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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04737122




Registration number
NCT04737122
Ethics application status
Date submitted
26/11/2020
Date registered
3/02/2021
Date last updated
10/10/2023

Titles & IDs
Public title
Study of LM-061 in Subjects in Advanced Tumors
Scientific title
A Phase I, First-in-Human, Open-Label, Dose Escalation Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of LM-061 Tablet in Subjects With Advanced Tumors
Secondary ID [1] 0 0
LM061-01-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Tumours 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LM-061
Treatment: Drugs - Toripalimab

Experimental: LM-061 single agent escalation - The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. The subject in single agent dose levels will be administered multiple oral doses of LM-061 once daily.

Experimental: LM-061 combination escalation - The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. The subjects in combination dose levels will be administered multiple oral doses once daily of LM-061 and Toripalimab fixed dose injections every 3 weeks


Treatment: Drugs: LM-061
Oral dose with approximately 240 mL water in the fasting condition, and food will be forbidden 1 h prior to administration and 2h after dose. QD for continuous 28 days, and 4 weeks as one treatment cycle.

Treatment: Drugs: Toripalimab
For subjects in combination escalation levels, toripalimab will be administered 240mg, IV, every 3 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events and serious adverse events
Timepoint [1] 0 0
: From screening up to 1 year
Primary outcome [2] 0 0
Dose-limiting toxicities (DLT)
Timepoint [2] 0 0
: Cycle 1 of each cohort. Duration of one cycle is 28 days
Primary outcome [3] 0 0
Change in Vital Signs-ear temperature
Timepoint [3] 0 0
Baseline (Week 0) through approximately 1 year after first administration of LM061
Primary outcome [4] 0 0
Change in Vital Signs-pluse rate
Timepoint [4] 0 0
Baseline (Week 0) through approximately 1 year after first administration of LM061
Primary outcome [5] 0 0
Change in Vital Signs-blood pressure
Timepoint [5] 0 0
Baseline (Week 0) through approximately 1 year after first administration of LM061
Primary outcome [6] 0 0
Change in Electrocardiogram (ECG)-RR interval
Timepoint [6] 0 0
Baseline (Week 0) through approximately 1 year after first administration of LM061
Primary outcome [7] 0 0
Change in Electrocardiogram (ECG)-QT interval
Timepoint [7] 0 0
Baseline (Week 0) through approximately 1 year after first administration of LM061
Primary outcome [8] 0 0
Change in Electrocardiogram (ECG)-QRS duration
Timepoint [8] 0 0
Baseline (Week 0) through approximately 1 year after first administration of LM061
Primary outcome [9] 0 0
Incidence of Abnormal Clinical Laboratory Test Results-hematology
Timepoint [9] 0 0
Baseline (Week 0) through approximately 1 year after first administration of LM061
Primary outcome [10] 0 0
Incidence of Abnormal Clinical Laboratory Test Results-Biochemistry
Timepoint [10] 0 0
Baseline (Week 0) through approximately 1 year after first administration of LM061
Primary outcome [11] 0 0
Incidence of Abnormal Clinical Laboratory Test Results-Urinalysis
Timepoint [11] 0 0
Baseline (Week 0) through approximately 1 year after first administration of LM061
Primary outcome [12] 0 0
Incidence of Abnormal Clinical Laboratory Test Results-Coagulation test
Timepoint [12] 0 0
Baseline (Week 0) through approximately 1 year after first administration of LM061
Secondary outcome [1] 0 0
7. Area under the serum concentration versus time curve within one dosing interval (AUCtau)
Timepoint [1] 0 0
Up to 1 year
Secondary outcome [2] 0 0
Volume of distribution (Vd)
Timepoint [2] 0 0
Up to 1 year
Secondary outcome [3] 0 0
Volume of distribution at steady state (Vss)
Timepoint [3] 0 0
Up to 1 year
Secondary outcome [4] 0 0
Maximum serum concentration (Cmax)
Timepoint [4] 0 0
Up to 1 year
Secondary outcome [5] 0 0
Trough concentration before the next dose is administered (Ctrough)
Timepoint [5] 0 0
Up to 1 year
Secondary outcome [6] 0 0
Time to reach maximum serum concentration (Tmax)
Timepoint [6] 0 0
Up to 1 year
Secondary outcome [7] 0 0
Clearance (CL)
Timepoint [7] 0 0
Up to 1 year
Secondary outcome [8] 0 0
Terminal half-life (T1/2)
Timepoint [8] 0 0
Up to 1 year
Secondary outcome [9] 0 0
Dose proportionality
Timepoint [9] 0 0
Up to 1 year
Secondary outcome [10] 0 0
Objective response rate (ORR)
Timepoint [10] 0 0
Up to 1 year
Secondary outcome [11] 0 0
Best of response (BOR)
Timepoint [11] 0 0
Up to 1 year
Secondary outcome [12] 0 0
Disease control rate (DCR)
Timepoint [12] 0 0
Up to 1 year

Eligibility
Key inclusion criteria
- Volunteer to participate in clinical trial, sign a written informed consent form, and
be able to comply with clinical visits and study related procedures;

- Male or female subjects 18 to 75 years old (both inclusive) when sign the informed
consent;

- Study population: the subjects with advanced malignant tumors confirmed by histology
or cytology, and have failed standard treatment, or have no standard treatment, or not
suitable for standard treatment at present;

- ECOG score 0-1;

- The estimated survival time is not less than 3 months;

- The functional of bone marrow reserve and organs must meet the following requirements
(without ongoing continuous supportive treatment):

- Bone marrow reserve: Neutrophil count (NE#) = 1.5×109/L, platelet count (PLT) = 759 0
×109/L; for patients with hematologic malignancies, platelet count = 75 × 109/L, and
hemoglobin (HGB) > 9.0 g/dL (no blood transfusion or hematopoietic stimulating factor
therapy within 14 days);

- Coagulation function: activated partial thromboplastin time (APTT) prolong = 1.5×
upper limit of normal (ULN), and international standard ratio (INR) = 1.5;

- Liver function: total bilirubin (TBIL) = 1.5×ULN, alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) = 2.5×ULN (if there is liver metastasis, ALT or AST=
5×ULN);

- Kidney function: Creatinine clearance rate =50 mL/min (using Cockcroft-Gault formula,
see Appendix 1) or serum creatinine =1.5×ULN; qualitative urine protein =1+ or
qualitative urine protein =2+, but 24-hour urine protein <1g;

- Cardiac function: left ventricular ejection fraction (LVEF) = 50%; ECG is basically
normal, and corrected QT interval (QTcF) =450 ms and 470 ms for male and female,
respectively;

- Eligible subjects with fertility (male and female) must agree to use reliable
contraceptive methods (hormonal or barrier method or abstinence, etc.) with their
partners during the trial period and at least 3 months after the last administration;
women of childbearing age (Refer to Appendix 2 for definitions) The subject's serum
pregnancy test must be negative within 7 days prior to the first administration.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Have received chemotherapy, radiotherapy, biological therapy, endocrine therapy,
immune checkpoint inhibitor therapy and other anti-tumor treatments within 4 weeks
prior to first dose of IMP, except for the following items:

- Have used nitrosourea or Mitomycin C within 6 weeks prior to first dose of IMP;

- Have used oral fluorouracil and small molecule targeted drugs within 2 weeks prior to
first dose of IMP or 5 half-lives of the IMP (whichever is longer);

- Have used herbal therapy with anti-tumor indications are within 2 weeks prior to first
dose of IMP;

- Have received other Non-approved clinical trial drugs or treatments within 4 weeks
prior to first dose of IMP;

- Have undergone major organ surgery (excluding biopsy) or have had significant trauma
or invasive dental procedures (such as tooth extraction, dental implant) within 4
weeks prior to first dose of IMP, or required elective surgery during the trial
period;

- Have serious unhealable wounds/ulcers/bone fractures within 4 weeks prior to first
dose of IMP;

- Are taking (or cannot be stopped at least 1 week prior to first dose of IMP) any drug
that is known to strongly inhibit or induce CYP3A4 (see Appendix 3 for details);

- The histopathological type of the tumor is head and neck or lung squamous cell
carcinoma, or other tumors with bleeding tendency as judged by the investigator;

- Bleeding events of grade 3 or above occurred within 6 months before the first dose of
IMP or currently =grade 2 bleeding or factors judged by the investigator to have a
high risk of bleeding (such as active peptic ulcer or esophageal varices) at present;

- The adverse reactions of previous anti-tumor treatments have not yet recovered to
CTCAE 5.0 grade evaluation =1 (except for toxicity judged by the investigator to have
no safety risk, such as hair loss, grade 2 peripheral neurotoxicity, etc.);

- Central nervous system metastasis or meningeal metastasis with clinical symptoms, or
other evidence that the subject's central nervous system metastasis or meningeal
metastasis has not been controlled, and the investigator judges it to be unsuitable
for inclusion;

- Gastrointestinal perforation, abdominal fistula, or intra-abdominal abscess occurred
within 6 months before the first dose of the IMP; or the investigator has determined
that there are high-risk factors for the formation of cavity organ perforation/fistula
(such as tumor infiltration in the cavity Outer layer of the wall); inflammatory bowel
disease (including ulcerative colitis and Crohn's disease), diverticulitis,
cholecystitis, symptomatic cholangitis or appendicitis;

- Unable to be dosed orally, or there are conditions that have been judged by the
investigators to seriously affect the absorption of the gastrointestinal tract, such
as dysphagia, nausea and vomiting that are difficult to control, intestinal
obstruction, and gastric outlet obstruction;

- Have active infection 1 week before the first dose of IMP and currently need systemic
anti-infective treatment;

- HIV infection, active HBV infection (HBV DNA exceeds the ULN), active HCV infection
(HCV RNA exceeds the ULN);

- Have a history of serious cardiovascular and cerebrovascular diseases, including but
not limited to:

- Severe heart rhythm or conduction abnormalities, such as ventricular arrhythmia that
requires clinical intervention, grade ?-? atrioventricular block, etc.;

- Thromboembolic events requiring therapeutic anticoagulation, or subjects with venous
filters;

- According to the New York Heart Association (NYHA) standards, subjects with grade
III~IV cardiac insufficiency;

- Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other
cardiovascular and cerebrovascular events of grade 3 or above occurred within 6 months
before the first administration of IMP;

- Clinically uncontrollable hypertension (blood pressure cannot be controlled at
systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg after standard
antihypertensive treatment);

- Any factors that increase the risk of QTc prolongation or arrhythmia, such as heart
failure, hypokalemia, congenital long QT syndrome, use of any concomitant drugs that
are known or may prolong the QT interval (see Appendix 3 for details);

- The third gap effusion that cannot be controlled clinically is not suitable for
inclusion in the study judged by the investigator;

- Known history of drug abuse;

- Subjects with mental disorders or poor compliance;

- Women who are pregnant or breastfeeding;

- Cannot tolerate venous blood sampling;

- Known to be allergic to LM-061 tablets or any of its excipients;

- Has history of other serious systemic diseases judged by the investigator, or other
reasons are not suitable for participating in the study.

- (Combination escalation levels only ) Known history of intolerable to any prior
anti-PD-1/PD-L1 or CTLA-4 therapy;

- (Combination escalation levels only) Known to take systemic corticosteroids (> 10 mg
daily prednisone equivalents) or other systemic immunosuppressive medications
(including, but not limited to, prednisone, dexamethasone, cyclophosphamide,
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within
2 weeks prior to the first dosing of LM-061 and toripalimab. Usage of topical, ocular,
intra-articular, intranasal, and inhalational corticosteroids is allowed;

- (Combination escalation levels only) Have a known or suspected history of an
autoimmune disorder;

- (Combination escalation levels only) Have a history of primary immunodeficiency;

- (Combination escalation levels only) Subjects from endemic area will be specifically
screened for tuberculosis. Subjects with activetuberculosis are excluded;

- (Combination escalation levels only) History of (non-infectious) pneumonitis that
required corticosteroids or current pneumonitis, or history of interstitial lung
disease.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2022
Sample size
Target
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St George Private Hospital - Kogarah
Recruitment postcode(s) [1] 0 0
2217 - Kogarah

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
LaNova Medicines Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase I, open-label, dose escalation study to evaluate the safety, tolerability,
PK, and preliminary efficacy of LM-061 in subjects with advanced tumors.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04737122
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Vinod Ganju
Address 0 0
Peninsula & South Eastern Hematology and Oncology group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04737122