doctors can contact Genentech Access Solutions at (888) 249-4918. More information is also available at View Source." target="_blank" title="View Source." rel="nofollow">View Source
In addition, Alecensa is being studied for use as an initial (first-line) treatment for people with advanced ALK-positive NSCLC. ALEX is a global, randomized Phase III study comparing Alecensa to crizotinib as an initial treatment for people with advanced NSCLC whose tumors were characterized as ALK-positive by a companion VENTANA ALK (D5F3) CDx Assay immunohistochemistry (IHC) test developed by Roche Diagnostics. This study is part of the company’s commitment to convert the current accelerated approval in people with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib to a full approval as an initial treatment.
About NP28761 (Study 1) and NP28673 (Study 2)
Study 1 is a Phase II North American, single-arm, open-label, multicenter trial evaluating the safety and efficacy of Alecensa (600 mg orally twice daily) in 87 people with ALK-positive NSCLC whose disease progressed on crizotinib. Study 2 is a Phase I/II global, single-arm, open-label, multicenter trial evaluating the safety and efficacy of Alecensa (600 mg orally twice daily) in 138 people with ALK-positive NSCLC whose disease progressed on crizotinib. People in the Phase II studies received 600 mg of Alecensa orally twice daily. In both trials, the primary endpoint was ORR according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as evaluated by an Independent Review Committee (IRC). Secondary endpoints included DOR and efficacy against disease that had spread to the CNS (CNS ORR and CNS DOR). See full press release for a summary of the efficacy and safety data from both studies that support this approval
aOf 51 people in the subgroup, 35 (69 percent) had received prior brain radiation, including 25 (49 percent) who completed radiation treatment at least 6 months before starting treatment with Alecensa.
The most common Grade 3 or higher adverse events in the pooled analysis of both studies were an increase in muscle enzymes (creatine phosphokinase; 4.6 percent), shortness of breath (dyspnea; 3.6 percent), increased liver enzymes (aspartate transaminase; 3.6 percent, and alanine transaminase; 4.8 percent), evidence of liver dysfunction (hyperbilirubinemia; 2.4 percent), increased blood glucose (hyperglycemia; 2 percent), decreased levels of minerals (hypokalemia; 4 percent, hypophosphatemia; 2.8 percent, and hyponatremia; 2 percent), decreased red blood cells (anemia; 2 percent) and decreased white blood cells (lymphopenia; 4.6 percent).
About Lung Cancer
According to the American Cancer Society, it is estimated that more than 221,000 Americans will be diagnosed with lung cancer in 2015, and NSCLC accounts for 85 percent of all lung cancers. It is estimated that approximately 60 percent of lung cancer diagnoses in the United States are made when the disease is in the advanced stages. Approximately 5 percent of people with NSCLC in the United States are ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history.
About Genentech Access Solutions
Access Solutions is part of Genentech’s commitment to helping people access the Genentech medicines they are prescribed, regardless of their ability to pay. The team of 350 in-house specialists at Access Solutions is dedicated to helping people navigate the access and reimbursement process, and to providing assistance to eligible patients in the United States who are uninsured or cannot afford the out-of-pocket costs for their medicine. To date, the team has helped more than 1.2 million patients access the medicines they need. Please contact Access Solutions (866) 4ACCESS/(866) 422-2377 or visit View Source for more information.
About Alecensa
Alecensa is a kinase inhibitor approved for the treatment of people with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.
This indication is approved under accelerated approval based on tumor response rate and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Important Safety Information
Everyone reacts differently to treatment with Alecensa. It’s important to know the most serious and most common side effects with Alecensa.
A doctor may lower the dose or stop treatment with Alecensa if any serious side effects occur. Patients taking Alecensa should contact their doctor right away if they have any of the following side effects.
Alecensa may cause serious side effects, including:
Liver problems (hepatotoxicity). Alecensa may cause liver injury. A doctor will do blood tests at least every 2 weeks for the first 2 months and as needed during treatment with Alecensa. Patients taking Alecensa should tell their doctor right away if they experience any of the following signs and symptoms:
Feeling tired
Feeling less hungry than usual
Yellowing of the skin or whites of the eyes
Dark urine
Itchy skin
Nausea or vomiting
Pain on the right side of stomach area
Bleeding or bruising more easily than normal
Lung problems. Alecensa may cause severe or life-threatening swelling (inflammation) of the lungs during treatment. Symptoms may be similar to those symptoms from lung cancer. Patients taking Alecensa should tell their doctor right away if they have any new or worsening symptoms, including:
Trouble breathing
Shortness of breath
Fever
Cough
Slow heartbeat (bradycardia). Alecensa may cause very slow heartbeats that can be severe. A doctor will check a patient’s heart rate and blood pressure during treatment with Alecensa. Patients taking Alecensa should tell their doctor right away if they feel dizzy, lightheaded, or faint during treatment with Alecensa. Patients taking Alecensa should tell their doctor if they take any heart or blood pressure medicines.
Muscle pain, tenderness, and weakness (myalgia). Muscle problems are common with Alecensa and can be severe. A doctor will do blood tests at least every 2 weeks for the first month and as needed during treatment with Alecensa. Patients taking Alecensa should tell their doctor right away if they have any new or worsening signs and symptoms of muscle problems, including unexplained muscle pain or muscle pain that does not go away, tenderness, or weakness.
Before taking Alecensa, patients should tell their doctor about all medical conditions, including if they:
Have liver problems
Have lung or breathing problems
Have a slow heartbeat
Are pregnant or plan to become pregnant. Alecensa can harm an unborn baby. Patients taking Alecensa should tell their doctor right away if they become pregnant during treatment with Alecensa or think they may be pregnant
Women who are able to become pregnant should use effective birth control during treatment with Alecensa and for one week after the final dose of Alecensa
Men who have female partners that are able to become pregnant should use effective birth control during treatment with Alecensa and for three months after the final dose of Alecensa
Are breastfeeding or plan to breastfeed. It is not known if Alecensa passes into breast milk. A patient should not breastfeed during treatment with Alecensa and for one week after the final dose of Alecensa. Patients should talk with their dotcotr about the best way to feed their baby during this time.
Patients taking Alecensa should tell their doctor about all the medicines they take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements.
Patients taking Alecensa should avoid spending time in the sunlight during treatment with Alecensa and for seven days after the final dose of Alecensa. Patients taking Alecensa may burn more easily and get severe sunburns. Patients taking Alecensa should use sunscreen and lip balm with a SPF 50 or greater to help protect against sunburn.
The most common side effects of Alecensa include:
Tiredness
Constipation
Swelling in hands, feet, ankles, and eyelids
These are not all of the possible side effects of Alecensa. For more information, patients should ask their doctor or pharmacist. Patients should call their doctor for medical advice about side effects.
Report side effects to the FDA at (800) FDA-1088 or View Source Patients and caregivers may also report side effects to Genentech at (888) 835-2555.
Please see additional Important Safety Information in full Prescribing Information, including Patient Information.
About Genentech in Lung Cancer
Lung cancer is a major area of focus and investment for Genentech, 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 three 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.
Author: [email protected]
Biothera Announces Clinical Study to Evaluate Combination Therapy of Imprime PGG and Merck’s Checkpoint Inhibitor Keytruda in Patients with Non-Small Cell Lung Cancer
On December 10, 2015 Biothera Pharmaceutical Inc., reported plans for a Phase 1b/2 clinical study in non-small lung cancer (NSCLC) patients to evaluate the ability of Biothera’s Imprime PGG to enhance responses to pembrolizumab (Keytruda), the anti-PD-1 antibody from Merck (NYSE:MRK), known as MSD outside the United States and Canada (Press release, Biothera Pharmaceuticals, DEC 10, 2015, View Source [SID1234562110]). Merck will provide funding and clinical supplies of pembrolizumab for the investigator-initiated study under the direction of Lawrence Feldman, M.D., of the University of Illinois at Chicago. The trial is expected to begin in the first quarter of 2016.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Imprime PGG is a first-in-class, systemically administered beta glucan PAMP (pathogen associated molecular pattern) that triggers a robust, integrated immune response shown to enhance the anti-tumor efficacy of checkpoint inhibitors (PD-1, PD-L1 antibodies), anti-angiogenic antibodies and tumor-targeting monoclonal antibodies (mAbs). To date, Imprime PGG has shown promising efficacy in combination with mAbs in two Phase 2 studies of patients with NSCLC.
"Preclinical results for the combination therapy with Imprime PGG show the potential to expand the number of patients who can respond to Keytruda, as well as enhance the robustness of their response," said Dr. Feldman, Associate Professor of Medicine, College of Medicine at the University of Illinois at Chicago and principal investigator for the study. "The results for combination therapy with Imprime PGG have been encouraging, and I look forward to the progress of the upcoming study."
Biothera research has demonstrated that Imprime PGG activates key immune responses, including enhancement of dendritic cell maturation and presentation of antigen and co-stimulatory signals to T cells. The effect is to establish a critical link between the innate and adaptive immune systems, resulting in an expansion of T cell populations and inducing the production of the anti-tumor cytokine interferon gamma (IFN-γ). Imprime PGG also has been demonstrated to increase PD-L1 expression on tumor cells and tumor-associated macrophages, which also may enhance patient responses to pembrolizumab.
"Imprime PGG acts as an ignition switch to drive a coordinated response involving both the innate and adaptive immune systems to recognize and kill cancer cells," said Jose Iglesias, M.D., Chief Medical Officer, Biothera Pharmaceutical Inc. "In the anticipated Phase 1b/2 study, Imprime is expected to perform a dual role of enhancing antigen presentation, which helps more T cells target cancer, and upregulating PD-L1 expression to provide pembrolizumab more opportunities to disrupt or inhibit PD-1/PD-L1 interaction."
The Phase 1b/2 study is scheduled to begin dosing of patients in Q1 2016, with plans to enroll up to 58 patients with NSCLC following their progression on first line platinum-based chemotherapy. The phase 1b element of the trial is a dose-escalation study of up to 12 patients receiving Imprime PGG in combination with pembrolizumab. The phase 2 element of the study will test whether the addition of Imprime PGG to pembrolizumab increases median progression free survival and overall survival in up to 46 subjects.
10-Q – Quarterly report [Sections 13 or 15(d)]
(Filing, 10-Q, Peregrine Pharmaceuticals, DEC 10, 2015, View Source [SID:1234508531])
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!
Karus Therapeutics Announces Strategic Collaboration with The University of Texas MD Anderson Cancer Center
On December 10, 2015 Karus Therapeutics (‘Karus’), a leader in the development of innovative medicines with breakthrough potential in the treatment of hematological cancers and solid tumor immunotherapy, reported that it has entered into a strategic pre-clinical and clinical collaboration with The University of Texas MD Anderson Cancer Center (Press release, Karus Therapeutics, DEC 10, 2015, View Source [SID1234516772]). The collaboration will include both of Karus’s lead cancer candidates, KA2237 and KA2507.
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!
Under the agreement, MD Anderson the world’s leading cancer research and care center, will work collaboratively on a number of preclinical studies with a focus on identifying optimal drug combinations and the appropriate patient populations for further clinical development.
KA2237 is a dual-PI3K-p110β/δ inhibitor that exerts both a targeted anti-cancer and tumor immunotherapeutic action with broad potential to treat hematological and solid malignancies as a single-agent and in combination. The first clinical trial under the collaboration is expected to commence in H1 2016 and will establish the maximum tolerated dose (MTD) of KA2237 in lymphoma patients.
KA2507, a selective-HDAC6 inhibitor, also has both a targeted therapy and immunotherapeutic action and has potential in the treatment of multiple myeloma, B- and T-cell lymphomas and PD-L1 expressing solid tumors.
Dr. Simon Kerry, CEO of Karus Therapeutics commented: "MD Anderson is at the forefront of research and development in innovative cancer therapies and we are delighted that their scientific and clinical teams share Karus’s enthusiasm for KA2237 and KA2507. We look forward to working with world-class scientists and clinicians to maximize the efficiency with which we can move our programs into the clinic. Furthermore, with access to a large patient population at the Center we will be able to accelerate our clinical studies, bringing us one step closer to transforming the treatment of cancers with a high unmet medical need through our proprietary, isoform-selective PI3K-p110β/δ and HDAC6 inhibitors.
"At the heart of all we do is what is best for our patients, and research such as this that combines the best of academia and private industry may very well bring new solutions to how we treat these cancers," said Robert Orlowski, M.D., chair, ad interim of Lymphoma/Myeloma at MD Anderson.
Roche presents early data on investigational cancer immunotherapy atezolizumab in combination with nab-paclitaxel chemotherapy in patients with specific type of advanced breast cancer
On December 10, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported results from a phase Ib study of the investigational cancer immunotherapy atezolizumab (MPDL3280A) used in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (TNBC) (Press release, Hoffmann-La Roche , DEC 10, 2015, View Source [SID:1234508535]). The study showed that the combination shrank tumours (overall response rate, including unconfirmed responses) in 70.8% of people, [n=24; 95% confidence interval, (CI): 48.9, 87.4]. 11 of 17 responses (65%) continued on treatment at time of data cut-off. The highest overall response rate observed [88.9% (CI: 51.7, 99.7)] was in people receiving their initial (1st line) treatment for metastatic disease, with 1 confirmed complete responder. Responses were observed in both PD-L1 positive and PD-L1 negative patients. In addition, some patients with evidence of RECIST based progressive disease developed further response with continued treatment. Adverse events (AEs) were consistent with what has previously been reported for treatment of nab-paclitaxel alone, with 56% of patients (n=32) experiencing Grade 3–4 AEs. These data were presented at the San Antonio Breast Cancer Symposium 2015 congress.1
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!
"We are encouraged that a high proportion of people responded to combined treatment with atezolizumab and nab-paclitaxel chemotherapy, regardless of their PD-L1 expression," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "This result indicates that combinations may provide a way to increase the benefits of atezolizumab in a wide range of people with triple-negative breast cancer."
Based on these results and the observed activity of single-agent atezolizumab in these patients, Roche is evaluating the combination of atezolizumab and nab-paclitaxel in a phase III study (IMpassion130; NCT02425891) of patients with previously untreated metastatic TNBC.
About the phase Ib study of atezolizumab in combination with nab-paclitaxel
This part of the multicentre, multi-arm phase Ib study aimed to evaluate atezolizumab in combination with weekly nab-paclitaxel in patients with metastatic TNBC previously treated with systemic cytotoxic therapy
Primary endpoints were safety and tolerability, with secondary endpoints including efficacy using RECIST v1.1 criteria (best overall response, objective response rate, duration of response, progression-free survival), pharmacokinetics, as well as biomarker analyses
Patients received atezolizumab 800 mg once every 2 weeks (days 1 and 15) with nab-paclitaxel 125 mg/m2 weekly (days 1, 8 and 15) for 3 weeks in 4-week cycles, until loss of clinical benefit
All patients were women with a median age of 58 years (range 32–75 years)
PD-L1 expression was assessed for both tumour cells (TCs) and immune cells (ICs); people were scored as IC0, 1, 2 or 3 and TC0, 1, 2 or 3 with an immunohistochemistry (IHC) test being developed by Roche Tissue Diagnostics
Expression of PD-L1 in TNBC was mostly restricted to IC
Efficacy
Summary of Best Overall Responses by RECIST v1.1
Objective Response Rate by PD-L1 Expression Levela
Safety
Treatment-related Adverse Eventsa
AEs, adverse events
About triple-negative breast cancer
Triple-negative breast cancer (TNBC) refers to any breast cancer that does not express oestrogen receptor (ER), progesterone receptor (PR) or overexpress the HER2 receptor. Approximately 10%–20% of all breast cancers are TNBC, and have a worse prognosis compared with other breast cancer subtypes.2, 3 TNBC is associated with more frequent recurrence, shorter disease-free interval and earlier visceral metastases. Patients with metastatic TNBC have decreased survival compared with patients with other subtypes of breast cancer, with a median survival of 6 to 13 months.4, 5, 6 Currently, chemotherapy is the mainstay of treatment for metastatic TNBC, although clinical practice patterns vary worldwide.
About atezolizumab
Atezolizumab (also known as MPDL3280A) is an investigational monoclonal antibody designed to target and bind to a protein called PD-L1, which is expressed on TCs and tumour-infiltrating ICs. 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, atezolizumab may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.
About Roche in cancer immunotherapy
For more than 30 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.
About personalised cancer immunotherapy
The aim of personalised cancer immunotherapy (PCI) is to provide individual patients with treatment options that are tailored to their specific needs. Our PCI research and development programme comprises more than 20 investigational candidates, eight of which are in clinical trials. All studies include the prospective evaluation of biomarkers to determine which people may be appropriate candidates for our medicines. In the case of atezolizumab (also known as MPDL3280A), PCI begins with the PD-L1 (programmed death ligand-1) IHC assay based on the SP142 antibody developed by Roche Tissue Diagnostics. The goal of PD-L1 as a biomarker is to identify those people most likely to experience clinical benefit with atezolizumab as a single agent and which people may be appropriate candidates for combination therapies; the purpose is not to exclude patients from atezolizumab therapy, but rather to enable the design of combinations that will provide the greatest chance for transformative responses. The ability to combine atezolizumab with multiple chemotherapies may provide new treatment options to people across a broad range of tumours regardless of their level of PD-L1 expression.