LOXO-BCL-20001

This is an open-label, multi-center Phase 1 study of LOXO-338 in patients with advanced hematologic malignancies who have received standard therapy. This study will be conducted in 2 parts. Part 1 will evaluate LOXO-338 as monotherapy. If safety and initial evidence of efficacy of LOXO-338 monotherapy are confirmed, Part 2 will evaluate the combination of LOXO-338 with LOXO-305.

Inclusion Criteria

1. B-cell malignancy
2. Prior therapy:
   1. CLL/SLL, MCL, or WM: received at least 2 prior lines of therapy
   2. Other NHL or MM: have failed standard therapy and, in the opinion of the investigator, have no options available known to provide benefit for the patient’s condition
3. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–2

Exclusion Criteria

1. Known or suspected history of central nervous system (CNS) involvement
2. History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T cell (CAR-T) therapy within the past 60 days
3. Known Human Immunodeficiency Virus (HIV) positive, regardless of CD4 count. Unknown or negative status eligible

Study Requirements

Part 1: LOXO-338 Monotherapy

• To determine the MTD/RP2D of oral LOXO-338 in patients with previously treated:
  • CLL/SLL o
  • Other NHLs

  Part 2: LOXO-338 and LOXO-305 Combination

• To determine the safety profile and tolerability of LOXO-338 when given in combination with LOXO-305 in patients with previously treated
  • CLL/SLL
  • oother NHLs and other protocol allowed B-cell malignancies including multiple myeloma (MM)

There will be:

• Appropriate laboratories to monitor electrolytes including phosphate, calcium, uric acid, andcomplete blood count (CBC)
• Safety observations including physical examination, assessment of vital signs including bodyweight, ECOG PS, clinical AEs, laboratory variables (hematology, serum or plasma chemistries,and urinalysis), and electrocardiograms (ECGs)