On January 28, 2021 Charles River Laboratories International, Inc. (NYSE: CRL) reported that it has entered into a strategic partnership with Cypre, Inc., a biotechnology company that is using 3D hydrogel technology to advance the understanding of the tumor microenvironment and predict therapeutic efficacy (Press release, Charles River Laboratories, JAN 28, 2021, View Source [SID1234574398]). The partnership will provide Charles River clients with access to Cypre’s proprietary 3D tumor model platform, Falcon-X, which will expand Charles River’s 3D in vitro testing services to further optimize immuno-oncological approaches for its clients.

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The Falcon-X 3D In Vitro Tumor Assay Platform is a high content analysis screening option for cancer immunotherapy and targeted therapy. Utilizing Cypre’s patented 3D hydrogel patterning technology, Symphony and VersaGel, and proprietary methods that synergize with the breadth and depth of Charles River’s tumor model collection, the platform recreates the tumor microenvironment and enables predictive screening of innovative immuno-oncology compounds. As a part of Charles River’s integrated tumor model service platform, including patient-derived xenografts (PDX), Falcon-X will provide human data that translates to the clinic and identifies the efficacy of specific immunotherapy and targeted therapeutic treatments for patients.

Charles River offers a range of cancer cell-based assays, including PDX assays and assays representing the entire tumor microenvironment (TME), so therapies are not only tested for their effect on real patient materials, but also their interaction with the human immune systems. Through this collaboration, Charles River will now have a critical new addition to our human oncology assay repertoire, allowing identification of therapeutics that overcome cancer immunotherapy resistance.

The partnership will also allow Cypre to screen multiple therapeutic modalities alone or in combination utilizing Charles River’s genomically annotated and in vivo characterized cancer model database. The database is comprised of more than 700 tumor models, including PDX, cell lines and cell line derived xenografts. These models have been extensively profiled for histological features, molecular data, and sensitivity to standard-of-care compounds, allowing a precise selection of suitable tumor models for preclinical anti-cancer agent testing. The biological advantages of PDX include the retention of histological and genetic characteristics of the donor tumor and the preservation of cell-autonomous heterogeneity, which increase the translational relevance of the Cypre platform significantly. The breadth and depth of Charles River’s cancer model database enable the offering of a clinically relevant tumor panel in Cypre’s innovative 3D platform, and the platform’s compelling predictivity for in vivo PDX models allows streamlined programs and translation to the clinic.

Approved Quotes

"Immunotherapy is a complex, yet promising area of development in cancer treatment. Cypre’s platform enables the ideal tumor culturing conditions for assaying various immunotherapies and targeted therapies and provides robust, reproducible data sets without compromising throughput that strongly correlates to our PDX in vivo results. By broadening our 3D in vitro services with this collaboration, we can provide our clients with a complete, integrated tumor model service platform." – Birgit Girshick, Corporate Executive Vice President, Discovery and Safety Assessment, Biologics Testing Solutions, and Avian Vaccine Services, Charles River
"Charles River is the premier CRO in discovery and early development services, and we are thrilled to partner with their team to drive a combined offering. Our Falcon-X platform provides Charles River customers with expanded access to patient-derived 3D in vitro screening services and a new way to assay the immune cell compartment within the tumor microenvironment. We look forward to building this relationship and providing more customers with our unique solution that will improve targeted and immuno-therapeutic options for cancer patients." – Kolin Hribar, PhD, Founder and CEO, Cypre

On January 28, 2021 VolitionRx Limited (NYSE AMERICAN: VNRX) ("Volition"), a multi-national epigenetics company developing simple, easy to use, cost effective blood tests to help diagnose a range of cancers and other diseases in both humans and animals, reported that has an abstract presented at the world’s largest lung cancer meeting, the WCLC, which is being held virtually this year (Press release, VolitionRX, JAN 28, 2021, View Source [SID1234574397]).

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The poster presentation given by Dr. Tung-Ming Tsai of the National Taiwan University Hospital will be featured in the WCLC’s Screening and Early Detection session and is entitled "Circulating Nucleosomes in Lung Cancer Diagnosis following Low-Dose Computed Tomography". The key message from the presentation is that, based on an interim analysis of a subset of subjects in an ongoing study, Nu.Q assays could help identify non-cancerous nodules following a scan thereby reducing unnecessary biopsies by as much as 32%.

Watch a short interview where Chief Scientific Officer, Dr. Jake Micallef discusses the results – View Source

Professor Chen Jin-Shing, Principal Investigator of the study said "The results of this interim analysis of a subset of our 1,200-subject study are very promising. Low-Dose Computed tomography (LDCT) is the widely accepted standard for screening of individuals at high risk of lung cancer. However, LDCT has several limitations including poor specificity (high false positives). Results from this study suggest that Nucleosomes and Histone PTMs may discriminate well between non-cancerous benign nodules versus early-stage lung cancer (stages 0, I and II) in non-familial lung cancer history patients. The ability to distinguish between cancerous and non-cancerous nodules could reduce both unnecessary biopsies and the frequency of radiation exposure from repeated LDCT scanning. To accomplish this result through a non-invasive blood test would be an important step forward in lung cancer screening. We look forward to completing the study and publishing our findings in the coming months."

Dr. Jasmine Kway, Chief Executive Officer of Singapore Volition said "Lung cancer remains the deadliest of all the cancers and there is a high unmet clinical need for improved diagnosis. We are hopeful that our Nu.Q assays can help identify non-cancerous nodules following a scan. We are delighted that our world-renowned collaborators are presenting this data at such a prestigious conference and share our collaborator’s excitement to complete this study and share the findings at scientific conferences later this year."

The abstract can be found here.

To view the poster presentation video please register for the WCLC here

About the Study

A large-scale lung cancer study is being conducted under the supervision of Professor Chen Jin-Shing in the Department of Surgery of the prestigious National Taiwan University Hospital ("NTUH"). The study will include 1,200 subjects receiving LDCT scans, including 1,000 with lung cancer. Collection commenced in the summer of 2019 and will be completed in May 2021. This interim analysis is based on a subset of 220 subjects.

On January 28, 2021 Amgen (NASDAQ: AMGN) reported results from the Phase 2 cohort of the CodeBreaK 100 clinical study evaluating investigational sotorasib (AMG 510) in 126 patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) (Press release, Amgen, JAN 28, 2021, View Source [SID1234574396]). The results will be presented during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC) and are the first from a completed pivotal Phase 2 study in NSCLC with a median follow-up of more than one year.

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Sotorasib demonstrated a confirmed objective response rate (ORR) and disease control rate (DCR) of 37.1% and 80.6%, respectively, and a median duration of response of 10 months (data cutoff of Dec.1, 2020; median follow-up time was 12.2 months). The results also highlighted that sotorasib is the first KRASG12C inhibitor to show progression-free survival (median of 6.8 months) in a Phase 2 study, which is consistent with earlier Phase 1 results in previously treated patients with KRAS G12C-mutated advanced NSCLC.

Patients were treated with sotorasib 960 mg once daily orally. Prior to the trial, 81% of patients had progressed on both platinum-based chemotherapy and PD1/L1 inhibitors, with the remainder progressing after having received one of these therapies.

"Patients with advanced non-small cell lung cancer who have failed first-line treatment face extremely poor outcomes with limited treatment options available to them, and Amgen has been committed to changing that," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "Targeting KRAS has been a 40-year quest by scientists and researchers around the world, and we are extremely pleased that sotorasib has successfully demonstrated rapid, deep and durable responses in this registrational Phase 2 study that was conducted in record time. We are proud that sotorasib may potentially become the first approved targeted therapy for these patients."

Over 80% of patients achieved disease control, including three complete responses and 43 partial responses, and the median best tumor shrinkage among all responders (n=46) was 60%. The median time to objective response was 1.4 months. Sotorasib had a favorable benefit-risk profile with most treatment-related adverse events (TRAEs) mild-to-moderate (grade 1 or 2) and no treatment-related deaths. Grade 3 TRAEs were reported in 25 (19.8%) patients and only one patient (0.8%) reported a Grade 4 TRAE. The most frequently reported TRAEs (any grade) were diarrhea (31.0%), nausea (19.0%), increased alanine aminotransferase (15.1%) and increased aspartate aminotransferase (15.1%). TRAEs led to treatment discontinuation in only 7.1% of patients.

"These results are encouraging and clinically meaningful for patients with advanced NSCLC harboring the KRAS G12C mutation," said Bob T. Li, MD, PhD, MPH, medical oncologist and principal investigator at Memorial Sloan Kettering Cancer Center. "These are patients who have progressive disease after standard treatment, so they need additional treatments, and the fact that we are seeing rapid tumor shrinkages and durable responses in these patients, is for me a step forward and a win for patients."

In exploratory analyses, encouraging tumor response to sotorasib was observed across a range of biomarker subgroups, including patients with negative or low PD-L1 expression level and those with STK11 mutation. This co-mutation has been associated with poor outcomes in NSCLC patients treated with checkpoint inhibitors and chemotherapy.

"Despite recent treatment advances, survival outcomes remain poor for patients with advanced stage non-small cell lung cancer on second and third-line therapies with the KRAS G12C mutation. Currently there are no targeted treatment options for them, and I am excited about the advances that Amgen is pioneering in this field to potentially help improve patient outcomes," said Dr. Upal Basu Roy, vice president of Research, LUNGevity.

Following recent regulatory submissions in the U.S., European Union, Australia, Brazil, Canada and UK, Amgen is working with regulatory agencies across the globe to bring sotorasib to NSCLC patients as quickly as possible. Sotorasib has achieved Breakthrough Therapy Designation in the U.S.

NSCLC accounts for 80%-85% of all lung cancers, and most patients (66%) have advanced or metastatic disease at initial diagnosis.1,2 KRAS G12C is one of the most common driver mutations in NSCLC and there is a high unmet need and poor outcomes associated in the second-line treatment of KRAS G12C driven NSCLC.3 In the U.S., about 13% of patients with NSCLC harbor the KRAS G12C mutation,4,5 and each year approximately 25,000 new patients in the U.S. are diagnosed with KRAS G12C-mutated NSCLC.6

Amgen Webcast Investor Call
Amgen will host a webcast call for the investment community in conjunction with WCLC 2020. On Friday, Jan. 29, 2021, at 5 p.m. PST, David M. Reese, M.D., executive vice president of Research and Development at Amgen, along with members of Amgen’s clinical development team and clinical investigators, will discuss registrational Phase 2 NSCLC data being presented on the Company’s investigational KRASG12C inhibitor sotorasib.

Live audio of the conference call will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public. The webcast, as with other selected presentations regarding developments in Amgen’s business given at certain investor and medical conferences, can be accessed on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

To learn more about Amgen’s innovative pipeline with diverse modalities and genetically validated targets, please visit www.AmgenOncology.com.

About Sotorasib
Amgen has taken on one of the toughest challenges of the last 40 years in cancer research by developing sotorasib, an investigational KRASG12C inhibitor.7 Sotorasib was the first KRASG12C inhibitor to enter the clinic and is being studied in the broadest clinical program exploring 10 combinations with global sites spanning five continents. In just over two years, the sotorasib clinical program has established the largest clinical data set with more than 700 patients studied across 13 tumor types to date.

Sotorasib has demonstrated a positive benefit-risk profile with fast, deep and durable anticancer activity in patients with NSCLC harboring the KRAS G12C mutation with a once daily oral formulation. Promising responses have also been observed in multiple other solid tumors.8

About CodeBreaK
The CodeBreaK clinical development program for Amgen’s investigational drug sotorasib is designed to treat patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers.

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors. Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline. The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and topline results are expected in 2021.

A global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in patients with KRAS G12C-mutated NSCLC (CodeBreaK 200) is currently recruiting. Amgen also has more than 10 Phase 1b combination studies across various advanced solid tumors (CodeBreaK 101) open for enrollment.

On January 28, 2021 Amgen (NASDAQ:AMGN) reported that it will report its fourth quarter and full year 2020 financial results on Tuesday, Feb. 2, 2021, after the close of the U.S. financial markets (Press release, Amgen, JAN 28, 2021, View Source [SID1234574394]). The announcement will be followed by a conference call with the investment community at 5 p.m. EST. Participating in the call from Amgen will be Robert A. Bradway, chairman and chief executive officer, and other members of Amgen’s senior management team.

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Live audio of the conference call will be simultaneously broadcast over the internet and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

On January 28, 2021 The Janssen Pharmaceutical Companies of Johnson & Johnson reported new data from the Phase 1 CHRYSALIS study, which evaluated amivantamab in patients with metastatic or unresectable non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease progressed on or after platinum-based chemotherapy (Press release, Johnson & Johnson, JAN 28, 2021, View Source [SID1234574392]).1 These data were presented for the first time in an oral presentation at the International Association for the Study of Lung Cancer’s (IASLC) 2020 World Conference on Lung Cancer (WCLC) Singapore. The key findings showed robust activity and durable responses with a tolerable and manageable safety profile (Abstract #3031) in patients with NSCLC and EGFR exon 20 insertion mutations, a mutation for which no targeted therapies are currently approved.1,2,3

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Amivantamab is an investigational, fully-human EGFR and MET bispecific antibody with immune cell-directing activity that targets tumours with activating and resistance EGFR and MET mutations and amplifications.4,5,6,7 Janssen has filed regulatory submissions in Europe and the U.S. seeking approval of amivantamab for the treatment of patients with NSCLC and EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.8,9 These applications mark the first-ever regulatory submissions for a treatment for patients with NSCLC and EGFR exon 20 insertion mutations.10

"There is a significant need for new treatment options for patients with NSCLC and EGFR exon 20 insertion mutations whose disease generally does not respond well to chemotherapy and the tyrosine kinase inhibitors used to treat other EGFR mutations," said Joshua K. Sabari, M.D., New York University Langone’s Perlmutter Cancer Centre and presenting investigator. "Results from the CHRYSALIS study presented today demonstrate the potential for amivantamab to address this critical unmet need and provide an important clinical benefit to patients."

In this analysis of the Phase 1 CHRYSALIS study, investigators assessed the efficacy and safety of amivantamab in patients with NSCLC and EGFR exon 20 insertion mutations, who had progressed on prior platinum-based chemotherapy, and were treated at the recommended Phase 2 dose (RP2D of 1050 mg [1400 mg for a patient weight of ≥80 kg] amivantamab).1 Disease response using overall response rate (ORR), per Response Evaluation Criteria in Solid Tumours Version 1.1* (RECIST v1.1) was the primary endpoint.1 Other endpoints included duration of response (DOR), clinical benefit rate (CBR), progression-free survival (PFS) and overall survival (OS).1,11 In the post-platinum efficacy cohort (n=81), the ORR as assessed by blinded independent central review was 40 percent (n=32; 95 percent CI, 29 – 51), with three patients (4 percent) having complete responses and 29 patients (36 percent) achieving partial responses (PR).1 Responses were durable with median duration of response of 11.1 months (95 percent CI, 6.9 – not reached), with 63 percent (n=20/32) having responses of at least six months or greater duration.1 Median PFS was 8.3 months (95 percent CI, 6.5 – 10.9) and median overall survival was 22.8 months (95 percent CI, 14.6 – not reached).1 The clinical benefit rate (≥PR or stable disease ≥11 weeks) was 74 percent (95 percent CI, 63 – 83).1

Among patients treated with amivantamab monotherapy (n=114) at the RP2D, the most common treatment-emergent adverse events (AEs) were rash (86 percent), infusion-related reactions (IRR; 66 percent) and paronychia (45 percent).1 Additional AEs were stomatitis (21 percent) and pruritus (17 percent).1 Grade ≥3 AEs were reported in 35 percent of patients, of which 16 percent were considered treatment-related with rash (4 percent) and IRR (3 percent) being most frequent.1 No treatment-related deaths were reported.1 The incidence of treatment-related AEs leading to dose reduction and discontinuation was 13 percent and 4 percent, respectively.1

"The data presented today further demonstrates the potential of amivantamab as a targeted therapy for a patient population which harbours a very resistant mutation and urgently needs new therapeutic options," said Joaquín Casariego, M.D., Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen-Cilag, S.A. "We are committed to exploring further the role this innovation may have in addressing the unmet needs for many more patients and their families."

EGFR mutations, leading to uncontrolled cancer cell growth and division,12 are some of the most common mutations in NSCLC.13 EGFR exon 20 insertion mutations are the third most prevalent primary EGFR mutation and account for 3.7 – 10 percent of all EGFR mutations.3,14 These mutations, however, often go undetected because of the limited use of Next Generation Sequencing (NGS) testing.2,15 Additional Janssen-sponsored data presented in a featured poster at WCLC (Abstract #3399) showed that polymerase chain reaction (PCR) genetic testing is projected to miss 50 percent or more of tumours with EGFR exon 20 mutations.16

A Janssen-sponsored mini oral presentation at WCLC (Abstract #3390) highlights the need for new treatments, as cancer driven by EGFR exon 20 insertion mutations is generally insensitive to approved EGFR tyrosine kinase inhibitor (TKI) treatments and carries a worse prognosis compared with cancer driven by more common EGFR mutations, including exon 19 deletions/L858R substitutions.17 After 34 months median follow-up, patients with EGFR exon 20 insertion mutations experienced a 75 percent increased risk of death. The study also found that the five-year survival rate for exon 20 insertion mutations is 8 percent compared to 19 percent for other EGFR mutations.17

Janssen submitted a Marketing Authorisation Application (MAA) for amivantamab to the European Medicines Agency (EMA) in December 2020.9 The clinical development programme for amivantamab in untreated advanced EGFR-mutated NSCLC includes the Phase 3 MARIPOSA and PAPILLON combination trials.18,19

*RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumours, which is a standard way to measure how well solid tumours respond to treatment and is based on whether tumours shrink, stay the same, or get bigger.20

About the Phase 1 CHRYSALIS Study21

CHRYSALIS (NCT02609776) is an open-label, multicentre, first-in-human study to evaluate the safety, pharmacokinetics and preliminary efficacy of amivantamab as a monotherapy and in combinations including lazertinib or chemotherapy for the treatment of NSCLC.** The study will enrol 460 patients with advanced NSCLC. The study consists of two parts. The first part consists of amivantamab monotherapy and combination dose escalations and the second part is amivantamab monotherapy and combination dose escalations and expansions.

**In 2018, Janssen entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib.

About Amivantamab

Amivantamab is an investigational, fully-human EGFR-MET bispecific antibody with immune cell-directing activity that targets tumours with activating and resistance EGFR mutations and MET mutations and amplifications.4,5,6,7 Amivantamab is being studied as a monotherapy in patients with EGFR exon 20 insertion mutations. Amivantamab is also being studied in combination with lazertinib, a third-generation TKI,22 in adult patients with advanced NSCLC.21 The production and development of the antibody followed Janssen Biotech, Inc.’s licensing agreement with Genmab for use of its DuoBody technology platform.

About Non-Small Cell Lung Cancer (NSCLC)

In Europe, it is estimated that over 470,000 patients were diagnosed with lung cancer in 2018, with around 85 percent diagnosed with NSCLC.23,24 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.25 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.26 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase supporting cell growth and division.12 EGFR mutations are present in 10 to 15 percent of patients with NSCLC adenocarcinoma and occur in 40 to 50 percent of Asian patients.27 The five-year survival rate for all patients with metastatic NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.28,29 Estimated median overall survival for patients with NSCLC and EGFR exon 20 insertion mutations is shorter than in patients with exon 19 deletions or L858R substitutions.28