Ph1 Study of LOXO-338 in Advanced Hematologic Malignancies Patients

• Research type

  Research Study

• Full title

  A Phase 1 Study of Oral LOXO-338, a Selective BCL-2 Inhibitor, in Patients with Advanced Hematologic Malignancies

• IRAS ID

  1005126

• Contact name

  Yolanda Villalobos

• Contact email

  yvillalobos@loxooncology.com

• Sponsor organisation

  Eli Lilly and Company

• Eudract number

  2021-000060-30

• Clinicaltrials.gov Identifier

  NCT05024045

• Research summary

  Advanced haematologic malignancies (cancers of the blood, bone marrow and lymph nodes) represent a diverse collection of diseases including chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), non-Hodgkin lymphoma (NHL), Waldenström macroglobulinemia (WM) and multiple myeloma (MM). These cancers are often dependent on a protein called B-cell lymphoma-2 (BCL-2). Advanced haemotologic malignancies have proven very difficult to treat and remain an area of a significant unmet medical need.

  LOXO-BCL-20001 is a two-part, non-randomised, open-label, multicentre study evaluating oral administration of LOXO-338 in patients with advanced haematologic malignancies who have been previously treated with standard therapy for their underlying malignancy. This study has two-parts: Part 1 will evaluate LOXO-338 as monotherapy. Part 2 will evaluate the combination of LOXO-338 with BTK inhibitor, pirtobrutinib.
  
  LOXO-338 is a BCL-2 inhibitor designed to block the function of BCL-2 in advanced haematologic malignancies.
  LOXO-338 (either alone or with pirtobrutinib) will be administered in cycles defined as 28 days. In both parts of the study there will be parallel groups for flat dose LOXO-338 administration and an escalating dose of LOXO-338.

  The primary objective of Part 1 is to determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of oral LOXO-338 in patients with previously treated CLL/SLL or other non-Hodgkin lymphomas (NHLs) and B-cell malignancies. Also, to determine the effect of LOXO-338 on response rates in Waldenström macroglobulinemia (WM) and hematologic response rates in AL amyloidosis.

  The primary objective of Part 2 is to determine the safety profile and tolerability of LOXO-338 when given in combination with pirtobrutinib in patients with previously treated:
  o CLL/SLL
  o Other NHLs and other protocol allowed B-cell malignancies

  Approximately 316 patients will participate in the study globally.

• REC name

  West of Scotland REC 1

• REC reference

  22/WS/0133

• Date of REC Opinion

  29 Sep 2022

• REC opinion

  Further Information Unfavourable Opinion