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

Prior treatment

• Persistent clinically significant non-hematological toxicity related to previous treatments. The presence of alopecia and NCI-CTC grade \<2 symptomatic peripheral neuropathy is allowed.
• Other relevant diseases or adverse clinical conditions:
  • Congestive heart failure or angina pectoris, myocardial infarction within 12 months before inclusion in the study.
  • Uncontrolled arterial hypertension or cardiac arrhythmias (i.e., requiring a change in medication within the last 3 months or hospital admission within the past 6 months).
  • History of significant neurological or psychiatric disorders
• The patient is known to be human immunodeficiency virus (HIV) positive, unless the patient is on antiviral therapy with HIV RNA levels \<50 copies/mL; Hepatitis B surface antigen-positive or active hepatitis C infection, unless treated with undetectable hepatitis B DNA or hepatitis C RNA levels; or active CMV infection (IgM positive).
• Concomitant anti-tumor therapy within 14 days prior to Day 1 of Cycle 1.
• Prior allogeneic transplantation in the last 3 months or currently active GVHD with immunosuppressive treatment
• If a COVID-19 vaccine is administered, it should be done \>72 hours prior to study treatment initiation or after the completion of the dose-limiting toxicity (DLT) period (if patient is participating in the dose-escalation phase").

Other illness

• History of any other neoplastic disease in the last five years (except basal cell carcinoma, skin epithelioma or carcinoma in situ of any site)
• History of clinically significant hypotension.
• History of clinically significant allergic or hyper-sensitivity reactions.
• History or known clinically significant vascular disease or known high risk of vascular disease (as assessed by the treating physician) including (but not limited to):
  • Thromboembolism
  • Peripheral arterial disease
  • Vasculitis
• Clinically significant or active infection.
• Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis)

Other

• Pregnant or lactating women; men and women of reproductive potential\* (as defined in the Appendix 2) who are not using effective contraceptive methods (combined hormonal contraception associated with inhibition of ovulation; progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, sexual abstinenence).
  • \*A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy.
• Limitation of the patient's ability to comply with the treatment or follow-up protocol.

• Age ≥18 years
• Performance status (ECOG) ≤ 2
• Life expectancy ≥3 months
• Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
• Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
• Patients diagnosed with chronic lymphocytic leukemia (CLL), B-cell lymphomas, and multiple myeloma (MM) who are ineligible to reveive the available treatments.
• Adequate hematological or biochemical parameters as specified below
  • Hemoglobin \> 8.0 g/dl (without transfusion support within 7 days)
  • Platelets count \> 75 x109/L (without transfusional support within 7 days). In patients with bone marrow infiltration, the platelets count may be ≥50 x109/L.
  • Absolute neutrophil count (ANC) \> 0.75 x109/L (without G-CSF support within 7 days)
  • Aspartate transaminase (AST): \<2.5 x the upper limit range (in patients with no liver metastases or \<5 x ULN in patients with liver metastases)
  • Alanine transaminase (ALT): \< 2.5 x the upper limit range (in patients with no liver metastases or \<5 x ULN in patients with liver metastases)
  • Total bilirubin: \< 2 x the upper limit range.
  • Calculated or measured creatinine clearance: \>30 mL/min (calculated from the Cockcroft-Gault formula).
• Left ventricular ejection fraction \> 50% or above the Institutional Lower Limit of Normal (LLN), whichever is lower, determined by echocardiogram.