Trial Title:
Safety, Pharmacokinetics, and Clinical Activity of LP-284 in Adult Patients With Relapsed or Refractory Lymphomas and Solid Tumors
NCT ID:
NCT06132503
Condition:
Relapsed or Refractory Lymphomas
Advanced Solid Tumor
Conditions: Official terms:
Lymphoma
Conditions: Keywords:
LP-284
Phase 1a/1b
Lantern Pharma
Cancer
lymphoma
DLBCL
MCL
Sarcoma
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
LP-284
Description:
LP-284 is a small molecule alkylating agent causing tumor cell death through DNA damage.
Arm group label:
Phase 1 Single Arm Multicenter Study to Assess the Safety and Tolerability of LP-284
Summary:
The goal of this clinical trial is to evaluate the safety and tolerability of escalating
doses of LP-284 and to determine the maximum tolerated dose (MTD) and the recommended
Phase 2 dose (RP2D) in patients with relapsed or refractory (R/R) lymphomas and solid
tumors. The secondary objectives are to characterize the pharmacokinetics (PK) of LP-284
and to assess clinical activity of LP-284.
Detailed description:
This FIH study is an open-label Phase 1a/1b dose escalation and dose expansion study in
adult patients with R/R lymphoma and solid tumors. Patients who provide informed consent
and meet the eligibility criteria for the study will be enrolled and treated with LP-284
administered intravenously (IV) on Days 1, 8, 15 of a 28-day schedule.
The study will be conducted in 2 parts: dose escalation with MTD and/or RP2D confirmation
(Phase 1a) and dose expansion (Phase 1b). Up to 30 evaluable patients will be enrolled in
Phase 1a; the total number of patients will depend on the number of dose levels explored.
Up to 40 evaluable patients will be enrolled in each of the 2 cohorts of MCL and DLBCL
tumors in Phase 1b.
Patients will remain on study treatment for up to a total of one-year OR until disease
progression, unacceptable toxicity, withdrawal of consent, any study-specific
discontinuation criteria are met, or the Investigator determines that it is in the best
interest of the patient to discontinue study treatment, whichever is shorter.
Criteria for eligibility:
Criteria:
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
investigator and Sponsor (e.g., Grade 2 chemotherapy-induced neuropathy or
hypothyroidism from prior immunotherapy treatment)
4. Ongoing unstable cardiovascular function:
- Symptomatic ischemia, or
- Uncontrolled clinically significant conduction abnormalities (i.e., ventricular
tachycardia on anti-arrhythmia is excluded; 1st degree atrioventricular block
or asymptomatic left anterior fascicular block /right bundle branch block will
not be excluded), or
- Congestive heart failure of New York Heart Association Class ≥ III, or
- 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. Hepatitis B and/or hepatitis C infection (as detected by positive testing for
hepatitis B surface antigen [HbsAg] or antibody to hepatitis C virus with
confirmatory testing) 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 breastfeeding.
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 or male patients able to father
children and female patients of childbearing potential who are unwilling or unable
to use highly effective methods of contraception as outlined in this protocol for
the duration of the study and for at least 3 months (male) or 6 months (female)
after last dose of study drug.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Cancer and Blood Specialty Clinic
Address:
City:
Los Alamitos
Zip:
90720
Country:
United States
Status:
Recruiting
Contact:
Last name:
Trong Nguyen
Phone:
562-735-0602
Email:
tnguyen@cbsclinic.com
Investigator:
Last name:
Nihal Abdulla, MD
Email:
Principal Investigator
Investigator:
Last name:
Vu Phan, MD
Email:
Sub-Investigator
Facility:
Name:
START Mountain Region
Address:
City:
West Valley City
Zip:
84119
Country:
United States
Status:
Recruiting
Contact:
Last name:
Marie Asay
Phone:
801-907-4770
Email:
marie.asay@startthecure.com
Investigator:
Last name:
William B McKean, MD
Email:
Principal Investigator
Start date:
January 3, 2023
Completion date:
November 30, 2028
Lead sponsor:
Agency:
Lantern Pharma Inc.
Agency class:
Industry
Source:
Lantern Pharma Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06132503
