A Phase I Study of Anetumab Ravtansine in Combination With Either Anti-PD-1 Antibody, or Anti-CTLA4 and Anti-PD-1 Antibodies or Anti-PD-1 Antibody and Gemcitabine in Mesothelin-Positive Advanced Pancreatic Adenocarcinoma

This phase I trial studies the side effects and best dose of anetumab ravtansine when given together with nivolumab, ipilimumab and gemcitabine hydrochloride in treating patients with mesothelin positive pancreatic cancer that has spread to other places in the body (advanced). Anetumab ravtansine is a monoclonal antibody, called anetumab ravtansine, linked to a chemotherapy drug called DM4. Anetumab attaches to mesothelin positive cancer cells in a targeted way and delivers DM4 to kill them. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving anetumab ravtansine together with nivolumab, ipilimumab, and gemcitabine hydrochloride may work better in treating patients with pancreatic cancer.

Start Date09 Dec 2019

Sponsor / Collaborator

National Cancer Institute

NCT03926143 / TerminatedPhase 2

An Open-label, Multicenter Rollover Study to Provide Continued Treatment With Anetumab Ravtansine for Participants With Solid Tumors Who Were Enrolled in Previous Bayer-sponsored Studies

The purpose of this study is to enable patients with solid tumors, who received anetumab ravtansine in a Bayer-sponsored clinical trial, to continue treatment after their respective study has been closed. The patients will be observed to collect information on how safe and efficient the drug is.

Start Date03 Jun 2019

Sponsor / Collaborator

Bayer AG

NCT03587311 / Active, not recruitingPhase 2IIT

A Randomized Phase 2 Study of Bevacizumab and Either Weekly Anetumab Ravtansine or Weekly Paclitaxel in Platinum-Resistant or Platinum Refractory Ovarian Cancer

This phase II trial studies the side effects of bevacizumab and anetumab ravtansine or paclitaxel in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that does not respond to treatment (refractory). Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Anetumab ravtansine is a drug that targets a protein in the body called mesothelin, which can be found in some ovarian, pancreatic and other tumors. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving bevacizumab and anetumab ravtansine or paclitaxel may work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

Start Date12 Oct 2018

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Anetumab ravtansine

100 Translational Medicine associated with Anetumab ravtansine

100 Patents (Medical) associated with Anetumab ravtansine

Literatures (Medical) associated with Anetumab ravtansine

01 Sep 2024·Lung Cancer

Randomized trial of anetumab ravtansine and pembrolizumab compared to pembrolizumab for mesothelioma

Article

Author: Mansfield, Aaron S ; Cao, Liang ; Zamboni, William ; Arnold, Susanne M ; Pacheco, Jose ; Smith, Katherine E R ; Koczywas, Marianna ; Kwiatkowski, David J ; Dizona, Paul ; Villaruz, Liza C ; Moscow, Jeffrey A ; Chen, Li ; Bazhenova, Lyudmila A ; Bradbury, Penelope ; Lou, Yanyan ; Kindler, Hedy L ; Patel, Shiven ; Patel, Kashish ; Khalil, Maya ; Forde, Patrick ; Vivien Yin, Jun ; Adjei, Alex ; Rolfo, Christian ; Shapiro, Geoffrey ; Costello, Brian A ; Xia, Bing ; Sharon, Elad ; Hassan, Raffit ; Mikula, Elizabeth

PURPOSEThe mesothelin-targeting antibody-drug conjugate anetumab ravtansine was evaluated in combination with the programmed cell death-1 (PD-1) inhibitor pembrolizumab based on the common expression of mesothelin and reports of activity in mesothelioma.PATIENTS AND METHODSA phase 1 safety run-in of the combination of anetumab ravtansine (6.5 mg/kg iv q3weeks) and pembrolizumab (200 mg, IV q3weeks) was conducted, followed by a phase 2 randomization to the combination or pembrolizumab alone at medical centers across the United States and Canada in the National Cancer Institute's Experimental Therapeutics Clinical Trials Network. Patients with pleural mesothelioma that expressed mesothelin and had previously received platinum-based therapy were eligible.RESULTSIn phase 1 (n = 12) only one dose limiting toxicity was observed and the rules for dose reduction were not met. In phase 2, there was no difference in the confirmed response rates between the combination group (n = 18, 2 partial responses [PR], 11 %) and the pembrolizumab group (n = 17, 1 PR, 6 %; z = -0.5523, p = 0.29116). The median PFS was 12.2 months (95 % CI 5.1-not evaluable [NE]) for the combination, and 3.9 months for pembrolizumab (95 % CI 2.1-NE)(HR=0.55, p = 0.20). Patients with high baseline levels of soluble mesothelin who received anetumab ravtansine had a median PFS of 5 months.CONCLUSIONSThe numeric difference in PFS between treatment groups was not statistically significant, likely related to a smaller than planned sample size. High levels of soluble mesothelin should potentially be considered to select against the use of mesothelin-targeting therapies in development that are neutralized by soluble mesothelin.

01 Apr 2023·International Journal of Gynecologic Cancer

Safety and activity of anti-mesothelin antibody–drug conjugate anetumab ravtansine in combination with pegylated-liposomal doxorubicin in platinum-resistant ovarian cancer: multicenter, phase Ib dose escalation and expansion study

Article

Author: Coleman, Robert L ; Santin, Alessandro D ; González-Martín, Antonio ; Monk, Bradley J ; Kasten, Linda ; Diab, Sami ; Vergote, Ignace ; Moore, Kathleen ; Copeland, Larry J ; Schulz, Anke ; Bulat, Iurie ; Siegel, Jonathan ; Köchert, Karl ; Herzog, Thomas J ; Oaknin, Ana ; Elbi, Cem ; Walter, Annette O ; Romero, Ignacio ; Schlicker, Andreas ; Childs, Barrett H

ObjectivesAnetumab ravtansine is an antibody-drug conjugate consisting of a fully human anti-mesothelin monoclonal antibody conjugated to cytotoxic maytansinoid tubulin inhibitor DM4. Mesothelin is highly expressed in ovarian cancer. This phase Ib study determines the safety, pharmacokinetics, and anti-tumor activity of anetumab ravtansine and pegylated liposomal doxorubicin in mesothelin-expressing platinum-resistant ovarian cancer.MethodsAnetumab ravtansine (5.5 or 6.5 mg/kg) and pegylated liposomal doxorubicin (30 mg/m2) were administered intravenously every 3 weeks to 65 patients with platinum-resistant epithelial ovarian cancer. Mesothelin expression was assessed by central immunohistochemistry. Adverse events, tumor response (RECIST 1.1), and progression-free survival were determined. Biomarker samples were assessed by ELISA and next-generation sequencing.ResultsIn dose escalation, nine patients received anetumab ravtansine across two doses (5.5 or 6.5 mg/kg). The maximum tolerated dose of anetumab ravtansine was 6.5 mg/kg every 3 weeks and no dose-limiting toxicities were observed. In dose expansion, 56 patients were treated at the maximum tolerated dose. The most common treatment-emergent adverse events of any grade were nausea (47.7%), decreased appetite (43.1%), fatigue (38.5%), diarrhea (32.3%), and corneal disorder (29.2%). In all treated patients the objective response rate was 27.7% (95% CI 17.3% to 40.2%), including one complete (1.5%) and 17 partial responses (26.2%), with median duration of response of 7.6 (95% CI 3.3 to 10.2) months and median progression-free survival of 5.0 (95% CI 3.2 to 6.0) months. In an exploratory analysis of a sub-set of patients (n=19) with high mesothelin expression who received ≤3 prior lines of systemic therapy, the objective response rate was 42.1% (95% CI 20.3% to 66.5%) with a median duration of response of 8.3 (95% CI 4.1 to 12.0) months and median progression-free survival of 8.5 (95% CI 4.0 to 11.4) months.ConclusionsAnetumab ravtansine and pegylated liposomal doxorubicin showed tolerability and promising clinical activity. These results established the dose schedule and the mesothelin-positive target population of this combination for a phase III study in platinum-resistant ovarian cancer.Trial registration numberNCT02751918.

01 Apr 2022·The Lancet OncologyQ1 · MEDICINE

Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial

Q1 · MEDICINE

Article

Author: Köchert, Karl ; Jennens, Ross ; Kasten, Linda ; Nowak, Anna K ; Siegel, Jonathan M ; Ceresoli, Giovanni L ; Childs, Barrett H ; Walter, Annette O ; Taylor, Paul ; Santoro, Armando ; Blumenschein, George ; Aerts, Joachim G J V ; Van Meerbeeck, Jan P ; Novello, Silvia ; Calabrò, Luana ; Burgers, Jacobus A ; Serwatowski, Piotr ; Bearz, Alessandra ; Greystoke, Alastair ; Hassan, Raffit ; Elbi, Cem ; Kindler, Hedy L ; Ponce, Santiago ; Spicer, James ; Cedrés, Susana ; Fennell, Dean A ; Nackaerts, Kristiaan

BACKGROUNDFew treatment options exist for second-line treatment of malignant pleural mesothelioma. We aimed to assess the antibody-drug conjugate anetumab ravtansine versus vinorelbine in patients with unresectable locally advanced or metastatic disease overexpressing mesothelin who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab.METHODSIn this phase 2, randomised, open-label study, done at 76 hospitals in 14 countries, we enrolled adults (aged ≥18 years) with unresectable locally advanced or metastatic malignant pleural mesothelioma, an Eastern Cooperative Oncology Group performance status of 0-1, and who had progressed on first-line platinum-pemetrexed chemotherapy with or without bevacizumab. Participants were prospectively screened for mesothelin overexpression (defined as 2+ or 3+ mesothelin membrane staining intensity on at least 30% of viable tumour cells by immunohistochemistry) and were randomly assigned (2:1), using an interactive voice and web response system provided by the sponsor, to receive intravenous anetumab ravtansine (6·5 mg/kg on day 1 of each 21-day cycle) or intravenous vinorelbine (30 mg/m² once every week) until progression, toxicity, or death. The primary endpoint was progression-free survival according to blinded central radiology review, assessed in the intention-to-treat population, with safety assessed in all participants who received any study treatment. This study is registered with ClinicalTrials.gov, NCT02610140, and is now completed.FINDINGSBetween Dec 3, 2015, and May 31, 2017, 589 patients were enrolled and 248 mesothelin-overexpressing patients were randomly allocated to the two treatment groups (166 patients were randomly assigned to receive anetumab ravtansine and 82 patients were randomly assigned to receive vinorelbine). 105 (63%) of 166 patients treated with anetumab ravtansine (median follow-up 4·0 months [IQR 1·4-5·5]) versus 43 (52%) of 82 patients treated with vinorelbine (3·9 months [1·4-5·4]) had disease progression or died (median progression-free survival 4·3 months [95% CI 4·1-5·2] vs 4·5 months [4·1-5·8]; hazard ratio 1·22 [0·85-1·74]; log-rank p=0·86). The most common grade 3 or worse adverse events were neutropenia (one [1%] of 163 patients for anetumab ravtansine vs 28 [39%] of 72 patients for vinorelbine), pneumonia (seven [4%] vs five [7%]), neutrophil count decrease (two [1%] vs 12 [17%]), and dyspnoea (nine [6%] vs three [4%]). Serious drug-related treatment-emergent adverse events occurred in 12 (7%) patients treated with anetumab ravtansine and 11 (15%) patients treated with vinorelbine. Ten (6%) treatment-emergent deaths occurred with anetumab ravtansine: pneumonia (three [2%]), dyspnoea (two [1%]), sepsis (two [1%]), atrial fibrillation (one [1%]), physical deterioration (one [1%]), hepatic failure (one [1%]), mesothelioma (one [1%]), and renal failure (one [1%]; one patient had 3 events). One (1%) treatment-emergent death occurred in the vinorelbine group (pneumonia).INTERPRETATIONAnetumab ravtansine showed a manageable safety profile and was not superior to vinorelbine. Further studies are needed to define active treatments in relapsed mesothelin-expressing malignant pleural mesothelioma.FUNDINGBayer Healthcare Pharmaceuticals.

News (Medical) associated with Anetumab ravtansine

26 Jun 2023

·www.prnewswire.com

Innovent and RemeGen Enter into Clinical Trial Collaboration Investigating Combination Therapy of TYVYT® (sintilimab injection) and Novel ADC Candidates for Advanced Solid Tumors in China

ROCKVILLE, Md. and SUZHOU, China, June 25, 2023 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, and RemeGen Co., Ltd. (688331.SH/09995.HK), today announced that they entered into a clinical trial collaboration and supply agreement with for the combination therapies of TYVYT® (sintilimab injection) with RC88, a novel mesothelin(MSLN)-targeting antibody-drug conjugate (ADC), or RC108, a novel c-Met-targeting ADC, respectively, as potential treatment options for advanced solid tumors in China. Under the agreement, Innovent will provide clinical drug supplies of TYVYT® (sintilimab injection) during the clinical trial collaboration. RemeGen will conduct Phase 1/2a clinical studies to evaluate the anti-tumor activity and safety of the combination therapy of TYVYT® (sintilimab injection) with RC88 or RC108 in Chinese patients with advanced solid tumors. TYVYT® (sintilimab injection) is an innovative PD-1 inhibitor co-developed by Innovent and Eli Lilly and Company. In China, sintilimab has been approved for seven indications and included in the National Reimbursement Drug List (NRDL) for six indications. TYVYT® (sintilimab injection) is the only PD-1 inhibitor for the first-line treatment of five high-incidence cancer types in the NRDL – including non-squamous NSCLC, squamous NSCLC, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer, as well as the first and the only immunotherapy medicine for gastric cancer in the NRDL. RC88 is a novel MSLN-targeting ADC independently developed by RemeGen. RC88 is currently being investigated in an ongoing Phase 1 clinical trial, which was approved by the NMPA in November 2018. The preliminary results demonstrated anti-tumor activity and a manageable safety profile of RC88 monotherapy in MSLN-positive advanced solid tumors. Preclinical studies also showed that RC88 can selectively delivers a potent cytotoxic payload to MSLN-expressing cells through internalization, thus inducing G2/M arrest and apoptosis. When combined with PD-1/PD-L1 or other immune checkpoint inhibitors (ICIs), RC88 can induce immunogenic cell death (ICD), releasing a series of signaling molecules to further activate T cells, enhance tumor immune response, and synergistically exert a stronger anti-tumor effect. RC108 is a novel c-Met targeting ADC independently developed by RemeGen. RC108 is currently being investigated in an ongoing Phase 1 clinical trial, which was approved by the NMPA in November 2020. The preliminary results demonstrated anti-tumor activity and a manageable safety profile of RC108 monotherapy in c-Met-positive advanced solid tumors. Preclinical studies also showed that RC108 can induce tumor-specific adaptive immunity and increase the infiltration of T cells into the tumor microenvironment, while anti-PD-1 monoclonal antibody can activate T cells to enhance anti-tumor killing effect. Therefore, it is expected that the combination therapy of RC108 and sintilimab can not only improve antigen presenting by dendritic cells , but also boost the tumor killing of T cells, therefore bringing in synergistic tumor inhibition effect. Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to collaborate with RemeGen to further explore the combination therapy potential of sintilimab injection and novel ADC candidates. Preclinical studies has suggested the synergistic anti-tumor effects, which supports the investigation of combining ADCs with an anti-PD-1 monoclonal antibody to improve patient outcomes and overcome drug-resistance. As immunotherapy advanced into next era of development, we hope to strengthen the leading position of sintilimab as a backbone immunotherapy as well as investigate the new opportunities of combination therapies, and provide better treatment options for more cancer patients. " Ms. Na Su, Senior Vice President of RemeGen, stated "Collaborating with Innovent is an important advancement in the research and commercialization strategy for the combination therapy of RC88 and RC108. The combination of RC88 and RC108 with sintilimab provides an innovative treatment approach that targets two different targets simultaneously. The mechanisms are complementary and synergistic, helping to overcome or delay resistance, achieve multi-pathway targeting of tumors, and provide an efficient solution for unmet clinical needs." About RC88 ADC RC88 is a novel anti-mesothelin ADC developed by RemeGen, which is formed by a recombinant humanized anti-MSLN monoclonal antibody conjugated to the microtubule inhibitor MMAE via a Linker. It includes an MSLN antibody moiety (also known as RC88 naked antibody), a linker, and a small molecule moiety of the cytotoxic pentapeptide MMAE. RC88 binds hMSLN with high affinity and specificity and can compete with endogenous ligands. It can kill tumor cells with different expression levels of MSLN, and the killing effect is positively correlated with the expression of MSLN. Functional studies on the Fc fragment showed that the Fc-mediated effect was not a major role in the effect of this drug. Based on promising preclinical data, a phase 1 study has been moving forward quickly. About RC108 ADC RC108 is a targeted antibody-drug conjugate (ADC) developed by RemeGen for the treatment of solid tumors with positive expression of the cell-matrix epithelial transition factor (c-MET). RC108 consists of a c-MET targeting antibody, a linker, and a small molecule cytotoxin. Its mechanism of action is similar to RC48, as it can selectively bind to c-MET-positive tumor cells, mediate antibody internalization, and effectively deliver the cytotoxin to cancer cells, achieving a good tumor-killing effect. In November 2020, RemeGen received approval from the National Medical Products Administration to conduct Phase 1 clinical trials of RC108 targeting c-MET-positive advanced solid tumors in China. The trial is currently progressing smoothly, and preliminary results show that RC108 has anti-tumor activity against c-MET-expressing solid tumors and is well-tolerated. In December 2022, RC108 obtained clinical trial permission from the U.S. Food and Drug Administration (FDA) to conduct clinical research in patients with c-MET-positive solid tumors. In April 2023, a combination therapy involving RC108 was approved to conduct Phase 1b/2 clinical research in China, targeting patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR mutations who have failed treatment with MET expression of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Preclinical study results showed that RC108 induces tumor-specific adaptive immunity, increases T-cell infiltration into the tumor microenvironment, and PD-1 monoclonal antibodies activate T-cells, enhancing anti-tumor immune responses. Therefore, it is expected that the combination of RC108 and PD-1 antibodies can enhance dendritic cell presentation of tumor antigens and strengthen T-cell killing of tumor cells, resulting in an enhanced synergistic anti-tumor effect. About Sintilimab Sintilimab, marketed as TYVYT® (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells[i]. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials. In China, sintilimab has been approved for seven indications and included in the National Reimbursement Drug List (NRDL) for six indications. The updated NRDL reimbursement scope of TYVYT® (sintilimab injection) include: For the treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma; For the treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma; For the treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations; For the treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer; For the treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment; For the treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy. Additionally, sintilimab has been approved in combination with bevacizumab and chemotherapy (pemetrexed and cisplatin) for the treatment of patients with EGFR-mutated nsqNSCLC who progressed after EGFR-TKI therapy. Besides, two clinical studies of sintilimab have met their primary endpoints: Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma; Phase 3 study of sintilimab monotherapy as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy. About Innovent Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines in the fields of oncology, metabolism, autoimmunity, ophthalmology and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK. Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 35 valuable assets in the fields of cancer, metabolic disorder, autoimmune disease and other major therapeutic areas, with 8 approved products on the market. These include: TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) , Pemazyre® (pemigatinib oral inhibitor), olverembatinib (BCR-ABL TKI) , Cyramza® (ramucirumab) and Retsevmo® (selpercatinib). An additional 3 assets are under NMPA NDA review, 6 assets are in Phase 3 or pivotal clinical trials, and 18 more molecules are in clinical studies. Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Roche, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: . and . Note: TYVYT® (sintilimab injection) is not an approved product in the United States. BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab biosimilar injection) are not approved products in the United States. TYVYT® (sintilimab injection, Innovent) BYVASDA® (bevacizumab biosimilar injection, Innovent) HALPRYZA® (rituximab biosimilar injection, Innovent) SULINNO® (adalimumab biosimilar injection, Innovent) Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan. CYRAMZA® (ramucirumab, Eli Lilly). CYRAMZA® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China. Retsevmo® (Selpercatinib, Eli Lilly). Retsevmo® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China. Disclaimer: Innovent does not recommend any off-label usage. About RemeGen RemeGen Co., Ltd. (RemeGen) is a leading fully integrated biopharmaceutical company in China headquartered in Yantai, Shandong Province, China, and RemeGen has labs/offices in Beijing, Shanghai, California and Maryland. The company is committed to the discovery, development and commercialization of innovative and differentiated biologics for the treatment of autoimmune, oncology and ophthalmic diseases with unmet medical needs in China and globally. Currently, more than 20 biologics candidates are under development, and seven products with more than 20 indications are in clinical trials or have entered the commercialization stage. Among them, the first BLyS/APRIL dual-targeting fusion protein novel biologics globally for the treatment of SLE, Telitacicept was approved for marketing on March 9, 2021; and China's first domestically made antibody-drug conjugate Disitamab Vedotin was approved for marketing on June 8, 2021. RemeGen was listed on the Hong Kong Stock Exchange on November 9, 2020 (stock code: 09995.HK) and on the Science and Technology Board of the Shanghai Stock Exchange on March 31, 2022 (stock code: 688331.SH). Innovent's Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions. SOURCE Innovent Biologics

ImmunotherapyClinical ResultPhase 1Drug ApprovalLicense out/in

22 Mar 2023

·www.businesswire.com

HR Positive/ Her2 Negative Breast Cancer - Pipeline Insight, 2023 - ResearchAndMarkets.com

DUBLIN--( BUSINESS WIRE )--The "HR Positive/ Her2 Negative Breast Cancer - Pipeline Insight, 2023" clinical trials has been added to ResearchAndMarkets.com's offering. This "HR Positive/ HER2 Negative Breast Cancer - Pipeline Insight, 2023" report provides comprehensive insights about 50+ companies and 53+ pipeline drugs in HR Positive/ HER2 Negative Breast Cancer pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. Geography Covered Global coverage HR Positive/ HER2 Negative Breast Cancer: Overview Three common tests employed to test for HER2 levels are chromogenic in situ hybridization (CISH), immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Depending on the levels of HER2 or ERBB2 in the laboratory test breast cancer is classified as HER2 or ERBB2 positive or HER2 negative breast cancer. In HER2 or ERBB2 receptors in a normal breast maintains growth, division and repairing while in HER2 or ERBB2 positive breast cancer over-expression of HER2 or ERBB2 is seen. In case of HER2 negative breast cancer the levels of HER2 protein is in normal. The present goal of therapy for early HR+/HER2- breast cancer (BC) is to optimize disease-free survival (DFS) and overall survival (OS) rates with the currently available therapies while avoiding any relevant long-term sequalae. Local therapies have evolved toward less aggressive techniques (i.e. breast-preserving surgery, sentinel lymph node biopsy and intraoperative radiotherapy), which significantly reduce the long-term sequalae observed with more radical treatments. Endocrine therapy (ET) is still the cornerstone of adjuvant treatment because it significantly reduces BC relapse and mortality. Adjuvant chemotherapy is today recommended only for a particular subset of patients with a high risk of recurrence with ET alone, identified through genomic assays, age and/or disease stage. Bisphosphonates reduce the risk of bone metastasis and produce a slight although statistically significant improvement in survival in postmenopausal women. The CDK 4/6 inhibitor abemaciclib has been recently approved by the US FDA for patients at high risk of relapse. The report outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the HR Positive/ HER2 Negative Breast Cancer pipeline landscape is provided which includes the disease overview and HR Positive/ HER2 Negative Breast Cancer treatment guidelines. The assessment part of the report embraces, in depth HR Positive/ HER2 Negative Breast Cancer commercial assessment and clinical assessment of the pipeline products under development. Report Highlights The companies and academics are working to assess challenges and seek opportunities that could influence HR Positive/ HER2 Negative Breast Cancer R&D. The therapies under development are focused on novel approaches to treat/improve HR Positive/ HER2 Negative Breast Cancer. HR Positive/ HER2 Negative Breast Cancer Emerging Drugs Chapters This segment of the HR Positive/ HER2 Negative Breast Cancer report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases. HR Positive/ HER2 Negative Breast Cancer Emerging Drugs Camizestrant: AstraZeneca Camizestrant is a potent, next-generation oral SERD and pure ER? antagonist, that has demonstrated anti-cancer activity across a range of preclinical models, including those with ER-activating mutations. The asset has been shown to promising anti-tumour profile when administered alone or in combination with palbociclib and thus, the company is running a Phase III trial for the same. Dato-DXd: Daiichi Sankyo, Inc. Datopotamab deruxtecan (Dato-DXd) is an investigational currently in Phase III for HR-positive, HER2- negative breast cancer. It is a TROP2 directed antibody drug conjugate (ADC) designed using Daiichi Sankyo's proprietary DXd ADC technology, datopotamab deruxtecan is one of the three lead ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca's ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads, an exatecan derivative, via tetrapeptide-based cleavable linkers. CX-2009: CytomX Therapeutics CX-2009 is a Probody drug conjugate that consists of a humanized anti-CD166 monoclonal antibody conjugated to DM4, a potent microtubule inhibitor known to be active against multiple cancer types. It is currently being tested in Phase II trial in Advanced HR-Positive/HER2-Negative Breast Cancer and of Praluzatamab Ravtansine as Monotherapy and in Combination with Pacmilimab (CX-072) in Advanced Triple-Negative Breast Cancer. RGT-419B: Regor Therapeutics RGT-419B is a new generation of CDK inhibitor with an optimized kinase activity spectrum. The clinical development program of RGT-419B is designed to address the unmet medical needs of patients who are refractory or have relapsed after previous treatment, providing new opportunities to improve survival and quality of life for patients with advanced/metastatic breast cancer. It is currently being tested in Phase I trial in in subjects with Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Advanced/Metastatic Breast Cancer. HR Positive/ HER2 Negative Breast Cancer: Therapeutic Assessment This segment of the report provides insights about the different HR Positive/ HER2 Negative Breast Cancer drugs segregated based on following parameters that define the scope of the report, such as: Major Players in HR Positive/ HER2 Negative Breast Cancer There are approx. 50+ key companies which are developing the therapies for HR Positive/ HER2 Negative Breast Cancer. The companies which have their HR Positive/ HER2 Negative Breast Cancer drug candidates in the most advanced stage, i.e. phase III include, AstraZeneca. Phases The report covers around 53+ products under different phases of clinical development like Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration HR Positive/ HER2 Negative Breast Cancer pipeline report provides the therapeutic assessment of the pipeline drugs by the Route of Administration. Products have been categorized under various ROAs such as Intra-articular Intraocular Intrathecal Intravenous Ophthalmic Oral Parenteral Subcutaneous Topical Transdermal Molecule Type Products have been categorized under various Molecule types such as Oligonucleotide Peptide Small molecule Product Type Drugs have been categorized under various product types like Mono, Combination and Mono/Combination. HR Positive/ HER2 Negative Breast Cancer: Pipeline Development Activities The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses HR Positive/ HER2 Negative Breast Cancer therapeutic drugs key players involved in developing key drugs. Pipeline Development Activities The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging HR Positive/ HER2 Negative Breast Cancer drugs. HR Positive/ HER2 Negative Breast Cancer Report Insights HR Positive/ HER2 Negative Breast Cancer Pipeline Analysis Therapeutic Assessment Unmet Needs Impact of Drugs HR Positive/ HER2 Negative Breast Cancer Report Assessment Pipeline Product Profiles Therapeutic Assessment Pipeline Assessment Inactive drugs assessment Unmet Needs Key Questions Answered Current Treatment Scenario and Emerging Therapies: How many companies are developing HR Positive/ HER2 Negative Breast Cancer drugs? How many HR Positive/ HER2 Negative Breast Cancer drugs are developed by each company? How many emerging drugs are in mid-stage, and late-stage of development for the treatment of HR Positive/ HER2 Negative Breast Cancer? What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the HR Positive/ HER2 Negative Breast Cancer therapeutics? What are the recent trends, drug types and novel technologies developed to overcome the limitation of existing therapies? What are the clinical studies going on for HR Positive/ HER2 Negative Breast Cancer and their status? What are the key designations that have been granted to the emerging drugs? Key Players Regor Therapeuics Seagen Inc. CytomX Therapeutics Taizhou EOC Pharma Chia Tai Tianqing Pharmaceutical Group AstraZeneca Daiichi Sankyo, Inc. Tyme, Inc. Seagen Inc. Context Therapeutics Eisai Inc. Shanghai Hengrui Pharmaceutical Co., Ltd. Jiangsu Simcere Pharmaceutical Co., Kind Pharmaceuticals Merus N.V. Atossa Therapeutics Roche Ellipses Pharma Key Products RGT-419B SGN-B7H4V CX-2009 EOC202 TQB3616 Camizestrant Dato-DXd SM-88 SGN-B7H4V Onapristone Giredestrant H3B-6545 Z-endoxifen MCLA-128 EP0062 HRS8807 SCR-6852 AND019 For more information about this clinical trials report visit https://www.researchandmarkets.com/r/g7co1l About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

Phase 1Phase 2Phase 3

03 Feb 2023

·www.fiercebiotech.com

Bruised by high profile cancer setbacks, Sanofi CEO plots early-stage path 'back to the magic'

Sanofi will take a “pragmatic” approach to cancer development, said CEO Paul Hudson. Could we see Sanofi give up on cancer? Not according to Paul Hudson, although the CEO admitted that after some struggles with its headline candidates, the French pharma might seek solace earlier in its pipeline. “We have to concede that maybe our efforts are naturally moving towards an earlier oncology positioning,” Hudson said on a fourth-quarter earnings call this morning. “We're doing some very interesting things, setting a very high bar—but it is earlier. So it consumes a little less investment [and] it allows us to allocate more towards the areas where we're having a really important effect.” Hudson referenced “the setback with amcenestrant,” an oral selective estrogen receptor degrader (SERD) that Sanofi decided to drop in August after getting a look at a phase 3 interim analysis. Another of the Big Pharma’s cancer bets, an IL-2 molecule dubbed SAR444245, has been pushed back from phase 2 to a phase 1/2 trial after posting lower-than-expected efficacy data. “With our IL-2 retreating to phase 1/2 on the dose interval, we may yet still come back and say something very meaningful with the interval reduction, what that means in efficacy,” he explained on the call. “The ability to reduce the interval was one of the reasons why we took the decision to invest in it in the first place.” Sanofi won’t keep a foot in the oncology space solely for historic reasons, the CEO said, pointing to the company’s decision to walk away from diabetes R&D. Instead, the Big Pharma will take a “pragmatic” approach to cancer development. “So we may go back to the magic a bit earlier in oncology,” he added. The company’s cancer pipeline is already heavily weighted to early-stage. Its phase 3 oncology programs all center around new indications for approved immunotherapy Sarclisa or a phase 3 trial for the antibody-drug conjugate tusamitamab ravtansine. An interim analysis of the tusamitamab trial in non-small cell lung cancer is due in the second half of the year. In contrast, Sanofi lists 11 different candidates in phase 1 development for cancer indications, including an mRNA therapy in partnership with BioNTech and SAR446309, a HER2 T-cell engager brought on board as part of the $1 billion acquisition of Amunix. One area where Sanofi does remain “very excited”—in the words of Sanofi’s R&D head John Reed—is natural killer (NK) cell engagers. Sanofi, which bought allogeneic or "off-the-shelf" NK cell platform developer Kiadis for $358 million back in 2020, recently went back for a second helping of its NK cell engager collaboration with Innate Pharma. Despite Senti Bio and Fate Therapeutics culling some NK programs in recent weeks, Reed remained upbeat about Sanofi’s offering. “It's early days…and we hope to have a lot more to say about it as we approach the end of this year,” Reed added.

Phase 3Phase 1AcquisitionImmunotherapy

100 Deals associated with Anetumab ravtansine

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Phase 2	PL	Bayer AG	03 Jun 2019
Solid tumor	Phase 2	IT	Bayer AG	03 Jun 2019
Solid tumor	Phase 2	US	Bayer AG	03 Jun 2019
Solid tumor	Phase 2	FR	Bayer AG	03 Jun 2019
Epithelioid mesothelioma, malignant	Phase 2	US	Bayer AG	03 Feb 2016
Epithelioid mesothelioma, malignant	Phase 2	IT	Bayer AG	03 Feb 2016
Mesothelin positive Solid Tumors	Phase 2	IT	Bayer AG	03 Feb 2016
Mesothelin positive Solid Tumors	Phase 2	US	Bayer AG	03 Feb 2016
Neoplasms	Phase 2	JP	Bayer AG	14 Aug 2015
Advanced Malignant Solid Neoplasm	Phase 2	US	Bayer AG	07 Sep 2011

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03126630 (CTgov)	Phase 1/2	Malignant Pleural Mesothelioma	49	Pharmacological Study+pembrolizumab (Group I (Pembrolizumab))	jpzrautbaw(oryqadeyta) = frutrbxubw tqppajlkdg (evlrobzlke, tctuzijgso - yowfvrgoil) View more	-	16 Oct 2024
NCT03126630 (CTgov)	Phase 1/2	Malignant Pleural Mesothelioma	49	Pharmacological Study+Anetumab Ravtansine+pembrolizumab (Group II (Anetumab Ravtansine, Pembrolizumab))	jpzrautbaw(oryqadeyta) = qaycrbszgx tqppajlkdg (evlrobzlke, wkivtbmjxb - hadwihyihm) View more	-	16 Oct 2024
NCT03126630 (WCLC2023) Manual	Phase 1/2	Malignant Pleural Mesothelioma Mesothelin Positive	35	Anetumab ravtansine + Pembrolizumab	vmpqhuihuc(yosougvdre) = gkrcwivlot yvcbozthpt (bgqjotuxdm ) View more	Negative	10 Sep 2023
NCT03126630 (WCLC2023) Manual	Phase 1/2	Malignant Pleural Mesothelioma Mesothelin Positive	35	Pembrolizumab	vmpqhuihuc(yosougvdre) = pizlzjuxgv yvcbozthpt (bgqjotuxdm ) View more	Negative	10 Sep 2023
NCT03926143 (CTgov)	Phase 2	Solid tumor	9	Anetumab Ravtansine	dcduqupfex(bmxgermwro) = zpasbdsknx wetgvrdpdo (vpqjhbicmc, mfvgqkztke - ooukpeykqu) View more	-	04 Aug 2023
NCT03587311 (NCI 10150, ASCO2022)	Phase 2	Platinum-Resistant Ovarian Carcinoma	57	Anetumab ravtansine (AR) + bevacizumab (ARB)	(epbnmagiqs) = ljtabaombo jencppmjvd (qfsqvjrial ) View more	Negative	02 Jun 2022
NCT03587311 (NCI 10150, ASCO2022)	Phase 2	Platinum-Resistant Ovarian Carcinoma	57	Weekly paclitaxel + bevacizumab (PB)	(epbnmagiqs) = hzqyqbimpb jencppmjvd (qfsqvjrial ) View more	Negative	02 Jun 2022
IGCS2020	Phase 1	Platinum-Resistant Primary Peritoneal Carcinoma mesothelin-positive	65	Anetumab ravtansine	(uatjvvlufy) = drlquyesme tsawuqgjfl (bxpblavysl, 16.0–38.5) View more	-	13 Nov 2020
IGCS2020	Phase 1		65	Pegylated liposomal doxorubicin	(ulnebuyqxk) = sutpcsmcab inhdclvrbj (prujyjunxw )	-	13 Nov 2020
NCT01439152 (Pubmed \| J Urol) Manual	Phase 1	Solid tumor	116	Anetumab Ravtansine	(kbkopgftry) = uuyqlxdbks jltlyqhdiu (jwwhnojgjh ) View more	Positive	01 Jun 2020
NCT03455556 (CTgov)	Phase 1	Non-small cell lung cancer stage IIIA \| Non-small cell lung cancer stage IIIB \| Advanced Lung Non-Small Cell Carcinoma	1	Laboratory Biomarker Analysis+Anetumab Ravtansine+Atezolizumab	afkvjcvkre(xppgnldgpw) = rcsnmiadfa frmabdcubf (jcqoczxsyw, grulwkyfbg - pwyruweuvw) View more	-	15 May 2020
NCT02839681 (CTgov)	Phase 2	Lung Cancer \| Adenocarcinoma of Lung	2	Blood test+Anetumab Ravtansine	(rfyzqtleaj) = okrkyyhmlz vhbwtmskbg (vkybnadvhf, igfdkqyysu - lhnxikkhsw) View more	-	21 May 2019
NCT01439152 (ASCO2016)	Phase 1	Mesothelin positive Neoplasms	147	Anetumab ravtansine (AR)	udlnifyrfq(ecpijwryde) = Adverse events (AEs) were similar to the mesothelin-ADC inhibitor class, including reversible keratopathy, asymptomatic liver function test increases, and gastrointestinal disorders msjvgqyvhp (nfjvxyyejn ) View more	Positive	20 May 2016
AACR2013	Phase 1	HR-positive/HER2-low Solid Tumors	32	BAY 94-9343	(gyhkvzamqk) = cfionlefof lwmhvcrojv (hnqiyjbtql ) View more	-	15 Apr 2013

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