A Study Evaluating the Safety, Tolerability of LPM3480226 Tablets in Patients With Advanced Solid Tumors

NCT03844438 | Unknown Phase 1

• 1 other identifier: LY01013-CHN -101
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a non-randomized, open, multiple administration and dose escalation phase 1 clinical trial evaluating the safety, tolerability, and pharmacokinetic/pharmacodynamics Characteristics of multiple oral administration of LPM3480226 in patients with advanced solid tumors., determine its dose-limiting toxicity and maximum tolerated dose, and initially observe its clinical effectiveness, and explore the metabolites in plasma after administration.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of LPM3480226 assessed by adverse events

  Collection of adverse events throughout the study as a measure of safety and tolerability.

  1 cycle (28 days)

Secondary Outcomes (2)

• AUC

  1 cycle (28 days)

• CMax

  1 cycle (28 days)

Study Arms (1)

LPM3480226

EXPERIMENTAL

LPM3480226 tablet will be orally administered，bid，28 days are considered as 1 cycle. The starting dose was 50 mg and the subsequent dose was increased according to the protocol of 100 mg,200 mg,400 mg,600mg.

Drug: LPM3480226

Interventions

LPM3480226 DRUG

The starting dose was 50 mg and the subsequent dose was increased according to the protocol of 100 mg, 200 mg, 400 mg, 600mg.

LPM3480226

Eligibility Criteria

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

You may qualify if:

• The subject has voluntarily signed the written informed consent form (ICF)
• Male or female patients aged 18 to 75 years (18 years and 75 years are inclusive)
• Advanced solid tumors confirmed by histology or cytology (the following tumors may be preferred: melanoma, bladder cancer, kidney cancer, head and neck cancer, lung cancer, etc.);
• Standard treatment is ineffective, subjects refuse to accept or cannot tolerate standard treatment, or there is no standard effective treatment;
• The patient should have at least one measurable lesion as the target lesion (according to RECIST 1.1 criteria)
• The Eastern Cooperative Oncology Group (ECOG) performance status score is \< 2 point.
• The predictable survival duration is ≥ 3 months
• Laboratory results during screening: absolute neutrophil count ≥ 1.5× 109/L; platelet count≥ 90× 109/L; hemoglobin≥ 90 g/L; Total bilirubin ≤1.5×upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5×ULN for the subjects without liver metastasis and ALT and AST\< 5×ULN for the subjects with liver metastasis.; creatinine clearance ≥ 50 mL/min （Cockcroft-Gault formula)
• QTc interval male ≤ 450 ms female≤ 470 ms；
• The female subjects and male subjects of childbearing age and the partners of the male subjects agree to take reliable contraceptive measures during the study period and within 6 months after infusion of the study drugs

You may not qualify if:

• There are any active autoimmune diseases or a history of autoimmune diseases \[including but not limited to: rheumatoid arthritis, ankylosing spondylitis, autoimmune hemolytic anemia, interstitial pneumonia, uveitis, inflammation Intestinal disease, autoimmune hepatitis, autoimmune hypophysitis, glomerulonephritis, hyperthyroidism or decreased thyroid function (subclinical patients can be included), allergic asthma (where asthma in childhood has been completely relieved, and no intervention needed in adults can be included. Patients with asthma who need bronchodilators for medical intervention cannot be included.), and patients with vitiligo and type 1 diabetes can be included\];
• Brain metastases, spinal cord compression, or cancerous meningitis, or brain CT or MRI scans confirmed brain metastases during screening period;
• have gastrointestinal diseases that may affect the absorption of the drug, or have undergone gastrointestinal surgery, which may affect the drug absorption by the investigator;
• Previously received radiotherapy, chemotherapy, surgery, or small molecule targeted therapy, less than 4 weeks prior to the first dose after treatment (if you had previously received nitrosourea or mitomycin chemotherapy, the time between the end of chemotherapy and the first dose Less than 6 weeks);
• Continue to use immunosuppressants (including but not limited to: tacrolimus, cyclosporine, etc.), systemic or topical hormonal therapy (dose \> 10 mg / day prednisone or corresponding equivalent of other hormones)within 2 weeks prior to the first dose;
• Those who have received any vaccine within 28 days prior to the first dose;
• Any drug that affects tryptophan metabolism is used within 28 days prior to the first dose, including but not limited to: serotonin reuptake inhibitors (eg, fluoxetine, paroxetine, fluvoxamine, sertraline, Citalopram, escitalopram, etc.), tryptophan hydroxylase inhibitors (eg, trossostat ethyl ester, p-chlorophenylalanine, etc.);
• Those who have used CYP3A4 strong inducers or strong inhibitors within 2 weeks before the first dose or within 5 half-life periods (for long periods of time) (see Annex V);
• Immunological "checkpoint" inhibitors (including but not limited to: anti-PD-1/PD-L1/PD-L2 monoclonal antibodies, anti-CTLA-4 monoclonal antibodies) were used within 42 days prior to the first dose;
• A monoamine oxidase inhibitor or a drug having a monoamine oxidase inhibitory action (eg, pethidine hydrochloride, linezolid, methylene blue, etc.) is used 3 weeks before the first administration or within 5 half-life periods (for long periods of time);
• Interferon-treated within 6 months prior to the first dose;
• Those who have used IDO/TDO inhibitors in the past;
• Active infections;
• Any of Hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab), acquired immunodeficiency syndrome antibody (Anti-HIV) or treponema pallidum antibody (TP-Ab) is positive;
• Those who received any other study drug or participated in another interventional clinical study 28 days before the first dose (42 days for mAbs);

Sponsors & Collaborators

• Luye Pharma Group Ltd.: lead
• Nanjing Bangnuo Biotechnology Co. Ltd: collaborator

Study Sites (1)

Beijing Cancer Hospital

Beijing, 100000, China

RECRUITING

Related Publications (1)

• Al-Zoubi RM, Elaarag M, Al-Qudimat AR, Al-Hurani EA, Fares ZE, Farhan A, Al-Zoubi SR, Khan A, Agouni A, Shkoor M, Bawadi H, Zakaria ZZ, Al Zoubi M, Alrumaihi K. IDO and TDO inhibitors in cancer immunotherapy: mechanisms, clinical development, and future directions. Front Pharmacol. 2025 Sep 16;16:1632446. doi: 10.3389/fphar.2025.1632446. eCollection 2025.

  PMID: 41035912 DERIVED

Central Study Contacts

Yuli Sun

CONTACT

010 5281 9375; sunyuli@luye.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2019
• First Posted: February 18, 2019
• Study Start: December 18, 2018
• Primary Completion: October 28, 2020
• Study Completion: March 1, 2022
• Last Updated: February 20, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)