A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL

This study includes 2 parts: phase 1 (dose escalation) and phase 2 (dose expansion). In phase
1, patients will be enrolled using an accelerated titration design. The starting dose of
LOXO-305 in oral tablet form is 25 mg/day (e.g., 25 mg once daily [QD]). Once the MTD and/or
RP2D is identified, patients will be enrolled to one of six phase 2 dose expansion cohorts
depending on tumor histology, tumor genotype, and prior treatment history. Cycle length will
be 28 days.

Inclusion Criteria:

- Histologically confirmed CLL/SLL or NHL intolerant to standard of care therapies.

- Histologically confirmed CLL/SLL or NHL which has failed standard of care therapies

- ≥ 2 prior lines of therapy.

- No more than 2 lines of prior chemotherapy-containing treatment regimens for initial
phase 1 patients then no restriction.

- For initial phase 1 patients, able to tolerate potentially subtherapeutic doses of
LOXO-305 for the 28-day DLT window in the opinion of the investigator and with
documented sponsor approval.

- Eastern Cooperative Oncology Group (ECOG) 0-2.

- Adequate hematologic, hepatic and renal function.

- Ability to receive study drug therapy orally.

- Willingness of men and women of reproductive potential to observe conventional and
effective birth control.

Exclusion Criteria:

- Transformation (e.g., Richter's transformation, prolymphocytic leukemia, transformed
NHL, blastoid lymphoma) prior to planned start of LOXO-305.

- Investigational agent or anticancer therapy within 2 weeks prior to planned start of
LOXO-305. In addition, no concurrent investigational therapy is permitted.

- Major surgery within 4 weeks prior to planned start of LOXO-305.

- Radiotherapy with a limited field of radiation for palliation within 7 days of the
first dose of study treatment.

- Pregnancy or lactation.

- Patients requiring therapeutic anticoagulation.

- Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2
or greater at the time of starting study treatment except for alopecia.

- History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen
receptor-modified T-cell (CAR-T) therapy within the past 100 days (180 days before the
PK trigger).

- Known central nervous system (CNS) involvement by lymphoma.

- Active uncontrolled auto-immune cytopenia.

- Clinically significant, uncontrolled cardiac, cardiovascular disease or history of
myocardial infarction within 6 months prior to planned start of LOXO-305.

- Active uncontrolled systemic bacterial, viral, fungal or parasitic infection.

- Tested positive for Human Immunodeficiency Virus (HIV) is excluded.

- Clinically significant active malabsorption syndrome.

- Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or
inducers.

- Treatment with proton pump inhibitors (PPIs) within 7 days of starting LOXO-305.

Active second malignancy unless in remission and with life expectancy > 2 years.