On May 16, 2019 AstraZeneca reported that it will present new research across an industry-leading Oncology portfolio, including data for its transformational cancer medicines Lynparza (olaparib) and Imfinzi (durvalumab) at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, US, 31 May to 4 June 2019 (Press release, AstraZeneca, MAY 16, 2019, View Source [SID1234536390]).

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!

In all, the Company will present 93 abstracts spanning multiple tumour types, including 12 oral presentations with one plenary session and four late-breakers. Highlights include:

Late-breaking results from the Lynparza POLO trial, the first positive Phase III trial of any PARP inhibitor in germline BRCA-mutated (gBRCAm) metastatic pancreatic cancer, a devastating diagnosis with critical unmet medical need. This is the first Phase III trial to validate a targeted treatment in a biomarker-selected population of pancreatic cancer.
Results of the Phase III SOLO-3 trial highlighting the efficacy for Lynparza monotherapy vs. standard-of-care chemotherapy in treating patients with gBRCAm advanced ovarian cancer who had two or more prior lines of treatment. This data underscores Lynparza’s clinical benefit irrespective of line of treatment for women with BRCAm advanced ovarian cancer and the importance of knowing BRCA status at diagnosis.
Three-year overall survival (OS) data from the Phase III PACIFIC trial providing new evidence of the long-term survival benefit for Imfinzi in unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease had not progressed following chemoradiation therapy. Imfinzi is the only immunotherapy to demonstrate significant OS benefits in this curative-intent setting, and this data reaffirms the PACIFIC regimen as the standard of care for these patients.
Dave Fredrickson, Executive Vice President, Oncology, said: "AstraZeneca continues to break traditional treatment boundaries through new targeted approaches and the prioritisation of earlier intervention. This year at ASCO (Free ASCO Whitepaper), our data for Lynparza in BRCA-mutated metastatic pancreatic cancer and for Imfinzi in unresectable Stage III non-small cell lung cancer illustrate our ambition to change medical practice for better patient outcomes."

Breaking treatment boundaries

AstraZeneca is committed to redefining disease treatment for patient populations with unmet needs. This will be evidenced at the ASCO (Free ASCO Whitepaper) meeting for patients with PARP-mediated tumours, HER2-low expressing tumours, and AKT-mutated tumours.

The plenary presentation of results from the Phase III POLO trial will detail the progression-free survival (PFS) and important clinical benefit of Lynparza in patients with metastatic pancreatic cancer, a population that has seen very little treatment progress over the past 40 years (Abstract #LBA4).

New data on Lynparza will also be shared in advanced ovarian cancer, including the results of the Phase III SOLO-3 trial highlighting the efficacy for Lynparza monotherapy vs. standard-of-care chemotherapy in treating patients with gBRCAm advanced ovarian cancer who had two or more prior lines of treatment (Abstract #5506).

Furthermore, the Phase II TOPARP-B trial, sponsored by the Institute of Cancer Research (UK), will highlight the anti-tumour activity of Lynparza in patients with heavily-pretreated metastatic castration-resistant prostate cancer with DDR gene defects (Abstract #5005). The Phase II GeparOLA trial, conducted by the German Breast Group and German AGO-B Breast Study Group, will help define the safety and efficacy of Lynparza, compared to platinum-based chemotherapy, in the neoadjuvant setting in HER2-negative early breast cancer and in patients with homologous recombination deficiency (Abstract #506).

The design of the Phase III DESTINY-Breast04 trial evaluating trastuzumab deruxtecan (DS-8201) in metastatic breast cancer with HER2-low expressing tumours will be presented at this year’s ASCO (Free ASCO Whitepaper) meeting (Abstract #TPS1102). The antibody drug conjugate (ADC) co-developed with Daiichi Sankyo has the potential to redefine breast cancer treatment. Two publications in Lancet Oncology recently highlighted the Phase I dose-expansion results for trastuzumab deruxtecan in HER2-positive metastatic breast and gastric cancers.

In addition, data will be presented from the Phase II FAKTION trial, sponsored by Velindre NHS Trust, on the combination of the AKT inhibitor capivasertib (AZD5363) plus Faslodex (fulvestrant) in patients with relapsed metastatic oestrogen receptor (ER)-positive breast cancer (Abstract #1005). AKT mutations occur across several different cancers and may be a target for treatment tailored to tumour genes rather than cancer types.

Treating patients earlier in their disease

AstraZeneca made a significant breakthrough in the treatment of NSCLC beginning in 2017 with the Phase III PACIFIC trial demonstrating unprecedented PFS and subsequently OS benefits for patients with unresectable, Stage III NSCLC treated with Imfinzi vs. standard of care. At this year’s ASCO (Free ASCO Whitepaper) meeting, AstraZeneca will provide new evidence of the long-term survival benefit of Imfinzi with a three-year OS update (Abstract #8526).

Sub-analysis presentations of Phase III data from SOLO-1, the only trial of a PARP inhibitor to demonstrate improvement in PFS for women with BRCAm advanced ovarian cancer as a 1st-line maintenance treatment, will reinforce the potential of using Lynparza earlier in the treatment pathway (Abstract #5539).

Raising the bar for better outcomes

New data from the Phase III FLAURA trial will explore clinical outcomes associated with the detection of epidermal growth factor receptor (EGFR) mutations in plasma at three or six weeks after starting treatment with Tagrisso (osimertinib) (Abstract #9020). With the presentation of the Phase II SAVANNAH trial design, AstraZeneca will explain how it will explore the combination of Tagrisso and savolitinib to potentially overcome MET-driven EGFR tyrosine kinase inhibitor (TKI) resistance following Tagrisso treatment in EGFR-mutated NSCLC (Abstract #TPS9119).

Despite recent therapeutic progress, platinum-resistant ovarian cancer remains a therapeutic challenge. Results of a multicenter, double-blind Phase II trial conducted by the Princess Margaret, California, Chicago and Mayo Phase II Consortia will show for the first time increased OS data with the Wee-1 inhibitor adavosertib when associated with the antimetabolite medicine gemcitabine (Abstract #5518).

A focus on haematology

The diverse haematology pipeline aims to deliver new medicines in a range of blood cancers with critical unmet medical need

AstraZeneca has established haematology as one of its key areas of focus. At the ASCO (Free ASCO Whitepaper) meeting and the upcoming 24th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), 13-16 June 2019, the Company will present long-term trial follow-up data showing the promising response rate, duration of response and safety profile of the Bruton’s tyrosine kinase (BTK) inhibitor Calquence (acalabrutinib) in chronic lymphocytic leukaemia (CLL), including:

Three-year results from the Phase Ib/II ACE-CL-003 trial evaluating Calquence and obinutuzumab in treatment-naïve and previously-treated CLL (Abstract #7500)
19-month results from the Phase II ACE-CL-208 trial of Calquence in patients with relapsed or refractory CLL intolerant to ibrutinib (Abstract #7530)
These data are part of a robust development programme that includes two pivotal clinical trials for Calquence in CLL with full data anticipated in 2019: the Phase III ASCEND (ACE-CL-309) trial in relapsed or refractory CLL, which recently met its primary endpoint, and the ongoing Phase III ELEVATE-TN (ACE-CL-007) trial evaluating Calquence with and without obinutuzumab in front-line CLL.

Key AstraZeneca presentations at ASCO (Free ASCO Whitepaper) 2019

Lead author

Abstract title

Presentation details

Immuno-Oncology

Gray, JE

Three-year overall survival update from the PACIFIC trial.

Abstract #8526

Poster Board #282

Poster Session – Lung Cancer – Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

Sunday 2 June, 8:00-11:00am

Hall A

Planchard, D

First subsequent treatment after discontinuation of durvalumab in unresectable, Stage III NSCLC patients from PACIFIC.

Abstract #9054

Poster Board #377

Poster Session – Lung Cancer – Non-Small Cell Metastatic

Sunday 2 June, 8:00-11:00am

Hall A

Rizvi, NA

Blood tumor mutational burden (bTMB) and tumor PD-L1 as predictive biomarkers of survival in MYSTIC: first-line durvalumab (D) ± tremelimumab (T) vs chemotherapy (CT) in metastatic (m) NSCLC.

Abstract #9016

Poster Board #339

Poster Discussion – Lung Cancer – Non-Small Cell Metastatic

Sunday 2 June, 4:30-6:00pm

Hall D1

Garon, EB

Patient-reported outcomes (PROs) with first-line durvalumab (D) ± tremelimumab (T) vs chemotherapy (CT) in metastatic NSCLC: results from MYSTIC.

Abstract #9048

Poster Board #371

Poster Presentation – Lung Cancer – Non-Small Cell Metastatic

Sunday 2 June, 8:00-11:00am

Hall A

Bradley, JD

PACIFIC-2: phase 3 study of concurrent durvalumab and platinum-based chemoradiotherapy in patients with unresectable, stage III NSCLC.

Abstract #TPS8573

Poster Board #327a

Poster Presentation – Lung Cancer – Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers

Sunday 2 June, 8:00-11:00am

Hall A

DNA damage response

Kindler, H

Olaparib as maintenance treatment following first-line platinum-based chemotherapy (PBC) in patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC): Phase III POLO trial.

Abstract #LBA4

Plenary Session Including the Distinguished Achievement Award and Science of Oncology Award Lecture

Sunday 2 June, 3:15-3:30pm

Hall B1

Penson, R

Olaparib monotherapy versus (vs) chemotherapy for germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase III SOLO3 trial.

Abstract #5506

Oral Abstract Session – Gynecologic Cancer

Monday 3 June, 3:15-3:27pm

S406

Colombo, N

Adverse events (AEs) with maintenance olaparib in newly diagnosed patients (pts) with advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): Phase III SOLO1 trial.

Abstract #5539

Poster Board #362

Poster Session – Gynecologic Cancer

Saturday 1 June, 1:15-4:15pm

Hall A

Mateo, J

TOPARP-B: A phase II randomized trial of the poly(ADP)-ribose polymerase (PARP) inhibitor olaparib for metastatic castration resistant prostate cancers (mCRPC) with DNA damage repair (DDR) alterations.

Abstract #5005

Oral Abstract Session – Genitourinary (Prostate) Cancer

Friday 31 May, 4:09-4:21pm

Arie Crown Theater

Lheureux, S

A randomized double-blind placebo-controlled phase II trial comparing gemcitabine monotherapy to gemcitabine in combination with adavosertib in women with recurrent, platinum resistant epithelial ovarian cancer: A trial of the Princess Margaret, California, Chicago and Mayo Phase II Consortia.

Abstract #5518

Poster Board #341

Poster Session – Gynaecologic Cancer

Saturday 1 June, 4:30-6:00pm

Hall A

Fasching, P

GeparOLA: A randomized phase II trial to assess the efficacy of paclitaxel and olaparib in comparison to paclitaxel/carboplatin followed by epirubicin/cyclophosphamide as neoadjuvant chemotherapy in patients (pts) with HER2-negative early breast cancer (BC) and homologous recombination deficiency (HRD).

Abstract #506

Oral Abstract Session – Breast Cancer -Local/Regional/Adjuvant

Monday 3 June, 11:45-11:57pm

Hall D2

Tumour drivers and resistance

Oxnard, GR

SAVANNAH: A Phase II trial of osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-driven (MET+), locally advanced or metastatic non-small cell lung cancer (NSCLC), following disease progression on osimertinib.

Abstract #TPS9119

Poster Board #439b

Poster Session – Lung Cancer – Non-Small Cell Metastatic

Sunday 2 June, 8:00-11:00am

Hall A

Zhou, C

Early clearance of plasma EGFR mutations as a predictor of response to osimertinib and comparator EGFR-TKIs in the FLAURA trial.

Abstract #9020

Poster Board #343

Poster Session – Lung Cancer – Non-Small Cell Metastatic

Sunday 2 June, 8:00-11:00am

Hall A

Jones, RH

Capivasertib (AZD5363) plus fulvestrant versus placebo plus fulvestrant after relapse or progression on an aromatase inhibitor in metastatic ER-positive breast cancer (FAKTION): A randomized, double-blind, placebo-controlled, phase II trial.

Abstract #1005

Oral Abstract Session – Breast Cancer – Metastatic

Tuesday 4 June, 11:09-11:21am

Hall D1

Haematology

Woyach, J

Acalabrutinib with obinutuzumab (Ob) in treatment-naive (TN) and relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Three-year follow-up.

Abstract #7500

Oral Abstract Session – Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia

Tuesday 4 June, 9:45-9:57am

E451

Rogers, KA

Phase 2 study of acalabrutinib in ibrutinib (IBR)-intolerant patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).

Abstract #7530

Poster Board #284

Poster Session – Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia

Monday 3 June, 8:00-11:00am

Hall A

Trastuzumab deruxtecan (DS-8201)

Modi, S

A phase III, multicenter, randomized, open label trial of [fam-] trastuzumab deruxtecan (DS-8201a) versus investigator’s choice in HER2-low breast cancer.

Abstract #TPS1102

Poster Board #182a

Poster Session – Breast Cancer – Metastatic

Sunday 2 June, 8:00-11:00am

Hall A

In addition to the scientific presentations and press releases planned at the ASCO (Free ASCO Whitepaper) meeting, AstraZeneca and its partner MSD (MSD: known as Merck & Co., Inc. inside the US and Canada) will host a press briefing on Sunday 2 June, on Lynparza. For more information, please contact AstraZeneca Global Media Relations.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On May 16, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) has approved Venclexta (venetoclax) in combination with Gazyva (obinutuzumab) for the treatment of people with previously untreated chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) (Press release, Hoffmann-La Roche, MAY 16, 2019, View Source [SID1234536389]).

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!

"Venclexta plus Gazyva is the only chemotherapy-free option of fixed duration that provides durable responses to help people live longer without progression of their disease, compared to a standard-of-care," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Today’s approval represents our long-standing commitment to helping people with blood cancers throughout the course of their disease, and we are excited to provide this new option for untreated chronic lymphocytic leukaemia."

The approval is based on the results of the randomised phase III CLL14 study, which evaluated 12-month, fixed-duration treatment with Venclexta plus Gazyva compared to Gazyva plus chlorambucil. Results showed the combination of Venclexta plus Gazyva produced a durable and significant reduction in the risk of disease worsening or death (progression-free survival [PFS], as assessed by Independent Review Committee) by 67% compared to Gazyva plus chlorambucil, a current standard-of-care (HR=0.33; 95% CI 0.22-0.51; p<0.0001). Venclexta plus Gazyva showed deep and clinically meaningful responses characterised by a higher rate of minimal residual disease (MRD)-negativity in the bone marrow compared to Gazyva plus chlorambucil (MRD-negativity of 57% vs. 17%) and peripheral blood (MRD-negativity of 76% vs. 35%). MRD-negativity means no cancer can be detected using a specific and highly sensitive test, defined as less than one CLL cell in 10,000 white blood cells.

Results of the study will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2019. The CLL14 study is being conducted in cooperation with the German CLL Study Group (GCLLSG), headed by Michael Hallek, MD, University of Cologne.

The most common adverse reactions with Venclexta plus Gazyva were low white blood cell count, diarrhoea, fatigue, nausea, low red blood cell count, and upper respiratory tract infection.

The FDA rapidly reviewed and approved the supplemental New Drug Application (sNDA) under the FDA’s Real-Time Oncology Review (RTOR) and Assessment Aid pilot programmes. This is the second regimen of Roche medicines approved under the RTOR pilot programme, which is exploring a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. The sNDA was also granted Priority Review, a designation given to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. The FDA previously granted Breakthrough Therapy Designation for Venclexta in combination with Gazyva for the treatment of previously untreated CLL with co-existing medical conditions. Additional submissions of the CLL14 data to health authorities around the world are ongoing.

Venclexta is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche group, in the US and commercialised by AbbVie outside of the US.

About the CLL14 Study
CLL14 (NCT02242942) is a randomised phase III study evaluating the combination of fixed-duration Venclexta plus Gazyva compared to Gazyva plus chlorambucil in patients with previously untreated chronic lymphocytic leukaemia (CLL) and co-existing medical conditions. 432 patients with previously untreated CLL were randomly assigned to receive either a 12-month duration of Venclexta alongside six-month duration of Gazyva (Arm A) or six-month duration of Gazyva plus chlorambucil followed by an additional six-month duration of chlorambucil (Arm B). Arm A started with an initial cycle of Gazyva followed by a five-week Venclexta dose ramp-up to help reduce tumour burden. The primary endpoint of the study is investigator-assessed progression-free survival (PFS). Secondary endpoints include PFS assessed by independent review committee (IRC), minimal residual disease (MRD) status, overall response (OR), complete response (with or without complete blood count recovery, CR/CRi), overall survival (OS), duration of response (DOR), event-free survival (EFS), time to next CLL treatment (TTNT) and safety. The CLL14 study is being conducted in cooperation with the German CLL Study Group (GCLLSG), headed by Michael Hallek, MD, University of Cologne.

The most common adverse reactions with Venclexta plus Gazyva were low white blood cell count, diarrhoea, fatigue, nausea, low red blood cell count, and upper respiratory tract infection.

About Venclexta/Venclyxto (venetoclax)
Venclexta/Venclyxto is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumours, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta/Venclyxto blocks the BCL-2 protein and works to restore the process of apoptosis.
Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the US and commercialised by AbbVie, under the brand name Venclyxto, outside of the US. Together, the companies are committed to research with Venclexta/Venclyxto, which is currently being studied in clinical trials across several types of blood and other cancers.

In the US, Venclexta has been granted five Breakthrough Therapy Designations by the US Food and Drug Administration: one for previously untreated CLL, two for relapsed or refractory CLL and two for previously untreated acute myeloid leukaemia.

About Gazyva/Gazyvaro (obinutuzumab)
Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyva/Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system. Gazyva is marketed as Gazyvaro in the EU and Switzerland.

Gazyva/Gazyvaro is currently approved in more than 90 countries in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia, in more than 80 countries in combination with bendamustine for people with certain types of previously treated follicular lymphoma and in more than 70 countries in combination with chemotherapy for previously untreated follicular lymphoma.

Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

About the German CLL Study Group (GCLLSG)
Founded in 1996 and headed by Michael Hallek, MD, the GCLLSG has been running various phase III, phase II and phase I trials in chronic lymphocytic leukaemia (CLL) with the goal to provide optimal treatment to patients suffering from this disease. Among those were landmark trials like the CLL8 and the CLL11 trials which led to the current standard of care in CLL. For many years, GCLLSG has been aiming to improve not just the treatment of younger and physically fit patients, but also that of elderly and less fit patients. These patients are generally underrepresented in clinical trials although they constitute the majority of CLL patients treated by doctors in daily practice. The GCLLSG is an independent non-profit research organisation supported by the German Cancer Aid (Deutsche Krebshilfe) www.dcllsg.de.

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes polatuzumab vedotin, an anti-CD79b antibody drug conjugate; idasanutlin, a small molecule which inhibits the interaction of MDM2 with p53; T-cell engaging bispecific antibodies targeting both CD20 and CD3, and Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

On May 16, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported positive data from the Phase I/II STARTRK-NG study, evaluating the investigational medicine entrectinib in children and adolescents with recurrent or refractory solid tumours with and without neurotrophic tyrosine receptor kinase (NTRK), ROS1 or anaplastic lymphoma kinase (ALK) gene fusions (Press release, Hoffmann-La Roche, MAY 16, 2019, View Source [SID1234536388]). The study showed entrectinib shrank tumours (objective response rate; ORR) in all children and adolescents who had NTRK, ROS1 or ALK fusion-positive solid tumours (11 of 11 patients), including two patients achieving a complete response.1 Of the 11 patients, five patients with primary high-grade tumours in the central nervous system (CNS) had an objective response, including one patient with a complete response.1 The safety profile of entrectinib was consistent with that seen in previous analyses.1 Data will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on Sunday, 2 June, 2019, from 8:00 – 8:12 am CDT (Abstract 10009), and was part of yesterday’s official ASCO (Free ASCO Whitepaper) presscast.

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 by the results we have seen with entrectinib in children with paediatric and adolescent cancers, including those with tumours in the brain," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "The STARTRK-NG study underscores the importance of combining comprehensive genomic profiling with targeted therapies and supports our approach to providing people with personalised medicines developed specifically for their type of cancer."

Additional data for entrectinib across different tumour types and patient populations will also be presented at ASCO (Free ASCO Whitepaper), highlighting the company’s unique approach to personalised healthcare through advances in targeted therapies, diagnostics and data analytics:

Initial results from an integrated analysis of the Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials, evaluating the efficacy of entrectinib in adults with solid tumours and CNS metastases, will be presented on Saturday, 1 June, 2019, in a poster session from 3:00 – 4:30 pm CDT (Abstract 3017).
Results from a Real World Data study, evaluating time-to-treatment discontinuation and progression-free survival as endpoints for comparative efficacy analysis of clinical trials of entrectinib and crizotinib for the treatment of people with ROS1-positive non-small cell lung cancer (NSCLC), will be presented during a poster session on Sunday, 2 June, 2019, from 8:00 – 11:00 am CDT (Abstract 9070).
The FDA recently granted Priority Review for entrectinib for both the treatment of paediatric and adult patients with NTRK fusion-positive, locally advanced or metastatic solid tumours who have either progressed following prior therapies or as an initial therapy when there are no acceptable standard therapies, and for the treatment of people with metastatic ROS1-positive NSCLC.2 These NDAs are based on results from the integrated analysis of the Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials, and data from the STARTRK-NG study. The FDA is expected to make a decision on approval by 18 August, 2019.2

About the STARTRK-NG study
STARTRK-NG is a Phase I/II open-label dose-escalation and expansion study evaluating the safety and efficacy of entrectinib in children and adolescent patients with no curative first-line treatment option, recurrent or refractory extracranial solid tumours or primary CNS tumours, with or without NTRK, ROS1 or ALK fusions.1 Response, assessed by Investigator, was classified as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) using Response Assessment in Neuro-Oncology (RANO) for CNS tumours, Response Evaluation Criteria in Solid Tumors (RECIST), and Curie score (CS) for NBL.1 The study enrolled 29 children and adolescents aged 4.9 months through to 20 years (median age of 7 years) who had recurrent or refractory solid tumours, and 28 were evaluated for response.1 Of the 28 children and adolescents evaluated, 11 children were identified to have tumours with NTRK, ROS1 or ALK fusions and one with ALK F1174L-mutated neuroblastoma (NBL).1 A summary of the results are included below.

Complete responses were observed in 2 patients with tumours harbouring NTRK and ALK fusions: 1 with an NTRK fusion-positive primary CNS tumour and 1 with an ALK fusion-positive inflammatory myofibroblastic tumour. Another complete response was observed in 1 neuroblastoma patient with an ALK F1174L mutation.1
Partial responses were observed in 9 patients, 3 unconfirmed at the time of the clinical cut-off date, across NTRK, ROS1 and ALK fusion-positive primary CNS (n=4) and extracranial (n=5) solid tumours.1
Median duration of therapy for confirmed fusion-positive responders was 10.51 months (3.8 to 17.7 months), and median time to response was 1.89 months (1 to 1.9 months).1
The safety profile of entrectinib was consistent with that seen in previous analyses. Treatment-related adverse events were most frequently National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Grade 1 or 2, leading to discontinuation in 6.9% of patients.1
About NTRK fusion-positive cancer
Neurotrophic tyrosine receptor kinase (NTRK) fusion-positive cancer occurs when the NTRK1/2/3 genes fuse with other genes, resulting in altered TRK proteins (TRKA/TRKB/TRKC) that can activate signaling pathways involved in proliferation of certain types of cancer. NTRK gene fusions are tumour-agnostic, meaning they are present in tumours irrespective of site of origin. These fusions have been identified in a broad range of solid tumour types, including breast, cholangiocarcinoma, colorectal, gynaecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.3

About entrectinib
Entrectinib (RXDX-101) is an investigational, oral medicine in development for the treatment of locally advanced or metastatic solid tumours that harbour NTRK1/2/3 or ROS1 gene fusions. It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer.4,5 Entrectinib can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusions.4,5 Entrectinib is being investigated across a range of solid tumour types, including breast, cholangiocarcinoma, colorectal, gynaecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.2,3

Entrectinib has been granted Breakthrough Therapy Designation (BTD) by the FDA; Priority Medicines (PRIME) designation by the European Medicines Agency (EMA); and Sakigake designation by the Japanese health authorities for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or have no acceptable standard therapies.2

On May 16, 2019 Immunocore Limited, a leading T cell receptor (TCR) biotechnology company, reported that it will present new mechanism of action data in advanced uveal and cutaneous melanoma from the tebentafusp clinical research programme at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on 3 June 2019 (Press release, Immunocore, MAY 16, 2019, View Source [SID1234536361]). Tebentafusp (IMCgp100) is a novel bispecific biologic T cell receptor therapy with an anti-CD3 immune-redirecting effector function and specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma.

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!

"At ASCO (Free ASCO Whitepaper), we will present clinical and biomarker data from our lead bispecific tebentafusp programme that provide insight into its mechanism of action," said David Berman, Head of Research and Development at Immunocore. "We believe these data will translate across our ImmTAC platform and provide another step towards identifying which patient populations benefit."

Poster discussion/poster: Pharmacodynamic effect of IMCgp100 (TCR–CD3 bispecific) on peripheral cytokines and association with overall survival in patients with advanced melanoma (Abstract #9523, Poster #94)

Highlighting new mechanism of action results for tebentafusp (IMCgp100), this poster will be presented by Mark Middleton, MD, Head, Department of Oncology, University of Oxford, on Monday 3 June, 1:15-4:45 p.m. CDT in Hall A.
The poster will also be discussed by Sophie Piperno-Neumann, MD, Department of Medical Oncology, Institut Curie, in the Melanoma/Skin Cancers poster discussion session on Monday 3 June, 4:30-6:00 p.m. CDT in Room E451.
Poster: Relationship between clinical efficacy and AEs of IMCgp100, a novel bispecific TCR–anti-CD3, in patients with advanced melanoma (Abstract #9530, Poster #101)

In a retrospective analysis, reporting the potential association of rash with overall survival and temporal association of key cytokines with cytokine mediated adverse events for tebentafusp (IMCgp100), this poster will be presented by Omid Hamid, MD, Chief of Translational Research and Immunotherapy and Director of Melanoma Therapeutics, Angeles Clinic, in the Melanoma/Skin Cancers poster session on Monday 3 June, 1:15-4:45 p.m. CDT in Hall A.
Analyses presented at the meeting stemmed from a Phase 1 clinical trial assessing the safety and tolerability of tebentafusp (NCT01211262).

About Tebentafusp

Tebentafusp is a novel bispecific biologic T cell redirection therapy with an anti-CD3 immune-redirecting effector function that specifically targets the melanoma associated antigen gp100. It is now in pivotal studies for metastatic uveal melanoma. Tebentafusp has Fast Track Designation and Orphan Drug Designation in the US and Promising Innovative Medicine designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma. For more information about enrolling tebentafusp clinical trials for metastatic uveal melanoma, please visit ClinicalTrials.gov (NCT03070392).

On May 15, 2019 Scintomics GmbH and 1717 Life Science Ventures GmbH reported to have signed an agreement to collaborate in the development of the theranostic pair PentixaFor / PentixaTher (Press release, Scintomics, MAY 15, 2019, View Source [SID1234561514]).

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!

PentixaPharm GmbH, based in Würzburg, is committed to develop PentixaFor and PentixaTher as a theranostic radiopharmaceutical pair, specifically targeting the CXCR4-receptor expressed in most fast progressing diseases, particularly malignant cancers.

Interviews: "We are delighted that in 1717 LSV we have found a strong partner with an outstanding expertise in the clinical development of precision oncologics. Taking the various recent and successful proof-of-concept studies with PentixaFor and PentixaTher in men into account, this joint venture creates optimal conditions for the effective and swift clinical development of this unrivalled and unique pair of theranostic drugs", said Prof. Hans-Jürgen Wester, PhD, Founder of Scintomics and Chair for Pharmaceutical Radiochemistry at the Technical University of Munich (TUM), Germany.

"The introduction of 68Ga-PentixaFor may be regarded as a milestone for clinical PET imaging of CXCR4 expressing malignancies", added Dr. Hakim Bouterfa Co-founder of 1717 LSV GmbH and CEO of PentixaPharm. "Now we will focus on the next major step to provide CXCR4-directed endoradiotherapy in prospective clinical trials."

About PentixaFor / PentixaTher

This theranostic pair specifically targets the CXCR4-CXCR12 axis, which is significantly involved in the interaction and proliferation of hematologic and solid tumors and their protective environment. The Gallium-68 based PET agent PentixaFor has demonstrated advanced imaging not only for several different hematologic indications – including leukaemia, lymphoma, and multiple myeloma – but also for other solid tumors like adrenocortical carcinoma, and small cell lung cancer. In addition, other disease conditions, such as atherosclerosis, myocardial infarction, splenosis and stroke and can be targeted with this tracer. The therapeutic counterpart PentixaTher, labeled with α- or β-emitters, offers new treatment options for individualised medicine in terms of endoradiotherapy.