AXL inhibitors(AXL receptor tyrosine kinase inhibitors), RET inhibitors(Tyrosine-protein kinase receptor RET inhibitors), ROS1 inhibitors(Proto-oncogene tyrosine-protein kinase ROS inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [7]

Active Indication

Thyroid CancerDifferentiated Thyroid Gland CarcinomaHepatocellular Carcinoma+ [70]

Inactive Indication

Advanced CholangiocarcinomaAdvanced Lung Non-Small Cell CarcinomaAdvanced Pancreatic Adenocarcinoma+ [45]

Originator Organization

Exelixis, Inc.

Active Organization

Exelixis, Inc.Ipsen Pharma SAS

Ipsen SA

+ [9]

Inactive Organization

Augusta University Research Institute

The General Hospital Corp.

The University of Chicago

+ [2]

Drug Highest PhaseApproved

First Approval Date

US (29 Nov 2012),

Thyroid Cancer, Medullary

RegulationPriority Review (US), Breakthrough Therapy (US), Fast Track (US), Orphan Drug (US)

Structure

Molecular FormulaC32H30FN3O10

InChIKeyHFCFMRYTXDINDK-WNQIDUERSA-N

CAS Registry1140909-48-3

260

Clinical Trials associated with Cabozantinib (s)-Malate

NCT05859217 / Not yet recruitingPhase 2IIT

A Multi-center Phase II Study of Combining Cabozantinib and Atezolizumab as the 1st Line Therapy for PD-L1 Negative Advanced/Metastatic NSCLC (Cabatezo-1)

NSCLC patients with low expression level of PD-L1, esp. those with its level less than 1%, do not derive much benefit from anti-PD-1/L1 therapy (e.g. atezoilzumab). In this study, investigators hypothesize that the combination of cabozantinib (a multi-kinase inhibitor) and atezolizumab will result in better therapeutic value.

Start Date01 Dec 2024

Sponsor / Collaborator

Exelixis, Inc.

[+1]

NCT06341712 / Not yet recruitingPhase 2

A Phase II, Randomized, Open-label Study to Assess the Efficacy, Safety, and Pharmacokinetics (PK) of Maintenance Cabozantinib (XL184) Plus Best Supportive Care (BSC) Versus BSC in Children, Adolescents and Young Adults (AYA) With Unresectable Residual Osteosarcoma Either at Diagnosis or at First Relapse After Standard Treatment

The participants of this study will be children, adolescents, and young adults with residual osteosarcoma, which cannot be removed completely through surgery.
Participants will have achieved a partial response or stable disease at the end of conventional chemotherapy. Osteosarcoma is cancer of the bone. The cancer cells make immature bone cells, known as osteoid.
Osteosarcoma is very rare, but it is the most common type of bone cancer in children and teens. It is most common in teens and young adults.
In this study, participants will receive either cabozantinib and best supportive care or the best supportive care alone. Best supportive care will be provided at the investigator's discretion and according to institutional guidelines.
It includes antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management (including radiotherapy), etc. but does not include tumor specific therapy.
Cabozantinib will be taken by mouth (orally), as a tablet, once a day. Cabozantinib will be provided to participants who tolerate it for as long as their disease does not progress. Participants in the study receiving best supportive care alone may switch to treatment with cabozantinib and best supportive care if their disease progresses and if other eligibility criteria are met.
Participants may withdraw consent to participate at any time.
The estimated duration of the study for participants is 24 months, however a participant could remain in the study longer if demonstrating treatment benefit.

Start Date13 Jun 2024

Sponsor / Collaborator

Ipsen SA

NCT06364631 / RecruitingPhase 3IIT

First Line Randomised Study Platform to Optimize Treatment in Patients With Metastatic Renal Cell Carcinoma

Systemic therapy for renal cell carcinoma (RCC) relies on 2 classes of agents: anti-angiogenic targeted therapy (Vascular endothelial growth factor Tyrosine Kinase Inhibitor- VEGFR TKI) and immune checkpoint inhibitor (ICI), targeting either PD1/PDL1 axis or CTLA4. Combination therapy is SOC for clear cell RCC in all guidelines with either ICI-ICI or ICI-VEGFR TKI. However, no head-to-head comparison have been performed between the 2 approaches and patients are treated based on physician decision without clinical /biomarker factors to guide treatment selection. PDL1 staining is, to date, the biomarker that has demonstrated its ability to enrich for overall survival benefit favoring ICI-ICI strategy in PDL1(+) and ICI-VEGFR TKI in PDL1(-) patients.
Study design has been developed to demonstrate that ICI-ICI is superior to ICI-VEGFR TKI in prolonging Overall Survival (OS) for PDL1(+) patients and to demonstrate that ICI-VEGFR TKI is superior to ICI-ICI in prolonging Progression Free Survival (PFS) and OS for PDL1(-) patients.

Start Date12 Apr 2024

Sponsor / Collaborator

Gustave Roussy, Cancer Campus, Grand Paris

[+12]

100 Clinical Results associated with Cabozantinib (s)-Malate

100 Translational Medicine associated with Cabozantinib (s)-Malate

100 Patents (Medical) associated with Cabozantinib (s)-Malate

1,523

Literatures (Medical) associated with Cabozantinib (s)-Malate

01 Feb 2024·European journal of pharmacology

Drug-repurposing by virtual and experimental screening of PFKFB3 inhibitors for pancreatic cancer therapy

Article

Author: Duan, Hong-Quan ; Yu, Yang ; Zhong, Zhi-Xin ; Qin, Nan ; Jiang, Xiao ; Li, Xiao-Lei ; Cao, Xin ; Liu, Lu ; Chen, Ying ; Duan, Xiao-Chuan ; Ni, Tian-Wen ; Li, Xu-Zhao

Pancreatic cancer (PC) is the most frequently occurring cancer, with few effective treatments and a 5-year survival rate of only about 11%. It is characterized by stiff interstitium and pressure on blood vessels, leading to an increased glycolytic metabolism. PFKFB3 plays an important role in glycolysis, and its products (fructose-2,6-bisphosphate), which are allosteric PFK1 activators, limit the glycolytic rate. In this study, 14 PFKFB3 inhibitors were obtained by virtually screening the FDA-approved compound library. Subsequently, the in-vitro investigations confirmed that Lomitapide and Cabozantinib S-malate exhibit the excellent potential to inhibit PFKFB3. The combined administration of Lomitapide and Gemcitabine at a certain molar ratio indicated an enhanced anti-tumor effect in Orthotopic Pancreatic Cancer (OPC) models. This investigation provides a new treatment strategy for PC therapy.

01 Feb 2024·Cancer chemotherapy and pharmacology

Are novel oral oncolytics underdosed in obese patients?

Article

Author: Beijnen, Jos H ; van der Meer, Ellen K O ; Huitema, Alwin D R ; Lin, Lishi ; Steeghs, Neeltje

Abstract:

Purpose:

Data on the effects of obesity on drug exposure of oral targeted oncolytics is scarce. Therefore, the aim of this study was to investigate the influence of body weight and body mass index (BMI) on trough levels of oral oncolytics with an exposure–response relationship. The oral oncolytics of interest were abiraterone, alectinib, cabozantinib, crizotinib, imatinib, pazopanib, sunitinib and trametinib.

Methods:

This retrospective cohort study included patients treated with the selected oral oncolytics at the standard dose, with a measured trough level at steady state and with available body weight. The Spearman’s correlation test was used to determine the correlation between body weight and trough levels. The Fisher’s exact text was used to compare the frequency of inadequate trough levels between BMI categories.

Results:

1265 patients were included across the different oral oncolytics. A negative correlation coefficient was observed between weight and trough levels for crizotinib (n = 75), imatinib (n = 201) and trametinib (n = 310), respectively, ρ = − 0.41, ρ = − 0.24 and ρ = − 0.23, all with a p-value < 0.001. For crizotinib, a higher percentage of patients with a body weight > 100 kg had inadequate trough levels. No statistically significant differences were observed in the frequency of inadequate trough levels between BMI categories.

Conclusion:

Higher body weight was only correlated with lower plasma trough levels for crizotinib, imatinib, and trametinib. Therefore, patients with a high body weight may require dose escalation to obtain adequate target levels when treated with these oral oncolytics.

01 Feb 2024·Anticancer research

Relationship Between Adverse Events and Progression-free Survival in Patients Receiving Cabozantinib for Previously Treated Metastatic Renal Cell Carcinoma

Article

Author: Furuse, Hiroshi ; Miyake, Hideaki ; Watanabe, Kyohei ; Watanabe, Hiromitsu ; Takemura, Ayana ; Nagata, Masao ; Motoyama, Daisuke ; Matsushita, Yuto ; Sugiyama, Momoko ; Tamura, Keita ; Otsuka, Atsushi ; Sato, Ryo

BACKGROUND/AIM:

Although the adverse events (AEs) of drugs, such as sunitinib and axitinib, have been shown to predict treatment responses, evidence to support cabozantinib-induced AEs as predictors of responses to treatment for metastatic renal cell carcinoma (mRCC) is limited. Therefore, we herein investigated the relationship between AE profiles and progression-free survival (PFS) in patients receiving cabozantinib for previously treated mRCC.

PATIENTS AND METHODS:

The present study retrospectively analyzed 40 patients receiving cabozantinib for previously treated mRCC between July 2020 and August 2022. PFS was estimated using the Kaplan-Meier method and the impact of several parameters, including cabozantinib-induced AEs, on PFS was investigated by a Cox proportional regression analysis.

RESULTS:

The median observation period was 15 (2-29) months, during which time 31 patients (77.5%) progressed, with median PFS of 11 months. Thirty-nine patients (97.5%) developed at least one AE. Liver toxicity occurred in 16 patients (40.0%) and hand-foot syndrome, hypertension, and diarrhea in 14 each (17.5%). Only hypertension correlated with longer PFS. A multivariate analysis identified hypertension as an independent prognostic factor for PFS (p=0.049).

CONCLUSION:

These results suggest the potential of treatment-induced hypertension as a significant predictor of prolonged PFS in patients receiving cabozantinib for mRCC.

298

News (Medical) associated with Cabozantinib (s)-Malate

02 Jul 2024

·www.biospace.com

Ipsen expands collaboration and license agreement for development of Cabometyx® in advanced neuroendocrine tumors based on positive CABINET Phase III trial

Decision adds to existing collaboration agreement with Exelixis, permitting Ipsen to seek potential marketing authorizations for Cabometyx® (cabozantinib) in advanced pancreatic and extra pancreatic neuroendocrine tumors outside of the U.S. and Japan Agreement based on CABINET Phase III trial, led by the Alliance for Clinical Trials in Oncology, which demonstrated improvements in progression-free survival for Cabometyx versus placebo1 Ipsen has engaged with regulatory authorities in the European Union and will submit a regulatory filing on the basis of these data PARIS, FRANCE, 2 July 2024 - Ipsen (Euronext: IPN; ADR: IPSEY) announced today confirmation of an expanded collaboration and license agreement with Exelixis, Inc. for the development of Cabometyx® (cabozantinib) in advanced pancreatic neuroendocrine tumors (pNETs) and advanced extra-pancreatic neuroendocrine tumors (epNETs). The agreement is based on positive outcomes from the CABINET Phase III trial, led by the Alliance for Clinical Trials in Oncology and sponsored by the National Cancer Institute (NCI), which investigated Cabometyx versus placebo in people living with advanced pNETs or advanced epNETs whose disease had progressed after prior systemic therapy. An independent Data and Safety Monitoring Board recommended to stop accrual to the study, unblind patients and allow crossover from placebo to Cabometyx. This was due to early efficacy demonstrated at an interim analysis in both of the trial’s cohorts, with clinically meaningful improvements in progression-free survival (PFS).1 “With many people diagnosed with neuroendocrine tumors at an advanced stage of disease and treatment options limited upon progression, the need for efficacious new therapies is extensive,” said Christelle Huguet, EVP and Head of Research and Development, Ipsen. “The positive results demonstrated for Cabometyx within the CABINET Phase III trial represent clinically meaningful improvements in progression-free survival at a challenging stage of disease where there are few or no available treatment options. We look forward to discussing these clinical findings with regulatory authorities.” Neuroendocrine tumors (NETs) are a group of uncommon tumors that develop in the cells of the neuroendocrine system throughout the body.2,3 The symptoms of NETs are often not distinct and difficult to identify, leading to delays in diagnosis, with 58% of people presenting with metastatic disease at diagnosis.3 The number of people newly diagnosed with NETs is believed to be rising due to increasing awareness and better methods of diagnosis, with approximately 35 in every 100,000 people currently living with NETs globally.3,4 The survival rate varies greatly depending on the primary site and stage of disease, however for people living with advanced pNETs which has spread to distant parts of the body, the prognosis is poor, with a five-year survival rate of 23%.5 CABINET Phase III trial Data from the study, which demonstrated PFS benefits at interim analyses, were presented at the European Society for Medical Oncology Congress 2023 by Professor Jennifer Chan, MD, MPH, Dana-Farber Cancer Institute, Boston:1 In the pNET cohort, at a median follow-up of 16.7 months, median PFS based on local radiology review was 11.4 months for Cabometyx versus 3.0 months for placebo (hazard ratio (HR) 0.27 [95% confidence interval (CI) 0.14-0.49] p<0.0001)1 In the epNET cohort, at a median follow-up of 13.9 months, median PFS based on local radiology review was 8.3 months for Cabometyx versus 3.2 months for placebo (HR 0.45 [95% CI 0.30-0.66] p<0.0001)1 The safety pro Cabometyx observed in each cohort was consistent with its known safety profile; no new safety signals were identified1 ENDS About Cabometyx Cabometyx (cabozantinib) is a small molecule that inhibits multiple receptor tyrosine kinases, including VEGFRs, MET, RET and the TAM family (TYRO3, MER, AXL).6 These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis (the growth of new blood vessels that tumors need to grow), drug resistance, modulation of immune activities and maintenance of the tumor microenvironment.6,7,8,9 In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of Cabometyx outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited (Takeda) for the commercialization and further clinical development of Cabometyx for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize Cabometyx in the U.S. In over 60 countries outside of the U.S. and Japan, including in the E.U., Cabometyx is currently indicated as a:7 Monotherapy for advanced renal cell carcinoma (aRCC). as first-line treatment of adults with intermediate- or poor-risk disease. in adults following prior VEGFR-targeted therapy. In combination with nivolumab for the first-line treatment of aRCC in adults. Monotherapy for the treatment of adults living with locally advanced or metastatic differentiated thyroid carcinoma, refractory or not eligible to radioactive iodine who have progressed during or after prior systemic therapy. Monotherapy for the treatment of hepatocellular carcinoma in adults who have previously been treated with sorafenib. The detailed recommendations for the use of Cabometyx are described in the Summary of Product Characteristics (EU SmPC). About neuroendocrine tumors NETs are relatively uncommon and develop from cells of the neuroendocrine system; thus, can arise from a variety of locations throughout the body.2,3 The most common sites of NETs include the gastrointestinal (GI) tract, lungs and pancreas.2,10 Most NETs take years to develop and grow slowly, however some NETs can be fast-growing.2 The symptoms of NETs are often difficult to identify leading to patients being seen by multiple specialists and undergoing extensive testing before diagnosis is confirmed.3 As a result, almost a third of people take at least 5 years to be diagnosed with NETs.3 The five-year survival rate is dependent on the primary site of disease. For advanced GI-NET and lung NETs, where the cancer has spread to distant parts of the body, the five-year survival rates are 68% and 55%, respectively.11,12 For people diagnosed with advanced pNET, however, the prognosis is poor, with a five-year survival rate of 23%.5 About CABINET CABINET (randomized, double-blinded Phase III trial of CABozantinib versus placebo In patients with advanced NEuroendocrine Tumors after progression on prior therapy) is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded National Clinical Trials Network, as part of Exelixis’ collaboration through a Cooperative Research and Development Agreement with the NCI’s Cancer Therapy Evaluation Program. The multicenter, Phase III CABINET pivotal trial enrolled a total of 290 patients in the U.S at the time of the interim analyses. Patients were randomized 2:1 to Cabometyx or placebo in two separate cohorts (pNET, n=93; epNET, n=197). The epNET cohort included patients with the following primary tumor sites: gastrointestinal tract, lung, unknown and other. Each cohort was randomized separately and had its own statistical analysis plan. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression or intolerance after at least one U.S. Food and Drug Administration-approved line of prior therapy other than somatostatin analogs. The primary endpoint in each cohort was PFS per RECIST 1.1 by retrospective independent central review. Upon confirmation of disease progression, patients were unblinded, and those receiving placebo were permitted to cross over to open-label therapy with Cabometyx. Secondary endpoints included overall survival, radiographic response rate and safety. More information about this trial is available at ClinicalTrials.gov. About Ipsen We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience. Our pipeline is fuelled by external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 80 countries. Ipsen is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com. Ipsen contacts Investors Craig Marks | +44 7584 349 193 Media Joanna Parish | +44 7840 023 741 Emma Roper | +44 7711 766 517 Disclaimers and/or Forward-Looking Statements The forward-looking statements, objectives and targets contained herein are based on Ipsen’s management strategy, current views and assumptions. Such statements involve known and unknown risks and uncertainties that may cause actual results, performance or events to differ materially from those anticipated herein. All of the above risks could affect Ipsen’s future ability to achieve its financial targets, which were set assuming reasonable macroeconomic conditions based on the information available today. Use of the words ‘believes’, ‘anticipates’ and ‘expects’ and similar expressions are intended to identify forward-looking statements, including Ipsen’s expectations regarding future events, including regulatory filings and determinations. Moreover, the targets described in this document were prepared without taking into account external-growth assumptions and potential future acquisitions, which may alter these parameters. These objectives are based on data and assumptions regarded as reasonable by Ipsen. These targets depend on conditions or facts likely to happen in the future, and not exclusively on historical data. Actual results may depart significantly from these targets given the occurrence of certain risks and uncertainties, notably the fact that a promising medicine in early development phase or clinical trial may end up never being launched on the market or reaching its commercial targets, notably for regulatory or competition reasons. Ipsen must face or might face competition from generic medicine that might translate into a loss of market share. Furthermore, the research and development process involves several stages each of which involves the substantial risk that Ipsen may fail to achieve its objectives and be forced to abandon its efforts with regards to a medicine in which it has invested significant sums. Therefore, Ipsen cannot be certain that favorable results obtained during preclinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safe and effective nature of the medicine concerned. There can be no guarantees a medicine will receive the necessary regulatory approvals or that the medicine will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Other risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation; global trends toward healthcare cost containment; technological advances, new medicine and patents attained by competitors; challenges inherent in new-medicine development, including obtaining regulatory approval; Ipsen’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Ipsen’s patents and other protections for innovative medicines; and the exposure to litigation, including patent litigation, and/or regulatory actions. Ipsen also depends on third parties to develop and market some of its medicines which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to Ipsen’s activities and financial results. Ipsen cannot be certain that its partners will fulfil their obligations. It might be unable to obtain any benefit from those agreements. A default by any of Ipsen’s partners could generate lower revenues than expected. Such situations could have a negative impact on Ipsen’s business, financial position or performance. Ipsen expressly disclaims any obligation or undertaking to update or revise any forward-looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law. Ipsen’s business is subject to the risk factors outlined in its registration documents filed with the French Autorité des Marchés Financiers. The risks and uncertainties set out are not exhaustive and the reader is advised to refer to Ipsen’s latest Universal Registration Document, available on ipsen.com. References 1 Chan et al. Alliance A021602: Ph 3, double-blinded study of Cabozantinib vs Placebo for advanced NETs after progression on prior therapy (CABINET). As presented at ESMO Congress 2023 during the ‘Proffered Paper session - NETs and endocrine tumours’ on 22 October 2023 08:40-08:50 CEST, Madrid, Spain. 2 Neuroendocrine tumor (NET). Accessed June 2024. 3 Singh et al. Patient-Reported Burden of a Neuroendocrine Tumor (NET) Diagnosis: Results From the First Global Survey of Patients With NETs. J Glob Oncol. 2017 Feb; 3(1): 43–53. 4 Durma et al. Epidemiology of Neuroendocrine Neoplasms and Results of Their Treatment with [177Lu]Lu-DOTA-TATE or [177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE—A Six-Year Experience in High-Reference Polish Neuroendocrine Neoplasm Center. Cancers 2023, 15(22), 5466; 5 Survival Rates for Pancreatic Neuroendocrine Tumor. American Cancer Society Available at: Accessed June 2024. Accessed June 2024. 6 El-Khoueiry A. et al., Cabozantinib: An evolving therapy for hepatocellular carcinoma. Cancer Treatment Reviews. 2021 Jul;98:102221. DOI: 10.1016/j.ctrv.2021.102221. 7 European Medicines Agency. Cabometyx® (cabozantinib) EU Summary of Product Characteristics. Available from: . Last accessed: June 2024 8 Yakes M. et al., Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;10:2298–2308. DOI: 10.1158/1535-7163.MCT-11-0264 9 Hsu et al., AXL and MET in Hepatocellular Carcinoma: A Systematic Literature Review. Liver Cancer 2021 DOI: 10.1159/000520501 10 Jamal et al. Neuroendocrine tumor of the kidney. Diagnostic challenge and successful therapy. Urology Annals 11(4):p 435-438, Oct–Dec 2019. DOI: 10.4103/UA.UA_169_18 11 Survival Rates for Gastrointestinal Carcinoid Tumors. ACS website. Available at: Accessed June 2024. 12 Survival Rates for Lung Carcinoid Tumors. ACS website. Available at: Accessed June 2024. Attachment Ipsen PR_CABINET Opt-in_02072024

Phase 3Clinical ResultLicense out/in

28 Jun 2024

·www.biospace.com

City of Hope Study Suggests Changing the Gut Microbiome Improves Health Outcomes for People Newly Diagnosed With Metastatic Kidney Cancer

City of Hope developed a novel use of biotherapeutic product CBM588 in the treatment of cancer; new research suggests the agent adjusts people’s microbiome, possibly leading to enhanced effectiveness of Food and Drug Administration-approved cancer immunotherapies Scientists are in discussions to translate City of Hope’s promising phase 1 trial results into a global phase 2/3 trial sponsored by the SWOG Cancer Research Network LOS ANGELES--(BUSINESS WIRE)-- Physician scientists from City of Hope, one of the largest cancer research and treatment organizations in the United States, found that people with metastatic kidney cancer who orally took a live biotherapeutic product called CBM588 while in treatment with immunotherapy and enzymatic tyrosine kinase inhibitors experienced improved health outcomes. The phase 1 trial was published today in Nature Medicine. Microorganisms in the gut modulate the immune system. City of Hope researchers are now in discussions with the global SWOG Cancer Research Network to design a phase 2/3 trial to assess the City of Hope-identified novel use of CBM588 and microbiome modulation in people with advanced cancer. Sumanta Pal, M.D., professor and vice chair of academic affairs in City of Hope’s Department of Medical Oncology & Therapeutics Research, is slated to be co-leader of the potential phase 2/3 SWOG trial. “We at City of Hope are the first to demonstrate a live bacterial product’s ability to improve clinical outcomes for patients with kidney cancer treated with immunotherapy. CBM588 could be exciting in cancer treatment because of its potential to enhance the efficacy of immune checkpoint inhibitor-based treatment, improve patient outcomes and modulate the gut microbiota in beneficial ways,” said Pal, a City of Hope medical oncologist and corresponding author of the new study. “Ongoing and larger clinical trials are crucial to validate these benefits and address current challenges. If the positive results observed in this small trial and a previous trial with nivolumab and ipilimumab are confirmed, CBM588 could become a valuable supplement in the treatment of various cancers, particularly for patients treated with immune checkpoint inhibitors." An estimated 44% of U.S. patients with cancer in 2018 were eligible for checkpoint inhibitor drugs, according to a JAMA Network Open article that flags the increasing trend of this percentage. In the single-center, phase 1 trial, 30 people with metastatic kidney cancer were randomized to receive cabozantinib, an inhibitor of vascular endothelial growth factor receptor, and targeted immunotherapy nivolumab with or without CBM588 as first-line treatment. Participants’ gut microbiome were analyzed via stool samples in the beginning for a baseline and then 13 weeks into treatment. City of Hope has granted an exclusive worldwide license to Osel for intellectual property on the novel use of CBM588 to enhance the efficacy of checkpoint inhibitors used to treat cancer, including metastatic renal cell carcinoma. Scientists from Osel and Miyarisan Pharmaceutical Co. Ltd, the manufacturer of CBM588, collaborated on the study. To date, many studies on lung cancer, melanoma and metastatic kidney cancer, among other diseases, have shown that the composition of the gut microbiome could predict immunotherapy outcomes for patients with cancer. Current guidelines for metastatic renal cell carcinoma (kidney cancer) recommend that newly diagnosed patients receive either dual checkpoint inhibitor therapy or a combination of immunotherapy and tyrosine kinase inhibitor, but most patients eventually experience disease progression while on treatment. Positive patient outcomes usually do not last, and subsequent treatments are largely palliative rather than curative. So, physician scientists are looking to combine current strategies with new treatments that do not introduce toxic side effects, such as through microbiome modulation. In the trial, City of Hope researchers observed an increase in the abundance of unclassified Ruminococcaceae genera, which has been linked with improved clinical outcomes with immune checkpoint inhibitors in recent studies. Clostridium butyricum MIYAIRI 588, the bacterium in CBM588, produces butyric acid, which is critical for intestinal health and is a well-known immunomodulator. “While not yet part of standard cancer treatment protocols, microbiome modulation is a promising area of research with the potential to enhance the efficacy of cancer therapies, particularly immunotherapies. Current applications are primarily within clinical trials, but the growing body of evidence suggests that microbiome-based interventions may soon become a valuable component of cancer treatment strategies,” said Hedyeh Ebrahimi, M.D, M.P.H., City of Hope postdoctoral medical oncology fellow and first author of the study. City of Hope is accelerating its research on the direct link between a healthy gut and the effectiveness of immune therapies, such as CAR T cell therapy. Its enhanced microbiome program spans from basic to clinical research and includes studying the gut microbiome’s role in protecting transplant patients from complications experienced during their recovery. “This study demonstrates again that the microbiome has an important role in the efficacy and toxicity of cancer immunotherapy and can be targeted to improve outcome,” said Marcel van den Brink, M.D., Ph.D., president of City of Hope Los Angeles and City of Hope National Medical Center, and the Deana and Steve Campbell Chief Physician Executive Distinguished Chair. The Nature Medicine study entitled “Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial” was supported by Exelixis Inc. (XL184-IST123). CBM588 was supplied by Miyarisan Pharmaceutical Co., Ltd. and Osel Inc. About City of Hope City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn. View source version on businesswire.com: Contacts Zen Logsdon 626-409-9367 zlogsdon@coh.org Source: City of Hope View this news release online at:

Phase 1ImmunotherapyLicense out/inClinical Result

27 Jun 2024

·www.prnewswire.com

American Cancer Society Projects Over 2 Million New Cases in 2024: Biotech Innovations Respond

USA News Group News Commentary Issued on behalf of Oncolytics Biotech Inc. VANCOUVER, BC, June 27, 2024 /PRNewswire/ -- USA News Group News Commentary – According to the American Cancer Society, 2024 will be the first year the USA expects to have more than 2 million new cancer cases. In order to respond to the rising rates of cancer, the National Cancer Institute is making calls for change in how cancer clinical research is performed "Because our patients can't wait." According to Spherical Insights, the Global Oncology Drugs Market is projected to grow by 11.5% CAGR through 2033 to US$564.5 billion, highlighting the need for more effective therapies and incentives for those who develop them. The biotech sector is actively addressing this need, with recent notable developments from several companies, including: O ncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), GSK plc (NYSE: GSK), Guardant Health, Inc. (NASDAQ: GH), Exelixis, Inc. (NASDAQ: EXEL), and Gilead Sciences, Inc. (NASDAQ: GILD). The article continued: According to the World Health Organization, the global cancer burden is growing amidst a mounting need for services. As well, an alarming trend is emerging, where cancer cases in younger people are rising sharply. Oncolytics Biotech® Announces Productive FDA Type C Meeting on its Metastatic Breast Cancer Program Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapy for oncology, today announced that the Company received productive feedback from its Type C meeting with the U.S. Food and Drug Administration (FDA), supporting the planned potential registration-enabling trial for pelareorep in HR+/HER2- metastatic breast cancer (mBC). The FDA supports progression-free survival as the primary endpoint of the study, with overall survival as a key secondary endpoint. The Company's proposed study will enroll patients who have failed hormonal therapy and have received no more than one line of antibody-drug conjugate (ADC) therapy. "Aligning with the FDA on key design elements and objectives of our planned registrational trial for pelareorep marks a critical step towards bringing this innovative treatment to patients," said Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics. "Our de-risked program builds on compelling data and key learnings from two randomized studies, BRACELET-1 and IND-213, which demonstrated clinically meaningful benefit in patients receiving pelareorep and paclitaxel compared to paclitaxel alone. Additionally, translational data from the AWARE-1 study highlights pelareorep's immune-mediated mechanism of action in breast cancer patients. We are now well-positioned to deliver on our mission of making pelareorep available to breast cancer patients in need of better treatment options." Wayne Pisano, Interim CEO and Chair of the Board of Oncolytics, commented, "We are appreciative of the thoughtful dialog with the FDA and are pleased to have reached an important regulatory milestone that provides a clear path forward for pelareorep's advancement towards registration in HR+/HER2- mBC. Looking ahead, initiating a registration-enabling trial has become a major corporate objective, and in parallel, we remain on track to report survival data from the BRACELET-1 study in HR+/HER2- mBC in the second half of the year. We believe these data will further bolster our compelling data package and underscores the therapeutic potential of pelareorep. We remain committed to improving the standard of care and addressing the high unmet medical needs of these patients." CONTINUED… Read this and more news for Oncolytics Biotech at: In other industry developments and happenings in the market this week include: GSK plc (NYSE: GSK), a global biopharma company, recently released positive results from an interim analysis of the DREAMM-8 phase III head-to-head trial evaluating belantamab mafodotin, in combination with pomalidomide plus dexamethasone (PomDex), versus a standard of care, bortezomib plus PomDex, as a second line and later treatment for relapsed or refractory multiple myeloma. As per the release, the drug combination reduced the risk of disease progression or death by nearly 50% versus standard of care. "With the robust results from the DREAMM-8 phase III head-to-head trial, we now have consistent data from two phase III trials supporting the potential for belantamab mafodotin combinations to redefine the treatment of multiple myeloma at or after first relapse," said Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, of GSK. "This is exciting news given the high unmet need for new and efficacious combinations once patients relapse or stop responding to initial treatments. We continue to share data and discuss our path forward with regulators." Guardant Health, Inc. (NASDAQ: GH), a leading precision oncology company, recently announced the launch of a new version of its Guardant360 TissueNext test that expanded the number of genes it identifies in a tumor tissue sample to 498. In addition to the panel expansion, Guardant has improved the test's operational workflow for a faster turnaround time. "The launch of the new Guardant360 TissueNext test is another step forward in our mission to conquer cancer with data," said Helmy Eltouky, Chairman and co-CEO of Guardant Health. "In addition to identifying guideline-recommended biomarkers, the upgraded test now provides more comprehensive gene coverage, so oncologists can make better informed decisions about the optimal treatment strategy for their patients with advanced cancer and help improve their outcomes." Exelixis, Inc. (NASDAQ: EXEL), a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care, recently settled two patent litigations with Cipla Ltd. and Cipla USA, Inc. (collectively Cipla) in response to Cipla's Abbreviated New Drug Application (ANDA) seeking approval to market generic versions of CABOMETYX® (cabozantinib) tablets prior to the expiration of the applicable patents. Prior to the settlement earlier this year, Exelixis also announced detailed results of its Phase 3 CONTACT-02 pivotal trial evaluating the above-mentioned cabozantinib in combination with atezolizumab in metastatic castration-resistant prostate cancer at this year's ASCO GU 2024 event. As per the results, the combination reduced the risk of disease progression or death by 35%. "Given there are limited options after progression on novel hormonal therapy, we recognize the need for a regimen that can delay disease progression, that has an acceptable tolerability profile and that is widely available to patients who may not have the means or desire to travel to specialized centers for other therapies," said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. "We look forward to discussing these important results with the U.S. Food and Drug Administration, and to learning more in the next analysis of overall survival, anticipated this year." Through its recently-acquired Kite subsidiary, Gilead Sciences, Inc. (NASDAQ: GILD) recently announced results from three new analyses for Yescarta (axicabtagene ciloleucel) in relapsed/refractory (R/R) large B-cell lymphoma (LBCL), including both new clinical research and real-world evidence highlighting manufacturing and product characteristics of Yescarta, and outpatient administration of both Yescarta and Tecartus® (brexucabtagene autoleucel) at the 2024 European Hematology Association (EHA) Annual Congress, June 13-16, Madrid. "We are committed to improving survival outcomes for people living with difficult-to-treat blood cancers," said Ibrahim Elhoussieny, Vice President, Medical Affairs, of Kite. "These new data support the potential benefit of utilizing Yescarta in earlier lines of treatment, both in terms of manufacturing success and product characteristics. Additional data support the safety and feasibility of administering CAR T-cell therapy in the outpatient setting. These data contribute to the body of evidence for efficient utilization and delivery of Yescarta and Tecartus and further support our ambition for patients." Source: CONTACT: USA NEWS GROUP [email protected] (604) 265-2873 DISCLAIMER: Nothing in this publication should be considered as personalized financial advice. We are not licensed under securities laws to address your particular financial situation. No communication by our employees to you should be deemed as personalized financial advice. Please consult a licensed financial advisor before making any investment decision. This is a paid advertisement and is neither an offer nor recommendation to buy or sell any security. We hold no investment licenses and are thus neither licensed nor qualified to provide investment advice. The content in this report or email is not provided to any individual with a view toward their individual circumstances. USA News Group is a wholly-owned subsidiary of Market IQ Media Group, Inc. ("MIQ"). MIQ has been paid a fee for Oncolytics Biotech Inc. advertising and digital media from the company directly. There may be 3rd parties who may have shares of Oncolytics Biotech Inc., and may liquidate their shares which could have a negative effect on the price of the stock. This compensation constitutes a conflict of interest as to our ability to remain objective in our communication regarding the profiled company. Because of this conflict, individuals are strongly encouraged to not use this publication as the basis for any investment decision. The owner/operator of MIQ own shares of Oncolytics Biotech Inc. which were purchased in the open market, and reserve the right to buy and sell, and will buy and sell shares of Oncolytics Biotech Inc. at any time without any further notice commencing immediately and ongoing. We also expect further compensation as an ongoing digital media effort to increase visibility for the company, no further notice will be given, but let this disclaimer serve as notice that all material, including this article, which is disseminated by MIQ has been approved by Oncolytics Biotech Inc.; this is a paid advertisement, we currently own shares of Oncolytics Biotech Inc. and will buy and sell shares of the company in the open market, or through private placements, and/or other investment vehicles. While all information is believed to be reliable, it is not guaranteed by us to be accurate. Individuals should assume that all information contained in our newsletter is not trustworthy unless verified by their own independent research. Also, because events and circumstances frequently do not occur as expected, there will likely be differences between the any predictions and actual results. Always consult a licensed investment professional before making any investment decision. Be extremely careful, investing in securities carries a high degree of risk; you may likely lose some or all of the investment. SOURCE USA News Group

Phase 3Clinical ResultImmunotherapy

100 Deals associated with Cabozantinib (s)-Malate

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KEGG	Wiki	ATC	Drug Bank
D10095	Cabozantinib (s)-Malate	L01XE26	DB08875

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Thyroid Cancer	US	Exelixis, Inc.	17 Sep 2021
Differentiated Thyroid Gland Carcinoma	KR	Ipsen Ltd.	26 Sep 2017
Hepatocellular Carcinoma	EU	Ipsen Pharma SAS	09 Sep 2016
Hepatocellular Carcinoma	IS	Ipsen Pharma SAS	09 Sep 2016
Hepatocellular Carcinoma	LI	Ipsen Pharma SAS	09 Sep 2016
Hepatocellular Carcinoma	NO	Ipsen Pharma SAS	09 Sep 2016
Renal Cell Carcinoma	EU	Ipsen Pharma SAS	09 Sep 2016
Renal Cell Carcinoma	IS	Ipsen Pharma SAS	09 Sep 2016
Renal Cell Carcinoma	LI	Ipsen Pharma SAS	09 Sep 2016
Renal Cell Carcinoma	NO	Ipsen Pharma SAS	09 Sep 2016
Advanced Renal Cell Carcinoma	US	Exelixis, Inc.	25 Apr 2016
Metastatic Thyroid Gland Medullary Carcinoma	EU	Ipsen Pharma SAS	21 Mar 2014
Metastatic Thyroid Gland Medullary Carcinoma	IS	Ipsen Pharma SAS	21 Mar 2014
Metastatic Thyroid Gland Medullary Carcinoma	LI	Ipsen Pharma SAS	21 Mar 2014
Metastatic Thyroid Gland Medullary Carcinoma	NO	Ipsen Pharma SAS	21 Mar 2014
Thyroid Cancer, Medullary	US	Exelixis, Inc.	29 Nov 2012

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	NDA/BLA	CN	Jiangsu Hansoh Pharmaceutical Co. Ltd.	28 Sep 2020
Adenocarcinoma of prostate	Phase 3	US	Exelixis, Inc.	30 Jun 2020
Adenocarcinoma of prostate	Phase 3	JP	Exelixis, Inc.	30 Jun 2020
Adenocarcinoma of prostate	Phase 3	AR	Exelixis, Inc.	30 Jun 2020
Adenocarcinoma of prostate	Phase 3	AU	Exelixis, Inc.	30 Jun 2020
Adenocarcinoma of prostate	Phase 3	AT	Exelixis, Inc.	30 Jun 2020
Adenocarcinoma of prostate	Phase 3	BE	Exelixis, Inc.	30 Jun 2020
Adenocarcinoma of prostate	Phase 3	BR	Exelixis, Inc.	30 Jun 2020
Adenocarcinoma of prostate	Phase 3	CA	Exelixis, Inc.	30 Jun 2020
Adenocarcinoma of prostate	Phase 3	CL	Exelixis, Inc.	30 Jun 2020

Clinical Result

Indication

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03141177 (CM9ER, ASCO2024) Manual	Phase 3	Advanced Renal Cell Carcinoma First line	651	Cabozantinib plus nivolumab (CN)	afcrdfqsjf(vbabkbjvvt) = tafzgmuvrq aqxotqnidw (rmjbnlvkqs ) View more	Positive	24 May 2024
NCT03141177 (CM9ER, ASCO2024) Manual	Phase 3	Advanced Renal Cell Carcinoma First line	651	Sunitinib (SUN)	afcrdfqsjf(vbabkbjvvt) = scbwlvemjb aqxotqnidw (rmjbnlvkqs ) View more	Positive	24 May 2024
NCT03141177 (CheckMate 9ER, ASCO2024) Manual	Phase 3	Advanced Renal Cell Carcinoma First line	651	Nivolumab + Cabozantinib	yedzmwcypu(ukngmkfdie) = qafvzjunyt bsvlgmuejs (yhpnxrgqbq ) View more	Positive	24 May 2024
NCT03141177 (CheckMate 9ER, ASCO2024) Manual	Phase 3	Advanced Renal Cell Carcinoma First line	651	Sunitinib	yedzmwcypu(ukngmkfdie) = tlpjhrbsqp bsvlgmuejs (yhpnxrgqbq ) View more	Positive	24 May 2024
NCT05007613 (phase II trial, ASCO2024)	Phase 2	Advanced Esophageal Squamous Cell Carcinoma	-	Anti-PD-L1 therapy	gwiiwwvwna(pzxarvzjvh) = dbbupvngww btehkabwyz (rznvnhnzin )	-	24 May 2024
NCT03370718 (Pubmed)	Phase 2	Adrenocortical Carcinoma	18	Cabozantinib 60 mg	njwroaobml(qasetxlzal) = Treatment-related adverse events of grade 3 or worse occurred in 11 (61%) of 18 patients fiqlszyfwe (pelaqmirmy )	Positive	09 Apr 2024
NCT04588051 (Pubmed)	Phase 2	Hepatocellular Carcinoma immune checkpoint inhibitor (ICI)	47	Cabozantinib 60mg/day	nfporhrwbn(fcqzldsjyy) = sbcyaxixiv xxzbzfiscy (zjounqagte ) View more	-	26 Mar 2024
NCT04868773 (Phase 1 Study of Cabozantinib and Trifluridine/Tipiracil in Metastatic Colorectal Adenocarcinoma, Pubmed)	Phase 1	Metastatic Colorectal Carcinoma	15	Cabozantinib 20 mg	wexngzvfei(iftkdkximo) = Most common any grade (G) treatment related adverse events (TRAE) were diarrhea (50%), nausea (42%), neutropenia (42%), fatigue (33%), and rash (25%) fvumtbmdhd (tvyyutfhtl )	Positive	01 Mar 2024
NCT05122546 (ASCO_GU2024) Manual	Phase 1	Metastatic Renal Cell Carcinoma	30	cabozantinib +nivolumab	soxbhawnpk(twhigjlsxv) = mmjzriubao szykohfvyy (kvpmpodwgs )	Positive	25 Jan 2024
NCT05122546 (ASCO_GU2024) Manual	Phase 1	Metastatic Renal Cell Carcinoma	30	cabozantinib +nivolumab+CBM588	soxbhawnpk(twhigjlsxv) = auauyiqlzl szykohfvyy (kvpmpodwgs )	Positive	25 Jan 2024
NCT03685448 (UNICAB, ASCO_GU2024) Manual	Phase 2	Renal Cell Carcinoma	31	Cabozantinib	xqzefxiyoa(dkfblplkad) = pjjzzzrmty bxeddnabxn (nnjwbuqlnk ) View more	Positive	25 Jan 2024
NCT03534804 (PemCab, ASCO_GU2024) Manual	Phase 2	Transitional Cell Carcinoma First line	36	Pembrolizumab+Cabozantinib	dlphhmjjgz(fgafydnhaz) = ttgsxqprtc mxtrvrbqyq (swxdpmilbc ) View more	Positive	25 Jan 2024
NCT04400474 (CABATEN \| GETNE-T1914, ASCO_GU2024) Manual	Phase 2	Adrenocortical Carcinoma	24	Cabozantinib+atezolizumab	inxncrcwqb(nqnptorhei) = sxavawwmps axnxauetcp (krvhvwlbue, 1 - 27) View more	Positive	25 Jan 2024

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