On December 16, 2020 Amgen (NASDAQ:AMGN) reported submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for sotorasib, an investigational KRASG12C inhibitor for the treatment of patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, following at least one prior systemic therapy (Press release, Amgen, DEC 16, 2020, View Source [SID1234572953]).

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"Sotorasib was the first KRASG12C inhibitor to enter the clinic and now is on track to potentially be the first approved targeted therapy for patients with advanced NSCLC harboring the KRAS G12C mutation. In the U.S., about 13% of patients with NSCLC have the KRAS G12C mutation and face a significant unmet need," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "This submission, along with these other important regulatory achievements, underscore Amgen’s commitment to bringing this potential treatment option to patients as quickly as possible."

The NDA is being reviewed by the FDA under its Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process that ensures safe and effective treatments are made available to patients as early as possible.1

The submission is supported by positive Phase 2 results in patients with locally advanced or metastatic NSCLC from the CodeBreaK 100 clinical study, whose cancer had progressed despite prior treatment with chemotherapy and/or immunotherapy. In the study, treatment with sotorasib provided durable anticancer activity with a positive benefit-risk profile.2 These results will be presented at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC) Presidential Symposium in January 2021.

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.3 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 across four continents. In just over two years, the sotorasib clinical program has established the deepest clinical data set with more than 600 patients studied across 13 tumor types.

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

KRAS G12C is the most common KRAS mutation in NSCLC.4,5 In the U.S., about 13% of patients with NSCLC harbor the KRAS G12C mutation.6 There is a high unmet need and poor outcomes in the second-line treatment of KRAS G12C-driven NSCLC and, currently, there are no KRASG12C targeted therapies approved.7

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. As the most advanced KRAS G12C clinical development program, CodeBreaK has enrolled more than 600 patients across 13 tumor types since its inception.

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutated 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, 123 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 several Phase 1b combination studies across various advanced solid tumors (CodeBreaK 101) open for enrollment.

For information, please visit www.codebreaktrials.com.

About Amgen Oncology
Amgen Oncology is searching for and finding answers to incredibly complex questions that will advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient’s life – not just their cancer journey – so they can take control of their lives.

For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.

At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the center of everything we do.

To learn more about Amgen’s innovative pipeline with diverse modalities and genetically validated targets, please visit AmgenOncology.com. For more information, follow us on www.twitter.com/amgenoncology.

On December 16, 2020 Amgen (NASDAQ:AMGN) reported that its Board of Directors declared a $1.76 per share dividend for the first quarter of 2021 (Press release, Amgen, DEC 16, 2020, View Source [SID1234572952]). The dividend will be paid on March 8, 2021, to all stockholders of record as of the close of business on February 15, 2021. This represents a 10% increase from that paid in each of the previous four quarters.

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On December 16, 2020 GRAIL, Inc., a healthcare company whose mission is to detect cancer early,reported that new analyses estimating the potential of GRAIL’s multi-cancer early detection blood test to find more cancers earlier and save lives (Press release, Grail, DEC 16, 2020, View Source [SID1234572950]).

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Published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the analysis used epidemiologic modeling to estimate the potential impact of adding an annual multi-cancer early detection blood test, such as GRAIL’s Galleri, to standard of care cancer screenings. The model estimates a potential reduction in late-stage (stage III and IV) cancer diagnoses by more than half in the U.S. population, aged 50-79. This decrease in late-stage diagnoses could translate to a reduction in five-year cancer deaths by 39% among those detected earlier, equating to an overall reduction of all five-year cancer deaths by 26%.

Today, the majority of cancers are found too late when outcomes are often fatal, because most deadly cancers have no available screening tests. Current guideline-recommended screenings are critical, but in the U.S. they cover only five cancers and screen for a single cancer at a time. Cancers responsible for nearly 71% of cancer deaths have no recommended early detection screening.

In clinical validation studies, an earlier version of Galleri demonstrated the ability to detect more than 50 types of cancers — over 45 of which lack recommended screening tests in the U.S. — with a low false positive rate of less than 1%. When a cancer was detected, the test also determined where in the body the cancer signal was located with high accuracy, all from a single blood draw.

"What we learned through this advanced modeling analysis is that GRAIL’s multi-cancer early detection test, based on identifying methylation signals in the circulating DNA, has the potential to substantially reduce overall cancer deaths," said Joshua Ofman, MD, MSHS, Chief Medical Officer and External Affairs at GRAIL. "A simple blood test like Galleri, that can detect more than 50 types of cancers and dramatically increase the cancer detection rate in the population, holds great potential to improve public health and save lives."

The cancer "interception model" — as the researchers describe it — uses published test performance data from GRAIL’s foundational Circulating Cell-free Genome Atlas (CCGA) study, including the cancer detection rate across all stages. It employs data from the U.S. Surveillance, Epidemiology, and End Results (SEER) program to quantify the stages at which cancers are currently diagnosed to understand the total number of cancers detected, and the potential reductions — or interceptions — in late-stage cancer diagnoses and associated deaths that could occur by adding GRAIL’s multi-cancer early detection test to standard of care cancer screenings in the U.S population, ages 50-79.

"Nearly all prior modeling efforts have focused on single cancer screening programs, leaving a gap in models addressing the potential population health benefits of multi-cancer early detection," said Christine D. Berg, MD, Special Volunteer, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. "Nothing like GRAIL’s test exists today, making rigorous modeling our current best approach to quantify the magnitude of the potential impact this innovative genomic technology could have on people across the U.S. through earlier cancer detection."

Galleri is expected to be available in the U.S. in 2021 and is currently available under investigational use in GRAIL’s first interventional study, PATHFINDER, where it is being used to guide clinical care. Galleri is also expected to be offered to patients in the United Kingdom (UK) starting in 2021 as part of a partnership with the UK’s National Health Service to support its Long Term Plan for earlier cancer diagnoses in an effort to transform cancer outcomes.

On December 16, 2020 Transgene (Paris:TNG) (Euronext Paris: TNG) reported that Management will participate in the upcoming investor events set out below (Press release, Transgene, DEC 16, 2020, View Source [SID1234572949]).

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Transgene will meet institutional investors at the 10th Annual LifeSci Advisors Corporate Access Event (virtual event) from January 6th to 14th, 2021 in conjunction with the J.P. Morgan Healthcare conference.

The Company will also attend:

Oddo BHF Digital Forum: January 7 to 13, 2021
Biomed Event (virtual event): January 26 & 27, 2021

On December 16, 2020 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a late clinical-stage biopharmaceutical Company focused on oncology, reported results from the triple combination arm of the Company’s COMBAT/KEYNOTE-202 clinical study evaluating motixafortide (BL-8040) in combination with KEYTRUDA (pembrolizumab) and chemotherapy in patients with second-line stage IV pancreatic ductal adenocarcinoma (PDAC) (Press release, BioLineRx, DEC 16, 2020, View Source [SID1234572948]).

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A total of 43 patients initially diagnosed with unresectable stage IV metastatic PDAC, who had progressed following first-line gemcitabine-based therapy, were enrolled in the triple combination arm. Patients received motixafortide monotherapy priming treatment for five days, followed by combination cycles of motixafortide, KEYTRUDA and chemotherapy (Onivyde/5-fluorouracil/leucovorin) until progression. The primary endpoint of the study is the objective response rate (ORR); secondary endpoints include confirmed objective response rate (cORR), overall survival (OS), progression free survival (PFS), and disease control rate (DCR).

The results of the study showed substantial improvement as compared to historical results across all study endpoints. Data are summarized below for the evaluable patients in the study (n=38).

Data summary:

COMBAT/KEYNOTE

HISTORICAL DATA

Median overall survival (mOS)

6.5 months

4.7 months1

Median progression free survival (mPFS)

4.0 months

2.7-3.1 months2,3

Confirmed overall response rate (cORR)

13.2%

7.7%3

Overall response rate (ORR)

21.2%

16%1

Disease control rate (DCR)

63.2%

29-52%2,4

1 Macarulla Mercade et al, Pancreas 2020
2 Petrelli et al Eu J Cancer 2017
3 Onivyde prescribing information
4 Wang Gillam Eu J Cancer 2019

The combination was generally well tolerated, with a safety profile consistent with the individual safety profile of each component alone; adverse event (AE) and severe adverse event (SAE) profiles were as expected with chemotherapy-based treatment regimens. Of note, certain safety advantages were demonstrated by the triple combination of motixafortide, KEYTRUDA and chemotherapy, when compared to historical data relating to the specific chemotherapy used in the study. These safety advantages include incidence of grade 3 neutropenia (7% versus historical data of 20%) and incidence of grade 3 infections (7% versus historical data of 17%).

"These results are highly encouraging in light of the extremely challenging population, even among PDAC patients, in this study cohort," said Manuel Hidalgo, MD, PhD, Chief of the Division of Hematology and Medical Oncology and a Senior Member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center, and principal investigator of this study. "All patients were initially diagnosed at stage IV, and greater than 70% had liver metastases, key contributing factors to very poor prognoses. I believe the results from this study strongly support further development."

"We are extremely pleased with these results, which demonstrate a meaningful improvement versus historical data across all study endpoints," stated Philip Serlin, Chief Executive Officer of BioLineRx. "The consistent improvement across all study endpoints represents a key differentiating factor relative to other compounds that showed improvement in only one endpoint in their initial studies and eventually failed in advanced studies. These positive results are further supported by a long-lasting median durability of clinical benefit of 5.6 months that we observed in this trial.

"Pancreatic cancer is one of the most difficult cancers to treat, with five-year survival rates of just 9% overall, and 3% for the greater-than-50% of patients initially diagnosed at stage IV. Therefore, even marginal improvements in survival endpoints in pivotal studies have been considered clinically meaningful and sufficient for regulatory approval. These positive efficacy results across all endpoints give us a high degree of confidence in their repeatability in a randomized trial and we plan to meet with the regulatory authorities in order to agree on the fastest pathway forward in this indication.

"In addition, we believe these results clearly support investigating the motixafortide/immune-checkpoint-inhibitor platform with other standard-of-care chemotherapies in earlier PDAC treatment lines, as well as in other ‘cold’ solid tumors. To that end, we are currently investigating motixafortide in combination with an anti-PD-1 and chemotherapy (gemcitabine and nab-paclitaxel) in first-line pancreatic cancer, and we are assessing potential combinations in other solid-tumor indications as well.

"These data are particularly exciting in light of the strikingly positive results of the interim analysis from our Phase 3 GENESIS study of motixafortide in stem cell mobilization that we recently announced in October. Motixafortide has now demonstrated clinical utility in two therapeutic areas through multiple mechanisms of action, supporting our belief that it can serve as the backbone of a number of promising combination therapies to treat a broad range of cancer types," Mr. Serlin concluded.

BioLineRx plans to present the full data set at an upcoming medical conference.

KOL Webinar Information
BioLineRx will host a KOL webinar today, December 16, 2020 at 8:00 a.m. EST. The webinar will feature presentations by Key Opinion Leaders (KOLs) Gulam Manji, M.D., Ph.D. (Columbia University Medical Center), Manuel Hidalgo, M.D., Ph.D. (Weill Cornell Medicine), and Talia Golan, M.D. (Sheba Medical Center), who will discuss the current treatment landscape and unmet medical need in treating patients with pancreatic cancer, and the COMBAT study data. BioLineRx’s management team will also discuss the COMBAT results. Drs. Hidalgo and Golan will be available to answer questions following the formal presentations.

Interested parties can register for the webinar here.

About COMBAT/KEYNOTE-202
The Phase 2a COMBAT/KEYNOTE-202 study was originally designed as an open-label, multinational, multicenter, single-arm trial to evaluate the safety, tolerability and efficacy of the dual combination of motixafortide and KEYTRUDA, an anti-PD-1 therapy marketed by Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada), in 37 subjects with metastatic pancreatic adenocarcinoma (2L-5L). The dual combination study was conducted under a clinical trial collaboration agreement signed in 2016 between BioLineRx and MSD, through a subsidiary, where MSD provided KEYTRUDA and BioLineRx was the study sponsor and owns all rights to motixafortide.

In July 2018, the Company announced the expansion of the collaboration with MSD to include a triple combination arm, as part of the COMBAT/KEYNOTE-202 study investigating the safety, tolerability and efficacy of motixafortide, KEYTRUDA and chemotherapy in 43 patients initially diagnosed with unresectable stage IV metastatic PDAC, who had progressed following first-line gemcitabine-based therapy. These results are being announced today.

The study was carried out primarily in the US, Spain and Israel.

About Motixafortide in Cancer Immunotherapy
Motixafortide is targeting CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including PDAC. CXCR4 plays a key role in tumor growth, invasion, angiogenesis, metastasis and therapeutic resistance, and CXCR4 overexpression has been shown to be correlated with poor prognosis.

Motixafortide is a short synthetic peptide used as a platform for cancer immunotherapy with unique features allowing it to function as a best-in-class antagonist of CXCR4. It shows high-affinity, long receptor occupancy and acts as an inverse agonist.

In a number of clinical and preclinical studies, motixafortide has been shown to affect multiple modes of action in ‘cold’ tumors, including immune cell trafficking, tumor infiltration by immune effector T cells, and reduction in immunosuppressive cells (such as MDSCs) within the tumor microenvironment, turning ‘cold’ tumors, such as pancreatic cancer, into "hot" (i.e., sensitizing them to immune checkpoint inhibitors and chemotherapy).

About Pancreatic Cancer
Pancreatic cancer has a low rate of early diagnosis and a poor prognosis. Its incidence rate in the US is estimated at 3.2% of new cancer cases. In 2018, approximately 450,000 individuals globally were diagnosed with this condition, 55,000 of them in the US; and the incidence of pancreatic cancer is expected to continue to increase. Symptoms are usually non-specific and as a result, pancreatic cancer is often not diagnosed until it reaches an advanced stage. Surgical resection does not offer adequate treatment since only 20% of patients have resectable tumors at the time of diagnosis. Even among patients who undergo resection for pancreatic cancer and have tumor-free margins, the five-year survival rate is only 10%-25%. The overall five-year survival rate among pancreatic cancer patients is 9%, which constitutes the highest mortality rate among solid tumor malignancies. The overall median survival is less than one year from diagnosis, highlighting the need for the development of new therapeutic options.

Despite advances in chemotherapeutics and immunotherapy, increases in median and overall survival rates in pancreatic cancer have been modest. Pancreatic cancer remains an area of unmet medical need, with no new approved therapies since the approval of nab-paclitaxel (Abraxane) in combination with gemcitabine for first-line treatment in 2013 and Onivyde in combination with fluorouracil and leucovorin for second-line treatment in 2015. The limited clinical benefits demonstrated by these existing standard treatment options reinforce the need for additional approaches.