Trial Title:
A First-in-Human, Phase 1/2 Study of LAT010 in Patients with Advanced Solid Tumors (LIGHTSPEED-1)
NCT ID:
NCT06277219
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Long-Acting Thyroid Stimulator
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
LAT010
Description:
LAT010 monotherapy
Arm group label:
Phase 1 LAT010 Dose Escalation
Arm group label:
Phase 2 LAT010 Dose Expansion
Intervention type:
Drug
Intervention name:
LAT010 + ICI
Description:
LAT010 combination with PD-1 inhibitor
Arm group label:
Phase 2 LAT010 Dose Expansion
Summary:
This is an open-label, multicenter, Phase 1/2, first-in-human (FIH), dose-escalation and
cohort-expansion study of LAT010 to evaluate the safety, tolerability, immunogenicity,
PK, PD, and antitumor activity in patients with advanced solid tumors. The study consists
of 2 parts: Phase 1 dose-escalation and Phase 2 cohort expansion.
Detailed description:
Interleukin-2 (IL-2) agonists have shown significant antitumor activities but are
associated with severe toxic side effects, due to prioritized activation of high-affinity
IL-2 receptor (i.e., IL2Rαβγ). LAT010 is a human IL-2 based immunocytokine designed to
exclusively interact with intermediate-affinity IL-2 receptor (i.e., IL2Rβγ) but not the
high-affinity IL2Rαβγ receptor. Its exceptional selectivity in activating CD8+ T cells
and NK cells may confer the clinical benefits of IL-2 in promoting antitumor immunity
without the associated safety concerns.
Phase 1 of the study will examine LAT010 in an accelerated and standard "3+3"
dose-escalation design. It consists of 7 planned cohorts. Approximately 20 to 50 patients
with locally advanced or metastatic solid tumors will be enrolled in the cohorts. Each
treatment cycle consists of 4 weeks, during which patients will receive an IV injection
of LAT010 at the assigned dose once weekly. The DLT observation period is the first
treatment cycle (28 days).
Phase 2 will be initiated after the MTD or a RP2D has been determined in Phase 1.
Approximately up to 30 patients per cohort by tumor type will be enrolled to further
evaluate the safety and efficacy of LAT010 in the treatment of selected tumor types at
multiple dose levels based on the results of Phase 1. The primary objective of Phase 2
study is to define the preliminary efficacy in the setting of advanced cancers with high
unmet medical needs.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
For Phase 1 and Phase 2:
1. Patients have voluntarily signed the informed consent.
2. Patients are willing and able to comply with the protocol-related procedures
(including screening evaluations), such as visits, treatment plans, laboratory
assessments, and other requirements of the study.
3. Male or female aged ≥18 years old.
4. Patients meet the following diagnoses:
- Patients have histologically or cytologically documented diagnosis of locally
advanced or metastatic solid tumors with evidence of progressive disease
according to RECIST 1.1, and
- Patients are intolerant to or have progressed on all established standard
therapies associated with clinical benefit or patients consent that they may be
delaying or forgoing treatments known to confer a clinical benefit for their
disease, or
- No additional established line of standard therapy is available, or
- There is a contraindication for the indicated standard therapies in the opinion
of the Investigator.
(Note: Tumor types of primary interest in Phase 1 include but are not limited to
malignant melanoma, renal cell carcinoma, non-small cell lung cancer, gastric
carcinoma, hepatocellular carcinoma, pancreatic adenocarcinoma, breast carcinoma,
ovarian carcinoma, and colorectal carcinoma.)
5. Patients have at least one measurable tumor lesion, defined as a lesion with the
longest measurable diameter of non-lymph node lesions by imaging (CT/MRI) of ≥10 mm
or the short diameter of a single pathological lymph node lesion of ≥15 mm.
6. Expected life expectancy of >12 weeks per the Investigator.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for Phase 1.
ECOG score of 0 to 2 for Phase 2.
8. If a patient has had prior major surgery, at least 4 weeks must have elapsed at the
time of screening.
9. Patients have adequate pulmonary, cardiovascular, hematological, liver, and renal
function, per Investigator assessment.
10. Patients have not received any IL-2 therapy within 12 months before the first dose
of LAT010.
11. Laboratory values at screening are as follows:
a. Hematology: i. Absolute neutrophil count (ANC) ≥1,500 cells/mm3 ii. Platelet
count ≥75,000 cells/mm3 (no blood components or cell growth factors are used as
supportive care within 7 days before the first dose of LAT010) iii. Hemoglobin ≥9.0
g/dL, transfusion of red blood cells allowed to reach threshold target if >7 days b.
Renal: i. Creatinine clearance >30 mL/min as derived from the Cockcroft-Gault
glomerular filtration rate estimation c. Coagulation: i. International Normalized
Ratio (INR) ≤1.5× the upper limit of normal (ULN) ii. Prothrombin time (PT) or
activated partial thromboplastin time (APTT) ≤1.5×ULN unless undergoing
anticoagulation therapy d. Liver: i. Aspartate transaminase (AST) and alanine
transaminase (ALT) ≤3.0×ULN without liver metastasis or ≤5×ULN with liver metastasis
ii. Bilirubin <1.5×ULN (unless Gilbert syndrome is confirmed)
12. Any toxicity of previous treatment has recovered to Grade ≤1, unless the toxicity is
judged by the Investigator to pose no safety risk, such as alopecia (any grade) or
fatigue (up to Grade 2 allowed).
13. Female patients of childbearing potential and sexually active male patients with
female partners of childbearing potential must agree to use effective contraceptive
measures (including concomitant use of a spermicide with barrier method,
intrauterine device, or hormonal contraceptives) from signing the informed consent
form to at least 90 days after the last dose of LAT010. Female patients of
childbearing age and women <12 months after menopause must have a negative pregnancy
test result within 7 days before the first dose of LAT010.
14. Male patients must not donate sperm starting at screening and throughout the study
period and for at least 90 days after the final study drug administration.
For Phase 2 only:
15. Patients must meet the following criteria:
1. Patients are willing and able to undergo baseline and on-treatment biopsies of
the tumor. If a patient has residual tumor masses that can only be accessed
with significant risk, available archived biopsies (frozen or formalin-fixed)
may serve as baseline specimens with the Sponsor's approval.
2. Patients have been diagnosed and histologically confirmed with a tumor type
being selected for the Phase 2 trial.
3. Patients have received the established standard therapies for the selected
tumor type prior to enrolling to this study and patients consent that they may
be delaying or forgoing specific treatments known to confer a clinical benefit
for their disease.
4. Must have received no more than 1 prior line of anti-angiogenic therapy, e.g.,
anti-vascular endothelial growth factor (anti-VEGF) therapy
Exclusion Criteria:
1. Cardiovascular exclusions:
1. Patient has a medical history of an arterial thrombotic event, stroke, or
transient ischemia attack within the past 6 months.
2. Patient has a medical history of symptomatic congestive heart failure (New York
Heart Association classes III or IV) or an uncontrolled clinically significant
cardiac arrhythmia that requires treatment.
3. Patient has a medical history of myocardial infarction or unstable angina
within 6 months before the first dose of LAT010.
4. Patient has a QTc prolongation to >480 milliseconds (ms) based on a 12-lead
ECGs in triplicate.
2. Other exclusions:
1. Patient is actively enrolled in another clinical study, unless it is an
observational (noninterventional) clinical study or the follow-up component of
an interventional study.
2. Use of another systemic anti-cancer therapy within 3 weeks or 5 half- lives
after the first dose of LAT010, whichever is shorter.
3. Patient has active central nervous system (CNS) metastases. However, definitely
treated CNS metastases (such as surgery, radiotherapy) that are stable for at
least 2 weeks prior to the first dose of LAT010 are acceptable.
4. Patient has another active primary malignancy that has not been treated with
curative intent. Exceptions could be made upon discussion with the Medical
Monitor. However, non-metastatic cutaneous basal cell or squamous cell
carcinoma, or non-muscle invasive bladder cancer are acceptable.
5. Patient has history of severe irAEs from a previous treatment, which are
defined as a Grade 4 event requiring corticosteroid treatment or a Grade 3
event requiring corticosteroid treatment of >10 mg/day prednisone or equivalent
dose for >12 weeks.
3. Recent medical concerns exclusions:
1. Patient has evidence of active infection requiring IV antibiotics within 7 days
prior to the first dose of LAT010.
2. Patient has active uncontrolled bleeding within 7 days prior to the first dose
of LAT010.
3. Patient has serious or non-healing wound, fistula, skin ulcer, or non-healing
bone fracture within 7 days prior to the first dose of LAT010.
4. Patient has had a live virus vaccine within 30 days prior to the first dose of
LAT010 (Note: Inactivated seasonal flu vaccine is acceptable. COVID-19
vaccination is also allowed.)
4. Patient has known replicating human immunodeficiency virus infection, active
hepatitis B infection, or hepatitis C infection. However, hepatitis B virus (HBV)
carriers without active disease (HBV DNA titer < 1000 cps/mL or 200 IU/mL) or
patients with cured hepatitis C (negative HCV RNA test) may be enrolled. Patients
with treated non-replicative disease are acceptable.
5. Patient is taking corticosteroids >10 mg/day of prednisone or equivalent.
6. Patient has had an organ transplantation or is on systemic immunosuppressive
therapy.
7. Patient has a positive test result for Severe Acute Respiratory Syndrome Coronavirus
2 (SARS-CoV-2) viral RNA test, either asymptomatic or present with symptoms of
Coronavirus disease 2019 (COVID-19) on Day -2 or Day -1.
8. Patient has a serious illness considered by the Investigator to be unsuitable for
participating in this study.
9. Any condition that, in the opinion of the Investigator, may interfere with the
evaluation of the study drug or interpretation of the patient's safety or study
results.
10. Patient has a history of sensitivity to LAT010, or components thereof, or a history
of drug or other allergy that in the opinion of the Investigator or Medical Monitor
(if appropriate), contraindicates their participation.
11. Patient has any illness, medical condition, organ system dysfunction, or social
situation, including mental illness or substance abuse, that is deemed by the
Investigator to be likely to interfere with a patient's ability to sign the informed
consent form (ICF), adversely affect the patient's ability to cooperate and
participate in the study, or compromise the interpretation of study results.
12. Patient is breastfeeding or pregnant as confirmed by pregnancy tests performed
within 7 days before the first dose of LAT010.
13. Patient is unwilling or unable to follow protocol requirements.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
D&H Cancer Research Center
Address:
City:
Margate
Zip:
33063
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alexander J Chacin, FMD
Phone:
689-333-0231
Email:
achacin@dhnrc.com
Contact backup:
Last name:
Angheli Vega, FMD
Phone:
954-323-2422
Email:
avega@dhnrc.com
Contact backup:
Last name:
Emilio P Araujo-Mino, MD
Facility:
Name:
Huntsman Cancer Institute
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Jeana McKenney
Phone:
801.213.8414
Email:
jeana.mckenney@hci.utah.edu
Contact backup:
Last name:
Benjamin L Maughan, MD
Start date:
June 5, 2024
Completion date:
March 2027
Lead sponsor:
Agency:
Latticon Antibody Therapeutics, Inc
Agency class:
Industry
Source:
Latticon Antibody Therapeutics, Inc
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06277219
