On December 6, 2017 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported that it will present updated interim results from a Phase II clinical trial of Puma’s drug neratinib at the 2017 San Antonio Breast Cancer Symposium (SABCS) that is currently taking place in San Antonio, Texas (Press release, Puma Biotechnology, DEC 6, 2017, View Source [SID1234522411]). The presentation entitled, "Effects of adding budesonide or colestipol to loperamide prophylaxis on neratinib-associated diarrhea in patients with HER2-positive early stage breast cancer: the CONTROL trial," will be presented at a poster session on December 7 at 5:00 p.m. CST. A full copy of the poster is available on the Puma Biotechnology website.

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Neratinib was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets.

The main adverse event seen to date in clinical trials of neratinib is diarrhea and, more specifically, grade 3 diarrhea. In the Phase III ExteNET trial of neratinib as extended adjuvant treatment of HER2-positive early stage breast cancer that has previously been treated with adjuvant Herceptin, 95.4% of the patients experienced all grade diarrhea and 39.8% of the patients experienced grade 3 or higher diarrhea (there was one event of grade 4 diarrhea). The CONTROL trial is an international, open-label, Phase II study investigating the use of loperamide prophylaxis with or without other agents in the reduction of neratinib-associated diarrhea that has a primary endpoint of the incidence of grade 3 diarrhea.

In the CONTROL trial, patients with HER2-positive early stage breast cancer who had completed trastuzumab-based adjuvant therapy received neratinib daily for a period of one year. The trial initially tested high dose loperamide prophylaxis given for the first 2 cycles (56 days) of treatment (12 mg on days 1-14, 8 mg on days 15-56 and as needed thereafter). The CONTROL trial was then expanded to include two additional cohorts. One cohort received the combination of loperamide and budesonide and the other cohort received the combination of loperamide plus colestipol. Budesonide is a locally acting corticosteroid that the Company believes targets the inflammation identified in a preclinical model of neratinib-induced diarrhea and colestipol is a bile acid sequestrant that the Company believes targets potential bile acid malabsorption that could result from such inflammation.

The interim analysis of the trial presented in the poster included a total of 137 patients who received neratinib plus loperamide prophylaxis, 64 patients who received neratinib plus loperamide prophylaxis for 2 cycles and budesonide for 1 cycle, and 120 patients who received neratinib plus loperamide prophylaxis for 1 cycle and colestipol for 1 cycle.

The results of the trial showed that the incidence of grade 3 diarrhea for the 137 patients who received the loperamide prophylaxis was 30.7%. For the 137 patients who received the loperamide prophylaxis, the median number of grade 3 diarrhea episodes per patient was 1 and the median cumulative duration of grade 3 diarrhea was 3 days. For the 137 patients who received loperamide prophylaxis, 20.4% discontinued neratinib due to diarrhea.

For the 64 patients who received the combination of loperamide plus budesonide, the results of the trial showed that the incidence of grade 3 diarrhea was 26.6%. The median number of grade 3 diarrhea episodes per patient was 1 and the median cumulative duration of grade 3 diarrhea was 2 days. For the 64 patients who received loperamide plus budesonide prophylaxis, 10.9% discontinued neratinib due to diarrhea.

For the 120 patients who received the combination of loperamide plus colestipol, the results of the trial showed that the incidence of grade 3 diarrhea was 10.8%. The median number of grade 3 diarrhea episodes per patient was 1 and the median cumulative duration of grade 3 diarrhea was 3 days. For the 120 patients who received loperamide plus colestipol prophylaxis, 1.7% discontinued neratinib due to diarrhea. Further information is provided in Table 1 below:

Table 1: Characteristics of Treatment-Emergent Diarrhea

Study CONTROL ExteNET
Loperamide + Loperamide + Loperamide
Loperamide budesonide colestipol prn
(n=137) (n=64) (n=120) (n=1408)
Diarrhea, %
Any grade 79.6 86.0 66.7 95.4
Grade 1 24.8 25.0 30.0 22.9
Grade 2 24.1 34.4 25.8 32.5
Grade 3a 30.7 26.6 10.8 39.8
Grade 4 0 0 0 0.1

Median cumulative duration, days
Any grade 14.0 24.0 16.0 59.0
Grade ≥2 5.0 6.0 3.5 10.0
Grade ≥3a 3.0 2.0 3.0 5.0

Median diarrhea episodes/patient
Any grade 2.0 9.0 2.5 8.0
Grade ≥2 2.0 3.0 1.0 3.0
Grade ≥3a 1.0 1.0 1.0 2.0

Action taken, %
Dose hold 15.3 18.8 9.2 33.9
Dose reduction 7.3 3.1 4.2 26.4
Discontinuation 20.4 10.9 1.7 16.8
Hospitalization 1.5 0 0 1.4

Duration of neratinib treatment, months
Median 11.5 11.9 3.7 11.6

a No grade 4 events in the CONTROL study; one grade 4 event in the ExteNET study.

Hope S. Rugo, MD, USCF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, said, "We are pleased to see the maturation of the data supporting observations of a reduction in incidence, severity and duration of neratinib-associated diarrhea with loperamide prophylaxis, loperamide plus budesonide prophylaxis or the loperamide plus colestipol prophylaxis. Along with the continued reduction in the incidence and severity of grade 3 diarrhea with neratinib, diarrhea appears to be acute, self-limiting and manageable. The addition of budesonide or colestipol to loperamide prophylaxis appears to greatly improve the tolerability of neratinib and we look forward to the completion of the colestipol cohort."

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, "We are pleased to see the reductions in the incidence of severe neratinib-related diarrhea in the CONTROL trial when using the loperamide, loperamide plus budesonide or loperamide plus colestipol regimens. The severe diarrhea appears to become more acute, whereby it does not typically recur after the first month. We are also very encouraged by the improvements in tolerability that have been seen to date in the budesonide and the colestipol cohorts. This is a marked improvement in tolerability over what was seen in the ExteNET trial and we look forward to continuing to monitor this in the loperamide plus colestipol cohort."

About HER2-Positive Breast Cancer

Approximately 20% to 25% of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

IMPORTANT SAFETY INFORMATION

NERLYNX (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early-stage HER2 overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

Diarrhea: Aggressively manage diarrhea occurring despite recommended prophylaxis with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥ 2 diarrhea that occurs after maximal dose reduction.
Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold NERLYNX in patients experiencing Grade 3 liver abnormalities and permanently discontinue NERLYNX in patients experiencing Grade 4 liver abnormalities.
Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
ADVERSE REACTIONS: The most common adverse reactions (≥ 5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased and urinary tract infection.

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) and www.NERLYNX.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

DRUG INTERACTIONS:

Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors (PPI) and H2-receptor antagonists. Separate NERLYNX by 3 hours after antacid dosing.
Strong or moderate CYP3A4 inhibitors: Avoid concomitant use.
Strong or moderate CYP3A4 inducers: Avoid concomitant use.
P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates when used concomitantly with NERLYNX.
USE IN SPECIFIC POPULATIONS:

Lactation: Advise women not to breastfeed.
Please see Full Prescribing Information for additional safety information.

The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given orally once daily with food, continuously for one year. Antidiarrheal prophylaxis should be initiated with the first dose of NERLYNX and continued during the first 2 months (56 days) of treatment and as needed thereafter.

To help ensure patients have access to NERLYNX, Puma has implemented the Puma Patient Lynx support program to assist patients and healthcare providers with reimbursement support and referrals to resources that can help with financial assistance. More information on the Puma Patient Lynx program can be found at www.NERLYNX.com or 1-855-816-5421.

On December 6, 2017 Transgene (Paris:TNG) (Euronext Paris: TNG), a company that designs and develops viral-based immunotherapies, and BioInvent International AB (OMXS: BINV), focused on the discovery and development of novel and first-in-class immuno-regulatory antibodies to treat cancer and reported that they have entered a collaboration to co-develop next generation oncolytic virus (OV) candidates encoding an anti-CTLA-4 antibody sequence – potentially with additional transgenes – capable of treating multiple solid tumors (Press release, Transgene, DEC 6, 2017, View Source [SID1234522412]).

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Under the terms of the agreement Transgene will contribute both its OV design and engineering expertise as well as its proprietary engineered Vaccinia virus, derived from its Invir.IOTM platform. These oncolytic viruses are designed to directly and selectively destroy cancer cells by the intracellular replication of the virus in the cancer cell (oncolysis). Oncolysis is important as it induces an immune response against tumors (immunogenic lysis). In addition, the replication of the virus allows the expression of the genes carried by the oncolytic viral genome including therapeutic "weapons" that have been specifically designed to attack the tumor.

BioInvent will provide its cancer biology and antibody expertise to the collaboration as well as anti-CTLA-4 monoclonal antibody coding sequences, generated through its proprietary n-CoDeR/FIRST platforms, which will be encoded from in Transgene’s Invir.IOTM viral vectors. The local expression of such therapeutic payloads in the cancer cell is expected to augment the anti-cancer effects of viral oncolysis, by efficiently modulating the tumor micro-environment and increasing the immunocompetency of the tumor.

Encoding BioInvent’s anti-CTLA-4 antibody sequence in Transgene’s latest improved Vaccinia virus, promises to optimize the efficacy of this potent checkpoint inhibitor, while reducing the side effects seen when it is given systemically. There is also the potential for this novel OV product to be significantly more effective than the combination of these single agents. Transgene has generated preclinical proof-of-concept data showing that an oncolytic Vaccinia virus encoded with a checkpoint inhibitor demonstrated better overall survival than the corresponding combination as separate single agents.

The collaboration’s research and development costs, as well as the revenues and royalties from candidates generated by the collaboration, will be shared 50:50.

Philippe Archinard, PhD, Chairman and CEO of Transgene, said: "We look forward to starting this first, exciting collaboration with BioInvent. We believe that the next generation of multi-functional OVs derived from our Invir.IOTM platform, armed with highly targeted immune modulators such as those engineered by BioInvent, will provide patients with better clinical outcomes. Based on the compelling preclinical data we have generated, we expect the resulting OVs to deliver a significant improvement in overall survival, with an enhanced safety profile when compared to administering an OV and checkpoint inhibitor separately."

Commenting on the agreement, Michael Oredsson, CEO of BioInvent, said: "We are very pleased to announce this first collaboration with Transgene which will allow us to leverage our cancer antibody biology and immuno-oncology expertise. We are looking forward to working with Transgene to generate the next generation OVs capable of expressing immune modulatory antibodies in the tumor, thus enhancing their efficacy and improving their safety profile. We are confident that such next generation oncolytic viruses have the potential to significantly improve treatment of solid tumors."

On December 6, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) has granted full approval for Avastin (bevacizumab) for the treatment of adults with glioblastoma that progressed following prior therapy (referred to as recurrent disease) (Press release, Hoffmann-La Roche, DEC 6, 2017, View Source [SID1234522404]). Avastin was previously granted provisional approval in this setting under the FDA’s accelerated approval program.

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"Glioblastoma is the most common and aggressive form of brain cancer and can be very difficult to treat," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Delaying disease progression and reducing the need for corticosteroids over the course of treatment are considered important goals for those impacted by this devastating disease where patients have limited treatment options."
This conversion to full approval was based on the totality of evidence of Avastin in glioblastoma, including data from the Phase III EORTC 26101 study. Avastin is now approved in the United States for nine distinct uses across six different types of cancer.

About the EORTC 26101 Study

EORTC 26101 is an independent Phase III, multicenter, randomized, open-label trial, conducted by the European Organization for Research and Treatment of Cancer (EORTC), which evaluated the addition of Avastin to lomustine chemotherapy in 432 patients with previously treated glioblastoma. The primary endpoint of the study was overall survival (OS), and progression-free survival (PFS) as assessed by investigator and overall response rate (ORR) were key secondary endpoints. Results showed the following:

There was no significant increase in OS with Avastin-based treatment (HR=0.91, p=0.4578).
As the primary endpoint was not met, all secondary endpoints should be considered descriptive only.

Avastin-based treatment increased the time to disease progression or death compared to chemotherapy alone (median PFS: 4.2 months vs. 1.5 months, HR=0.52, 95% CI: 0.41-0.64).

Among people taking corticosteroids at baseline (50 percent), more people were able to completely stop intake of corticosteroids while on treatment in the Avastin arm compared to the control arm (23 percent vs. 12 percent).

In the Avastin with lomustine arm, 22 percent of people discontinued treatment due to adverse reactions compared with 10 percent of people in the lomustine arm.

Adverse events were consistent with those seen in previous trials of Avastin across tumor types for approved indications.

About Glioblastoma

Glioma (cancer of the glial cells) is the most common type of malignant primary brain tumor (a tumor that originates in the brain), and represents nearly one-fourth of all primary brain tumors and three-fourths of all malignant tumors1. Glioblastoma (or glioblastoma multiforme) is the most common and the most aggressive type of glioma, accounting for more than half of all gliomas. It is estimated that more than 12,300 people will be diagnosed with glioblastoma in the United States in 20171.

About Avastin

With the initial approval in the United States for advanced colorectal cancer in 2004, Avastin became the first anti-angiogenic therapy made widely available for the treatment of patients with an advanced cancer.

Today, Avastin is continuing to transform cancer care through its proven survival benefit (overall survival and/or progression free survival) across several types of cancer. Avastin is approved in Europe for the treatment of advanced stages of breast cancer, colorectal cancer, non-small cell lung cancer, kidney cancer, ovarian cancer and cervical cancer, and is available in the United States for the treatment of colorectal cancer, non-small cell lung cancer, kidney cancer, cervical cancer and recurrent, platinum-resistant and platinum-sensitive ovarian cancer. In addition, Avastin is approved over 70 other countries worldwide for the treatment of patients with progressive glioblastoma following prior therapy. Avastin is approved in Japan for the treatment of the advanced stages of colorectal cancer, non-small cell lung cancer, cervical cancer, breast cancer, ovarian cancer and malignant glioma, including newly diagnosed glioblastoma.

Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today. Over 2.7 million patients have been treated with Avastin so far. A comprehensive clinical programme with more than 300 ongoing clinical trials is investigating the use of Avastin in over 50 tumour types.

On December 6, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported results from the positive, pivotal Phase III IMpower150 study of Tecentriq (atezolizumab) and Avastin (bevacizumab) plus chemotherapy (carboplatin and paclitaxel) in people with previously untreated advanced non-squamous non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, DEC 6, 2017, View Source [SID1234522415]). The study showed that people who received Tecentriq and Avastin plus chemotherapy had a 38 percent reduced risk of their disease worsening or death (progression-free survival, PFS) compared with those who received Avastin plus chemotherapy (hazard ratio [HR]=0.62; p<0.0001 95 % CI: 0.52-0.74; median PFS = 8.3 vs. 6.8 months). Importantly, a doubling of the 12-month landmark PFS rate was observed with the combination of Tecentriq and Avastin plus chemotherapy (37 percent) compared to Avastin plus chemotherapy (18 percent). The rate of tumour shrinkage (overall response rate, ORR), a secondary endpoint in the study, was higher in people treated with Tecentriq and Avastin plus chemotherapy compared with Avastin plus chemotherapy (64 percent vs. 48 percent). The safety profile of the Tecentriq and Avastin plus chemotherapy combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination.

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The analysis of the co-primary PFS endpoint in IMpower150 was assessed in two populations: all randomised people without an ALK* or EGFR** genetic mutation (intention-to-treat wild-type, ITT-WT) and in a subgroup of people who had a specific biomarker (T-effector "Teff" gene signature expression Teff WT). IMpower150 met its PFS co-primary endpoint per study protocol for both populations assessed. In the Teff-WT population, the combination of Tecentriq and Avastin plus chemotherapy reduced the risk of disease worsening or death by 49 percent compared to Avastin plus chemotherapy (HR=0.51; p<0.0001 95% CI: 0.38-0.68; median PFS = 11.3 vs 6.8 months).
"This Tecentriq study is the first positive Phase III combination trial that showed a cancer immunotherapy reduced the risk of the disease getting worse when used as an initial treatment in a broad group of people with advanced non-squamous NSCLC," Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "The IMpower150 study represents an important advance in lung cancer treatment, and we will submit these results to regulatory authorities around the world to potentially bring a new standard of care to people living with this disease as soon as possible."

The late-breaking IMpower150 data will be presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno Oncology Congress (Abstract #LBA1_PR) on Thursday, 7 December 6.15 pm. Central European Time (CET) and are also part of the official press programme. Early results from the co-primary endpoint of overall survival (OS) are encouraging. While they are not yet fully mature, these preliminary OS results will be presented at the ESMO (Free ESMO Whitepaper) IO congress. The next analysis of survival is expected in the first half of 2018.

About the IMpower150 study
IMpower150 is a multicentre, open-label, randomised, controlled Phase III study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and paclitaxel) with or without Avastin in people with stage IV or recurrent metastatic non-squamous NSCLC who had not been treated with chemotherapy for their advanced disease. It enrolled 1,202 people of which those with ALK and EGFR mutations were excluded from the primary ITT analysis. People were randomised (1:1:1) to receive:

Tecentriq plus carboplatin and paclitaxel (Arm A), or
Tecentriq and Avastin plus carboplatin and paclitaxel (Arm B), or
Avastin plus carboplatin and paclitaxel (Arm C, control arm).
During the treatment-induction phase, people in Arm A received Tecentriq administered intravenously at 1200 mg in combination with intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. Following the induction phase, people received maintenance treatment with Tecentriq (1200 mg every 3 weeks) until loss of clinical benefit or disease progression.

Due to pre-specified statistical testing hierarchy, Arm A vs Arm C has not been formally tested yet. IMpower150 was designed to formally compare Tecentriq plus chemotherapy (Arm A) versus Avastin plus chemotherapy (Arm C), only if Tecentriq and Avastin plus chemotherapy (Arm B) is shown to improve OS in the ITT-WT population compared to Avastin plus chemotherapy (Arm C). These OS results are expected in the first half of 2018.

People in Arm B received induction treatment with Tecentriq (1200 mg) and Avastin administered intravenously at 15 mg/kg in combination with intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. People then received maintenance treatment with the Tecentriq Avastin regimen until disease progression (Avastin) or loss of clinical benefit/disease progression (Tecentriq).

People in Arm C received induction treatment with Avastin administered intravenously at 15 mg/kg plus intravenous infusion of carboplatin and paclitaxel on Day 1 of a 3-week treatment cycle for 4 or 6 cycles. This was followed by maintenance treatment with Avastin alone until disease progression.

The co-primary endpoints were PFS, as determined by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1), and OS.

A summary of the IMpower150 Arm B vs Arm C PFS and ORR results are included below; additional data, including preliminary OS results and Arm A vs Arm C PFS will be presented as part of the Late-Breaking Abstract presentation.

The safety profile of Tecentriq and Avastin plus chemotherapy combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified with the combination. Serious adverse events related to treatment were observed in 25.4 percent of people who received Tecentriq and Avastin plus chemotherapy compared to 19.3 percent of those who received Avastin plus chemotherapy.

About NSCLC
Despite recent advances in the treatment of NSCLC, there is still a need for new treatment options. Lung cancer is the leading cause of cancer death globally1. Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.2 Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.2
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.

Currently, Roche has eight Phase III lung cancer studies underway, evaluating Tecentriq alone or in combination with other medicines.

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 the Tecentriq (atezolizumab) and Avastin (bevacizumab) combination

There is a strong scientific rationale to support the use of Tecentriq plus Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers, including first-line advanced NSCLC. 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.

On December 6, 2017 Ayala Pharmaceuticals, a biopharmaceutical company dedicated to developing targeted cancer therapies, reported that they have entered into an exclusive worldwide license agreement with Bristol-Myers Squibb for two gamma secretase inhibitors in development for the treatment of cancers with altered Notch genes (Press release, Ayala Pharmaceuticals, DEC 6, 2017, View Source [SID1234522417]).

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Under the terms of the license agreement, Ayala will have exclusive worldwide development and commercialization rights for BMS-906024 and BMS-986115, two gamma secretase inhibitors previously developed by BMS as a Notch inhibitor for oncology indications. In connection with the license, BMS received an upfront payment, became a shareholder of Ayala, and is eligible to receive certain development, regulatory, and sales-based milestones, as well as tiered annual net sales royalties. Ayala is responsible for all future development and commercialization of BMS-906024 and BMS-986115.

Israel Biotech Fund identified the opportunity, led the due diligence and syndicated with aMoon and Harel Insurance in 2017 to form Ayala. The new company intends to develop BMS-906024 as a precision medicine for niche orphan patient populations harboring Notch activating mutations.

"We believe BMS-906024 is the best in class gamma secretase inhibitor," said Ayala’s Chairman of the Board of Directors, David Sidransky, MD. "Although most Notch targeted clinical trials have traditionally recruited non-selected populations, our approach is to target patients with specific Notch alterations whose tumors are expected to respond directly to this treatment." Dr. Sidransky is a Co-Founder and Managing Partner of Israel Biotech Fund. He was Vice Chairman of ImClone Systems until its acquisition by Eli Lilly and the chairman and board member of several NASDAQ listed biotech companies.

"This is an exciting opportunity in personalized therapy for Oncology, bringing new hope to cancer patients with no approved treatment options," said Roni Mamluk, PhD, CEO at Ayala. "We plan to initiate phase 2 clinical trials in 2018." Roni Mamluk, is the former CEO of Chiasma and a member of its board of directors.

"Partnering with Ayala allows for the continued development of BMS-906024 and BMS-986115 and demonstrates our commitment to seeking opportunities that enable the continued development of drug candidates that might benefit certain patients," said Tim Reilly, Vice President, Head of Early Oncology Development at BMS. "Dr. Sidransky and Ayala are strategically positioned to focus their resources on the targeted development of these candidates for the treatment of cancers with altered Notch genes."