Safety, Pharmacokinetics, and Clinical Activity of LP-284 in Adult Patients With Relapsed or Refractory Lymphomas and Solid Tumors

Inclusion Criteria All Patients: Phase 1a and Phase 1b 1. Male or female aged ≥ 18 years on the day of signing informed consent. 2. Patient is capable of giving signed informed consent as described in Section 11.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 3. Eastern Cooperative Oncology Group (ECOG) performance status: 0-2 at screening. 4. For Lymphoma patients. At least one bi-dimensionally measurable disease site. The lesion must have a greatest transverse diameter of at least 1.5 cm and greatest perpendicular diameter of at least 1.0 cm at baseline. The lesion must be positive on positron emission tomography (PET) scan. Note: Patients without measurable disease per Lugano Classification \[9\] may be eligible for Part 1a, following discussion with the Investigator and the Sponsor, if the patient presents with non-measurable but assessable disease of any size unequivocally attributable to advanced lymphoma. 5. Adequate organ function at Screening and on C1D1 (pre-dose) defined as: Liver Function i Aspartate aminotransferase (AST), alanine transaminase (ALT) ≤ 3x upper limit of normal (ULN) or \< 5x ULN in cases of documented lymphoma involvement of liver. ii Total serum bilirubin ≤ 1.5 x ULN or \< 5x ULN if secondary to Gilbert's syndrome or documented lymphoma involvement of liver. Renal Function iii Serum creatinine clearance ≥60 mL/min, either measured or calculated using standard Cockcroft-Gault formula. iv Serum electrolyte (potassium, calcium, and magnesium) levels within the normal reference range (may be supplemented according to institutional standards). Bone Marrow Function: v Absolute neutrophil count (ANC) ≥ 1500/μL. (Phase 1b: ANC ≥ 1000/μL if documented by investigator as the normal baseline for the patient) vi Hemoglobin ≥ 8 g/dL (for those patients undergoing red blood cell \[RBC\] transfusion, hemoglobin must be evaluated after at least 14 days after the last RBC transfusion). vii Platelet count ≥ 100,000/μL (assessed ≥ 7 days following last platelet transfusion in patients with thrombocytopenia requiring platelets). (Phase 1b: ≥ 75,000/μL may be acceptable after discussion with the Sponsor) 6. Women of child-bearing potential (WOCBP) must agree to use highly effective contraceptive methods and avoid egg donation for the duration of study treatment and for 6 months after the last dose of study drug. 7. Women of child-bearing potential must have a negative serum pregnancy test at Screening and within 72 hours prior to the first dose of study drug. 8. Men must agree to use highly effective contraceptive methods and avoid sperm donation during the study treatment and for 3 months after the last dose of study drug if the partner is a WOCBP. Phase 1a ONLY: 9. Histologically confirmed diagnosis of B-cell NHL according to the 2016 World Health Organization (WHO) classification that has relapsed from or is refractory to at least two prior standard of care treatments or tumors for whom standard therapies are not available. Diffuse large B-cell lymphoma (DLBCL) includes: DLBCL not otherwise specified (NOS) with or without MYC and BCL2 and/or BCL6 rearrangements; Epstein-Barr virus (EBV) positive DLBCL, NOS; human herpesvirus 8 (HHV8) positive DLBCL, NOS; DLBCL associated with chronic inflammation; and Primary cutaneous DLBCL, leg type. Patients with indolent lymphoma are eligible if they meet criteria for systemic treatment. OR Histologically or pathologically confirmed advanced solid tumor that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available. Notes: Archival formalin fixed paraffin embedded (FFPE) tumor tissue is preferred but optional. Patients with small lymphocytic lymphoma (SLL) are only eligible if they do not require immediate cytoreductive therapy or if they do not have available treatments with potential benefit. Patients with solid tumors Only: Non-measurable or Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Eisenhauer, 2009) for solid tumors at Screening. Phase 1b ONLY 10. Histologically confirmed diagnosis of DLBCL or MCL according to the 2016 WHO classification. DLBCL includes: DLBCL not otherwise specified (NOS) with or without MYC and BCL2 and/or BCL6 rearrangements; Epstein-Barr virus (EBV) positive DLBCL, NOS; HHV8+ DLBCL, NOS; DLBCL associated with chronic inflammation; and Primary cutaneous DLBCL, leg type 11. Relapsed and/or refractory disease to at least two prior standard of care treatments or tumors for which no standard therapies are available. 12. Documented tumor alteration status. Archival (preferably collected within 6 months prior to first dose \[C1D1\]) FFPE tumor sample must be submitted for determination of genomic signature by Lantern Pharma's validated laboratory developed test regardless of whether a local test has been performed for enrollment. The FFPE testing results are not required for study entry. Exclusion Criteria All Patients: Phase 1a and Phase 1b Patients are excluded from the study if any of the following criteria apply: 1. History or suspicion of central nervous system (CNS) lymphoma or meningeal involvement or central nervous system (CNS) metastases. 2. History of or active concurrent malignancy other than NHL (Phase 1a and Phase 1b) or solid tumor (Phase 1a only) unless the patient has been disease-free for ≥ 2 years. Exceptions to the ≥ 2-year time limit include treated basal cell or localized squamous cell skin carcinoma, localized prostate cancer, or other localized carcinomas such as carcinoma in situ of cervix, breast, or bladder. 3. Clinically significant AEs that have not returned to baseline or ≤Grade 1 based on NCI-CTCAE prior to first dose of study drug, unless approved by the Sponsor. Patients with chronic Grade 2 toxicities may be eligible per the discretion of the investigat