Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
For Safety introduction phase,this study is to evaluate the safety and tolerability of LM-168 in combination with other anti-tumor treatment regimens in participants of advanced solid tumor trials, determine the maximum tolerated dose (MTD), and explore the recommended phase II dose (RP2D).
For Dose expansion phase,this study is to evaluate the preliminary antitumor activity of LM-168 in combination with other antitumor treatment regimens in participants of advanced solid tumor trials, measured by objective response rate (ORR)
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LM-168 + Tislelizumab Safety introduction | Experimental |
| |
| LM-168 Dose Expansion | Experimental |
| |
| LM-168 + Tislelizumab Dose Expansion | Experimental |
| |
| LM-168 + Tislelizumab +Other anti-tumor treatments Dose Expansion | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LM-168 | Drug | Q3W,Intravenous Drip |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of dose-limiting toxicity (DLT) | Safety introduction phase | 78 Weeks |
| Objective response rate (ORR) | Dose expansion phase | From start of treatment to date of documented disease progression, up to approximately 42 months |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of response (DoR) | Dose expansion phase | Time from initial response (CR or PR) to date of documented disease progression or death (due to any cause) whichever occurs first, up to approximately 42 months |
| Disease control rate (DCR) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Received any other investigational product or treatment within 28 days prior to the first dose of LM-168.
Received anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agents, any other immunotherapy or oncology immune-oncology (IO) drugs within 28 days prior to the first dose of LM-168; or permanently discontinued prior immunotherapy due to immune-related adverse events (irAEs). All adverse events (AEs) from previous anti-tumor treatments have not fully resolved or resolved to Grade 1 prior to screening. Requirement for additional immunosuppressants (other than low-dose corticosteroids) to control irAEs.
Received other anti-tumor treatments prior to the first dose of LM-168, as specified below:
AEs from prior anti-tumor treatments have not recovered to Grade ≤ 1 per NCI CTCAE Version 6.0. Exceptions include: toxicities assessed by the Investigator to pose no safety risks (e.g., alopecia), long-term radiation-related toxicities with Grade ≤ 2, and hypothyroidism stabilized with hormonal replacement therapy.
Uncontrolled tumor-related pain. Participants requiring analgesic treatment must have been on a stable analgesic dose prior to study entry.
Known active brain metastases or leptomeningeal metastases.
Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage.
Esophageal or gastric varices requiring immediate clinical intervention, or a history of variceal bleeding; except for participants with stable conditions confirmed by endoscopic evaluation within 3 months prior to the first study drug administration.
History of hepatic encephalopathy, hepatorenal syndrome, or cirrhosis classified as Child-Pugh Class B or higher.
Tumor invasion into adjacent vital organs (e.g., aorta, heart, pericardium, superior vena cava, trachea, esophagus, etc.), or at risk of developing esophagotracheal fistula or esophagopleural fistula.
Active or prior history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, chronic diarrhea).
History of Grade ≥ 3 hypersensitivity reactions to monoclonal antibody-based therapies.
Experienced Grade ≥ 3 irAEs during prior immunotherapy, or discontinued prior immunotherapy due to severe or life-threatening irAEs.
Received systemic corticosteroids (prednisone equivalent > 10 mg daily) or other systemic immunosuppressive agents (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor agents) within 2 weeks prior to the first dose of LM-168. Topical, ophthalmic, intra-articular, intranasal and inhaled corticosteroids are permitted.
Known history of autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, Guillain-Barré syndrome, multiple sclerosis and glomerulonephritis (see Appendix 3 for the complete list of autoimmune diseases). Exception: participants with autoimmune hypothyroidism maintained on a stable dose of thyroid replacement hormones.
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonia, interstitial lung disease or severe radiation pneumonitis; or evidence of active pneumonia on chest CT scan during the screening period.
Received any live vaccine within 28 days prior to the first dose.
Underwent major surgery or interventional procedures within 28 days prior to the first dose of LM-168 (excluding tumor biopsy, puncture and other minor procedures).
Severe cardiovascular and cerebrovascular diseases,
Uncontrolled or severe concomitant diseases, including ongoing or active infections (e.g., active COVID-19/SARS-CoV-2 infection, syphilis) requiring therapeutic antibiotics and/or other medications. SARS-CoV-2 testing is not mandatory for study enrollment but shall comply with local clinical practice guidelines and standards.
History of immunodeficiency disorders, including other acquired or congenital immunodeficiencies; or history of solid organ transplantation, allogeneic bone marrow transplantation or autologous hematopoietic stem cell transplantation.
Human Immunodeficiency Virus (HIV) infection, or active hepatitis infection (including tuberculosis, Hepatitis B Virus [HBV] and Hepatitis C Virus [HCV] infection),
History of other malignancies within 5 years prior to the first study drug administration. Exceptions include cured cutaneous squamous cell carcinoma, basal cell carcinoma, non-muscle invasive bladder cancer, localized low-risk prostate cancer (defined as Stage ≤ T2a, Gleason score ≤ 6, curatively treated at diagnosis with no biochemical recurrence of prostate-specific antigen [PSA; PSA ≤ 10 ng/mL if tested]), carcinoma in situ of cervix or breast, and other malignancies deemed appropriate for study participation by the Investigator.
Females of childbearing potential with a positive pregnancy test or who are breastfeeding.
Psychiatric illnesses or disorders that may interfere with study compliance.
Any other conditions that render the participants unsuitable for study participation, as determined by the Investigator.
Exclusion Criteria for the Combination cohort with Docetaxel
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| wei wang | Contact | 021-68889618 | weiwang@Lanovamed.com | |
| liang kong | Contact | 021-68889618 | Paulkong@lanovamed.com |
| Name | Affiliation | Role |
|---|---|---|
| lin shen | Peking University Cancer Hospital & Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Cancer Hospital | Beijing | Beijing Municipality | 201210 | China |
Not provided
| ID | Term |
|---|---|
| C000707970 | tislelizumab |
| D000077143 | Docetaxel |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Tislelizumab | Drug | Q3W,Intravenous Drip |
|
| Docetaxel injection | Drug | Q3W,Intravenous Drip |
|
Dose expansion phase
| From start of treatment to date of documented disease progression, up to approximately 42 months |
| Progression Free Survival (PFS) | Dose expansion phase | up to 42 months |
| Overall Survival (OS) | Dose expansion phase | up to 42 months |
| AE and SAE | Safety introduction phase/Dose expansion phase | From signing the ICF until 28 days after EOT or accept other anti-cancer therapy,up to 40 days after last study dose |
| Pharmacokinetic (PK) Parameter: Area Under the Concentration-time Curve from time zero to the last quantifiable concentration (AUC last) | safety introduction phase/Dose expansion phase | up to 42 months |
| Pharmacokinetic (PK) Parameter:Area Under the Concentration-time Curve over a dosing interval (τ) at steady state(AUC tau) | safety introduction phase/Dose expansion phase | up to 42 months |
| Pharmacokinetic (PK) Parameter:Maximum Observed Concentration(Cmax) | safety introduction phase/Dose expansion phase | up to 42 months |
| Pharmacokinetic (PK) Parameter:Time to Reach Maximum Concentration(Tmax) | safety introduction phase/Dose expansion phase | up to 42 months |
| Pharmacokinetic (PK) Parameter:Elimination Half-life(T 1/2) | safety introduction phase/Dose expansion phase | up to 42 months |
| Pharmacokinetic (PK) Parameter:Maximum Steady-State Concentration(Cmax, ss) | safety introduction phase/Dose expansion phase | up to 42 months |
| Pharmacokinetic (PK) Parameter:Minimum Steady-State Concentration(Cmin, ss) | safety introduction phase/Dose expansion phase | up to 42 months |
| Pharmacokinetic (PK) Parameter:Clearance at Steady State(CLss) | safety introduction phase/Dose expansion phase | up to 42 months |
| Pharmacokinetic (PK) Parameter:Volume of Distribution at Steady State(Vss) | safety introduction phase/Dose expansion phase | up to 42 months |
| Pharmacokinetic (PK) Parameter:Accumulation Ratio based on AUC(Rac, AUC) | safety introduction phase/Dose expansion phase | up to 42 months |
| Pharmacokinetic (PK) Parameter:Accumulation Ratio based on Cmax(Rac, Cmax) | safety introduction phase/Dose expansion phase | up to 42 months |
| Pharmacokinetic (PK) Parameter:Fluctuation Index / Degree of Fluctuation | safety introduction phase/Dose expansion phase | up to 42 months |
| immunogenicity Parameter:Anti-Drug Antibody(ADA) | safety introduction phase/Dose expansion phase | up to 42 months |
| immunogenicity Parameter:Neutralizing Antibody(Nab) | safety introduction phase/Dose expansion phase | up to 42 months |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |