A Phase 1/2 Study of IDP-121 in Patients With Relapsed/Refractory Hematologic Malignancies

Inclusion Criteria:

1. Age ≥18 years

2. Performance status (ECOG) ≤ 2

3. Life expectancy ≥3 months

4. Patient is, in the investigator's opinion, willing and able to comply with theprotocol requirements.

5. Patient has given voluntary written informed consent before performance of anystudy-related procedure not part of normal medical care, with the understanding thatconsent may be withdrawn by the patient at any time without prejudice to theirfuture medical care.

6. Patients diagnosed with chronic lymphocytic leukemia (CLL), B-cell lymphomas, andmultiple myeloma (MM) who are ineligible to reveive the available treatments.

7. Adequate hematological or biochemical parameters as specified below

8. Hemoglobin > 8.0 g/dl (without transfusion support within 7 days)

9. Platelets count > 75 x109/L (without transfusional support within 7 days). Inpatients with bone marrow infiltration, the platelets count may be ≥50 x109/L.

10. Absolute neutrophil count (ANC) > 0.75 x109/L (without G-CSF support within 7days)

11. Aspartate transaminase (AST): <2.5 x the upper limit range (in patients with noliver metastases or <5 x ULN in patients with liver metastases)

12. Alanine transaminase (ALT): < 2.5 x the upper limit range (in patients with noliver metastases or <5 x ULN in patients with liver metastases)

13. Total bilirubin: < 2 x the upper limit range.

14. Calculated or measured creatinine clearance: >30 mL/min (calculated from theCockcroft-Gault formula).

15. Left ventricular ejection fraction > 50% or above the Institutional Lower Limit ofNormal (LLN), whichever is lower, determined by echocardiogram.

Exclusion Criteria:

1. Persistent clinically significant non-hematological toxicity related to previoustreatments. The presence of alopecia and NCI-CTC grade <2 symptomatic peripheralneuropathy is allowed.

2. Pregnant or lactating women; men and women of reproductive potential* (as defined inthe Appendix 2) who are not using effective contraceptive methods (combined hormonalcontraception associated with inhibition of ovulation; progestogen-only hormonalcontraception associated with inhibition of ovulation, intrauterine device,intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomisedpartner, sexual abstinenence).

*A woman is considered of childbearing potential (WOCBP), i.e. fertile, followingmenarche and until becoming post-menopausal unless permanently sterile. A man isconsidered fertile after puberty unless permanently sterile by bilateralorchidectomy.

3. History of any other neoplastic disease in the last five years (except basal cellcarcinoma, skin epithelioma or carcinoma in situ of any site)

4. History of clinically significant hypotension.

5. History of clinically significant allergic or hyper-sensitivity reactions.

6. History or known clinically significant vascular disease or known high risk ofvascular disease (as assessed by the treating physician) including (but not limitedto):

• Thromboembolism

• Peripheral arterial disease

• Vasculitis

7. Other relevant diseases or adverse clinical conditions:

• Congestive heart failure or angina pectoris, myocardial infarction within 12months before inclusion in the study.

• Uncontrolled arterial hypertension or cardiac arrhythmias (i.e., requiring achange in medication within the last 3 months or hospital admission within thepast 6 months).

• History of significant neurological or psychiatric disorders

8. Clinically significant or active infection.

9. Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis)

10. The patient is known to be human immunodeficiency virus (HIV) positive, unless thepatient is on antiviral therapy with HIV RNA levels <50 copies/mL; Hepatitis Bsurface antigen-positive or active hepatitis C infection, unless treated withundetectable hepatitis B DNA or hepatitis C RNA levels; or active CMV infection (IgMpositive).

11. Concomitant anti-tumor therapy within 14 days prior to Day 1 of Cycle 1.

12. Prior allogeneic transplantation in the last 3 months or currently active GVHD withimmunosuppressive treatment

13. Limitation of the patient's ability to comply with the treatment or follow-upprotocol.

14. If a COVID-19 vaccine is administered, it should be done >72 hours prior to studytreatment initiation or after the completion of the dose-limiting toxicity (DLT)period (if patient is participating in the dose-escalation phase").