FDA grants priority review to Roche’s Tecentriq in combination with chemotherapy for the initial treatment of extensive-stage small cell lung cancer

On December 5, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for Tecentriq (atezolizumab), in combination with carboplatin and etoposide (chemotherapy), for the initial (first-line) treatment of people with extensive-stage small cell lung cancer (ES – SCLC) (Press release, Hoffmann-La Roche, DEC 5, 2018, View Source [SID1234531901]). The FDA is expected to make a decision on approval by 18 March 2019. 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 serious disease.

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!

"It’s been more than 20 years since there has been a new initial treatment option for extensive-stage small cell lung cancer that delivers a clinically meaningful survival benefit," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "We are working closely with the FDA to bring this Tecentriq-based regimen to people with this difficult-to-treat type of lung cancer as soon as possible."

This sBLA is based on results from the Phase III IMpower133 study, which met its co-primary endpoints of overall survival (OS) and progression-free survival (PFS) in the initial treatment of people with ES-SCLC. The safety profile of the combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified.

Tecentriq is currently approved by the FDA to treat people with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumour has ALK or EGFR gene abnormalities.

About the IMpower133 study
IMpower133 is a Phase III, multicentre, double-blinded, randomised placebo-controlled study evaluating the efficacy and safety of Tecentriq in combination with carboplatin and etoposide versus chemotherapy (carboplatin plus etoposide) alone in chemotherapy-naïve people with ES-SCLC. The study enrolled 403 people who were randomised equally (1:1) to receive:

Tecentriq in combination with carboplatin and etoposide (Arm A), or
Placebo in combination with carboplatin and etoposide (Arm B, control arm)
During the treatment-induction phase, people received treatment on 21-day cycles for four cycles, followed by maintenance with Tecentriq or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). Treatment could be continued until persistent radiographic PD or symptomatic deterioration was observed.

The co-primary endpoints were:

PFS as determined by the investigator using RECIST v1.1 in the intention-to-treat (ITT) population
OS in the ITT population
IMpower133 met its OS and PFS co-primary endpoints as per the study protocol. The analysis showed that Tecentriq and chemotherapy helped people live significantly longer, compared with chemotherapy alone (OS=12.3 versus 10.3 months; hazard ratio [HR]=0.70; 95% CI: 0.54–0.91; p=0.0069) in the ITT population. [1] The 1-year OS rate for people who received the Tecentriq-based combination was 51.7%, compared with 38.2% for people who received chemotherapy alone. The Tecentriq-based combination also significantly reduced the risk of disease worsening or death (PFS) compared with chemotherapy alone (PFS=5.2 versus 4.3 months; HR=0.77; 95% CI: 0.62–0.96; p=0.017).[1] The 1-year PFS rate for people who received the Tecentriq-based combination was 12.6%, compared with 5.4% for people who received chemotherapy alone. Safety for the Tecentriq and chemotherapy combination appeared to be consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination.

Grade 3–4 treatment-related adverse events (AEs) were reported in 56.6% of people receiving Tecentriq plus chemotherapy, compared with 56.1% of people receiving chemotherapy alone. [1]

About SCLC
Lung cancer is the leading cause of cancer death globally.[2] Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day. [2] Lung cancer can be broadly divided into two major types: non-small cell lung cancer (NSCLC) and SCLC, with SCLC accounting for approximately 15% of all lung cancer cases. [3] Survival rates for people with SCLC vary depending on the stage (extent) of the cancer at the time of diagnosis. [4] The five-year relative survival rate for people with stage I SCLC is approximately 31%; however, at stage IV, the five-year relative survival rate declines to approximately 2%.[5]

About Tecentriq
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 nine 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 80 countries for people with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma (mUC).

Replimune to Present at the BMO Capital Markets 2018 Prescriptions for Success Healthcare Conference

On December 5, 2018 Replimune Group Inc. (NASDAQ: REPL), a biotechnology company developing oncolytic immunotherapies derived from its Immulytic platform, reported that Robert Coffin, Ph.D., Chief Executive Officer and Director of Replimune, will present at the BMO Capital Markets 2018 Prescriptions for Success Healthcare Conference on Wednesday, December 12, 2018 at 2:40 PM ET at the Mandarin Oriental Hotel in New York, NY (Press release, Replimune, DEC 5, 2018, View Source [SID1234531896]).

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!


FDA Grants Priority Review to Genentech’s Tecentriq in Combination with Chemotherapy for the Initial Treatment of Extensive-Stage Small Cell Lung Cance

On December 5, 2018 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for Tecentriq (atezolizumab), in combination with carboplatin and etoposide (chemotherapy), for the initial (first-line) treatment of people with extensive-stage small cell lung cancer (ES-SCLC) (Press release, Genentech, DEC 5, 2018, View Source [SID1234531891]). The FDA is expected to make a decision on approval by March 18, 2019. 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 serious disease.

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!

"It’s been more than 20 years since there has been a new initial treatment option for extensive-stage small cell lung cancer that delivers a clinically meaningful survival benefit," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "We are working closely with the FDA to bring this Tecentriq-based regimen to people with this difficult-to-treat type of lung cancer as soon as possible."

This sBLA is based on results from the Phase III IMpower133 study, which met its co-primary endpoints of overall survival (OS) and progression-free survival (PFS) in the initial treatment of people with ES-SCLC. The safety profile of the combination was consistent with the safety profiles of the individual medicines, and no new safety signals were identified.

Tecentriq is currently approved by the FDA to treat people with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumor has ALK or EGFR gene abnormalities.

About the IMpower133 study

IMpower133 is a Phase III, multicenter, double-blinded, randomized placebo-controlled study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and etoposide) versus chemotherapy (carboplatin and etoposide) alone in chemotherapy-naïve people with ES-SCLC. The study enrolled 403 people who were randomized equally (1:1) to receive:

Tecentriq in combination with carboplatin and etoposide (Arm A), or
Placebo in combination with carboplatin and etoposide (Arm B, control arm)
During the treatment-induction phase, people received treatment on 21-day cycles for four cycles, followed by maintenance with Tecentriq or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Treatment could be continued until persistent radiographic PD or symptomatic deterioration was observed.

The co-primary endpoints were:

PFS as determined by the investigator using RECIST v1.1 in the intention-to-treat (ITT) population
OS in the ITT population
IMpower133 met its OS and PFS co-primary endpoints as per the study protocol. The analysis showed that Tecentriq and chemotherapy helped people live significantly longer compared to chemotherapy alone (OS=12.3 versus 10.3 months; hazard ratio [HR] = 0.70, 95 percent CI: 0.54-0.91; p=0.0069) in the ITT population. The one-year OS rate for people who received the Tecentriq-based combination was 51.7 percent compared to 38.2 percent for people who received chemotherapy alone. The Tecentriq-based combination also significantly reduced the risk of disease worsening or death compared to chemotherapy alone (PFS=5.2 versus 4.3 months; HR=0.77; 95 percent CI: 0.62-0.96; p=0.017). The one-year PFS rate for people who received the Tecentriq-based combination was 12.6 percent compared to 5.4 percent for people who received chemotherapy alone. Safety for the Tecentriq and chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. Grade 3-4 treatment-related adverse events (AEs) were reported in 56.6 percent of people receiving Tecentriq plus chemotherapy compared to 56.1 percent of people receiving chemotherapy alone.

About lung cancer

According to the American Cancer Society, it is estimated that more than 234,000 Americans will be diagnosed with lung cancer in 2018. Lung cancer can be broadly divided into two major types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most prevalent type, accounting for around 85 percent of all lung cancer cases, and SCLC accounting for approximately 15 percent of all cases. The majority (approximately 70 percent) of people with SCLC are diagnosed with ES-SCLC.

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

Tecentriq U.S. Indication (pronounced ‘tē-SEN-trik’)

Tecentriq is a prescription medicine used to treat:

A type of bladder and urinary tract cancer called urothelial carcinoma.

Tecentriq may be used when your bladder cancer:
has spread or cannot be removed by surgery, and if you have any one of the following conditions:
you are not able to take chemotherapy that contains a medicine called cisplatin, and your doctor has tested your cancer and found high levels of a specific protein on your cancer called programmed death-ligand 1 (PD-L1), as determined by an FDA-approved test, or
you are not able to take chemotherapy that contains any platinum regardless of PD-L1 status on your cancer, or
you have tried chemotherapy that contains platinum, and it did not work or is no longer working
The approval of Tecentriq in these patients is based on a study that measured response rate and duration of response. There is an ongoing study to confirm clinical benefit.

A type of lung cancer called non-small cell lung cancer (NSCLC).

Tecentriq may be used when your lung cancer:
has spread or grown, and
you have tried chemotherapy that contains platinum, and it did not work or is no longer working
If your tumor has an abnormal EGFR or ALK gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.

It is not known if Tecentriq is safe and effective in children.

Important Safety Information

What is the most important information about Tecentriq?

Tecentriq can cause the immune system to attack normal organs and tissues and can affect the way they work. These problems can sometimes become serious or life threatening and can lead to death.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

Tecentriq can cause serious side effects, including:

Lung problems (pneumonitis)–signs and symptoms may include new or worsening cough, shortness of breath, and chest pain
Liver problems (hepatitis)–signs and symptoms of hepatitis may include yellowing of the skin or the whites of the eyes, severe nausea or vomiting, pain on the right side of the stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual
Intestinal problems (colitis)–signs and symptoms of colitis may include diarrhea (loose stools) or more bowel movements than usual, blood or mucous in the stools or dark, tarry, sticky stools, and severe stomach area (abdomen) pain or tenderness
Hormone gland problems (especially the thyroid, adrenal glands, pancreas, and pituitary)–signs and symptoms that the hormone glands are not working properly may include headaches that will not go away or unusual headaches, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, changes in mood or behavior (such as decreased sex drive, irritability, or forgetfulness), feeling cold, constipation, the voice gets deeper, urinating more often than usual, nausea or vomiting, and stomach area (abdomen) pain
Problems in other organs–signs and symptoms may include severe muscle weakness, numbness or tingling in hands or feet, confusion, blurry vision, double vision, or other vision problems, changes in mood or behavior, extreme sensitivity to light, neck stiffness, eye pain or redness, skin blisters or peeling, chest pain, irregular heartbeat, shortness of breath, or swelling of the ankles
Severe infections–signs and symptoms of infection may include fever, cough, flu-like symptoms, pain when urinating, and frequent urination or back pain
Severe infusion reactions–signs and symptoms of infusion reactions may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, swelling of the face or lips, dizziness, fever, feeling like passing out, and back or neck pain
Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with Tecentriq if patients have severe side effects.

Before receiving Tecentriq, patients should tell their healthcare provider about all of their medical conditions, including if they:

have immune system problems (such as Crohn’s disease, ulcerative colitis, or lupus); have had an organ transplant; have lung or breathing problems; have liver problems; have a condition that affects the nervous system (such as myasthenia gravis or Guillain-Barre syndrome); or are being treated for an infection
are pregnant or plan to become pregnant. Tecentriq can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with Tecentriq. If patients are able to become pregnant:
A healthcare provider should do a pregnancy test before they start treatment with Tecentriq.
They should use an effective method of birth control during their treatment and for at least 5 months after the last dose of Tecentriq.
are breastfeeding or plan to breastfeed. It is not known if Tecentriq passes into the breast milk. Do not breastfeed during treatment and for at least 5 months after the last dose of Tecentriq
Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq in people with urothelial carcinoma include:

feeling tired
decreased appetite
nausea
constipation
urinary tract infection
diarrhea
fever
The most common side effects of Tecentriq in people with non-small cell lung cancer include:

feeling tired
decreased appetite
muscle pain
cough
shortness of breath
Tecentriq may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of Tecentriq. Patients should ask their healthcare provider or pharmacist for more information. Patients should call their doctor for medical advice about side effects.

Additional product patent in the United States for HyNap-Dasa

On December 4, 2018 Xspray Pharma AB (Nasdaq First North: XSPRAY) ("Xspray" or the "Company") reported that the United States Patent and Trademark Office (USPTO) has granted a new patent in the United States to Xspray (Press release, Xspray, DEC 4, 2018, View Source [SID1234650104]). The new patent, US 10,143,683, covers the pharmaceutical composition of Xspray’s lead product candidate, HyNap-Dasa. This is Xspray’s third product patent in the US which is Xspray’s main market. The new patent will expireJanuary 11, 2033.
"This new patent approval in our most important market further confirms our innovative development work. Together with the previously communicated formal clinical bioequivalence for the company´s lead product candidate, HyNap-Dasa, this patent will be instrumental in our forthcoming negotiations with potential partners," says Per Andersson, CEO of Xspray.

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!

Xspray strives to obtain patents both for composition and methodology, and this new patent claims an amorphous solid dispersion (pharmaceutical composition) of dasatinib.

"The new patent for HyNap-Dasa has the broadest scope of all our composition patents in the US and makes it significantly more difficult for other companies to launch a dasatinib product based on amorphous solid dispersion formulation in the US market during the lifetime of this patent, i.e. up until 2033", says Per Andersson, CEO of Xspray.

Nordic Nanovector: Additional preclinical studies with CD37-targeting radioimmunotherapies for B-cell malignancies presented at ASH

On December 4, 2018 Nordic Nanovector ASA (OSE: NANO) reported that two new poster presentations from preclinical studies with CD37-targeting radioimmunotherapies were made at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (1-4 December 2018 in San Diego, CA, USA) (Press release, Nordic Nanovector, DEC 4, 2018, View Source [SID1234553485]). These posters were presented in addition to the results of the Phase 1/2 trial of Betalutin (177Lu-satetraxetan-lilotomab) in patients with relapsed/refractory indolent non-Hodgkin’s lymphoma – see separate announcement.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The posters are as follows:

Abstract 4422

Abstract title:

Targeted Alpha Therapy with 212Pb-NNV-003 for the Treatment of CD37 Positive B-Cell Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin Lymphoma (NHL)

Authors:

A. Saidi et al.

This poster describes results from a research collaboration to develop a novel CD37-targeting alpha therapy for B-cell malignancies and the results noted in the abstract were previously announced on 1 November 2018. The research collaboration was established in June 2015 with Orano Med (formerly known as AREVA Med) to develop and investigate a next-generation targeted alpha therapy, comprising Nordic Nanovector’s chimeric anti-CD37 antibody (NNV003) and lead-212 (212Pb), for the treatment of B-cell malignancies.

The preclinical studies investigated the dose-dependent efficacy and tolerability of 212Pb-NNV003 in human cell and mouse models of chronic lymphocytic leukaemia (CLL) and Burkitt’s lymphoma (a type of non-Hodgkin’s lymphoma, NHL). In the studies, 212Pb-NNV003 was found to be well tolerated and led to a 90-100% survival rate in mouse models of CLL and NHL.

Abstract 1371

Abstract title:

Cell Cycle Kinase Inhibitors Potentiate the Effect of 177lu-Lilotomab Satetraxetan in Treatment of Aggressive Diffuse Large B-Cell Lymphoma Cell Lines

Authors:

G.E. Rødland et al.

The poster describes results from a preclinical study aimed at identifying possible drug combinations involving Betalutin in two aggressive, radioimmunotherapy-resistant diffuse large B-cell lymphoma (DLBCL) cell lines. The study identified cell cycle kinase inhibitors as promising partners for combination treatment of aggressive DLBCL with Betalutin, warranting further exploration in preclinical models.

Both abstracts are available at View Source and the posters have been published on the Nordic Nanovector website – View Source

About ASH (Free ASH Whitepaper)

The ASH (Free ASH Whitepaper) annual meeting is the premier event for scientific exchange in the field of haematology, attracting more than 20,000 attendees from all over the world. Typically, more than 5,000 scientific abstracts are submitted each year, and more than 3,000 abstracts are accepted for oral and poster presentations through an extensive peer review process.