On September 20, 2021 Verastem Oncology (Nasdaq:VSTM), a biopharmaceutical company committed to advancing new medicines for patients battling cancer, reported a clinical collaboration agreement with Amgen to evaluate the combination of VS-6766, Verastem Oncology’s investigational dual RAF/MEK inhibitor, with Amgen’s KRAS G12C inhibitor LUMAKRASTM (sotorasib) in KRAS G12C-mutant non-small cell lung cancer (NSCLC) (Press release, Verastem, SEP 20, 2021, View Source [SID1234588006]).

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The Phase 1/2 trial will evaluate the safety, tolerability and efficacy of VS-6766 in combination with LUMAKRASTM in patients with KRAS G12C-mutant NSCLC who have not been previously treated with a KRAS G12C inhibitor as well as in patients who have progressed on a KRAS G12C inhibitor. The study will therefore investigate the potential benefits of a more complete vertical blockade of the RAS pathway with the combination of VS-6766 (RAF/MEK blockade) with LUMAKRASTM (G12C inhibition) in KRAS G12C-mutant locally advanced or metastatic NSCLC.

"Recent data indicate that acquired resistance to KRAS G12C inhibitors in patients occurs predominantly through additional mutations in the RAS pathway, many of which may be addressed with a downstream inhibitor such as VS-6766,"1 said Ramaswamy Govindan, M.D., Professor, Department of Medicine, Oncology Division at Washington University School of Medicine and lead investigator of the study. "This clinical study of VS-6766 and LUMAKRASTM will build on preclinical data showing synergy between these two agents, including tumor regression through deeper blockade of ERK pathway signaling."2

"We are pleased to partner with Amgen on this important research that could potentially expand treatment options for patients with KRAS G12C-mutant NSCLC," said Brian Stuglik, CEO of Verastem Oncology. "This collaboration advances our strategy to fully explore the potential of VS-6766 as a backbone of therapy to treat RAS pathway-driven cancers."

Verastem Oncology expects to initiate the clinical trial with VS-6766 and LUMAKRASTM by the end of 2021.

About KRAS Mutant Non-Small Cell Lung Cancer (NSCLC)

Approximately 85% of lung cancers are non-small cell lung cancer (NSCLC), which are the single leading cause of cancer deaths worldwide.3 KRAS mutation occurs in approximately 25% of NSCLC adenocarcinoma patients.4 Two of the most common types of KRAS mutations are G12C, which occurs in approximately 13% of patients with NSCLC adenocarcinoma, as well as G12V, which is present in approximately 7% of NSCLC.5,6 Currently, there is a high unmet need in the second-line treatment of KRAS mutant NSCLC.3,7

About VS-6766

VS-6766 (formerly known as CH5126766 and RO5126766) is a unique inhibitor of the RAF/MEK signaling pathway. In contrast to other MEK inhibitors in development, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK inhibitor VS-6766, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.8

Verastem Oncology has initiated Phase 2 registration-directed trials of VS-6766 with defactinib in patients with recurrent LGSOC and in patients with recurrent KRAS-G12V mutant NSCLC as part of its RAMP (Raf And Mek Program) clinical trials.

On September 20, 2021 miR Scientific reported that Data presented from a cross-validation study at the American Urological Association’s (AUA) 2021 Annual Meeting confirms that the miR Sentinel Prostate Cancer Test can detect and risk-classify prostate cancer at the molecular level with predictive accuracy of over 90%, based on a single urine sample (Press release, miR Scientific, SEP 20, 2021, View Source [SID1234588048]). This validation study follows and confirms the data on more than 1,400 patients published in The Journal of Urology in September 2020.

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When comparing the results of the miR Sentinel Prostate Cancer Test to systematic core needle biopsy in men presenting with initial suspicion of prostate cancer, the latest validation study demonstrated a 93% concordance between the two methods of screening and detection regarding the classification of clinically significant cancer. This 93% sensitivity of the miR Sentinel Prostate Cancer Test sets a new bar for detecting and classifying prostate cancer. The data further demonstrate the strong negative predictive value of the miR Sentinel Prostate Cancer Test with results showing the test correctly identified 96% (371/387) of men as having non-clinically significant cancer.

"Our mission to inclusively transform cancer management is further validated in this prospective study, demonstrating that the miR Sentinel Prostate Cancer Test is able to provide an accurate non-invasive means to identify the presence or absence of any prostate cancer and classify the molecular risk of disease becoming metastatic, and thereby lethal, prior to biopsy" says Sam Salman, Chairman and CEO of miR Scientific. "We believe that the accuracy, accessibility, and non-invasive features of our award-winning technology will impact the lives of millions of men and forever positively evolve the standard of care for urological cancers."

Cross-Validation Study Results

The data reported in this late-breaking abstract and presented by Laurence Klotz, MD, FRCSC at the AUA, is based on a study of 763 men over 45 years old, eligible for their first core needle biopsy. Pathology based on the core needle biopsy showed 354 (46%) were biopsy negative and 409 (54%) were biopsy positive. Of those 409 men found to have pathologic evidence of disease, 189 (25%) were classified as Grade Group 1 (GG1) representing non-clinically significant cancer, and 220 were classified as Grade Group 2 (GG2) or higher representing clinically significant cancer.

With just a urine liquid biopsy, the miR Sentinel Prostate Cancer Test identified 204 men with clinically significant cancer (intermediate or high risk), demonstrating 93% sensitivity (204/220) with the core needle biopsy. When evaluating men with non-clinically significant cancer, the miR Sentinel Prostate Cancer Test identified 371 out of 387 men, delivering 96% (371/387) sensitivity.

The data further examined the apparent false positive rate for clinically significant cancer by analyzing the sub-set of men who underwent both systematic biopsy and MRI-fusion biopsy, and who were negative on systematic biopsy. The data demonstrates >95% concordance been the positive MRI-guided biopsy and the miR Sentinel Prostate Cancer Test, indicating that the discordance between systematic biopsy results and the miR Sentinel Prostate Cancer Test are largely attributable to false negatives of biopsy.

Laurence Klotz, MD, FRCSC, Professor of Surgery at the University of Toronto, and Chief Medical Officer of miR Scientific LLC, said, "The key features of the test are the very high negative predictive value and the very high accuracy [in] identifying cancer. In addition to its quick turnaround, the test is highly scalable: the company will be able to perform a very large number of these tests right away."

Innovative Urine-based Liquid Biopsy

The miR Sentinel Prostate Cancer Test, which already received the Breakthrough Device Designation by the FDA, is a non-invasive molecular test based on the analysis of small non-coding RNAs (sncRNA) isolated from non-DRE urinary exosomes. It provides an innovative method to analyze sncRNAs derived from a simple, non-invasive urine specimen from age-eligible men. Using only the expression dynamics of these sncRNAs, a proprietary Statistical Classification Algorithm derives scores that classify patients according to the likelihood of being in the following four possible groups: no molecular evidence of prostate cancer; low-risk; intermediate-risk; or high-risk prostate cancer.

The miR Sentinel Prostate Cancer Test is expected to be commercially available in the United States and Puerto Rico at the end of this year.

On September 20, 2021 The US Oncology Network (The Network), the largest organization of its kind dedicated to advancing local cancer care and better patient outcomes, reported that it has appointed Jason Hammonds as its new president (Press release, US Oncology, SEP 20, 2021, View Source [SID1234590268]).

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Hammonds has supported The Network for more than 13 years in a range of leadership roles and brings deep industry experience and a stellar track record of accomplishments. Most recently, he served as senior vice president of operations for Texas Oncology, a member of The Network and the largest integrated, community-based oncology practice in the nation.

Previously, Hammonds held roles in both strategy and business development at McKesson , which supports The Network. There, he executed numerous growth activities that added more than 500 physicians to The Network during his tenure.

"I am excited and humbled to lead this phenomenal organization, which is dedicated to empowering physicians and practices to provide the highest quality of care possible to the cancer patients who need them," said Hammonds. "We will stay focused on what is best for the patient by evolving our approach to value-based care, supporting our research capabilities, advancing our operational excellence, and modernizing our technology infrastructure. My goal is to continue supporting The US Oncology Network to the best of our ability so its legacy of exceptional, compassionate care for patients in the community will thrive and move forward in an ever-changing industry."

"Jason has played an instrumental role in helping to grow and evolve The Network for over a decade, and his wide-ranging expertise and achievements make him the perfect fit to lead the organizations," said Kirk Kaminsky, president, U.S. Pharmaceutical, McKesson. "I look forward to working with him as we continue to grow The Network and our oncology ecosystem, aligning with McKesson’s mission of advancing health outcomes for all."

On September 20, 2021 Immunocore Holdings Plc (Nasdaq: IMCR), a late-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infectious and autoimmune disease, reported that new data from the Company’s lead program, tebentafusp (IMCgp100), at an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Press release, Immunocore, SEP 20, 2021, View Source [SID1234590903]).

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The findings presented by Alexander N. Shoushtari MD, medical oncologist at Memorial Sloan Kettering Cancer Center, demonstrated that reduction by Week 9 in circulating tumor DNA (ctDNA) while on tebentafusp is strongly associated with overall survival (OS). A majority (70%) of evaluable patients had any ctDNA reduction while 5% of patients had radiographic response per the RECISTv1.1 criteria. In addition, 14% of patients had complete ctDNA clearance and long OS; this included some patients with best response of stable or progressive disease. The analysis was based on the phase 2 trial of tebentafusp in HLA-A*02:01 positive, previously treated patients with metastatic uveal melanoma (mUM) (IMCgp100-102).

"Uveal melanoma is characterized by a defined set of unique mutations that can be measured in the blood as free circulating tumor DNA," said David Berman, Immunocore’s Head of Research and Development, "We found that the degree of ctDNA reduction from tebentafusp was strikingly correlated with overall survival. This association was observed even in patients whose tumor lesions appeared radiographically stable or progressing and suggests that clinical benefit from tebentafusp may occur even in patients who did not have a RECIST response."

The U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) have each accepted applications seeking the approval of tebentafusp for the treatment of HLA-A*02:01-positive ad

On September 20, 2021 BeyondSpring Pharmaceuticals (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a global pharmaceutical company focused on the development of cancer therapeutics, reported that will have a late-breaking oral presentation at the European Society for Medical Oncology 2021 Congress (Press release, BeyondSpring Pharmaceuticals, SEP 20, 2021, View Source;utm_medium=rss&utm_campaign=beyondspring-pharmaceuticals-announces-positive-final-phase-3-dublin-3-data-with-the-plinabulin-docetaxel-combination-versus-docetaxel-alone-in-2nd-3rd-line-non-small-cell-lung-cancer-patients-with-eg [SID1234587951]). This includes the final intention-to-treat (ITT) dataset from the Company’s DUBLIN-3 Phase 3 registrational trial of its first-in-class lead asset, plinabulin, in combination with docetaxel vs. docetaxel alone for the treatment of 2nd/3rd line non-small cell lung cancer (NSCLC) patients with EGFR wild type. Plinabulin is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer.

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The DUBLIN-3 Phase 3 trial is a randomized, active controlled, single blind to patients, global trial that enrolled 559 patients in 2nd and 3rd line NSCLC, EGFR wild type, with measurable lung lesion. Patients were treated on a 21-day cycle with infusion of docetaxel (75 mg/m2 on day 1) and plinabulin (30 mg/m2 on days 1 and 8) or with docetaxel alone (75 mg/m2 on day 1). The primary endpoint of OS was met in the ITT population (DP: n=278; D: n=281). The following summarizes the clinical results:

Primary endpoint (Overall Survival, ITT population):
mean OS (SE) months (M): DP 15.08 M (0.848) vs. D 12.77 M (0.676); p=0.0332
median OS (95% CI): DP 10.5 M (9.3, 11.9) vs. D 9.4 M (8.4, 10.7)
Log-rank p=0.0399; HR = 0.82
Key secondary endpoints (ITT population):
ORR (DP: 12.2% vs. D: 6.7%; p=0.0275)
PFS:
mean (SE): DP 6.0 M (0.4) vs. D 4.4 M (0.3); p=0.006
median (95% CI): DP 3.6 M (3.0, 4.4) vs. D 3.0 M (2.8, 3.7)
Log-rank p=0.008; HR=0.76
Incidence of Grade 4 neutropenia, cycle 1 day 8 (DP: 5.3% vs. D: 27.8%; p<0.0001)
24 Month OS rate (DP: 22.1% vs. D: 12.5%; p = 0.0072)
36 Month OS rate (DP: 11.7% vs. D: 5.3%; p = 0.0393)
48 Month OS rate (DP: 10.6% vs. D: 0%; p value cannot be calculated)
Q-TWiST – Quality-adjusted Time Without Symptoms of Disease and Toxicity (DP: 12.40 M vs. D: 10.47 M; 18.43% relative gain in Q-TWiST, p=0.0393).
Subset Analyses:
PD-1/PD-L1 exposed patients (DP: n=62; D: n=67; approx. 50% China/50% Western):
mean OS (SE): DP 18.33 M (1.909) vs D 13.97 M (1.320); p= 0.0602
median OS (95% CI): DP 12.3 M (9.34, 22.88); D 12.1 M (9.76, 13.77)
Log-rank p = 0.0643; HR = 0.68
24 Month OS rate (DP: 35.8% vs. D: 11.9%; p = 0.0026)
36 Month OS rate (DP: 12.5% vs. D: 5.0%; p = 0.2676)
48 Month OS rate (DP: 12.5% vs. D: 0%; p value cannot be calculated)
Safety:
DP is well tolerated, with lower grade 4 and grade 3/4 AE events per patient per year vs. D. No unexpected AE concerns were identified.
Trevor M. Feinstein, M.D., of the Piedmont Cancer Institute and a principal investigator for DUBLIN-3 commented, "The treatment of 2nd and 3rd line NSCLC, especially with EGFR wild type (wt) where tyrosine kinase inhibitors do not work, is an area of severe unmet medical need. EGFR wt represents about 85% of Western and about 70% Asian NSCLC patients. With immunotherapies moved to first line, docetaxel-based therapies are the mainstay therapy here. However, docetaxel-based therapy, although effective, has been known to cause safety concerns such as >40% severe neutropenia and can negatively impact patients’ quality of life (QoL)."

Baohui Han, M.D., Ph.D, Professor, Department of Respiratory Medicine, Shanghai Chest Hospital in China, co-principal investigator of the DUBLIN-3 trial and first author of the ESMO (Free ESMO Whitepaper) presentation, added, "DUBLIN-3 data demonstrate that, compared to docetaxel, plinabulin and docetaxel combination significantly improved treatment efficacy, including extending survival, and significantly reduced severe neutropenia. The >18% gain in Q-TWiST, a measure of survival time spent with good QoL, demonstrated that adding plinabulin to docetaxel led to a clinically meaningful benefit and a favorable benefit/risk ratio. Importantly, in PD-1/PD-L1 exposed patients in Dublin-3, the combination showed more pronounced long-term survival benefit, consistent with Plinabulin immume MOA. Thus, this combination has the potential to be the preferred 2nd/3rd line treatment for NSCLC with EGFR wt."

Lan Huang, Ph.D., BeyondSpring’s co-founder, chief executive officer and chairwoman, concluded, "When treating advanced cancer, we should focus on improving both the quantity and quality of life for patients, which the plinabulin and docetaxel combination has demonstrated in the DUBLIN-3 study. This study offers clinical evidence that plinabulin could be an important new weapon with a novel MOA in the arsenal that oncologists have to help patients with advanced NSCLC. We’re diligently working to prepare the NDA submission package for this indication in both the U.S. and China and are planning to file these NDAs in 1H 2022. The long-term survival data shown in the DUBLIN-3 study is evidence of the potential of plinabulin’s durable anti-cancer benefit, which we believe will be the gateway for its utility in the triple immuno-oncology combinations in multiple cancer indications, with the potential to help many patients in need."

ESMO Presentation Details

Title: A Global Phase (Ph) 3 Trial with the Plinabulin/Docetaxel (Plin/Doc) combination vs. Doc in 2nd/3rd Line NSCLC Patients (pts) with EGFR-wild type (wt) Progressing on a Prior Platinum-Based Regimen

Session: Proffered Paper session – NSCLC, metastatic 2

Date: September 20, 2021 from 8:10 – 8:20 a.m. ET

Location: Channel 4

Presentation Number: LBA48

Speaker: Trevor Feinstein, M.D., medical oncologist at the Piedmont Cancer Center, Fayetteville, Georgia, USA on behalf of Baohui Han, M.D., Ph.D, Professor in the Department of Respiratory Medicine, Shanghai Chest Hospital, China

Conference Call and Webcast Information
BeyondSpring’s management will host a conference call and webcast today at 10:00 a.m. Eastern Time. The dial-in numbers for the conference call are 1-877-451-6152 (U.S.) or 1-201-389-0879 (international). Please reference conference ID: 13723041. A live webcast will be available on BeyondSpring’s website at www.beyondspringpharma.com under "Events & Presentations" in the Investors section. An archived replay of the webcast will be available for 30 days.

About Plinabulin

Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer. It is a novel, intravenous infused, patent-protected, NDA stage asset for CIN prevention and a Phase 3 anti-cancer candidate for non-small cell lung cancer (NSCLC). Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells, and the second is early-onset of action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). It is being developed as a "pipeline in a drug" in multiple cancer indications.