| Eligibility |
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 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 the 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
1. Aspartate aminotransferase (AST), alanine transaminase (ALT) = 3x upper limit of
normal (ULN) or < 5x ULN in cases of documented lymphoma involvement of liver.
2. Total serum bilirubin = 1.5 x ULN or < 5x ULN if secondary to Gilbert's syndrome
or documented lymphoma involvement of liver.
Renal Function
3. Serum creatinine clearance =60 mL/min , either measured or calculated using
standard Cockcroft-Gault formula.
4. serum electrolyte (potassium, calcium, and magnesium) levels within the normal
reference range (may be supplemented according to institutional standards).
Bone Marrow Function:
5. Absolute neutrophil count (ANC) = 1500/µL. (Phase 1b: ANC = 1000/µL if documented
by investigator as the normal baseline for the patient)
6. 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).
7. 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 for the duration of study treatment and 30 days 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 hrs prior to first dose of study drug.
8. Men must agree to use highly effective contraceptive methods during the study
treatment and for 30 days after the last dose of study drug if the partner is a WOCBP.
9. Resolved acute effects of any prior therapy to baseline severity or Grade =1 NCI CTCAE
except for AEs not constituting a safety risk such as alopecia.
Phase 1a ONLY
10. Histologically confirmed diagnosis of B-cell NHL according to the 2016 World Health
Organization (WHO) classification. 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
11. Archival formalin fixed paraffin embedded (FFPE) tumor tissue is optional. Relapsed
and/or refractory disease to at least two prior standard of care treatments or tumors
for whom standard therapies are not available.
Note: Patients with indolent NHL and 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.
12. 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. 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
1. Histologically confirmed diagnosis of DLBCL according to the 2016 WHO classification
including: 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, and
Mantle cell lymphoma
2. Relapsed and/or refractory disease to at least two prior standard of care treatments
or tumors for whom standard therapies are not available.
3. 16. Documented tumor mutation 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
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 or solid tumors 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. Patient has not recovered from any clinically significant adverse events (AEs) of
previous treatments to pre-treatment baseline or Grade 1 prior to first dose of study
drug.
4. Ongoing unstable cardiovascular function:
1. Symptomatic ischemia, or Uncontrolled clinically significant conduction
abnormalities (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st
degree atrioventricular block or asymptomatic left anterior fascicular block
/right bundle branch block will not be excluded), or
2. Congestive heart failure of New York Heart Association Class = III, or
3. Myocardial infarction within 3 months prior to Screening.
5. Congenital long QT syndrome, or a QT interval corrected by Fridericia's formula (QTcF)
= 470 ms (average of triplicate ECGs) at Screening and/or on C1D1 (pre-dose) except
for a documented bundle branch block or unless secondary to pacemaker. In the case of
a documented bundle branch block or a pacemaker, discussion with the Medical Monitor
is required prior to enrollment.
6. Thromboembolic or cerebrovascular event (i.e., transient ischemic attacks,
cerebrovascular accidents, pulmonary emboli, or clinically significant deep vein
thrombosis) = 6 months prior to first dose of study drug.
7. Infection requiring antibiotics, antivirals, or antifungals within 1 week prior to
first dose of study drug, unless such infection is adequately controlled (defined as
exhibiting no ongoing signs/symptoms related to the infection and with clinical
improvement). In the case of prophylactic use of these agents, discussion with the
Medical Monitor is required prior to enrollment.
8. Positive hepatitis B and/or hepatitis C serology or known seropositivity for or
history of active viral infection with human immunodeficiency virus (HIV).
9. Concurrent medical conditions including psychiatric disorders that in the judgment of
the Investigator will interfere with the patient's ability to participate or with
achieving the objectives of the study or pose a safety risk.
10. The patient is pregnant or breast feeding.
11. Prior allogeneic hematopoietic stem cell transplant.
12. Autologous hematopoietic stem cell transplant within 6 months prior to first dose of
study drug or patient has progressed within 6 months from the day of stem cell
infusion.
13. Radiation treatment within 4 weeks prior to the first dose of study drug, unless the
tumor site continues to increase in size after the patient has completed radiotherapy
treatment.
14. Major surgery requiring general anesthesia within 4 weeks prior to the first dose of
study drug. If a patient required general anesthesia within the prior 4 weeks,
consultation with the Medical Monitor is required prior to enrollment.
15. Received live vaccine within 1 month prior to the first dose of study drug.
16. Exposure to investigational or non-investigational anti-cancer therapy within 2 weeks
or within at least 5 half-lives (up to a maximum of 4 weeks from any
biologics/immunotherapies) prior to the first dose of study drug, whichever is
shorter.
Note: Low dose steroids (oral prednisone or equivalent = 20 mg/day), localized non-CNS
radiotherapy, are not criteria for exclusion.
17. Patient has completed a course of SARS-CoV-2 vaccine within 14 days prior to first
dose of study drug.
18. Patient is unable or unwilling to comply with all requirements of the study.
19. Patient with dependency on the Sponsor, Investigator or study site.
20. A person that is committed to an institution by official or judicial order.
21. Male patients with partners currently pregnant; male patients able to father children
and female patients of childbearing potential who are unwilling or unable to use two
highly effective methods of contraception as outlined in this protocol for the
duration of the study and for at least 30 days after last dose of study drug.
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