Linperlisib

Linperlisib achieved Overall Response Rate of 48% with 30% being Complete Response and manageable safety profile in the r/r PTCL phase 2 study SHANGHAI and SAN FRANCISCO, Dec. 11, 2023 /PRNewswire/ -- Shanghai Yingli Pharmaceutical Co., Ltd. (" Yingli Pharma"), a biopharmaceutical company focused on developing oral therapies for cancer and metabolic diseases, today announced the pivotal Phase 2 clinical trial results of the investigation of linperlisib in the treatment of patients with relapsed or refractory (r/r) peripheral T-cell lymphoma (PTCL). Linperlisib is a phosphoinositide 3-kinase delta (PI3Kδ) oral inhibitor, approved in China for treatment of patients with r/r follicular lymphoma after systemic therapy. "There is a vital need for new therapies to treat highly aggressive cancers such as r/r PTCL where there are very limited treatment options." said Dr. Jun Zhu, Professor, Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China, who was the leading investigator for this pivotal clinical trial. "In addition to the promising efficacy and well manageable safety of linperlisib in r/r PTCL, it is noteworthy that a high proportion of the treated patients were shown to have a complete response, and responses have been seen in all the major PTCL subtypes." "Our approach is to develop novel oral agents that will allow patients to safely administer at home," said Michael Hui, CEO of Yingli Pharma, "We are delighted that the encouraging results of this study support the use of linperlisib in this hard-to-treat disease and are excited to continue developing linperlisib in more indications. The company has applied for linperlisib marketing approval in r/r PTCL in China based on these pivotal study findings." Mr. Hui added, "We look forward to the results of an ongoing open-label multi-center Phase 2 study in the U.S. and Italy in r/r PTCL and r/r CTCL." Safe and effective treatment of r/r PTCL patients The pivotal r/r PTCL Phase 2 clinical trial enrolled 98 patients (pts) from May 2021 to October 2022 at 25 clinical sites in China. The pts had a median of two lines of prior systemic therapies. Sixty-four pts (73%) had refractory disease, 59 pts (67%) had relapsed disease, and 35 pts (40%) had both relapsed and refractory diseases. All patients received linperlisib at 80 mg QD, the RP2D for the drug, with a minimum of 6 months follow-up. The linperlisib-treated patients (Full Analysis Set N = 88) evaluated by Lugano criteria, had a 48% overall response rate, including 30% complete responses and 18% partial responses, as well as a 68% disease control rate. The median Duration of Response was not reached although the 6-month DOR rate was 75%. The median PFS was 5.5 months (95% CI, 3.5, 15.6) and the median OS was 14.2 months (95%CI, 7.9, not reached). Responses were observed across PTCL subtypes. Linperlisib was well tolerated with a differentiated and manageable safety profile, specifically having very low levels of immune-mediated toxicities. In the linperlisib-treated patient safety dataset (N=98) for the pivotal study, the most common hematologic treatment related adverse events (TRAEs) of Grade≥3 were neutropenia (32%), leukocytopenia (10%), Anemia (6%), Thrombocytopenia (5%), and Lymphocytopenia (5%). The most common nonhematologic TRAEs of Grade≥3 were pneumonia (14%) and upper respiratory tract infection (5%). Immune-mediated Grade≥3 TRAEs including elevated ALT, AST, diarrhea, colitis, rash were not reported or were <5%. Nine patients (9.2%) discontinued from the study due to various adverse events. The safety results of this study were consistent with previously reported data in other linperlisib clinical studies. About linperlisib Linperlisib, a next-generation PI3K-selective oral inhibitor, received marketing approval in China in 2022 for treatment of patients with relapsed and/or refractory follicular lymphoma after two or more systemic therapies. Linperlisib also received U.S. FDA Orphan Drug Designations for follicular lymphoma, chronic lymphocytic leukemia, and T cell lymphomas. Linperlisib is under investigation in multiple additional clinical trials as a monotherapy: frontline PTCL, r/r large granular T lymphocytic leukemia, r/r autoimmune hemolytic anemia; and in combination with other agents: in second line follicular lymphoma and marginal zone lymphoma, frontline PTCL, and r/r CTCL. In the U.S. and EU, linperlisib is being developed by 280Bio, Inc (San Francisco, CA., USA), a wholly-owned subsidiary of Yingli Pharma, in a Phase 2 clinical study in r/r T Cell Lymphomas [PTCL and CTCL]. About Yingli Pharma Shanghai Yingli Pharmaceutical Co., Ltd., founded in 2011 and located in the National Biomedical Industry Base of Shanghai Zhangjiang InnoPark, is a clinical-stage biotechnology company developing oral drugs for oncology and metabolic diseases. Yingli Pharma has partnered with Jiangsu Hengrui Pharmaceuticals Co., Ltd., for Greater China commercialization of linperlisib (Intarel®) in r/r follicular lymphoma that is conditionally approved, and other heme indications. Yingli Pharma is currently developing other oral agents in clinical stage from its oncology portfolio, including YL-13027 (TGFR1 inhibitor), YL17231 (pan-RAS inhibitor), YL-15293 (KRASG12C inhibitor), as well as a rich pipeline of additional novel oral agents in oncology. 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SAN FRANCISCO, Sept. 3, 2022 /PRNewswire/ -- Yingli Pharma (the "Company" or "Yingli"), a clinical stage biotechnology company developing oral small molecule drugs for cancers with high unmet need, announced today that the first patient has been dosed in a Phase 2 trial evaluating linperlisib, a potent inhibitor of the delta isoform of PI3 kinase (PI3Kδ) in patients with relapsed/refractory peripheral T/NK cell lymphoma (r/r PTCL). This single arm study will evaluate the safety, efficacy and pharmacokinetics of orally administered linperlisib under a strategic collaboration with The University of Texas MD Anderson Cancer Center. Additional trial sites will include medical centers in the United States and Italy. "We are pleased to commence this study of linperlisib in the United States in patients suffering from advanced PTCL," said Michael Hui, MBA, chief executive officer of Yingli. "Linperlisib is a next generation inhibitor of PI3Kδ with enhanced selectivity and potency to offer strong anti-tumor effect while minimizing potential adverse reactions. We are encouraged by the safety and preliminary efficacy data obtained in Phase 1 dose-finding studies in China and look forward to further evaluating linperlisib's potential in this Phase 2 study." "Patients living with advanced PTCL, an aggressive type of lymphoma, face limited treatment options and most do not respond or stop responding to available therapies. Linperlisib may provide a solution for these patients who need an expanded treatment armamentarium, and we're excited to continue studying the drug's potential as we start the Phase 2 study." Linperlisib, a convenient once daily oral drug, is a small molecule inhibitor of PI3Kδ, a validated target in lymphomas due to its critical role in cell proliferation and survival. This Phase 2 (NCT05274997), single arm, open-label trial will evaluate the safety, efficacy and pharmacokinetic properties of linperlisib monotherapy in adult patients with r/r PTCL who have failed at least one prior line of systemic therapy. Enrolled participants will receive linperlisib 80mg once daily orally in a 28-day cycle. The primary outcome is overall response rate to treatment. Secondary outcomes include duration of response, overall survival, progression-free survival, adverse effects and pharmacokinetics parameters. An estimated 97 patients will be enrolled in the study. About Linperlisib Linperlisib (YY-20394) is a highly selective and potent PI3Kδ inhibitor that has shown a favorable safety profile, encouraging anti-tumor activities and promising PK and pharmaceutical properties as an oral once-a-day agent in late-stage clinical development. A Phase 1 clinical trial was completed in 2020 demonstrating linperlisib to be a safe and tolerable agent, and a recommended Phase 2 dose of 80 mg QD was established. Linperlisib was awarded NMPA Breakthrough Therapy status in China, leading to a Phase 2 study in follicular lymphoma (FL) that was completed and submitted in 2021 to China marketing authority for approval. In addition, linperlisib received FDA Orphan Drug Designations for FL, CLL/SLL and T cell lymphoma. Multiple linperlisib clinical trials in FL, PTCL, other lymphomas, solid tumors, combination with gemcitabine/oxaliplatin in r/r DLBC and combination with therapeutic PD1 antibody are underway in China. Preliminary results of single agent linperlisib from a relapsed or recurrent PTCL Phase1b study were reported at ASCO 2021, indicating an overall response rate of 70% with 33% CRs for this difficult to treat and aggressive form of lymphoma. About Yingli Pharma Yingli Pharma is developing oral small molecule drugs with first-in-class or best-in-class potential for cancers with high unmet need. In addition to linperlisib, Yingli's clinical stage portfolio under development in U.S. and China also includes YL-13027, a TGFbeta Receptor 1 small molecule antagonist, currently in Phase 1, and YL-15293, a KRAS G12C inhibitor in Phase 1 studies that are part of a precision medicine program targeting oncogene drivers in cancer. Yingli is advancing several early-stage precision therapy programs leading to IND-enabling studies this year. For more information, visit http://www.yl-pharma.com