Study of LM-061 in Subjects in Advanced Tumors

NCT04737122 | Terminated Phase 1

• 1 other identifier: LM061-01-102
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Tumours

Outcome Measures

Primary Outcomes (12)

• Number of participants with adverse events and serious adverse events

  The safety profile of LM061 will be assessed by monitoring the adverse events (AE) per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

  : From screening up to 1 year

• Dose-limiting toxicities (DLT)

  DLT is defined as a toxicity (adverse event at least possibly related to LM061) occurring during the DLT observation period (the initial 21 days)

  : Cycle 1 of each cohort. Duration of one cycle is 28 days

• Change in Vital Signs-ear temperature

  Change in vital signs-ear temperature will be measured after the subject has been fully rested.

  Baseline (Week 0) through approximately 1 year after first administration of LM061

• Change in Vital Signs-pluse rate

  Change in vital signs-pluse rate will be measured after the subject has been fully rested.

  Baseline (Week 0) through approximately 1 year after first administration of LM061

• Change in Vital Signs-blood pressure

  Change in vital signs-blood pressure will be measured after the subject has been fully rested.

  Baseline (Week 0) through approximately 1 year after first administration of LM061

• Change in Electrocardiogram (ECG)-RR interval

  RR interval of 12-lead ECG will be performed in the supine position after the patients are fully rested at each timepoint for once. RR is the standard heart rate which calculated by 60 divided by heart rate.

  Baseline (Week 0) through approximately 1 year after first administration of LM061

• Change in Electrocardiogram (ECG)-QT interval

  QT interval of 12-lead ECG will be performed in the supine position after the patients are fully rested at each timepoint for once.

  Baseline (Week 0) through approximately 1 year after first administration of LM061

• Change in Electrocardiogram (ECG)-QRS duration

  QRS duration of 12-lead ECG will be performed in the supine position after the patients are fully rested at each timepoint for once.

  Baseline (Week 0) through approximately 1 year after first administration of LM061

• Incidence of Abnormal Clinical Laboratory Test Results-hematology

  Number of participants with incidence of abnormal clinical lab test results like hematology will be assessed.

  Baseline (Week 0) through approximately 1 year after first administration of LM061

• Incidence of Abnormal Clinical Laboratory Test Results-Biochemistry

  Number of participants with incidence of abnormal clinical lab test results like Biochemistry will be assessed.

  Baseline (Week 0) through approximately 1 year after first administration of LM061

• Incidence of Abnormal Clinical Laboratory Test Results-Urinalysis

  Number of participants with incidence of abnormal clinical lab test results like Urinalysis will be assessed.

  Baseline (Week 0) through approximately 1 year after first administration of LM061

• Incidence of Abnormal Clinical Laboratory Test Results-Coagulation test

  Number of participants with incidence of abnormal clinical lab test results like Coagulation test will be assessed.

  Baseline (Week 0) through approximately 1 year after first administration of LM061

Secondary Outcomes (12)

• 7. Area under the serum concentration versus time curve within one dosing interval (AUCtau)

  Up to 1 year

• Volume of distribution (Vd)

  Up to 1 year

• Volume of distribution at steady state (Vss)

  Up to 1 year

• Maximum serum concentration (Cmax)

  Up to 1 year

• Trough concentration before the next dose is administered (Ctrough)

  Up to 1 year

Study Arms (2)

LM-061 single agent escalation

EXPERIMENTAL

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.

Drug: LM-061

LM-061 combination escalation

EXPERIMENTAL

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

Drug: LM-061; Drug: Toripalimab

Interventions

LM-061 DRUG

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.

Also known as: Kinase inhibitor

LM-061 combination escalation; LM-061 single agent escalation

Toripalimab DRUG

For subjects in combination escalation levels, toripalimab will be administered 240mg, IV, every 3 weeks

LM-061 combination escalation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.);
• 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);

Sponsors & Collaborators

• LaNova Medicines Limited: lead

Study Sites (1)

St George Private Hospital

Kogarah, New South Wales, 2217, Australia

Location

MeSH Terms

Interventions

toripalimab

Study Officials

• Vinod Ganju

  Peninsula & South Eastern Hematology and Oncology group

  PRINCIPAL INVESTIGATOR

• Ganessan Kichenadasse

  Southern Oncology Clinical Research Unit

  PRINCIPAL INVESTIGATOR

• Paul De Souza

  St George Private Hospital

  PRINCIPAL INVESTIGATOR

• Gary Richardson

  Cabrini Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Arm1: LM-061 single agent escalation Arm2: LM-061 combination escalation

Study Record Dates

• First Submitted: November 26, 2020
• First Posted: February 3, 2021
• Study Start: May 6, 2021
• Primary Completion: July 19, 2022
• Study Completion: December 1, 2022
• Last Updated: October 10, 2023

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)