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Verastem Oncology and Amgen Partner to Evaluate VS-6766 in Combination with LUMAKRASTM (Sotorasib) in Patients with KRAS G12C-Mutant Non-Small Cell Lung Cancer

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.

Tempest Announces First Patient Dosed in Randomized Study Evaluating TPST-1120 in First-Line Regimen for Hepatocellular Carcinoma in Clinical Collaboration with Roche

On September 20, 2021 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing potentially first-in-class therapeutics that combine both targeted and immune-mediated mechanisms, reported the first patient has been dosed in the global randomized Phase 1b/2 clinical study evaluating TPST-1120, Tempest’s small molecule PPAR⍺ antagonist, in combination with the standard-of-care regimen of atezolizumab and bevacizumab in the first-line treatment of patients with advanced or metastatic hepatocellular carcinoma ("HCC") (Press release, Tempest Therapeutics, SEP 20, 2021, View Source [SID1234588005]). The trial is being conducted under a clinical collaboration with F. Hoffman La-Roche ("Roche").

"The initiation of this randomized TPST-1120 study in collaboration with Roche marks significant progress in the advancement of the Tempest clinical pipeline," said Sam Whiting, MD, Ph.D., chief medical officer of Tempest. "We continue to be excited about TPST-1120’s mechanism of action and are encouraged by its safety profile and early signals of clinical benefit seen in both monotherapy and combination studies. The Tempest team looks forward to further evaluation of TPST-1120 in this randomized combination in the first-line treatment of patients with HCC."

"Atezolizumab plus bevacizumab is the standard-of-care for most patients with HCC, but new combinations are needed to further improve patient outcomes," said Mark Yarchoan, M.D., Assistant Professor of Medicine at Johns Hopkins University School of Medicine and Co-Director of the Liver Cancer Multidisciplinary Clinic. "In preclinical models, TPST-1120’s mechanism of action is complementary with the immune mechanism of atezolizumab and the anti-VEGF mechanism of bevacizumab. Additionally, activation of the B-catenin pathway, which is quite common in HCC, has been associated with direct benefit from targeting the metabolic pathway inhibited by TPST-1120. For these reasons, the triplet regimen of the three drugs together is particularly interesting for evaluation in patients with HCC."

The Phase 1b/2 global randomized study will evaluate TPST-1120 in combination with the standard-of-care regimen of atezolizumab and bevacizumab in patients with advanced or metastatic HCC not previously treated with systemic therapy. At least 40 and up to 60 patients will receive the TPST-1120 combination at approximately 25 sites worldwide including the United States, Asia, and Europe, and will be compared to the standard-of-care atezolizumab and bevacizumab regimen with primary objectives of anti-tumor activity and safety. Under the terms of the collaboration agreement, Roche will manage the study operations for this global, multicenter trial. Tempest retains global development and commercialization rights to TPST-1120.

About TPST-1120

TPST-1120 is an oral, small molecule, selective PPAR⍺ antagonist. Tempest’s preclinical data suggest that TPST-1120 can kill tumor cells directly and target suppressive immune pathways in the tumor microenvironment. Both types of targeted cells can be dependent on fatty acid metabolism, which is regulated by the PPAR⍺ transcription factor. In extensive non-clinical studies, TPST-1120 as a monotherapy or in combination with other anti-cancer drugs resulted in significant reductions in tumor growth and stimulation of durable anti-tumor immunity. In an ongoing Phase 1 clinical trial, TPST-1120 has been well-tolerated by patients with advanced cancers as monotherapy and in combination with the PD-1 inhibitor nivolumab, and has demonstrated tumor reduction (including according to RECIST criteria), as well as biomarker modulation.

About Hepatocellular Carcinoma

HCC is an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide. Every year, more than 815,000 people worldwide are diagnosed with HCC. In the US, the number of liver cancer cases have more than tripled since 1980 and HCC represents the fastest-rising cause of cancer-related death, while in Europe, liver cancer is also on the rise. HCC develops predominantly in people with cirrhosis due to chronic hepatitis (B or C) or alcohol consumption, and typically presents at an advanced stage. The prognosis for unresectable HCC remains poor, with few systemic therapeutic options and a 1-year survival rate of less than 50% following diagnosis.

RAPT Therapeutics to Present at the 2021 Cantor Virtual Healthcare Conference

On September 20, 2021 RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based biopharmaceutical company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in oncology and inflammatory diseases, reported that Brian Wong, M.D., Ph.D., President and CEO, will present at the 2021 Cantor Virtual Healthcare Conference on Monday, September 27, 2021 at 2:00 p.m. EST (Press release, RAPT Therapeutics, SEP 20, 2021, https://investors.rapt.com/news-releases/news-release-details/rapt-therapeutics-present-2021-cantor-virtual-healthcare [SID1234588003]).

To access the live webcast or subsequent archived recording of the company presentation, please visit the RAPT Therapeutics website at https://investors.rapt.com/events-and-presentations.

Oncternal Therapeutics and Celularity Enter into Research Collaboration to Evaluate Targeted Placental-Derived Cellular Therapies

On September 20, 2021 Oncternal Therapeutics, Inc. ("Oncternal") (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, and Celularity Inc. ("Celularity") (Nasdaq: CELU), a clinical-stage biotechnology company developing off-the-shelf placental-derived allogeneic therapies, reported they have entered into a research collaboration to evaluate placental derived-cellular therapies targeting receptor-tyrosine kinase-like Orphan Receptor 1 (ROR1) (Press release, Oncternal Therapeutics, SEP 20, 2021, View Source [SID1234588001]). As part of the collaboration, Celularity will explore the use of Oncternal’s ROR1-targeted monoclonal antibody, cirmtuzumab, in combination with Celularity’s natural killer cells. ROR1 targeted chimeric antigen receptor (CAR) gene modification will also be explored in Celularity’s CYNK natural killer cell and CyCART T cell platforms in preclinical studies.

ROR1 is highly expressed by multiple solid tumors and hematological malignancies and confers both an aggressive phenotype and survival advantage to the tumor cells. Cirmtuzumab binding to ROR1 on leukemia and lymphoma cells decreases tumor cell proliferation and survival by blocking Wnt5a-induced activation, while it does not bind to adult tissues. Celularity will evaluate the use of cirmtuzumab in combination with CYNK-101, a placental derived-allogeneic NK cell therapy that has been genetically engineered to synergize with therapeutic antibodies. As part of the collaboration, Celularity will also evaluate ROR1-targeted CAR-NK and CAR-T cell therapies as extensions of its CYNK and CyCART programs, respectively.

"Our research studying ROR1 suggests the potential for a range of new targeted therapeutics, capable of addressing a wide variety of both solid tumors and hematological malignancies," said James Breitmeyer, M.D., Ph.D., founder, President and CEO of Oncternal. "We believe that targeted cellular therapies have the potential to extend the clinical benefit of our research and improve the standard of care for patients. However, the current limitations in efficacy, safety and availability of cellular therapies hinders their broader use. Celularity’s approach, leveraging the ability of placental-derived cells to differentiate and expand, has the potential to overcome these obstacles and could potentially offer more potent, tolerable and accessible cellular medicines and, in combination with our ROR1 targeting antibodies, address the significant unmet needs of patients."

Robert J. Hariri, M.D., Ph.D., founder, Chairperson and Chief Executive Officer of Celularity, added, "We are thrilled to enter this partnership with Oncternal to forge new therapeutic strategies for both solid tumors and hematological malignancies using our allogeneic placental-derived cell therapy product candidates with their innate stemness. Oncternal’s work has established ROR1 as an exciting target that could be utilized for the development of new and novel cellular medicines, and there is an immense potential for synergy combining two novel approaches to create exciting new pipeline candidates targeting a wide range of cancers. We look forward to working closely together to lead the next evolution of cellular medicines."

Lineage to Present at the 2021 Cantor Virtual Global Healthcare Conference on September 27, 2021

On September 20, 2021 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, reported that Brian M. Culley, the Company’s Chief Executive Officer, will be presenting at the 2021 Cantor Fitzgerald Virtual Global Healthcare Conference in a fireside chat hosted by Kristen Kluska, Director, Equity Research on September 27th, 2021 at 4pm ET / 1pm PT (Press release, Lineage Cell Therapeutics, SEP 20, 2021, View Source [SID1234587999]).

Interested parties can register to view both the on-demand and live industry presentations on the Events and Presentations section of Lineage’s website. Additional videos are available on the Media page of the Lineage website.