On July 13, 2022 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage, precision-oncology biopharmaceutical company, reported that updates related to the ongoing clinical programs for sapanisertib (CB-228) and mivavotinib (CB-659) will be presented at the upcoming International Association for Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC) and the 2022 Pan Pacific Lymphoma Conference, respectively (Press release, Calithera Biosciences, JUL 13, 2022, View Source [SID1234616665]).

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"Following our recent announcements that we’ve enrolled patients in both the mivavotinib and sapanisertib clinical trials, we are pleased that details of the mivavotinib trial-in-progress will be shared with the esteemed group of lymphoma physicians who attend the Pan Pacific Lymphoma Conference," said Susan Molineaux, PhD, president and chief executive officer of Calithera. "We are also very interested in the data collected by Dr. Jonathan Riess and colleagues in the investigator-led phase 1 trial combining sapanisertib with telaglenastat in patients with non-small cell lung cancer, particularly given that we are evaluating sapanisertib in patients with NRF2-mutated squamous non-small cell lung cancer in our own, ongoing company-sponsored trial.

"We’re proud of the progress we’ve continued to make in both the sapanisertib and mivavotinib clinical programs since we acquired these compounds late last year, and believe they have the potential to be first-in-class treatments addressing areas of high unmet need," said Molineaux.

During the Pan Pacific Lymphoma Conference taking place July 18-22 in Koloa, Hawaii, Reem Karmali, MD, MS, associate professor of Medicine at Northwestern University, will present a poster detailing the trial design of Calithera’s phase 2 study of mivavotinib, a spleen tyrosine kinase (SYK) inhibitor. The phase 2 trial (NCT05319028), which enrolled its first patient in June, is an open-label study of mivavotinib monotherapy in patients with relapsed/refractory non-GCB (ABC) diffuse large B-cell lymphoma (DLBCL). The main objectives of the study are to confirm previously seen single-agent activity in non-GCB DLBCL patients, evaluate activity according to MYD88/CD79b mutational status, and refine dose/schedule in this patient population. Approximately 50 non-GCB DLBCL patients, with or without MYD88/CD79b mutations, will be randomized 1:1 to one of two oral dose/schedule cohorts: a continuous dosing schedule (100 mg QD) or an induction dosing schedule (120 mg QD x 14 days, then 80 mg QD starting Day 15). Data from this trial could position Calithera to initiate a study with registrational intent in biomarker-specific DLBCL populations.

During an August 9 mini oral session at IASLC/2022 WCLC, Jonathan W. Riess, MD, MS, director of Thoracic Oncology and associate professor at UC Davis Comprehensive Cancer Center, will present dose-escalation findings from a multi-center phase 1/2 investigator-initiated study evaluating sapanisertib, a potent and selective dual mTORC 1/2 inhibitor, in combination with telaglenastat (CB-839), a novel, investigational glutaminase inhibitor, in biomarker-defined cohorts of patients with advanced non-small cell lung cancer (NSCLC). Sapanisertib targets a key survival mechanism in tumors harboring NRF2 mutations, which are found in a considerable sub-population of patients across multiple solid tumor types and are generally associated with a poorer prognosis. In pre-clinical studies, combining sapanisertib and telaglenastat showed synergistic anti-tumor activity.

After evaluating five combination dosing levels in 13 patients, researchers determined that the sapanisertib/telaglenastat combination is safe and tolerable at the recommended expansion dose (2 mg sapanisertib once daily, 800 mg telaglenastat twice daily). Researchers also observed tumor shrinkage among the majority of evaluable patients (5/8), including patients with lung cancers harboring KEAP1 or NRF2 mutations. As a next step, study investigators plan to enroll patients into one of four expansion cohorts evaluating sapanisertib plus telaglenastat in squamous NSCLC with and without NRF2 or KEAP1 mutations, and adenocarcinoma NSCLC with KRAS and KEAP1 or NRF2 mutations.

On July 13, 2022 Amgen reported that Early data from it’s ongoing trial on Lumakras (sotorasib) for non-small cell lung cancer (NSCLC) hinted at positive results from what could be a transformative combination of drugs versus cancer (Press release, BioSpace, JUL 13, 2022, View Source [SID1234616664]).

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According to Reuters, data is still on hold until August 7, and key details aren’t yet available. Amgen’s study is evaluating how Lumakras will perform when used alongside existing immunotherapies, such as Roche’s Tecentriq and Merck’s Keytruda. Industry observers are looking forward to the data, as the study is the first to showcase how this combination will fare at the World Conference on Lung Cancer (WCLC) in Vienna from August 6 to 9.

In an oral presentation on Lumakras at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in early June, Amgen shared positive early data from its Phase I/II study on the safety and efficacy of the drug for patients with pancreatic cancer. It was then that the company shared that it is also conducting a Phase II trial on Lumakras as a first-line treatment for people diagnosed with stage IV NSCLC whose tumors harbor a KRAS p.G12C mutation.

"Amgen continues to lead the science in KRASG12C inhibition and is committed to advancing research into how Lumakras can improve outcomes for more patients, including further defining resistance patterns to guide our robust combination treatment development program," David M. Reese, M.D., the executive vice president of research and development at Amgen said.

The U.S. Food and Drug Administration approved Lumakras in 2021 under accelerated approval for the treatment of advanced lung cancer cases with KRAS mutations whose conditions have worsened after receiving chemotherapy and other medications. In January this year, the Japanese government gave the green light for its healthcare system to use the drug for positive, unresectable, advanced and/or recurrent NSCLC that has progressed after systemic anticancer interventions.

"In just over three years since the first patient was dosed in the pivotal CodeBreaK 100 trial, LUMAKRAS is now approved in nearly 40 countries, illustrating our commitment to accelerating transformative medicines for patients living with cancers that have yet to be fully addressed," Reese stated.

"KRAS has challenged cancer researchers for more than 40 years, with many deeming it as ‘undruggable.’ The Lumakras development program was a race against cancer for Amgen’s scientists and clinical trial investigators who together have now successfully delivered this new medicine to patients in less than three years—from the first patient dosed to U.S. regulatory approval," Dr. Reese also said.

The approvals are based on positive results from the Phase II CodeBreak 100 trial in NSCLC. Lumakras is a 960 mg, orally administered drug given once a day. The latest study to be presented at WCLC will highlight the drug’s potency when combined with other existing medications.

On July 13, 2022 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported it will present two posters for its parallel lead programs, NVL-655, an ALK-selective inhibitor and NVL-520, a ROS1-selective inhibitor, at the IASLC 2022 World Conference on Lung Cancer (WCLC) Annual Meeting taking place August 6-9, 2022 in Vienna, Austria (Press release, Nuvalent, JUL 13, 2022, View Source [SID1234616663]). Posters will be archived on the Nuvalent website at www.nuvalent.com.

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The first poster characterizes NVL-655 alongside other ALK inhibitors in a patient-derived model of lorlatinib-resistant ALK-positive non-small cell lung cancer (NSCLC) with the treatment-emergent G1202R/T1151M compound resistance mutation. NVL-655 has previously demonstrated differentiation through broad preclinical activity across diverse ALK oncoproteins, resistance mutations, and tumor types while maintaining strong selectivity for ALK over TRKB. Nuvalent recently announced the first patient has been dosed with NVL-655 in the ALKOVE-1 Phase 1/2 study for patients with advanced ALK-positive NSCLC and other solid tumors.

A "Trial in Progress" poster will also be presented with background and study design for the ongoing ARROS-1 Phase 1/2 study of NVL-520 for patients with advanced ROS1-positive NSCLC and other solid tumors. The multicenter, open-label, dose-escalation and expansion trial is currently evaluating NVL-520 as an oral monotherapy in the Phase 1 portion of the study. Nuvalent plans to share preliminary dose-escalation data from ARROS-1 in the second half of 2022.

Details for the E-poster presentations are as follows:

Title: Preclinical Activity of NVL-655 in a Patient-Derived NSCLC Model with Lorlatinib-Resistant ALK G1202R/T1151M Mutation
Authors: H. Mizuta1, L. Bigot1, A. Tangpeerachaikul2, H.E. Pelish2, L. Friboulet1
Abstract Number: EP08.02-020
Session Category: Metastatic Non-small Cell Lung Cancer
Session Title: Molecular Targeted Treatments
Session Date and Time: August 7, 2022, 9:45am – 6:00pm CEST

1Gustave-Roussy, Villejuif, France; 2Nuvalent, Inc., Cambridge, MA, USA

Title: NVL-520, a Highly Selective ROS1 Inhibitor, in Patients with Advanced ROS1-Positive Solid Tumors: The Phase 1/2 ARROS-1 Study
Authors: A. Drilon1, S-H.I. Ou2, S. Gadgeel3, M. Johnson4, A. Spira5, G. Lopes6, B. Besse7, E. Felip8, A.J. van der Wekken9, A. Calles10, M.J. de Miguel11, D.R. Camidge12, Y. Elamin13, S. Liu14, J. Bauman15, D. Haggstrom16, G. Riley17, H.E. Pelish17, V.W. Zhu17, J.J. Lin18
Abstract Number: EP08.02-041
Session Category: Metastatic Non-small Cell Lung Cancer
Session Title: Molecular Targeted Treatments
Session Date and Time: August 7, 2022, 9:45am – 6:00pm CEST

1Memorial Sloan Kettering Cancer Center, New York/NY/USA ,2University Of California Irvine Medical Center, Orange/CA/USA ,3Henry Ford Cancer Institute, Detroit/MI/USA ,4Sarah Cannon Research Institute, Nashville/TN/USA,5NEXT Oncology – Virginia Cancer Specialists, Fairfax/VA/USA ,6Sylvester Comprehensive Cancer Center at the University of Miami and the Miller School of Medicine, Miami/FL/USA ,7Institut Gustave Roussy, Villejuif Cedex/FR,8Hospital Vall d’Hebron, Barcelona/ES ,9University of Groningen, University Medical Centre Groningen,Groningen/NL ,10Hospital Universitario Gregorio Marañón, Madrid/ES,11 START Madrid-HM CIOCC, Madrid/ES,12University of Colorado Cancer Center, Anschutz Medical Campus, Aurora/CO/USA ,13MD Anderson Cancer Center, Houston/TX/USA ,14Georgetown University, Washington/DC/USA ,15Fox Chase Cancer Center, Philadelphia/PA/USA,16Levine Cancer Institute, Atrium Health, Charlotte/NC/USA ,17Nuvalent, Inc., Cambridge/MA/USA ,18Massachusetts General Hospital, Boston/MA/USA

About NVL-655

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R / L1196M ("GRLM"), G1202R / G1269A ("GRGA"), or G1202R/L1198F ("GRLF"). NVL-655 has been optimized for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and drive more durable responses for patients. NVL-655 is currently being investigated in the ALKOVE-1 study (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.

About NVL-520

NVL-520 is a novel brain-penetrant ROS1-selective inhibitor designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with the prevalent G2032R resistance mutation and those with the S1986Y/F, L2026M, or D2033N resistance mutations. NVL-520 has been optimized for brain penetrance to potentially improve treatment options for patients with brain metastases. NVL-520 has been observed in preclinical studies to selectively inhibit wild-type ROS1 and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and drive more durable responses for patients. NVL-520 is currently being investigated in the ARROS-1 study (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors.

On July 13, 2022 Alpheus Medical, Inc, a privately held company developing a novel sonodynamic therapy (SDT) platform targeting solid body cancers, reported the U.S. Food and Drug Administration (FDA) has granted both Orphan Drug and Fast Track Designations to Alpheus Medical’s CV-01 delivery of sonodynamic therapy (SDT) as a potential treatment for patients with recurrent glioblastoma, the most common primary brain cancer, and other malignant gliomas (Press release, Alpheus Medical, JUL 13, 2022, View Source [SID1234616662]). Northwell Health’s North Shore University Hospital in Long Island, New York, is currently enrolling patients in the multi-center Phase 1 clinical trial. The First-in-Human trial will evaluate the safety, optimal dosage, and efficacy of Alpheus’ SDT platform in patients with recurrent high-grade glioma.

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"The diffuse nature of glioblastomas, often across the hemisphere, makes it an extremely challenging disease to treat. There are very few effective options, leading to poor patient outcomes, and a universally fatal disease," commented Michael Schulder, MD, Director of the Brain Tumor Center and Primary Investigator (PI) for the clinical trial at Northwell Health’s Institute for Neurology and Neurosurgery. "Alpheus’ sonodynamic therapy enables non-invasive, diffuse treatment across the hemisphere. It has the potential to change the landscape of high-grade glioma therapy and we are excited to be part of this important study."

Alpheus Medical’s proprietary, investigational SDT treatment is an innovative, non-invasive drug-device combination that targets cancer cells throughout the entire hemisphere using low-intensity, diffuse ultrasound. The SDT is administered in an outpatient setting and does not require imaging. The multi-center trial (NCT05362409) is designed to study the safety and optimal application of Alpheus’ SDT treatment, as well as efficacy, and is planned to enroll up to 33 patients.

"The FDA Fast Track and Orphan Drug Designations are significant milestones and highlight the importance of innovation within the field of brain cancer," stated Dr. Vijay Agarwal, CEO and founder of Alpheus Medical and a practicing brain tumor surgeon. "Built on a very successful pre-clinical program, we believe our proprietary SDT platform is a game changer and has the potential to significantly advance the treatment of gliomas."

The FDA Orphan Drug and Fast Track programs are designed to facilitate the development of important new therapies and to provide patients with serious and rare conditions access to treatment more quickly. Orphan Drug status is granted to investigational therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the U.S. It provides development incentives and post-approval marketing exclusivity for seven years. The Fast Track designation enables early and frequent communication between FDA and product sponsor throughout the development and review process.

On July 13, 2022 miR Scientific, LLC reported the miR Sentinel Prostate Cancer Test is now commercially available in the United States, Puerto Rico and select international markets (Press release, miR Scientific, JUL 13, 2022, View Source [SID1234616661]). miR Sentinel is a novel, urine-based, molecular test that analyzes small non-coding RNA using a proprietary biostatistical algorithm. The miR Sentinel Test assesses the risk of aggressive prostate cancer and is intended to aid in the clinical management of men >45 years of age at risk for prostate cancer.

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The results of a recent clinical study performed at multiple sites within the US and Puerto Rico were presented at the 2022 American Urological Association’s Annual Meeting. In the study cohort of ~1100 men, the miR Sentinel Test was shown to identify molecular evidence of prostate cancer in at-risk men with 98.5% sensitivity and distinguish clinically non-significant (nominally No Pathological Evidence of Prostate Cancer and Grade Group 1), from clinically significant prostate cancer (nominally Grade Groups 2-5) with a prognostic sensitivity of 83% 2.

"We believe that the miR Sentinel Test offers patients and providers a non-invasive means of accurately assessing a man’s prostate cancer risk, which could potentially reduce unnecessary biopsies and biopsy-related complications in men with low-risk of clinically significant prostate cancer, while prioritizing diagnostic and treatment resources to those men that potentially harbor clinically significant prostate cancer," said Sam Salman, Chairman and CEO of miR Scientific. "This aligns with miR Scientific’s vision to revolutionize prostate cancer disease management by improving accessibility and accuracy of the tools used to assess each man’s personal risk of aggressive disease."

In a subset analysis of men from this cohort where the findings of TRUS and MRI-guided biopsies disagreed on the presence of prostate cancer, the miR Sentinel Test was able to correctly identify 99% (71/72) of men found positive by either biopsy type while identifying all but 4 of 234 cases where prostate cancer was found by either TRUS or MRI resulting in a false negative rate of 1.7%. Additionally, 87% of men with PSA levels <3 found to have pathologic grade group 2 through 5 upon biopsy were identified by the miR Sentinel Test as having molecular evidence of intermediate or high risk of aggressive disease2. These findings suggest that the miR Sentinel Test may represent a significant improvement over the current standards of care and other tools being used to detect and classify prostate cancer.

"Accurate assessment of a man’s individual risk related to prostate cancer is one of the cornerstones of appropriate patient management. The miR Sentinel Test has the potential to provide a significant improvement over the current tools that are available to physicians," said Laurence Klotz, MD, FRCSC, CM, miR Scientific’s Chief Medical Officer, Professor of Surgery and Chair of Prostate Cancer Research, University of Toronto Sunnybrook. "The implementation of such an innovation into practice could have a dramatic impact on outcomes through appropriately guiding the need for further diagnostic workup in men with elevated risk of significant cancer and guiding treatment in those subsequently diagnosed."

The current version of the miR Sentinel Test represents a refined and clinically validated assessment developed for commercialization based on our comprehensive miR Sentinel PCC4 assay, which received FDA Breakthrough Device Designation in third quarter 2020 and the original three-test proof of concept, published in the Journal of Urology1 in September 2020.

Additional information on the miR Sentinel Prostate Cancer Test as well as information on how to access the test can be found by visiting miRSentinel.com or calling 855-55CALLMIR from the United States or +1 (855) 552-2556.