FCN-338 / Fosun Pharma - LARVOL DELTA

BCL-2 inhibition in Waldenström macroglobulinaemia and marginal zone lymphoma. (PubMed, Br J Haematol) - "We also summarize the preclinical and ongoing clinical experience with BCL-2 inhibitors, such as venetoclax, sonrotoclax, lisaftoclax and LOXO-338. BCL-2 inhibitors have emerged as safe and effective treatment options for treating patients with MZL and WM."

Journal • Review • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

PHASE 1 STUDY OF FCN-338, A NOVEL BCL-2 INHIBITOR IN RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA: SAFETY, PHARMACOKINETICS, AND PRELIMINARY EFFICACY (EHA 2025) - P1 | "FCN-338, a highly selective BCL-2 inhibitor, was well tolerated and showed promising antitumor activity in patients with R/R CLL/SLL. The dose of 400 mg QD warrants future Phase II investigation. Clinical trial information: CTR20202378, NCT04682808."

Clinical • P1 data • PK/PD data • Anemia • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Thrombocytopenia • BCL2L1

FCN-338 in Combination With Azacitidine or Chemotherapy in Myeloid Neoplasms (clinicaltrials.gov) - P2 | N=47 | Active, not recruiting | Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

New P2 trial • Oncology

A First-in-Human Phase I Study of LOXO-338, an Oral Selective Bcl-2 Inhibitor, in Patients With Advanced Hematologic Malignancies. (PubMed, Clin Lymphoma Myeloma Leuk) - P1 | "LOXO-338 was well tolerated with a favorable safety profile in previously treated patients with advanced hematologic malignancies. Preliminary efficacy was observed in this heavily pretreated population supporting further investigation."

Journal • P1 data • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Thrombocytopenia • BCL2 • BCL2L1

A first-in-human Phase 1 study of LOXO-338, an oral selective Bcl-2 inhibitor, in patients with advanced hematologic malignancies (Clin Lymphoma Myeloma Leuk) - P1 | N=316 | NCT05024045 | Sponsor: Eli Lilly and Company | "In total, 27 patients with CLL/SLL (n=10) or NHL (n=17) were treated. No dose-limiting toxicities occurred and the MTD was not reached. Treatment-emergent adverse events occurred in 23 patients (85%); anemia (22%) and fatigue (22%) were the most prevalent. Treatment-related adverse events (TRAEs) occurred in 15% and were mostly grade 1 (11%) or 2 (4%); grade ≥3 or serious TRAEs were not reported. Tumor lysis syndrome was not observed. The overall response rate was 19% (95% CI: 6.3, 38.1) and disease control rate was 67% (95% CI: 46, 83.5). LOXO-338 was orally bioavailable with dose-dependent increases in exposure."

P1 data • Chronic Lymphocytic Leukemia • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma

LOXO-BCL-20001: Study of Oral LOXO-338 in Patients With Advanced Blood Cancers (clinicaltrials.gov) - P1 | N=316 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2024 ➔ Dec 2025

Metastases • Trial completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

A Study of FCN-338 in Patients With Chronic CLL/SLL (clinicaltrials.gov) - P1 | N=99 | Active, not recruiting | Sponsor: Fochon Pharmaceuticals, Ltd. | Trial completion date: Jun 2024 ➔ Dec 2024 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

LOXO-BCL-20001: Study of Oral LOXO-338 in Patients With Advanced Blood Cancers (clinicaltrials.gov) - P1 | N=316 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2023 ➔ Dec 2024

Metastases • Trial completion date • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

A FIRST-IN-HUMAN PHASE 1 STUDY OF ORAL LOXO-338, A SELECTIVE BCL2 INHIBITOR, IN PATIENTS WITH ADVANCED HEMATOLOGIC MALIGNANCIES (EHA 2023) - P1 | "LOXO-338 also demonstrated dose-dependent tumor growth inhibition in various murine xenograft models, and showed improved efficacy in combination with pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor (Brandhuber B. et al. LOXO-338 demonstrated a favorable safety profile and was well tolerated at tested dose levels. Preliminary efficacy was observed with LOXO-338 monotherapy in patients with CLL/SLL. BCL2, B-CLL, Waldenstrom's macroglobulinemia, B cell lymphoma"

Clinical • Metastases • P1 data • Anemia • Bone Marrow Transplantation • Chronic Lymphocytic Leukemia • Fatigue • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • Transplantation • Waldenstrom Macroglobulinemia • BCL2L1

Emerging BCL 2 Inhibitors (SOHO 2023) - P1, P1/2, P1a/1b, P1b/2, P2 | "Among 52 patients with hematological malignancies the maximum tolerated dose (MTD) was not reached and no clinical TLS was observed.20 In this study of 22 evaluable patients with RR CLL there was an overall response rate (ORR) of 63.6% (14/22).20 A larger study of 114 patients with RR CLL evaluated lisaftoclax in combination with either the Bruton's tyrosine kinase inhibitor (BTKi) acalabrutinib or the anti CD20 monoclonal antibody rituximab (NCT04215809)...In CLL an overall response rate (ORR) to BGB-1147 of 100% as monotherapy was observed among 8 patients with RR disease.25 In 12 patients with RR MM, the ORR to BGB-1147 in combination with dexamethasone varied from 0–68% depending on the dose cohort.26 In combination with azacytidine in AML the ORR to BGB-11417 was 74% among those with treatment naïve (TN) disease (n=20/27) and 65% (n=13/20) in the cohort with RR disease.27 BGB-11417 monotherapy in 23 patients with RR NHL..."

IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Myelofibrosis • Non-Hodgkin’s Lymphoma • Oncology • Prolymphocytic Leukemia • Waldenstrom Macroglobulinemia • BCL2L1

LOXO-BCL-20001: Study of Oral LOXO-338 in Patients With Advanced Blood Cancers (clinicaltrials.gov) - P1 | N=316 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Apr 2024 ➔ Dec 2023 | Trial primary completion date: Apr 2024 ➔ May 2023

Metastases • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

A first-in-human phase 1 study of oral LOXO-338, a selective BCL2 inhibitor, in patients with advanced hematologic malignancies (trial in progress). (ASCO 2022) - P1 | "Secondary objectives include determining the safety profile, PK, and preliminary efficacy of LOXO-338 administered alone and in combination with pirtobrutinib. Antitumor activity will be evaluated based on overall response rate (ORR), progression-free survival (PFS), time to progression (TTP) and duration of response (DOR) according to disease-specific response criteria."

Clinical • P1 data • Amyloidosis • Bone Marrow Transplantation • Burkitt Lymphoma • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Thrombocytopenia • Transplantation • Waldenstrom Macroglobulinemia • BCL2L1

LOXO-BCL-20001: Study of Oral LOXO-338 in Patients With Advanced Blood Cancers (clinicaltrials.gov) - P1 | N=316 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

A First-in-Human Phase 1 Study of Oral LOXO-338, a Selective BCL2 Inhibitor, in Patients with Advanced Hematologic Malignancies (Trial in Progress) (ASH 2021) - "The BCL2 inhibitor venetoclax is approved for the treatment of CLL/SLL and acute myeloid leukemia and has activity in other lymphoid malignancies. Antitumor activity will be evaluated based on overall response rate (ORR), progression-free survival (PFS), time to progression (TTP) and duration of response (DOR) based on disease-specific response criteria per investigator assessment. Key objectives of part 2 are to determine the safety profile and tolerability, PK properties, and anti-tumor activity of LOXO-338 in combination with pirtobrutinib."

Clinical • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Burkitt Lymphoma • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma • Oncology • Richter's Syndrome • Thrombocytopenia • Transplantation • Waldenstrom Macroglobulinemia • BCL2L1

A FIRST-IN-HUMAN PHASE 1 STUDY OF ORAL LOXO-338, A SELECTIVE BCL2 INHIBITOR, IN PATIENTS WITH ADVANCED HEMATOLOGIC MALIGNANCIES (TRIAL IN PROGRESS) (EHA 2022) - P1 | "LOXO-338 also demonstrated dose-dependent tumor growth inhibition in various murine xenograft models, and showed improved efficacy in combination with pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor (Brandhuber et al. Antitumor activity will be evaluated based on overall response rate (ORR), progression-free survival (PFS), time to progression (TTP) and duration of response (DOR) based on disease-specific response criteria per investigator assessment. Results N/A Conclusion N/A"

Clinical • P1 data • Amyloidosis • Bone Marrow Transplantation • Burkitt Lymphoma • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Thrombocytopenia • Transplantation • Waldenstrom Macroglobulinemia • BCL2L1

A first-in-human phase 1 study of oral LOXO-338, a selective BCL2 inhibitor, in patients with advanced hematologic malignancies (trial in progress) (IMW 2022) - P1 | "The primary objectives of Part 1 are to determine the RP2D of oral LOXO-338 monotherapy and LOXO-338 in combination with pirtobrutinib for previously treated pts and to evaluate the antitumor activity in pts with WM and AL amyloidosis. Secondary objectives include assessment of the safety profile and tolerability, pharmacokinetic characteristics, and antitumor activity of LOXO-338 monotherapy and in combination with pirtobrutinib based on investigatorassessed overall response rate (ORR), progression-free survival (PFS), time to progression (TTP) and duration of response (DOR) as per disease-specific response criteria."

Clinical • P1 data • Amyloidosis • Bone Marrow Transplantation • Burkitt Lymphoma • Cardiovascular • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Thrombocytopenia • Transplantation • Waldenstrom Macroglobulinemia • BCL2L1

Fosun Pharma (02196): “FCN-338 tablets“ developed by Fosun Pharma was approved by the State Food and Drug Administration to carry out clinical trials [Google Translate] (jrj.com) - “Zhitong Finance A PP News, Fosun Pharma (02196) issued an announcement that recently, Chongqing Fuchuang Pharmaceutical Research Co., Ltd. (Fochuang Pharmaceutical), a holding subsidiary of the company, received approval from the National Medical Products Administration for the FCN-338 tablets developed by it. (Specifications: 10mg, 25mg, 100mg) Approval for clinical trials of relapsed or refractory B-cell lymphoma. Fuchuang Pharmaceutical intends to carry out a phase I clinical trial of the new drug in China (excluding Hong Kong, Macao and Taiwan regions, the same below) when the conditions are met in the near future.”

New P1 trial • Hematological Malignancies • Lymphoma • Oncology

Study of Oral LOXO-338 in Patients With Advanced Blood Cancers (clinicaltrials.gov) - P1; N=286; Recruiting; Sponsor: Eli Lilly and Company; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

Study of Oral LOXO-338 in Patients With Advanced Blood Cancers (clinicaltrials.gov) - P1; N=286; Not yet recruiting; Sponsor: Eli Lilly and Company

Clinical • New P1 trial • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia

[VIRTUAL] Preclinical characterization of LOXO-338, a novel, oral and selective BCL2 inhibitor (AACR 2021) - "Venetoclax is the only FDA-approved BCL2 inhibitor, indicated for use in CLL/SLL and acute myeloid leukemia (AML). This preclinical profile of LOXO-338 supports its nomination as a novel BCL2 inhibitor clinical candidate. A first-in-human Phase 1 clinical trial is planned for 2021."

Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Burkitt Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lung Cancer • Lymphoma • Multiple Myeloma • Neuroendocrine Tumor • Non-Hodgkin’s Lymphoma • Oncology • Small Cell Lung Cancer • Solid Tumor • BCL2L1

Lilly Announces Details of Presentations at 2021 American Association for Cancer Research (AACR) (PRNewswire) - "Lilly Oncology will present data from a study exploring safety and efficacy of its selective RET-kinase inhibitor Retevmo® (selpercatinib, 40 mg & 80 mg capsules) in patients with rearranged during transfection (RET) fusion-positive cancers outside of lung and thyroid cancer. Additionally, Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company, will present preclinical characterization data for an oral selective estrogen receptor degrader (SERD), BCL2 inhibitor, next-generation KRAS-G12C inhibitor, and next-generation RET inhibitor."

P1/2 data • P3 data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma

A Study of FCN-338 in Patients With Chronic CLL/SLL (clinicaltrials.gov) - P1; N=79; Recruiting; Sponsor: Fochon Pharmaceuticals, Ltd.

Clinical • New P1 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Lilly snags Fosun Pharma’s Bcl-2 inhibitor in USD 440m deal (GBI Health) - "China-based Shanghai Fosun Pharmaceutical (Group) Co., Ltd...announced a licensing agreement with US major Eli Lilly in relation to FCN-338, a selective B-cell lymphoma 2 (Bcl-2) small-molecule inhibitor developed in-house by Fosun subsidiary Fochon Pharmaceuticals Ltd. Lilly will take exclusive development, manufacturing and commercialization rights to the product outside of China mainland, Hong Kong, and Macau. Fosun will be paid USD 40 million upfront, USD 340 million in clinical development milestone payments and another USD 60 million in marketing milestone payments for a deal total of USD 440 million."

Licensing / partnership • Oncology