Patients With Advanced Solid Tumors
Conditions
Brief summary
This study is a Phase I clinical trial evaluating the safety, tolerability, pharmacokinetic characteristics, and preliminary antitumor efficacy of LNF2105 in patients with advanced solid tumors.
Interventions
DRUGLNF2105(Antibody-Drug Conjugate (ADC) targeting Nectin-4)
The dosage of LNF2105 was increased sequentially from 0.3 mg/kg, 0.6 mg/kg, 1.2 mg/kg, 2.0 mg/kg, 3.0 mg/kg, to 4.5 mg/kg.
Sponsors
Shandong New Time Pharmaceutical Co., LTD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female aged ≥18 years. 2. Patients with advanced solid tumors (including but not limited to urothelial carcinoma, breast cancer, non-small cell lung cancer, ovarian cancer, endometrial cancer, and cervical cancer) that have been histologically or cytologically confirmed as having failed/cannot tolerate/have no standard treatment/are currently unsuitable for standard treatment. 3. Able to provide previous Nectin-4 expression testing results or preserved/fresh tumor tissue for Nectin-4 expression testing. 4. At least one measurable lesion (CT or MRI long axis ≥ 10 mm, lymph node short axis ≥ 15 mm) according to RECIST v1.1 criteria. For lesions previously treated with radiotherapy, they will only be included as measurable lesions if there has been clear disease progression after radiotherapy. 5. The function of vital organs must meet the following requirements (no blood components or cytokines may be used within 14 days prior to the first dose). 7\) ECOG score 0-1. 8) Expected survival ≥ 3 months. 9) Willing to participate and sign informed consent form, and willing to follow the trial treatment protocol and visitation plan.
Exclusion criteria
1. Prior treatment with an antibody-drug conjugate (ADC) exhibiting one of the following characteristics: payload as a topoisomerase I inhibitor (TOP 1 inhibitor); antibody target as Nectin-4. 2. Received any P-glycoprotein (P-gp) inducer/inhibitor, strong CYP3A inhibitor, or breast cancer resistance protein (BCRP) inhibitor within 14 days prior to first administration (see Appendix 3 for the exclusion list). 3. Patients who received chemotherapy within 3 weeks or radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy, or other anti-tumor treatments within 4 weeks prior to first administration of the study drug, excluding the following. 4. Patients who received systemic glucocorticoid therapy or any other form of immunosuppressive therapy (equivalent to a prednisone dose \>10 mg/day) within 2 weeks prior to the first dose. 5. Patients whose adverse reactions to previous antitumor therapy have not recovered to a CTCAE 5.0 grade ≤1 or the level specified in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate of Safety and Tolerability of LNF2105 in Patients with Advanced Solid Tumors | Approximately 24months | Numbers of treatment emergent adverse events with severity determined using NCI CTCAE v6.0 after single or multiple doses of LNF2105. |
| To confirm Dose Limiting Toxicities (DLT) and determine MTD and RP2D for LNF2105 | 28 days | Occurrence of Dose Limiting Toxicities as defined in the protocol |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma concentration of LNF2105 (ADC), Total Antibody and Free Payload (Cmax) | Approximately 24 months | Maximum observed plasma concentration ofLNF2105 (ADC), Total Antibody and Free Payload after single and multiple doses |
| Time to reach Cmax of LNF2105 (ADC), Total Antibody and Free Payload (Tmax) | 24 month | The amount of time to reach Cmax after single and multiple dose administration of LNF2105 (ADC), Total Antibody and Free Payload |
| Total Area Under the plasma concentration-time curve of LNF2105 (ADC), Total Antibody and Free Payload (AUC) | 24 month | Area under the plasma concentration versus time curve after single and multiple dose administration of LNF2105 (ADC), Total Antibody and Free Payload |
| Minimum Plasma Concentration (Cmin) of LNF2105 (ADC), Total Antibody and Free Payload | 24 month | Minimum Plasma Concentration (Cmin) of of LNF2105 (ADC), Total Antibody and Free Payload after multiple doses |
| To evaluate the preliminary antitumor activity of LNF2105: Overall response rate (ORR) | Approximately 24months | ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) |
| To evaluate the preliminary antitumor activity of LNF2105: Progression free survival (PFS) | Approximately 24months | PFS per investigator assessed RECIST 1.1 |
| To evaluate the preliminary antitumor activity of LNF2105: Duration of response (DOR) | Approximately 24months | Anti-tumor preliminary efficacy will be evaluated of LNF2105 in accordance with RECIST v1.1 |
| To evaluate the preliminary antitumor activity of LNF2105: Disease control rate (DCR) | Approximately 24months | DCR per investigator assessed RECIST 1.1 |
| To evaluate the preliminary antitumor activity of LNF2105: Time to response (TTR) | Approximately 24months | TTR per investigator assessed RECIST 1.1 |
| To evaluate the preliminary antitumor activity of LNF2105: Overall survival (OS) | Approximately 24months | OS per investigator assessed RECIST 1.1 |
| To evaluate the immunogenicity of LNF2105 | Approximately 24months | To evaluate the levels of anti-drug antibody (ADA) generated by study participants. Confirmatory testing will be performed on ADA-positive samples; confirmed positive samples will undergo subsequent titer determination as appropriate. |
Contacts
CONTACTShaohong Yin
Outcome results
None listed